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1.
Mar Drugs ; 17(4)2019 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-30974812

RESUMO

Chitosanase has attracted great attention due to its potential applications in medicine, agriculture, and nutraceuticals. In this study, P. mucilaginosus TKU032, a bacterial strain isolated from Taiwanese soil, exhibited the highest chitosanase activity (0.53 U/mL) on medium containing shrimp heads as the sole carbon and nitrogen (C/N) source. Using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis, a chitosanase isolated from P. mucilaginosus TKU032 cultured on shrimp head medium was determined at approximately 59 kDa. The characterized chitosanase showed interesting properties with optimal temperature and thermal stability up to 70 °C. Three chitosan oligosaccharide (COS) fractions were isolated from hydrolyzed colloidal chitosan that was catalyzed by TKU032 chitosanase. Of these, fraction I showed the highest α-glucosidase inhibitor (aGI) activity (65.86% at 20 mg/mL); its inhibitory mechanism followed the mixed noncompetitive inhibition model. Fractions II and III exhibited strong 2,2-diphenyl1-picrylhydrazyl (DPPH) radical scavenging activity (79.00% at 12 mg/mL and 73.29% at 16 mg/mL, respectively). In summary, the COS fractions obtained by hydrolyzing colloidal chitosan with TKU032 chitosanase may have potential use in medical or nutraceutical fields due to their aGI and antioxidant activities.


Assuntos
Proteínas de Bactérias/isolamento & purificação , Fatores Biológicos/biossíntese , Glicosídeo Hidrolases/isolamento & purificação , Oligossacarídeos/biossíntese , Paenibacillus/metabolismo , Animais , Proteínas de Bactérias/metabolismo , Biocatálise , Fatores Biológicos/farmacologia , Quitosana/metabolismo , Crustáceos/química , Ensaios Enzimáticos/métodos , Depuradores de Radicais Livres/metabolismo , Depuradores de Radicais Livres/farmacologia , Proteínas Fúngicas/metabolismo , Inibidores de Glicosídeo Hidrolases/metabolismo , Inibidores de Glicosídeo Hidrolases/farmacologia , Glicosídeo Hidrolases/metabolismo , Temperatura Alta , Oligossacarídeos/farmacologia , Paenibacillus/isolamento & purificação , Estabilidade Proteica , Microbiologia do Solo , Especificidade por Substrato , alfa-Glucosidases/metabolismo
2.
Mar Drugs ; 17(4)2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30978965

RESUMO

Parkinson's disease (PD) is a neurodegenerative disorder caused by the loss of dopaminergic neurons, leading to the motor dysfunctions of patients. Although the etiology of PD is still unclear, the death of dopaminergic neurons during PD progress was revealed to be associated with the abnormal aggregation of α-synuclein, the elevation of oxidative stress, the dysfunction of mitochondrial functions, and the increase of neuroinflammation. However, current anti-PD therapies could only produce symptom-relieving effects, because they could not provide neuroprotective effects, stop or delay the degeneration of dopaminergic neurons. Marine-derived natural compounds, with their novel chemical structures and unique biological activities, may provide anti-PD neuroprotective effects. In this study, we have summarized anti-PD marine-derived natural products which have shown pharmacological activities by acting on various PD targets, such as α-synuclein, monoamine oxidase B, and reactive oxygen species. Moreover, marine-derived natural compounds currently evaluated in the clinical trials for the treatment of PD are also discussed.


Assuntos
Organismos Aquáticos , Fatores Biológicos/farmacologia , Neurônios Dopaminérgicos/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/tratamento farmacológico , Animais , Fatores Biológicos/isolamento & purificação , Fatores Biológicos/uso terapêutico , Ensaios Clínicos como Assunto , Neurônios Dopaminérgicos/citologia , Neurônios Dopaminérgicos/patologia , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Fármacos Neuroprotetores/isolamento & purificação , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Doença de Parkinson/patologia
3.
Ann Endocrinol (Paris) ; 80(2): 128-133, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30833018

RESUMO

In the modern world, type-2 diabetes mellitus has become a leading public healthcare problem, due to major risks of morbidity and mortality. Prevalence has increased significantly in recent decades. Treatment involves oral hypoglycemic agents or insulin replacement therapy. Development is ongoing for cell-based diabetes therapies using stem cells with the potential to differentiate into insulin-producing cells (IPCs): embryonic stem cells (ESCs), mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs), and stem cells from adult pancreas, liver, central nervous system, bone marrow and adipose tissue. Successful induction of iPSCs, however, depends on the quantity and quality of available stem cells and the development of adapted protocols determining the environment of extrinsic factors and involvement of small molecules. Validating such new cell therapies must be founded on this experimental rationale.


Assuntos
Fatores Biológicos/farmacologia , Diferenciação Celular/efeitos dos fármacos , Células Secretoras de Insulina/efeitos dos fármacos , Células-Tronco Pluripotentes/efeitos dos fármacos , Animais , Fatores Biológicos/análise , Fatores Biológicos/isolamento & purificação , Técnicas de Cultura de Células , Reprogramação Celular/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Insulina/metabolismo , Secreção de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/fisiologia , Pâncreas/citologia , Pâncreas/efeitos dos fármacos , Pâncreas/fisiologia , Células-Tronco Pluripotentes/citologia , Células-Tronco Pluripotentes/fisiologia , Bibliotecas de Moléculas Pequenas/análise
4.
J Cancer Res Ther ; 15(1): 176-184, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30880776

RESUMO

Context: Tilorone dihydrochloride is a therapeutic agent with a different mechanism in cancer. The species of Lactobacillus have an important role in cytotoxic effect. Aims: Because of unknown effects of tilorone and culture supernatants from Lactobacillus reuteri on hepatoma, the aim of this study is to evaluate apoptotic, cytotoxic, and therapeutic effects of tilorone on mouse hepatoma cell line with and without culture supernatants from L. reuteri. Materials and Methods: To do so, after cell line culture, cells were divided into different groups such as negative control, treatment with four doses of tilorone, positive control of supernatant (single dose), and combination therapy groups of different doses of tilorone with supernatant (constant doses), for 48 h. All groups were studied with pathologic tests, biochemical study, tetrazolium dye (3-(4, 5- dimethylthiazol -2-yl)-2, 5-diphenyltetrazolium bromide [MTT]) assay, and absolute real-time-polymerase chain reaction (RT-PCR) were done to assess Bax and Bcl-2 genes expression, as molecular studies. Results: MTT assay results revealed that the tilorone tissue culture IC50 (TCIC50) on the Hepa1-6 cell line was 50 µg/ml. RT-PCR analysis showed that tilorone dihydrochloride induced upregulation and downregulation in expression of Bax and Bcl-2, respectively. Simultaneous, antioxidant effect has also seen in a way that prevented necrosis, in biochemical analysis. These results were dose dependent and statistically significant compared to the control group. Conclusions: Based on these results, it appeared that this agent could be a good candidate for further evaluation as effective chemotherapy acting through the induction of apoptosis in hepatoma. The cell death caused through bacterial supernatant was rather necrosis than apoptosis.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Lactobacillus reuteri/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Tilorona/farmacologia , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose/efeitos dos fármacos , Fatores Biológicos/farmacologia , Fatores Biológicos/uso terapêutico , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Meios de Cultura/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Neoplasias Hepáticas/patologia , Camundongos , Tilorona/uso terapêutico
5.
Phytomedicine ; 57: 364-376, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30831485

RESUMO

BACKGROUND: Rice callus suspension culture (RCSC) has been shown to exhibit potent antiproliferative activity in multiple cancer cell lines. RCSC and its bioactive compounds can fill the need for drugs with no side effects. HYPOTHESIS/PURPOSE: The anti-inflammatory potential of RCSC and its bioactive fractions on normal colon epithelial cell lines, was investigated. STUDY DESIGN: Three cell lines, InEpC, NCM356 and CCD841-CoN were treated with proinflammatory cytokines followed by RCSC. Cytoplasmic and nuclear ROS were assayed with fluorescent microscopy and flow cytometer. Expression analysis of immune-related genes was performed in RCSC-treated cell lines. RCSC was fractionated using column chromatography and HPLC. Pooled fractions 10-18 was used to test for antiproliferative activity using colon adenocarcinoma cell line, SW620 and anti-inflammatory activity using CCD841-CoN. Mass spectrometric analysis was performed to identify candidate compounds in four fractions. RESULTS: RCSC treatment showed differential effects with higher cytoplasmic ROS levels in NCM356 and CCD841-CoN and lower ROS levels in InEpC. Nuclear generated ROS levels increased in all three treated cell lines. Flow cytometry analysis of propidium iodide stained cells indicated mitigation of cell death caused by inflammation in RCSC treated groups in both NCM356 and CCD841-CoN. Genes encoding transcription factors and cytokines were differentially regulated in NCM356 and CCD841-CoN cell lines treated with RCSC which provided insights into possible pathways. Analysis of pooled fractions 10-18 by HPLC identified 8 peaks. Cell viability assay with fractions 10-18 using SW620 showed that the number of viable cells were greatly reduced which was similar to 6X and 33X RCSC with very little effect on normal cells which similar to 1X RCSC. RCSC fractions increased nuclear and cytoplasmic ROS vs. both untreated and inflammatory control. Analysis of four fractions by mass spectrometry identified 4-deoxyphloridzin, 5'-methoxycurcumin, piceid and lupeol as candidate compounds which are likely to be responsible for the antiproliferative, anti-inflammatory and immune-regulating properties of RCSC. CONCLUSION: RCSC and its fractions showed anti-inflammatory activity on inflamed colon epithelial cells. Downstream target candidate genes which are likely to mediate RCSC effects were identified. Candidate compounds responsible for the antiproliferative and anti-inflammatory activity of RCSC and its fractions provide possible drug targets.


Assuntos
Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Fatores Biológicos/farmacologia , Fatores Imunológicos/farmacologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Oryza/citologia , Técnicas de Cultura de Tecidos/métodos , Adenocarcinoma , Anti-Inflamatórios/imunologia , Antineoplásicos/química , Fatores Biológicos/química , Morte Celular/efeitos dos fármacos , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Neoplasias Colorretais , Citocinas/genética , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Fatores Imunológicos/química , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/patologia , Oryza/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fatores de Transcrição/genética
6.
Molecules ; 24(2)2019 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-30654598

RESUMO

Mangifera odorata fruit, the hybrid forms between M. indica (mango) and M. foetida (bacang), has been shown to exhibit potential antioxidant activity, and the fruit waste could demonstrate functional and nutritional potential. In the present study, the nutritional composition (proximate, sugars, vitamins and minerals analyses), the anti-diabetic activities and phytochemical profile of M. odorata peel and seed kernel were investigated for the first time. The results indicated that seed kernel rich in fat, protein, carbohydrate, and ash while peel contained significantly greater amount of fiber, minerals, ß-Carotene and ascorbic acid compared to seed kernel. The samples were then extracted using different solvents (acetone, ethanol, methanol at 60%, v/v and pure deionized water) and their anti-diabetic activities (α-amylase and α-glucosidase inhibition assay) were determined. Seed kernel had the lowest IC50 values for α-amylase and α-glucosidase inhibition assay in 60% ethanol and 60% acetone, respectively. Due to the toxic effect and high volatility of acetone, the ethanolic extracts of samples were further analyses for their phytochemical profile using high performance liquid chromatography-mass spectrometry (LC-MS) and ultra-high-performance liquid chromatography electrospray ionization orbitrap tandem mass spectrometry (UHPLC-ESI-Orbitrap-MS/MS). The most abundant compounds identified were phenolic acid, ellagic acid, and flavonoid. These findings suggest that M. odorata fruit wastes, especially the seed kernel possesses promising ability to be used as functional ingredient in the food industry.


Assuntos
Inibidores Enzimáticos/isolamento & purificação , Hipoglicemiantes/isolamento & purificação , Mangifera/química , Extratos Vegetais/análise , Sementes/química , Fatores Biológicos/isolamento & purificação , Fatores Biológicos/farmacologia , Cromatografia Líquida de Alta Pressão , Inibidores Enzimáticos/farmacologia , Indústria de Processamento de Alimentos , Frutas/química , Alimento Funcional , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/farmacologia , Hipoglicemiantes/farmacologia , Valor Nutritivo , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Espectrometria de Massas em Tandem , alfa-Amilases/antagonistas & inibidores
7.
Mol Med Rep ; 19(2): 951-958, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30569151

RESUMO

Insufficient bone volume remains a key issue when using dental implants. Adipose tissue­derived stem cells (ADSCs) can accelerate bone healing when combined with dental implants. To improve the application of ADSCs for dental uses, the present study aimed to identify optimal implantation conditions. Mesenchymal stem cell­derived exosomes can induce naïve stem cells to differentiate through the osteogenic lineage. In the present study, exosomes derived from 3T3L1 preadipocytes (3T3L1­exo) were purified and characterized. The effects and potential mechanisms of 3T3L1­exo on 3T3L1 cell ossification were examined by reverse transcription­quantitative polymerase chain reaction, western blotting, electron microscopy, RNA sequencing and histological analysis. The current study confirmed that 3T3L1­exo enhanced 3T3L1 preadipocyte osteogenic differentiation, as revealed by upregulation of osteogenic differentiation­associated genes and increased Alizarin Red staining. Furthermore, the microRNA (miR) expression profiles of 3T3L1­exo and 3T3L1 preadipocytes were sequenced and compared. The results of a further analysis demonstrated that miR­223 expression was reduced in 3T3L1 preadipocytes stimulated by 3T3L1­exo compared with in unstimulated cells. This finding suggested that 3T3L1­exo promoted 3T3L1 bone formation by decreasing miR­223 through a competitive mechanism, another miRNA, or another factor. The mechanism by which miR­223 is decreased warrants further investigation. In conclusion, the application of 3T3L1­exo may be useful for investigating preadipocyte­induced bone regeneration.


Assuntos
Fatores Biológicos/farmacologia , Diferenciação Celular/efeitos dos fármacos , Exossomos/química , Regulação da Expressão Gênica/efeitos dos fármacos , MicroRNAs/genética , Osteogênese/efeitos dos fármacos , Células 3T3-L1 , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Animais , Biomarcadores/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Sialoproteína de Ligação à Integrina/genética , Sialoproteína de Ligação à Integrina/metabolismo , Camundongos , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Osteoblastos/citologia , Osteoblastos/metabolismo , Osteocalcina/genética , Osteocalcina/metabolismo , Osteogênese/genética , Fator de Transcrição Sp7/genética , Fator de Transcrição Sp7/metabolismo
8.
Sci Rep ; 8(1): 17844, 2018 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-30552373

RESUMO

Apple scab disease caused by the fungus Venturia inaequalis is a devastating disease that seriously affects quality and yield of apples. In order to understand the mechanisms involved in scab resistance, we performed gas chromatography-mass spectrometry based metabolomics analysis of the cell culture of scab resistant cultivar 'Florina' and scab susceptible cultivar 'Vista Bella' both prior -to and -following treatment with V. inaequalis elicitor (VIE). A total 21 metabolites were identified to be altered significantly in 'Florina' cell cultures upon VIE-treatment. Among 21 metabolites, formation of three new specialized metabolites aucuparin, noraucuparin and eriobofuran were observed only in resistant cultivar 'Florina' after the elicitor treatment. The score plots of principal component analysis (PCA) exhibited clear discrimination between untreated and VIE-treated samples. The alteration in metabolite levels correlated well with the changes in the transcript levels of selected secondary metabolite biosynthesis genes. Aucuparin, noraucuparin and eriobofuran isolated from the 'Florina' cultures showed significant inhibitory effect on the conidial germination of V. inaequalis. The results expand our understanding of the metabolic basis of scab-resistance in apple and therefore are of interest in apple breeding programs to fortify scab resistance potential of commercially grown apple cultivars.


Assuntos
Ascomicetos/crescimento & desenvolvimento , Resistência à Doença , Malus/química , Metabolômica/métodos , Doenças das Plantas/imunologia , Doenças das Plantas/microbiologia , Antifúngicos/isolamento & purificação , Antifúngicos/farmacologia , Ascomicetos/efeitos dos fármacos , Fatores Biológicos/isolamento & purificação , Fatores Biológicos/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Células Vegetais/química , Esporos Fúngicos/efeitos dos fármacos , Esporos Fúngicos/crescimento & desenvolvimento
9.
Asian Pac J Cancer Prev ; 19(12): 3307-3316, 2018 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-30583335

RESUMO

Background: There are evidences on the role of extracellular factors in cellular communication between cancer cells and non-cancerous cells to support tumor progression and a phenomenon of cancer cachexia. However, evidences are scarce to show the effects of extracellular factors from one carcinoma microenvironment upon growth and survival of another carcinoma. Methodology: To address the above issue, we have selected excised breast carcinoma tissue samples and in vitro grown MCF-7 sources of extracellular factors and tested their effects to evaluate growth and proliferation inhibitory potential against a cervical carcinoma cell line HeLa. Results: Data from the in vitro experiments like Trypan blue dye exclusion, MTT assay, cell cycle assay and annexin V/PI staining lead us to suggest that the extracellular factors collected from the culture medium of in vitro grown MCF-7 and excised breast carcinoma tissue play an apoptosis inducing and cell cycle arrest role in HeLa. In these in vitro experiments, we detected the presence of up to 40-50% apoptotic cell death in HeLa cells and increase in G2-M cell cycle phase from 11%-25% due to treatment with extracellular factors from human breast carcinoma cells. Discussion and Conclusion: These observations are novel and suggest that extracellular factors from breast carcinoma play an apoptosis inducing and growth inhibitory role upon on HeLa cells. This study can also support the concept of cancer cachexia and a possible hypothesis for rare chance of synchronous two or more primary tumor in a single patient.


Assuntos
Apoptose/efeitos dos fármacos , Fatores Biológicos/farmacologia , Neoplasias da Mama/metabolismo , Carcinoma/tratamento farmacológico , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Neoplasias do Colo do Útero/tratamento farmacológico , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Células HeLa , Humanos , Células MCF-7 , Microambiente Tumoral/fisiologia
10.
Int J Mol Sci ; 19(12)2018 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-30558112

RESUMO

Skin pigmentation represents one of the most peculiar traits of human beings and its alteration as a consequence of pathological conditions has a dramatic impact on the wellness of individuals and their social relationships. [...].


Assuntos
Transdução de Sinais , Pigmentação da Pele , Fatores Biológicos/farmacologia , Humanos , Melanócitos/metabolismo , Glicoproteínas de Membrana/metabolismo , Oxirredutases/metabolismo , Receptor Tipo 1 de Melanocortina/metabolismo , Fenômenos Fisiológicos da Pele/efeitos dos fármacos , Pigmentação da Pele/efeitos dos fármacos
11.
Best Pract Res Clin Gastroenterol ; 32-33: 9-15, 2018 Feb - Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30060944

RESUMO

European consensus guidelines and reimbursement policies position biologic drugs for ulcerative colitis (UC) as a third-line treatment, after failure of 5-aminosalicylic acid (5-ASA) and corticosteroids/thiopurines. While 5-ASA have a very favorable safety profile, (prolonged) use of corticosteroids and thiopurines is associated with potentially serious adverse events. The therapeutic landscape of UC is rapidly evolving and selective biologic drugs with improved safety are being introduced. The first biosimilars have entered the market, leading to improved cost-effectiveness of older biologic drugs. In addition, new insights have been gained in the importance of stringent therapeutic targets such as mucosal and histological healing to improve the long-term outcome of UC patients, and in the role of therapeutic drug monitoring and treatment optimization in this regard. In this manuscript we tackle the question of whether we should move directly from 5-ASA treatment to biologic drugs to offer better and/or safer care to UC patients.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Fatores Biológicos/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Mesalamina/uso terapêutico , Anti-Inflamatórios não Esteroides/farmacologia , Fatores Biológicos/farmacologia , Humanos , Mesalamina/farmacologia
12.
Molecules ; 23(9)2018 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-30158491

RESUMO

A few symptomatic drugs are currently available for Alzheimer's Disease (AD) therapy, but these molecules are only able to temporary improve the cognitive capacity of the patients if administered in the first stages of the pathology. Recently, important advances have been achieved about the knowledge of this complex condition, which is now considered a multi-factorial disease. Researchers are, thus, more oriented toward the preparation of molecules being able to contemporaneously act on different pathological features. To date, the inhibition of acetylcholinesterase (AChE) and of ß-amyloid (Aß) aggregation as well as the antioxidant activity and the removal and/or redistribution of metal ions at the level of the nervous system are the most common investigated targets for the treatment of AD. Since many natural compounds show multiple biological properties, a series of secondary metabolites of plants or fungi with suitable structural characteristics have been selected and assayed in order to evaluate their potential role in the preparation of multi-target agents. Out of six compounds evaluated, 1 showed the best activity as an antioxidant (EC50 = 2.6 ± 0.2 µmol/µmol of DPPH) while compound 2 proved to be effective in the inhibition of AChE (IC50 = 6.86 ± 0.67 µM) and Aß1⁻40 aggregation (IC50 = 74 ± 1 µM). Furthermore, compound 6 inhibited BChE (IC50 = 1.75 ± 0.59 µM) with a good selectivity toward AChE (IC50 = 86.0 ± 15.0 µM). Moreover, preliminary tests on metal chelation suggested a possible interaction between compounds 1, 3 and 4 and copper (II). Molecules with the best multi-target profiles will be used as starting hit compounds to appropriately address future studies of Structure-Activity Relationships (SARs).


Assuntos
Antioxidantes/química , Fatores Biológicos/química , Inibidores da Colinesterase/química , Agregados Proteicos/efeitos dos fármacos , Doença de Alzheimer/tratamento farmacológico , Antioxidantes/farmacologia , Fatores Biológicos/farmacologia , Inibidores da Colinesterase/farmacologia , Fungos/química , Humanos , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Pironas/química , Pironas/farmacologia , Metabolismo Secundário , Relação Estrutura-Atividade
13.
Expert Rev Clin Pharmacol ; 11(9): 879-887, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30136871

RESUMO

INTRODUCTION: Hidradenitis suppurativa (HS) is a chronic, inflammatory, and debilitating skin disease, which usually occurs after puberty with painful, deep-seated, inflammatory lesions in the apocrine gland-bearing areas of the body. Several pharmacologic agents have been described to reduce lesion activity and inflammation in HS. However, conventional treatment may not always get the desired results. Therefore, unconventional therapies must be taken into account. Areas covered: Recently, the better understanding of HS pathogenesis has been used to improve treatment strategies with many emerging conventional and unconventional therapeutics options. Adalimumab is the only FDA-approved biologic available for therapy of moderate-to-severe HS. Nevertheless, novel therapeutic approach, including both topical and systemic as well as novel laser device, showed good clinical outcome. Several molecules, such as tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), IL-17, IL-12, IL-23, phosphodiesterase 4 (PDE4), lymphocyte function-associated antigen 1 (LFA-1), and complement component 5a (C5a), are modulated by such new biologic agents in HS. Expert commentary: In the next years, many therapeutic options for HS will be available. Clinical trials showed the efficacy of several biologic drugs, antibiotics, laser light device. Novel therapeutic options seem to be promising, but dermatologists will have to evaluate their effectiveness and safety in daily clinical practice.


Assuntos
Fatores Biológicos/uso terapêutico , Hidradenite Supurativa/terapia , Terapia a Laser/métodos , Antibacterianos/uso terapêutico , Fatores Biológicos/farmacologia , Hidradenite Supurativa/patologia , Humanos , Índice de Gravidade de Doença , Resultado do Tratamento
14.
Expert Opin Ther Pat ; 28(8): 635-646, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30047807

RESUMO

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by an inflammatory process, with a global prevalence ranging from 0.3% to 1%. The overall cost of RA drugs is estimated in $20 billion worldwide and projected to grow to $36 billion by 2021. The current RA treatment strategy consists of the aggressive therapy directed to specific targets, after diagnostic confirmation and the stepped therapy directed by the stage of the disease, aiming at the clinical remission. Conventional (methotrexate, sulfasalazine, leflunomide) and biological (infliximab, adalimumab, tocilizumab) disease-modifying antirheumatic drugs may fail, produce only partial responses, or unwanted side effects, and consequently new antirheumatic drugs are being developed to overcome these limitations. Areas covered: In this review, the authors described the technological trends and the main players involved in the R&D process related to biological compounds employed in the treatment of RA, using patent documents as a source of technological information. Expert opinion: Current treatments for RA still mainly target the immune system, different inflammatory targets, and mediators. Other types of therapies have also been developed, such as vaccines and gene therapies. Despite these new techniques, the main compounds of interest remain the antibodies anti-TNF-α and anti-CD20, with novelties regarding preparation methods and combination targets.


Assuntos
Antirreumáticos/farmacologia , Artrite Reumatoide/tratamento farmacológico , Desenho de Drogas , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/farmacologia , Antígenos CD20/imunologia , Antirreumáticos/efeitos adversos , Artrite Reumatoide/imunologia , Artrite Reumatoide/patologia , Fatores Biológicos/efeitos adversos , Fatores Biológicos/farmacologia , Humanos , Patentes como Assunto , Fator de Necrose Tumoral alfa/antagonistas & inibidores
15.
Biomed Pharmacother ; 100: 583-589, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29500959

RESUMO

The recent mass emergence of Nomura's jellyfish (Nemopilema nomurai) has caused much economic and environmental damage. However, there is no innovative strategy to dispose of or utilize these jellyfish. Some reports suggest that the jellyfish may be bioactive resources and a source of important compounds with antibacterial activity. Here, we examined the effect of an aqueous extract of Nomura's jellyfish (AENJ) on lipopolysaccharide (LPS)-stimulated Raw 264.7 macrophages and a zebrafish model of inflammation and analyzed the underlying molecular mechanisms. AENJ downregulated inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNA levels in LPS-stimulated Raw 264.7 macrophages, with no apparent cytotoxic effects. However, AENJ had no effect on expression of other inflammation-related genes such as interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and MCP-1. Furthermore, AENJ reduced expression of nerve injury-induced protein 1 (Ninj1), which is an important adhesion molecule, thereby reducing cell adhesion to the extracellular matrix (ECM) in vitro. The inhibitory effect of AENJ on leukocytes was confirmed in LPS-microinjected zebrafish larvae; AENJ reduced the number of the infiltrate accumulating at the site of inflammation. In addition, AENJ suppressed the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9 in LPS-stimulated Raw 264.7 cells. Finally, AENJ blocked nuclear translocation of nuclear factor kappa B (NF-κB), a key transcription factor for inflammatory responses, in Raw 264.7 cells in a dose-dependent manner. Collectively, the data suggest that AENJ inhibits expression of COX and iNOS by blocking NF-κB signaling pathways and suppresses the activity of macrophages by downregulating Ninj1 and MMPs. Therefore, AENJ may be a useful preventive neutraceutical, or therapeutic agent against inflammatory disorders.


Assuntos
Fatores Biológicos/farmacologia , Modelos Animais de Doenças , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/toxicidade , Animais , Fatores Biológicos/isolamento & purificação , Fatores Biológicos/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Feminino , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Masculino , Camundongos , Células RAW 264.7 , Cifozoários , Água/farmacologia , Peixe-Zebra
16.
Biomed Pharmacother ; 101: 805-819, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29525677

RESUMO

Oxidative stress arises from an imbalance between the production of free radicals and antioxidant defences. Several studies have suggested that dietary antioxidants (such as polyphenols and berberine) may counteract oxidative stress through the involvement of the Sirtuin 1/Adenosine Monophosphate-Activated Protein Kinase (SIRT1/AMPK) pathway. The aim of this study was to evaluate the direct and specific antioxidant activity of some natural compounds, as well as their ability to modulate the expression of SIRT1 and the activation of AMPK. Quercetin, tyrosol, ferulic acid, catechin, berberine and curcumin were evaluated for their specific and direct antioxidant activity with TOSC assay. Their ability to modulate SIRT1 and AMPK was assessed by immunoblotting assay, while their cytotoxicity by CellTiter-Blue Cell Viability Assay. No statistically significant decrease (p > 0.05) in the number of viable cells was found upon challenging with the natural compounds. Quercetin exhibited the highest antioxidant activity against peroxyl radical and peroxinitrate derivates, while curcumin showed the best anti-hydroxyl activity with respect to the other compounds and, most importantly, respect to the reference antioxidants. Finally, all the tested compounds significantly increased the SIRT1 expression and the activation of AMPK. Our results clearly disclose the specific antioxidant activity of these natural compounds and their ability to increase SIRT1 expression and AMPK activation.


Assuntos
Antioxidantes/farmacologia , Fatores Biológicos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Sirtuína 1/biossíntese , Berberina/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Curcumina/farmacologia , Células HeLa , Humanos , Estresse Oxidativo/fisiologia , Proteínas Quinases/metabolismo , Quercetina/farmacologia
17.
J Pharm Biomed Anal ; 153: 9-15, 2018 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-29459236

RESUMO

Conventional isolation and identification of active compounds from herbs have been extensively reported by using various chromatographic and spectroscopic techniques. However, how to quickly discover new bioactive ingredients from natural sources still remains a challenging task due to the interference of their similar structures or matrices. Here, we present a grand approach for rapid analysis, forecast and discovery of bioactive compounds from herbs based on a hyphenated strategy of thin layer chromatography and ratiometric surface-enhanced Raman spectroscopy. The performance of the hyphenated strategy is first evaluated by analyzing four protoberberine alkaloids, berberine (BER), coptisine (COP), palmatine (PAT) and jatrorrhizine (JAT), from a typical herb Coptidis Rhizoma as an example. It has been demonstrated that this coupling method can identify the four compounds by characteristic peaks at 728, 708, 736 and 732 cm-1, and especially discriminate BER and COP (with similar migration distances) by ratiometric Raman intensity (I708/I728). The corresponding limits of detection are 0.1, 0.05, 0.1 and 0.5 µM, respectively, which are about 1-2 orders of magnitude lower than those of direct observation method under 254 nm UV lamp. Based on these findings, the proposed method further guides forecast and discovery of unknown compounds from traditional Chinese herb Typhonii Rhizoma. Results infer that two trace alkaloids (BER and COP) from the n-butanol extract of Typhonii Rhizoma are found for the first time. Moreover, in vitro experiments manifest that BER can effectively decrease the viability of human glioma U87 cells by inducing cell cycle arrest in a concentration-dependent manner.


Assuntos
Fatores Biológicos/química , Medicamentos de Ervas Chinesas/análise , Extratos Vegetais/química , Alcaloides/química , Alcaloides/farmacologia , Asteraceae/química , Berberina/análogos & derivados , Berberina/química , Berberina/farmacologia , Alcaloides de Berberina/química , Alcaloides de Berberina/farmacologia , Fatores Biológicos/farmacologia , Linhagem Celular Tumoral , Cromatografia em Camada Delgada/métodos , Humanos , Extratos Vegetais/farmacologia , Análise Espectral Raman/métodos
18.
Sci Rep ; 8(1): 1171, 2018 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-29352188

RESUMO

Microvesicles (MVs) released by cells are involved in a multitude of physiological events as important mediators of intercellular communication. MVs derived from mesenchymal stem cells (MSCs) contain various paracrine factors from the cells that primarily contribute to their therapeutic efficacy observed in numerous clinical trials. As nano-sized and bi-lipid layered vesicles retaining therapeutic potency equivalent to that of MSCs, MSC-derived MVs have been in focus as ideal medicinal candidates for regenerative medicine, and are preferred over MSC infusion therapy with their improved safety profiles. However, technical challenges in obtaining sufficient amounts of MVs have limited further progress in studies and clinical application. Of the multiple efforts to reinforce the therapeutic capacity of MSCs, few studies have reportedly examined the scale-up of MSC-derived MV production. In this study, we successfully amplified MV secretion from MSCs compared to the conventional culture method using a simple and efficient 3D-bioprocessing method. The MSC-derived MVs produced in our dynamic 3D-culture contained numerous therapeutic factors such as cytokines and micro-RNAs, and showed their therapeutic potency in in vitro efficacy evaluation. Our results may facilitate diverse applications of MSC-derived MVs from the bench to the bedside, which requires the large-scale production of MVs.


Assuntos
Fatores Biológicos/metabolismo , Fatores Biológicos/farmacologia , Micropartículas Derivadas de Células/metabolismo , Células-Tronco Mesenquimais/metabolismo , Técnicas de Cultura Celular por Lotes , Fatores Biológicos/uso terapêutico , Perfilação da Expressão Gênica , Humanos , Células-Tronco Mesenquimais/citologia , Neovascularização Fisiológica/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Tamanho da Partícula , Transcriptoma
19.
Mar Drugs ; 16(1)2018 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-29329235

RESUMO

Carotenoids are natural pigments that play pivotal roles in many physiological functions. The characteristics of carotenoids, their effects on health, and the cosmetic benefits of their usage have been under investigation for a long time; however, most reviews on this subject focus on carotenoids obtained from several microalgae, vegetables, fruits, and higher plants. Recently, microalgae have received much attention due to their abilities in producing novel bioactive metabolites, including a wide range of different carotenoids that can provide for health and cosmetic benefits. The main objectives of this review are to provide an updated view of recent work on the health and cosmetic benefits associated with carotenoid use, as well as to provide a list of microalgae that produce different types of carotenoids. This review could provide new insights to researchers on the potential role of carotenoids in improving human health.


Assuntos
Fatores Biológicos/farmacologia , Fatores Biológicos/uso terapêutico , Carotenoides/farmacologia , Carotenoides/uso terapêutico , Cosméticos/farmacologia , Cosméticos/uso terapêutico , Microalgas/metabolismo , Animais , Fatores Biológicos/metabolismo , Carotenoides/metabolismo , Cosméticos/metabolismo , Assistência à Saúde , Frutas/metabolismo , Humanos , Indústrias , Verduras/metabolismo
20.
Intern Emerg Med ; 13(2): 155-176, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29238905

RESUMO

Asthma is a chronic inflammatory multifactorial disorder of the airways characterized by the involvement of immune cells and mediators in its onset and maintenance. Traditional therapeutic strategies have been unsatisfactory in controlling the underlying pathology, especially in the more severe states. Hence in the last couple of decades, new biological approaches targeting molecular mediators have been developed. In this narrative review we examine biological agents currently available for the management of severe asthma, focusing our attention on their clinical application, pros and cons, and in particular on gaps regarding the use of these agents. The most well-known and used biologic agent in clinical practice is omalizumab, though there is emerging evidence for mepolizumab too. The future of these biological therapies is to broaden our knowledge of their practical use and ascertain predictive biomarkers, or define an algorithm, useful in the optimal application of these 'biological weapons'.


Assuntos
Asma/tratamento farmacológico , Fatores Biológicos/farmacologia , Fatores Biológicos/farmacocinética , Antiasmáticos/farmacocinética , Antiasmáticos/farmacologia , Antiasmáticos/uso terapêutico , Anticorpos Anti-Idiotípicos/farmacologia , Anticorpos Anti-Idiotípicos/uso terapêutico , Anticorpos Monoclonais/farmacocinética , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/farmacocinética , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Fatores Biológicos/uso terapêutico , Humanos , Interleucina-5/antagonistas & inibidores , Interleucina-5/farmacologia , Interleucina-5/uso terapêutico , Omalizumab/farmacocinética , Omalizumab/farmacologia , Omalizumab/uso terapêutico
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