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1.
Molecules ; 26(19)2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34641389

RESUMO

Widespread resistance in parasitic nematodes to most classes of anthelmintic drugs demands the discovery and development of novel compounds with distinct mechanisms of action to complement strategic or integrated parasite control programs. Products from nature-which assume a diverse 'chemical space'-have significant potential as a source of anthelmintic compounds. In the present study, we screened a collection of extracts (n = 7616) derived from marine invertebrates sampled from Australian waters in a high throughput bioassay for in vitro anti-parasitic activity against the barber's pole worm (Haemonchus contortus)-an economically important parasitic nematode of livestock animals. In this high throughput screen (HTS), we identified 58 active extracts that reduced larval motility by ≥70% (at 90 h), equating to an overall 'hit rate' of ~0.8%. Of these 58 extracts, 16 also inhibited larval development by ≥80% (at 168 h) and/or induced 'non-wild-type' (abnormal) larval phenotypes with reference to 'wild-type' (normal) larvae not exposed to extract (negative controls). Most active extracts (54 of 58) originated from sponges, three from chordates (tunicates) and one from a coral; these extracts represented 37 distinct species/taxa of 23 families. An analysis of samples by 1H NMR fingerprinting was utilised to dereplicate hits and to prioritise a set of 29 sponge samples for future chemical investigation. Overall, these results indicate that a range of sponge species from Australian waters represents a rich source of natural compounds with nematocidal or nematostatic properties. Our plan now is to focus on in-depth chemical investigations of the sample set prioritised herein.


Assuntos
Anti-Helmínticos/farmacologia , Hemoncose/tratamento farmacológico , Haemonchus/crescimento & desenvolvimento , Poríferos/química , Extratos de Tecidos/farmacologia , Animais , Anti-Helmínticos/isolamento & purificação , Hemoncose/parasitologia , Haemonchus/efeitos dos fármacos , Ensaios de Triagem em Larga Escala , Extratos de Tecidos/isolamento & purificação
2.
Int J Mol Sci ; 22(18)2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34575945

RESUMO

We investigated the effects of adipose-derived extract (AE) on cultured chondrocytes and in vivo cartilage destruction. AE was prepared from human adipose tissues using a nonenzymatic approach. Cultured human chondrocytes were stimulated with interleukin-1 beta (IL-1ß) with or without different concentrations of AE. The effects of co-treatment with AE on intracellular signaling pathways and their downstream gene and protein expressions were examined using real-time PCR, Western blotting, and immunofluorescence staining. Rat AE prepared from inguinal adipose tissues was intra-articularly delivered to the knee joints of rats with experimental osteoarthritis (OA), and the effect of AE on cartilage destruction was evaluated histologically. In vitro, co-treatment with IL-1ß combined with AE reduced activation of the p38 and ERK mitogen-activated protein kinase (MAPK) pathway and nuclear translocation of the p65 subunit of nuclear factor-kappa B (NF-κB), and subsequently downregulated the expressions of matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, IL-6, and IL-8, whereas it markedly upregulated the expression of IL-1 receptor type 2 (IL-1R2) in chondrocytes. Intra-articular injection of homologous AE significantly ameliorated cartilage destruction six weeks postoperatively in the rat OA model. These results suggested that AE may exert a chondroprotective effect, at least in part, through modulation of the IL-1ß-induced inflammatory signaling pathway by upregulation of IL-1R2 expression.


Assuntos
Inflamação/tratamento farmacológico , Interleucina-1beta/genética , Osteoartrite/tratamento farmacológico , Receptores Tipo II de Interleucina-1/genética , Tecido Adiposo/química , Animais , Cartilagem/efeitos dos fármacos , Cartilagem/patologia , Condrócitos/efeitos dos fármacos , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/genética , Inflamação/patologia , Osteoartrite/genética , Osteoartrite/patologia , Ratos , Transdução de Sinais/efeitos dos fármacos , Extratos de Tecidos/química , Extratos de Tecidos/farmacologia
3.
Int J Mol Sci ; 22(16)2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34445533

RESUMO

Aeromonas spp. cause many diseases in aquaculture habitats. Hermetia illucens (Hi) larvae were used as feed-in aquacultures and in eradicating pathogenic fish bacteria. In the present study, we applied consecutive extractions of the same biomass of BSFL fat using the acidic water-methanol solution. The major constituents of the sequential extracts (SEs) were free fatty acids (FFAs), and fatty acids derivatives as identified by gas chromatography spectrometry (GC-MS). Our improved procedure enabled gradual enrichment in the unsaturated fatty acids (USFAs) content in our SEs. The present study aimed to compare the composition and antimicrobial properties of SEs. Among actual fish pathogens, A. hydrophila and A. salmonicida demonstrated multiple drug resistance (MDR) against different recommended standard antibiotics: A. salmonicida was resistant to six, while A. hydrophila was resistant to four antibiotics from ten used in the present study. For the first time, we demonstrated the high dose-dependent antibacterial activity of each SE against Aeromonas spp., especially MDR A. salmonicida. The bacteriostatic and bactericidal (MIC/MBC) activity of SEs was significantly enhanced through the sequential extractions. The third sequential extract (AWME3) possessed the highest activity against Aeromonas spp.: inhibition zone diameters were in the range (21.47 ± 0.14-20.83 ± 0.22 mm) at a concentration of 40 mg/mL, MIC values ranged between 0.09 and 0.38 mg/mL for A. hydrophila and A. salmonicida, respectively. AWME3 MBC values recorded 0.19 and 0.38 mg/mL, while MIC50 values were 0.065 ± 0.004 and 0.22 ± 0.005 mg/mL against A. hydrophila and A. salmonicida, respectively. Thus, the larvae fat from Hermitia illucens may serve as an excellent reservoir of bioactive molecules with good capacity to eradicate the multidrug-resistant bacteria, having promising potential for practical application in the aquaculture field.


Assuntos
Aeromonas/patogenicidade , Antibacterianos/farmacologia , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Ácidos Graxos/farmacologia , Doenças dos Peixes/prevenção & controle , Larva/química , Extratos de Tecidos/farmacologia , Animais , Dípteros , Doenças dos Peixes/microbiologia , Peixes
4.
Front Immunol ; 12: 670159, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34456904

RESUMO

Intestinal fibrosis is induced by excessive myofibroblast proliferation and collagen deposition, which has been regarded as a general pathological feature in inflammatory bowel disease (IBD). Therefore, identifying clinical markers and targets to treat and prevent intestinal fibrosis is urgently needed. The traditional Chinese medicine maggot, commonly known as "wu gu chong", has been shown to reduce oxidative stress and alleviate inflammation in chronic colitis. This study investigated the mechanisms underlying the effects of maggot extract (ME) on inflammation-associated intestinal fibrosis in TGF-ß1-stimulated human intestinal fibroblasts (CCD-18Co cells) and dextran sodium sulphate (DSS)-induced chronic colitis murine model. To assess the severity of inflammation and fibrosis, histological and macroscopic evaluation were carried out. The results showed that ME was a significant inhibitor of body weight loss and colon length shortening in mice with chronic colitis. In addition, ME suppressed the intestinal fibrosis by downregulating TGF-ß1/SMADs pathway via upregulation of Nrf2 expression at both protein and mRNA levels. ME markedly increased the expression of Nrf2, thus resulting in a higher level of HO-1. After treatment with Nrf2 inhibitor (ML385) or siRNA-Nrf2 for deactivating Nrf2 pathway, the protective effects of ME were abolished both in vitro and in vivo. Moreover, the histopathological results for the major organs of DSS mice treated with ME showed no signs of clinically important abnormalities. Treatment with ME had no effect on the viability of CCD-18Co cells, suggesting its low in vitro cytotoxicity. Furthermore, ME could mediate intestine health by keeping the balance of the gut microbes through the enhancement of beneficial microbes and suppression of pathogenic microbes. In conclusion, this is the first ever report demonstrating that ME ameliorates inflammation-associated intestinal fibrosis by suppressing TGF-ß1/SMAD pathway via upregulation of Nrf2 expression. Our findings highlight the potential of Nrf2 as an effective therapeutic target for alleviating intestinal fibrosis.


Assuntos
Anti-Inflamatórios/farmacologia , Calliphoridae/química , Colite/prevenção & controle , Colo/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Extratos de Tecidos/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Calliphoridae/embriologia , Colite/induzido quimicamente , Colite/metabolismo , Colite/patologia , Colo/metabolismo , Colo/microbiologia , Colo/patologia , Sulfato de Dextrana , Modelos Animais de Doenças , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibrose , Microbioma Gastrointestinal , Humanos , Larva/química , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/genética , Células RAW 264.7 , Transdução de Sinais , Extratos de Tecidos/isolamento & purificação , Regulação para Cima
5.
Expert Rev Clin Pharmacol ; 14(10): 1253-1266, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34263692

RESUMO

Introduction: The proven efficacy of the cellular vaccine sipuleucel-T in 2010 led to optimism about immunotherapeutic approaches for the treatment of prostate cancer. Some surmised that prostate cancer might be an ideal target for immune-mediated killing given that the prostate is not an essential organ and expresses unique proteins including prostate-specific antigen, prostate-specific membrane antigen, and prostatic acid phosphatase that could be targeted without side effects. Subsequently, antibodies that inhibit the T cell checkpoints PD1 and CTLA4 were shown to stimulate antitumor immune responses, leading to tumor regression in several cancer types. These therapies have since been tested in several studies as treatments for prostate cancer, but appear to have limited efficacy in molecularly unselected patients.Areas covered: In this review, we discuss these studies and evaluate features of prostate cancer and its host environment that may render it generally resistant to CTLA4 and PD1 blockade. We provide an overview of alternate immune checkpoints that may hold greater significance in this disease.Expert opinion: Combination therapies to target multiple layers of alternate immune checkpoints may be required for an effective immune response to prostate cancer. We discuss combination therapies currently being investigated.


Assuntos
Vacinas Anticâncer/administração & dosagem , Imunoterapia/métodos , Neoplasias da Próstata/terapia , Resistencia a Medicamentos Antineoplásicos , Humanos , Inibidores de Checkpoint Imunológico/administração & dosagem , Masculino , Terapia de Alvo Molecular , Seleção de Pacientes , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/imunologia , Extratos de Tecidos/administração & dosagem
6.
Mar Drugs ; 19(5)2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-34064922

RESUMO

Metabolic syndrome-related diseases affect millions of people worldwide. It is well established that changes in nutritional habits and lifestyle can improve or prevent metabolic-related pathologies such as type-2 diabetes and obesity. Previous reports have shown that nutritional supplements have the capacity to limit glucose intolerance and suppress diabetes development. In this study, we investigated the effect of dietary supplementation with fish-derived extracts on obesity and type 2 diabetes and their impact on gut microbial composition. We showed that nutritional supplements containing Fish Complex (FC), Fish Complex combined with Cod Powder (FC + CP), or Cod Powder combined with Collagen (CP + C) improved glucose intolerance, independent of abdominal fat accumulation, in a mouse model of diet-induced obesity and type 2 diabetes. In addition, collagen-containing supplements distinctly modulate the gut microbiome in high-fat induced obesity in mice. Our results suggest that fish-derived supplements suppress diet-induced type 2 diabetes, which may be partly mediated through changes in the gut microbiome. Thus, fish-derived supplements and particularly the ones containing fish collagen have potential beneficial properties as dietary supplements in managing type 2 diabetes and metabolic syndrome via modulation of the gut microbiome.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Suplementos Nutricionais , Peixes , Microbioma Gastrointestinal/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Obesidade , Extratos de Tecidos/farmacologia , Gordura Abdominal/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/complicações , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais/microbiologia , Modelos Animais de Doenças , Feminino , Intolerância à Glucose/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Resistência à Insulina , Leptina/metabolismo , Camundongos Endogâmicos C57BL , Obesidade/induzido quimicamente , Obesidade/complicações , Extratos de Tecidos/isolamento & purificação , Extratos de Tecidos/uso terapêutico
7.
Mar Drugs ; 19(5)2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34068988

RESUMO

Fish gelatin and its hydrolysates exhibit a variety of biological characteristics, which include antihypertensive and antioxidant properties. In this study, fish gelatins were extracted from extrusion-pretreated tilapia scales, and then subjected to analyses to determine the physicochemical properties and antioxidant activity of the extracted gelatins. Our findings indicate that TSG2 (preconditioned with 1.26% citric acid) possessed the greatest extraction yield, as well as higher antioxidant activities compared with the other extracted gelatins. Hence, TSG2 was subjected to further hydrolyzation using different proteases and ultrafiltration conditions, which yielded four gelatin hydrolysates: TSGH1, TSGH2, TSGH3, and TSGH4. The results showed that TSGH4 (Pepsin + Pancreatin and ultrafiltration < 3000 Da) had a higher yield and greater antioxidant activity in comparison with the other gelatin hydrolysates. As such, TSGH4 was subjected to further fractionation using a Superdex peptide column and two-stage reverse-phase column HPLC chromatography, yielding a subfraction TSGH4-6-2-b, which possessed the highest 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity compared with the other fractions. Further LC-ESI/MS/MS analysis of TSGH4-6-2-b suggested two novel peptides (GYDEY and EPGKSGEQGAPGEAGAP), which could have potential as naturally-occurring peptides with antioxidant properties. These promising results suggest that these antioxidant peptides could have applications in food products, nutraceuticals, and cosmetics.


Assuntos
Antioxidantes/farmacologia , Ciclídeos , Gelatina/química , Gelatina/farmacologia , Escamas de Animais/química , Animais , Antioxidantes/química , Fenômenos Químicos , Cromatografia em Gel , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Cromatografia de Fase Reversa , Proteínas de Peixes/química , Proteínas de Peixes/isolamento & purificação , Proteínas de Peixes/farmacologia , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Gelatina/isolamento & purificação , Hidrólise , Peso Molecular , Peptídeo Hidrolases/química , Peptídeos/química , Peptídeos/isolamento & purificação , Peptídeos/farmacologia , Espectrometria de Massas por Ionização por Electrospray , Espectroscopia de Infravermelho com Transformada de Fourier , Espectrometria de Massas em Tandem , Extratos de Tecidos/análise , Extratos de Tecidos/química , Extratos de Tecidos/isolamento & purificação , Extratos de Tecidos/farmacologia
8.
J Food Sci ; 86(7): 3061-3074, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34151429

RESUMO

In order to optimize protein recovery from catfish byproducts by alkaline extraction, the effects of different factors, including particle size, mince-to-water ratio, pH, and extraction time were investigated. It was found that a protein recovery of about 30% could be achieved. Increases in pH (pH 10.5, 11, and 11.5) not only improved protein recovery, but also increased protein denaturation evidenced by decreased solubility, decreased α-helix, increased ß-sheet, and increased random coil. The color and texture of gels made from protein isolate were greatly affected by the pH values used for protein extraction. For the gels made from fillet mince, and protein isolates extracted at pH 10.5, 11, and 11.5, the "L" values were 78.96, 60.38, 57.74, and 54.39, the breaking forces were 205, 492, 585, and 458 g, and deformation values were 10.59, 8.07, 6.73, and 5.04 mm, respectively. Electrophoresis revealed protein degradation during alkali-aided extraction with MHC, the most predominant band, showing about 50% decrease in comparison with fillet mince. It also demonstrated that gelation not only caused cross-linking, but also autolysis with 53%, 56%, 59%, and 81% decrease in MHC intensity for fillet mince, protein isolates extracted at pH 10.5, 11, and 11.5, respectively. Fillet mince and protein isolates exhibited different storage modulus patterns during temperature sweep, implying different gelation mechanisms. This study proved the protein extracted from catfish byproducts was potential to be utilized as edible food components especially in gel making. PRACTICAL APPLICATION: Catfish byproducts, which account for 70% of total weight and 50% of total protein of catfish, are normally used as animal feed, fertilizer, or even waste. This study demonstrated the potential of the utilization of catfish wastes to develop edible food components. This could reduce the total processing waste being discarded into the environment and nutrient loss, therefore increasing profitability of catfish industry.


Assuntos
Proteínas de Peixes/farmacologia , Géis/química , Extratos de Tecidos/química , Animais , Peixes-Gato , Proteínas de Peixes/química , Concentração de Íons de Hidrogênio , Solubilidade , Temperatura
9.
J Biomed Nanotechnol ; 17(5): 873-888, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-34082873

RESUMO

Tissue engineering is a promising approach for the treatment of chronic lower back pain (LBP) caused by intervertebral disc degeneration (IDD) resulting from degeneration and inflammation of annulus fibrosus (AF) tissue. However, scaffold with an anti-inflammatory effect on AF cells has not been reported. In this study, we fabricated a polylactide-glycolide (PLGA)/poly-ε-caprolactone (PCL)Zdextran (DEX) composite membrane loaded with plastrum testudinis extract (PTE), a Traditional Chinese Medicine herbal extract, via electrospinning. The membranes were characterized by mechanical measurements and scanning electron microscopy (SEM). Using an in vitro inflammation model induced by interleukin (IL)-1ß, the cytocompatibility and anti-inflammatory effects of the composites were investigated by CCK-8 assay and flow cytometry. Potential regulatory mechanisms were examined by RT-qPCR and Western blotting. The results showed that the P10P8D2 (PLGA 10 g, PCL 8 g, DEX 2 g) composite nanofiber membrane exhibited the most uniform diameter distribution, best mechanical properties, a moderate degradation rate, and the best cytocompatibility characteristics. The optimal concentration of PTE was 120 µg/mL. Importantly, P10P8D2 combined with PTE exhibited anti-inflammatory and cell proliferation promotion effects. Moreover, the NF-κBB/NLRP3/IL-ß signaling pathway was inactivated. Our findings suggested that the nanofiber membrane composed of P10P8D2 and PTE has anti-inflammatory and pro-proliferation effects on AF cells. It may provide an effective strategy for AF tissue regeneration.


Assuntos
Anel Fibroso , Nanofibras , Anti-Inflamatórios/farmacologia , Caproatos , Dextranos , Lactonas , Extratos Vegetais , Poliésteres , Engenharia Tecidual , Extratos de Tecidos , Tecidos Suporte
10.
Int J Mol Sci ; 22(9)2021 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-34066758

RESUMO

Epoxy-fatty acids (EpFAs) are endogenous lipid mediators that have a large breadth of biological activities, including the regulation of blood pressure, inflammation, angiogenesis, and pain perception. For the past 20 years, soluble epoxide hydrolase (sEH) has been recognized as the primary enzyme for degrading EpFAs in vivo. The sEH converts EpFAs to the generally less biologically active 1,2-diols, which are quickly eliminated from the body. Thus, inhibitors of sEH are being developed as potential drug therapeutics for various diseases including neuropathic pain. Recent findings suggest that other epoxide hydrolases (EHs) such as microsomal epoxide hydrolase (mEH) and epoxide hydrolase-3 (EH3) can contribute significantly to the in vivo metabolism of EpFAs. In this study, we used two complementary approaches to probe the relative importance of sEH, mEH, and EH3 in 15 human tissue extracts: hydrolysis of 14,15-EET and 13,14-EDP using selective inhibitors and protein quantification. The sEH hydrolyzed the majority of EpFAs in all of the tissues investigated, mEH hydrolyzed a significant portion of EpFAs in several tissues, whereas no significant role in EpFAs metabolism was observed for EH3. Our findings indicate that residual mEH activity could limit the therapeutic efficacy of sEH inhibition in certain organs.


Assuntos
Epóxido Hidrolases/metabolismo , Ácidos Graxos/metabolismo , Microssomos/enzimologia , Especificidade de Órgãos , Epóxido Hidrolases/antagonistas & inibidores , Humanos , Hidrólise , Cinética , Proteínas Recombinantes/metabolismo , Solubilidade , Especificidade por Substrato , Extratos de Tecidos
11.
Artigo em Inglês | MEDLINE | ID: mdl-34097576

RESUMO

Sulphonamides (SAs) are widely used in animal husbandry. In our work, based on multi-walled carbon nanotubes, a novel residue method was developed for highly sensitive and determination trace levels of sulfamethoxazole, acetyl sulfamethoxazole and aditoprim in edible swine tissues by LC-MS/MS with magnetic solid-phase extraction. The samples were extracted using 2% ammoniated acetonitrile and purified by magnetic solid phase extraction (MSPE). Under the optimal conditions, good linearity was obtained ranging from 5 to 160 µg kg-1. The limits of detection (LOD) and quantification (LOQ) were 2 µg kg-1 and 5 µg kg-1 respectively. The average recoveries were 73.9-94.8% at different spiking levels. The inter-day RSDs were 6.2-10.7% and the intra-day RSDs were 2.4-5.4%. MSPE based on multi-walled carbon nanotubes was a simple and efficient method to enrich and separate the analyses and could be successfully applied for extraction of sulfamethoxazole, acetyl sulfamethoxazole and aditoprim residues in swine tissues.


Assuntos
Nanotubos de Carbono/química , Extração em Fase Sólida/métodos , Sulfametoxazol/análise , Extratos de Tecidos/análise , Trimetoprima/análogos & derivados , Animais , Cromatografia Líquida de Alta Pressão , Resíduos de Drogas/análise , Contaminação de Alimentos/análise , Humanos , Limite de Detecção , Fenômenos Magnéticos , Suínos , Espectrometria de Massas em Tandem , Trimetoprima/análise , Drogas Veterinárias/análise
12.
Sci Rep ; 11(1): 13157, 2021 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-34162937

RESUMO

Stimulator of interferon genes (STING) is a DNA sensor that responds to pathogens and induces type I interferon production. Herein, the role of STING in house dust mite extract (HDM)-induced allergic asthma was investigated. C57BL/6 wild-type (WT) and Sting-/- mice were intratracheally sensitized with HDM, and the bronchoalveolar lavage fluid (BALF), sera, lungs, and mediastinal lymph nodes (MLNs) were analyzed. The total and HDM-specific serum IgE levels were lower in Sting-/- mice than in WT mice. B cell and IgE-positive B cell proportion in BALF and MLNs, respectively, was significantly lower in Sting-/- mice than in WT mice. Additionally, cyclic GMP-AMP, a STING ligand, augmented total and HDM-specific serum IgE levels and B cell proportion in BALF when applied in combination with HDM. To elucidate the role of STING in IgE production, follicular helper T (Tfh) cells, which are involved in B cell maturation, were investigated. Tfh cell proportion in MLNs decreased in Sting-/- mice, and IL-4 and IL-13 production by HDM-restimulated MLN cells from HDM-sensitized mice was decreased in Sting-/- mice compared with WT mice. Thus, STING plays an important role in the maturation and class switching of IgE-producing B cells in allergic inflammation via Tfh cells.


Assuntos
Alérgenos/imunologia , Asma/genética , Imunoglobulina E/biossíntese , Proteínas de Membrana/fisiologia , Extratos de Tecidos/imunologia , Animais , Asma/etiologia , Asma/imunologia , Linfócitos B/imunologia , Líquido da Lavagem Broncoalveolar/citologia , Feminino , Switching de Imunoglobulina , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Interleucina-13/biossíntese , Interleucina-13/genética , Interleucina-4/biossíntese , Interleucina-4/genética , Proteínas de Membrana/deficiência , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Nucleotídeos Cíclicos/farmacologia , Pyroglyphidae , Reação em Cadeia da Polimerase em Tempo Real , Células T Auxiliares Foliculares/imunologia
13.
PLoS One ; 16(6): e0249291, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34077422

RESUMO

Naturally-derived proteins or peptides are promising biopolymers for tissue engineering applications owing to their health-promoting activity. Herein, we extracted proteins (~90%) from two-spotted cricket (Gryllus bimaculatus) and evaluated their osteoinductive potential in human bone marrow-derived mesenchymal stem cells (hBMSCs) under in vitro conditions. The extracted protein isolate was analyzed for the amino acid composition and the mass distribution of the constituent peptide fraction. Fourier transform infrared (FTIR) spectroscopy was used to determine the presence of biologically significant functional groups. The cricket protein isolate (CPI) exhibited characteristic protein peaks in the FTIR spectrum. Notably, an enhanced cell viability was observed in the presence of the extracted proteins, showing their biocompatibility. The CPI also exhibited antioxidant properties in a concentration-dependent manner. More significant mineralization was observed in the CPI-treated cells than in the control, suggesting their osteoinductive potential. The upregulation of the osteogenic marker genes (Runx2, ALP, OCN, and BSP) in CPI treated media compared with the control supports their osteoinductive nature. Therefore, cricket-derived protein isolates could be used as functional protein isolate for tissue engineering applications, especially for bone regeneration.


Assuntos
Antioxidantes/metabolismo , Diferenciação Celular , Proteínas de Insetos/administração & dosagem , Células-Tronco Mesenquimais/citologia , Osteogênese , Extratos de Tecidos/farmacologia , Animais , Células Cultivadas , Gryllidae , Humanos , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Engenharia Tecidual
14.
Asian Pac J Cancer Prev ; 22(5): 1365-1373, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-34048163

RESUMO

Cancer is an uncontrolled multiplication of cells. The desire efficacy and severe toxicity of current anticancer drugs urge exploring and investigating a better alternative to existing chemotherapeutics. Natural products of marine origin are excellent sources of potential new drugs of enhanced biological activities. OBJECTIVES: Thus, the cytotoxic effects along with investigating the mode of cell death exerted by fractions, AP-9, AP-THR, DS-8 and DS-9 fraction of Acanthaster planci, Diadema setosum sp., on the human cervical cancer cell line, HeLa. METHODS: The cytotoxicity of fractions has determined by using an MTS assay. The early and late apoptosis was studied by using the High content Screening (HCS) instrument. RESULTS: The four fractions produced effective cytotoxicity effects with IC50 values at 72hr of less than 20 µg/ml in the order of AP-9 > DS-9 > APTHR-9 > DS-8. The fraction s exhibited cytotoxicity via mediating apoptotic mode of cell death. The early apoptosis by exposure of phosphatidylserine to the outer leaflet of the plasma membrane and late apoptosis due to the presence of green stain (DNA fragmentation) in treated cells. CONCLUSION: The potent bioactive compounds might be responsible for inducing apoptosis in cancer cells and, thus, the potential to be a successful candidate for exploring upcoming chemotherapeutic drugs.


Assuntos
Antineoplásicos/farmacologia , Apoptose , Ouriços-do-Mar/química , Estrelas-do-Mar/química , Extratos de Tecidos/farmacologia , Neoplasias do Colo do Útero/tratamento farmacológico , Animais , Proliferação de Células , Feminino , Células HeLa , Humanos , Neoplasias do Colo do Útero/patologia
15.
J Ethnopharmacol ; 276: 114191, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-33971302

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Dynameron is a Byzantine medical compendium, divided into 24 sections, in accordance with the letters of the Greek alphabet. Being the largest medical and pharmaceutical book ever written in Byzantium, Dynameron contains 2667 recipes intended to treat many pathological conditions. A lot of information convey to us through prescriptions. In addition to plants, Nikolaos Myrepsos proposes the use of many animals, animal parts and animal by-products, for the treatment of various diseases. This article presents for the first time a full account of the animal products included in Dynameron. AIM OF THE STUDY: In continuation to our previous studies, this paper focuses on the use of animal products in composite medicines described in Dynameron. An effort was made to trace down the use of similar or identical animal products in texts of earlier medical writers. Recording recipes with animals or animal products intended for use in everyday medical practice highlights the timeless belief in their healing properties. MATERIALS AND METHODS: Our main source of material is the recent digital edition of Nikolaos Myrepsos' Dynameron. This huge treatise was written in the 13th century and reflects in many ways the long medical tradition of the Greek, the Hellenistic and the Roman eras, having also received influences from the materia medica of Arabic medicine. In addition, information from dictionaries and databases were cross-checked to confirm and classify the animals and their products and to identify them. For the various pathological conditions these products are meant for, we have used the current medical terminology. RESULTS: In the present study, we could identify the therapeutic use of 93 animals. In several instances, Myrepsos suggests the use of specific organs of an animal, and for that reason he includes in his treatise 16 anatomical parts of different animals. Moreover, Dynameron comprises also 34 animal by-products, such as milk and honey. Medicines of animal origin are used in recipes concerning diseases of the respiratory, the digestive, the cardiovascular and the urinary system, as well as gynecological diseases, and ailments of the eyes, the ears and the skin. CONCLUSIONS: Of the 2667 recipes of Dynameron, 344 recipes contain medicines of animal origin, which can be detected in totally 769 citations. In addition, 626 citations for animal by-products are found in 268 recipes. Honey and milk are quoted in 2136 recipes, mostly as excipients. Dietary instructions are present on many occasions, reflecting the attitude for a healthy everyday life, similar to the modern beliefs pertaining to food as an essential factor for a good health.


Assuntos
Produtos Biológicos/uso terapêutico , Extratos de Tecidos/uso terapêutico , Animais , Bizâncio , Bases de Dados Factuais , Mel , Humanos , Materia Medica , Medicina Tradicional , Leite
16.
J Ethnopharmacol ; 276: 114195, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-33974944

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Plastrum testudinis (PT) is a kind of single traditional Chinese medicine that can tonify kidney and strengthen bone. Plastrum testudinis extract (PTE) has been approved to promote the osteogenic differentiation of bone marrow-derived mesenchymal stem cells in vitro. However, the mechanism by which PTE reduces osteoclast differentiation has not yet been reported. AIM OF THE STUDY: To explore the potential of PTE as a therapeutic treatment for bone loss caused by senile osteoporosis (SOP). MATERIALS AND METHODS: We evaluated whether PTE could inhibit RANKL-induced osteoclast differentiation both in vitro and in vivo, and investigated PTE-induced phenotypes of human peripheral blood monocytes. RESULTS: We found that PTE inhibited osteoclast differentiation and bone resorption in vitro in a concentration-dependent manner and that PTE treatment is most effective during the early stages of osteoclastogenesis. Moreover, we found that PTE could block the NF-κB signaling pathway in vitro, leading to the down-regulation of osteoclast-specific genes including C-FOS and NFATC1. The results from our in vivo mouse study suggest that PTE treatment suppresses osteoclast formation and mitigates bone loss caused by SOP. Notably, we also found that PTE inhibited RANKL-induced osteoclast differentiation in human peripheral blood monocytes. CONCLUSION: Our results suggest that PTE treatment suppresses osteoclastogenesis and ameliorates bone loss caused by SOP by selectively blocking the nuclear translocation of NF-κB/p50.


Assuntos
Diferenciação Celular/efeitos dos fármacos , NF-kappa B/metabolismo , Osteoclastos/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Extratos de Tecidos/farmacologia , Animais , Reabsorção Óssea/induzido quimicamente , Reabsorção Óssea/tratamento farmacológico , Reabsorção Óssea/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Humanos , Lipopolissacarídeos/toxicidade , Masculino , Camundongos Endogâmicos C57BL , Subunidade p50 de NF-kappa B/metabolismo , Fatores de Transcrição NFATC/metabolismo , Osteoclastos/citologia , Osteoclastos/metabolismo , Osteogênese/efeitos dos fármacos , Osteoporose/etiologia , Osteoporose/metabolismo , Ligante RANK/toxicidade , Extratos de Tecidos/uso terapêutico
17.
J Ethnopharmacol ; 276: 114198, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-33984459

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Plastrum testudinis (PT) has been used in traditional Chinese medicine to treat bone diseases such as senile osteoporosis (SOP) for thousands of years. However, the underlying mechanisms remain largely unknown. AIM OF THE STUDY: This study aims to investigate the possible molecular mechanism of PT in the treatment of SOP using an integrated strategy of network pharmacology and experimental validation. MATERIALS AND METHODS: The compounds of PT and its targets were identified through the BATMAN-TCM database. The SOP-related targets were retrieved from the GeneCards database. Protein-protein interaction information was obtained by inputting the intersection targets into the STRING database. Cytoscape software was used to construct a protein-protein interaction network and a PT-compound-target-SOP network. Using Cytoscape and R software, we conducted GO function and KEGG pathway enrichment analyses. We also conducted in vivo and in vitro experiments to verify the network pharmacology findings. RESULTS: In total, 6 active compounds and 342 targets of PT were screened, of which 57 common targets were related to SOP. The GO biological process enrichment analysis identified 880 entries, mainly relating to the regulation of hormone response, the cell apoptotic process, the apoptotic signaling pathway, NF-kappaB transcription factor activity, fatty acid transportation, osteoclast differentiation, macrophage activation, and inflammatory response. The KEGG pathway enrichment analysis identified 52 entries, including 14 related signaling pathways, which mainly involved the TNF, MAPK, IL-17, AGE-RAGE, estrogen, relaxin, and other signaling pathways. Our in vivo experiments confirmed that PT alleviates SOP, while the in vitro experiments demonstrated that PT exerts a suppressive effect on osteoclast differentiation and bone resorption in a concentration-dependent manner. Furthermore, we observed that PT downregulates the expression of osteoclast-specific genes, including C-FOS, TNF, and BDNF, in the MAPK signaling pathway. CONCLUSION: Through network pharmacology and experimental validation, this study is the first to report that PT downregulates the expression of osteoclast-specific genes, including C-FOS, TNF, and BDNF, in the MAPK signaling pathway, thus exerting a suppressive effect on osteoclast differentiation and bone resorption, which may be the molecular mechanism for PT treatment of SOP.


Assuntos
Osteoporose/tratamento farmacológico , Extratos de Tecidos/farmacologia , Animais , Reabsorção Óssea/tratamento farmacológico , Reabsorção Óssea/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Diferenciação Celular/efeitos dos fármacos , Biologia Computacional , Bases de Dados Factuais , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Medicina Tradicional Chinesa , Camundongos Endogâmicos C57BL , Osteoclastos/efeitos dos fármacos , Osteoporose/metabolismo , Mapas de Interação de Proteínas/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-fos/metabolismo , Coluna Vertebral/diagnóstico por imagem , Extratos de Tecidos/química , Extratos de Tecidos/uso terapêutico , Fator de Necrose Tumoral alfa/metabolismo , Microtomografia por Raio-X
18.
Artigo em Inglês | MEDLINE | ID: mdl-33957353

RESUMO

Phorbas is a widely studied genus of marine sponge and produce structurally rich cytotoxic metabolites. Still, only few studies have assessed metabolites present in Brazilian species. To circumvent redundancy, in this work, we applied and herein report the use of a scouting liquid chromatographic system associate to the design of experiment produced by the DryLab® software to obtain a fast and efficient chromatographic separation of the active hexane fraction, further enabling untargeted high-resolution mass spectrometry (HRMS) data. To this end, a crude hydroalcoholic extract of the sponge Phorbas amaranthus collected in Brazilian coast was prepared and partitioned. The cytotoxicity of the crude extract and the fractions was evaluated using tumor cell culture models. Fragmentation pathways assembled from HRMS data allowed the annotation of 18 known Phorbas metabolites, while 17 metabolites were inferred based on Global Natural Product Social Molecular Networking (GNPS), matching with a further 29 metabolites annotated through molecular subnetwork. The workflow employed demonstrates that chromatographic method development can be accelerated by the use of automated scouting systems and DryLab®, which is useful for profiling natural product libraries, as well as data curation by molecular clusters and should be incorporated to the tools of natural product chemists.


Assuntos
Cromatografia Líquida/métodos , Poríferos , Extratos de Tecidos , Animais , Sobrevivência Celular/efeitos dos fármacos , Células HCT116 , Humanos , Lisofosfolipídeos/química , Poríferos/química , Poríferos/metabolismo , Esteroides/análise , Esteroides/química , Terpenos/análise , Terpenos/química , Extratos de Tecidos/análise , Extratos de Tecidos/metabolismo , Extratos de Tecidos/toxicidade
19.
Artigo em Inglês | MEDLINE | ID: mdl-34043493

RESUMO

A qualitative and quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the sensitive and exhaustive analysis of residues from triarylmethane dyes, triarylmethane-derivative dyes, phenothiazines, phenoxazines and xanthenes in aquaculture samples. For a wider and more robust detection of dye misuse on farms, other residue markers were also included the leuco forms of brilliant green, crystal violet and malachite green; one direct metabolite of Victoria pure blue BO and methylene blue and three bile acids, which are endogenous markers of the effects of dye contamination in fish. We optimised the extraction method by comparing several extraction solvents and sample solvents reported in the literature to have the best extraction efficiency. The residues were determined using a positive electrospray ionisation source. We assessed the parameters of this LC-MS/MS method by evaluating the matrix effects, identification and quantitative parameters according to the criteria stipulated in the European Commission Decision No. 2002/657/EC. A study on the applicability of the method was conducted on various aquaculture species and on a positive catfish.


Assuntos
Aquicultura/métodos , Corantes/análise , Uso Indevido de Medicamentos/prevenção & controle , Resíduos de Drogas/análise , Contaminação de Alimentos/análise , Poluentes Químicos da Água/análise , Animais , Ácidos e Sais Biliares/análise , Peixes-Gato , Cromatografia Líquida de Alta Pressão , Corantes/efeitos adversos , Violeta Genciana/análise , Humanos , Músculos/química , Compostos de Amônio Quaternário/análise , Corantes de Rosanilina/análise , Espectrometria de Massas em Tandem , Extratos de Tecidos/química
20.
ESC Heart Fail ; 8(4): 3360-3368, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33938158

RESUMO

AIMS: The major cardiovascular (CV) adverse effects observed with sipuleucel-T from large multi-institutional clinical trials included thromboembolic events, myocardial infarction, and congestive heart failure in up to 0.3% of patients with CV risk factors. The incidence, outcomes, and mechanisms in real-world clinical settings of these CV adverse effects to date have not been fully elucidated. Our study identified a patient with sipuleucel-T-induced inflammatory cardiomyopathy, which led to the identification of CV adverse effects associated with sipuleucel-T from a large pharmacovigilance database and elucidation of its potential mechanisms. METHODS AND RESULTS: Using the MedDRA term 'cardiac disorders' (System Organ Class level), CV adverse events associated with sipuleucel-T versus all other drugs were reviewed from VigiBase, a large pharmacovigilance database. Disproportionality analysis was calculated by the information component (IC), a Bayesian disproportionality indicator. A positive IC025 (IC 95% lower end credibility interval) value (>0) is the traditional threshold used in statistical signal detection at the Uppsala Monitoring Centre. From VigiBase, the total number of CV adverse drug reaction reported with sipuleucel-T was 306 out of a total of 22 980 104 adverse drug reactions in VigiBase on 10/25/2020. MedDRA preferred terms levels were grouped into major CV adverse drug reaction categories where we observed significant reports of myocardial ischaemia, supraventricular tachycardia (particularly atrial fibrillation/atrial flutter), congestive heart failure, and valvular disorders. Myocardial ischemia included acute myocardial infarction (IC025 2.3) with n = 4/26 (15%) of these individual case safety reports considered fatal. Among patients with 'cardiac failure congestive' (IC025 1.5), 11 of these 43 cases (26%) were fatal with 42 (98%) of these cases considered to be solely due to sipuleucel-T. CONCLUSIONS: Patients with CV risk factors who are receiving sipuleucel-T may be at higher risk for congestive heart failure, myocardial ischemia, and supraventricular tachycardia. Electrocardiograms during weekly sipuleucel-T infusions and left ventricular function monitoring with echocardiogram should be considered in these patients. Our findings are suggestive of another rare presentation of T-cell-mediated CV toxicity with cancer immunotherapy.


Assuntos
Miocardite , Farmacovigilância , Sistemas de Notificação de Reações Adversas a Medicamentos , Teorema de Bayes , Humanos , Extratos de Tecidos
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