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1.
Nutrients ; 13(2)2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33572926

RESUMO

Rosa canina L. is a natural polyphenol-rich medicinal plant that exhibits antioxidant and anti-inflammatory activities. Recent in vivo studies have demonstrated that a methanol extract of Rosa canina L. (RCME) has reversed an inflammatory bowel disease (IBD)-like phenotype that has been triggered by dextran sulfate sodium (DSS) in mice. In the current study, we investigated the effects of RCME on perturbations of cellular mechanisms induced by DSS-treatment of intestinal Caco-2 cells, including stress response in the endoplasmic reticulum (ER), protein trafficking and sorting as well as lipid rafts integrity and functional capacities of an intestinal enzyme. 6 days post-confluent cells were treated for 24 h with DSS (3%) or simultaneously with DSS (3%) and RCME (100 µg/mL) or exclusively with RCME (100 µg/mL) or not treated. The results obtained demonstrate the ability of RCME to counteract the substantial increase in the expression levels of several ER stress markers in DSS-treated cells. Concomitantly, the delayed trafficking of intestinal membrane glycoproteins sucrase-isomaltase (SI) and dipeptidyl peptidase 4 (DPP4) induced by DSS between the ER and the Golgi has been compromised by RCME. Furthermore, RCME restored the partially impaired polarized sorting of SI and DPP4 to the brush border membrane. An efficient sorting mechanism of SI and DPP4 is tightly associated with intact lipid rafts structures in the trans-Golgi network (TGN), which have been distorted by DSS and normalized by RCME. Finally, the enzymatic activities of SI are enhanced in the presence of RCME. Altogether, DSS treatment has triggered ER stress, impaired trafficking and function of membrane glycoproteins and distorted lipid rafts, all of which can be compromised by RCME. These findings indicate that the antioxidants in RCME act at two major sites in Caco-2 cells, the ER and the TGN and are thus capable of maintaining the membrane integrity by correcting the sorting of membrane-associated proteins.


Assuntos
Retículo Endoplasmático/efeitos dos fármacos , Doenças Inflamatórias Intestinais/terapia , Metanol/farmacologia , Extratos Vegetais/farmacologia , Transporte Proteico/efeitos dos fármacos , Rosa/química , Animais , Células CACO-2 , Sulfato de Dextrana , Dipeptidil Peptidase 4/metabolismo , Modelos Animais de Doenças , Humanos , Doenças Inflamatórias Intestinais/induzido quimicamente , Mucosa Intestinal/efeitos dos fármacos , Microdomínios da Membrana/metabolismo , Camundongos , Microvilosidades/metabolismo , Fenótipo , Complexo Sacarase-Isomaltase/metabolismo
2.
Am J Trop Med Hyg ; 103(5): 2085-2090, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32959767

RESUMO

Diseases caused by many highly pathogenic viruses, including Ebola virus (EBOV) and Lassa virus (LASV), present with nonspecific signs and symptoms that overlap with common tropical diseases such as malaria. Initial diagnostic tests performed on patients under investigation for viral hemorrhagic fevers routinely include analysis of peripheral blood smears to detect and quantify Plasmodium species. In light of recent and ongoing Ebola virus disease and Lassa fever epidemics, clinical laboratories around the world require protocols for dealing with highly infectious specimens from patients with suspected or confirmed high-consequence diseases. Few validated protocols for safe analysis of peripheral blood smears are available, revealing a need for further research. In this study, we evaluated the performance of two plastic microscope slide types that offer safe alternatives to glass slides, determined the temporal parameters required to inactivate EBOV and LASV in thin blood smears by methanol fixation, and assessed the virucidal activity of Giemsa stain. Both types of plastic microscope slides performed optimally; there were no significant differences in blood cell morphology or tinctorial properties nor were differences noted in Plasmodium ovale morphology or staining, when compared with glass slides. For both EBOV and LASV, viable viruses were not detected in thin blood smears following fixation in absolute methanol for at least 2 minutes. By contrast, viable EBOV and LASV were recovered from all Giemsa-stained thick blood smears.


Assuntos
Ebolavirus/efeitos dos fármacos , Doença pelo Vírus Ebola/virologia , Febre Lassa/virologia , Vírus Lassa/efeitos dos fármacos , Metanol/farmacologia , Inativação de Vírus/efeitos dos fármacos , Corantes Azur , Manejo de Espécimes
3.
Antimicrob Resist Infect Control ; 9(1): 129, 2020 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-32771064

RESUMO

OBJECTIVES: Hand sanitisers are urgently needed in the time of COVID-19, and as a result of shortages, some people have resorted to making their own formulations, including the repurposing of distilleries. We wish to highlight the importance of those producing hand sanitisers to avoid methylated spirits containing methanol and to follow WHO recommended formulations. METHODS: We explore and discuss reports of methanol toxicity through ingestion and transdermal absorption. We discuss the WHO formulations and explain the rationale behind the chosen ingredients. SHORT CONCLUSION: We advise those producing hand sanitisers to follow WHO recommended formulations, and advise those producing hand sanitisers using methylated spirits, to avoid formulations which contain methanol.


Assuntos
Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/prevenção & controle , Desinfetantes/farmacologia , Etanol/farmacologia , Metanol/farmacologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Betacoronavirus/fisiologia , Infecções por Coronavirus/virologia , Desinfetantes/química , Desinfetantes/normas , Desinfetantes/toxicidade , Composição de Medicamentos , Etanol/química , Desinfecção das Mãos/instrumentação , Humanos , Metanol/química , Metanol/toxicidade , Pneumonia Viral/virologia , Organização Mundial da Saúde
4.
Am J Physiol Lung Cell Mol Physiol ; 319(3): L497-L512, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32697651

RESUMO

Hyperoxia (HO)-induced lung injury contributes to bronchopulmonary dysplasia (BPD) in preterm newborns. Intractable wheezing seen in BPD survivors is associated with airway remodeling (AWRM). Sphingosine kinase 1 (SPHK1)/sphingosine-1-phosphate (S1P) signaling promotes HO-mediated neonatal BPD; however, its role in the sequela of AWRM is not known. We noted an increased concentration of S1P in tracheal aspirates of neonatal infants with severe BPD, and earlier, demonstrated that Sphk1-/- mice showed protection against HO-induced BPD. The role of SPHK1/S1P in promoting AWRM following exposure of neonates to HO was investigated in a murine model. Therapy using PF543, the specific SPHK1 inhibitor, during neonatal HO reduced alveolar simplification followed by reduced AWRM in adult mice. This was associated with reduced airway hyperreactivity to intravenous methacholine. Neonatal HO exposure was associated with increased expression of SPHK1 in lung tissue of adult mice, which was reduced with PF543 therapy in the neonatal stage. This was accompanied by amelioration of HO-induced reduction of E-cadherin in airway epithelium. This may be suggestive of arrested partial epithelial mesenchymal transition (EMT) induced by HO. In vitro studies using human primary airway epithelial cells (HAEpCs) showed that SPHK1 inhibition or deletion restored HO-induced reduction in E-cadherin and reduced formation of mitochondrial reactive oxygen species (mtROS). Blocking mtROS with MitoTempo attenuated HO-induced partial EMT of HAEpCs. These results collectively support a therapeutic role for PF543 in preventing HO-induced BPD in neonates and the long-term sequela of AWRM, thus conferring a long-term protection resulting in improved lung development and function.


Assuntos
Remodelação das Vias Aéreas/efeitos dos fármacos , Displasia Broncopulmonar/tratamento farmacológico , Hiperóxia/tratamento farmacológico , Metanol/análogos & derivados , Pirrolidinas/farmacologia , Animais , Animais Recém-Nascidos , Displasia Broncopulmonar/induzido quimicamente , Modelos Animais de Doenças , Hiperóxia/induzido quimicamente , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Metanol/farmacologia , Camundongos Knockout , Fosfotransferases (Aceptor do Grupo Álcool)/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
5.
World J Microbiol Biotechnol ; 36(2): 31, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32048066

RESUMO

Biogenic production of nanoparticles is eco-friendly, less expensive method with various medical and biological applications. Nanotechnology along with photodynamic therapy is gaining tremendous importance with enhanced efficacy. The present work was aimed to evaluate methanolic extracts and nanoparticles of two selected plants (Datura suavolens and Verbina tenuisecta) for cytotoxic photodynamic, antioxidant and antimicrobial study. Both extract and silver (5 mM) nanoparticles of Datura plant showed significant activities against bacterial strains. Maximum ZOI of 27.3 ± 1.6 mm was observed with nanoparticles of Datura branches with minimum inhibitory (MIC) value of 32 µg/ml. In case of antifungal and antioxidant assay samples were moderately active. Silver nanoparticles and extracts were effective against rhabdomyosarcoma cell line with lowest IC50 value of 42.5 ± 0.6 µg/ml and percent viability of 25.6 ± 1.3 of Verbena tenuisecta. However, nanoparticles of Datura leaves and branches were more potent with IC50 value of 2.4 ± 0.9 µg/ml and 7.8 ± 1.1 µg/ml respectively. The result of photodynamic study showed that efficacy of photosensitizer was enhanced and percent viability reduced when nanoparticles used as an adjunct. The color change and UV spectra (415‒425 nm) indicated the production of nanoparticles. Fourier transform infrared spectroscopy (FTIR) spectra showed presence of different functional groups e.g., hydroxyl, carbonyl and amino. Nanoparticles are sphenoid in morphology and size ranges between 20-150 nm. Current study showed these silver nanoparticles can be used as cytotoxic agent in photodynamic therapy and can play a critical role to establish medicinal potential of selected plants.


Assuntos
Datura/química , Metanol/farmacologia , Prata/farmacologia , Verbena/química , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Nanopartículas Metálicas , Metanol/química , Metanol/isolamento & purificação , Testes de Sensibilidade Microbiana , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/isolamento & purificação , Fármacos Fotossensibilizantes/farmacologia , Extratos Vegetais/química , Folhas de Planta/química , Prata/química , Prata/isolamento & purificação
6.
Int J Mol Sci ; 21(3)2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32033119

RESUMO

Treatment by volatile plant hormone methyl jasmonate (MeJA) leads to release of methanol and volatiles of lipoxygenase pathway (LOX volatiles) in a dose-dependent manner, but how the dose dependence is affected by stomatal openness is poorly known. We studied the rapid (0-60 min after treatment) response of stomatal conductance (Gs), net assimilation rate (A), and LOX and methanol emissions to varying MeJA concentrations (0.2-50 mM) in cucumber (Cucumis sativus) leaves with partly open stomata and in leaves with reduced Gs due to drought and darkness. Exposure to MeJA led to initial opening of stomata due to an osmotic shock, followed by MeJA concentration-dependent reduction in Gs, whereas A initially decreased, followed by recovery for lower MeJA concentrations and time-dependent decline for higher MeJA concentrations. Methanol and LOX emissions were elicited in a MeJA concentration-dependent manner, whereas the peak methanol emissions (15-20 min after MeJA application) preceded LOX emissions (20-60 min after application). Furthermore, peak methanol emissions occurred earlier in treatments with higher MeJA concentration, while the opposite was observed for LOX emissions. This difference reflected the circumstance where the rise of methanol release partly coincided with MeJA-dependent stomatal opening, while stronger stomatal closure at higher MeJA concentrations progressively delayed peak LOX emissions. We further observed that drought-dependent reduction in Gs ameliorated MeJA effects on foliage physiological characteristics, underscoring that MeJA primarily penetrates through the stomata. However, despite reduced Gs, dark pretreatment amplified stress-volatile release upon MeJA treatment, suggesting that increased leaf oxidative status due to sudden illumination can potentiate the MeJA response. Taken together, these results collectively demonstrate that the MeJA dose response of volatile emission is controlled by stomata that alter MeJA uptake and volatile release kinetics and by leaf oxidative status in a complex manner.


Assuntos
Acetatos/farmacologia , Cucumis sativus/efeitos dos fármacos , Cucumis sativus/fisiologia , Ciclopentanos/farmacologia , Oxilipinas/farmacologia , Folhas de Planta/fisiologia , Estômatos de Plantas/fisiologia , Estresse Fisiológico/fisiologia , Compostos Orgânicos Voláteis/metabolismo , Cucumis sativus/metabolismo , Metanol/farmacologia , Osmose/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Reguladores de Crescimento de Plantas/metabolismo , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/metabolismo , Estômatos de Plantas/efeitos dos fármacos , Estômatos de Plantas/metabolismo , Estresse Fisiológico/efeitos dos fármacos
7.
J Nat Med ; 74(2): 482-486, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31956959

RESUMO

In our previous study, we found that the methanolic extract of Sanoshashinto () (SHXXTM) exhibited significant vasorelaxant effects in vitro and antihypertensive effects in vivo, and baicalin and berberine were the main antihypertensive constituents in SHXXTM. We also speculated that the baicalin-berberine (BB) combination produced vasorelaxant effects by activating the NO/cGMP pathway, and the BKCa channel and the DAG/PKC/CPI-17 pathway were involved. In this study, we examined the vasorelaxant effects using helical strips of rat aorta pretreated with different activators or inhibitors. The results suggested that the KATP channel and the voltage-dependent Ca2+ channel (VDCC) were also involved in the vasorelaxant effects. Furthermore, we found that SHXXTM and the BB combination reduced left ventricular hypertrophy and altered gut microbiota. Together, the results indicated that Sanoshashinto might have comprehensive effects on ameliorating hypertension.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Metanol/uso terapêutico , Extratos Vegetais/uso terapêutico , Vasodilatadores/uso terapêutico , Animais , Modelos Animais de Doenças , Masculino , Metanol/farmacologia , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-Dawley , Vasodilatadores/farmacologia
8.
Fitoterapia ; 140: 104420, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31733344

RESUMO

We report for the first time the isolation of 2-furyl(phenyl)methanol (5) from the chloroform extracts of the Atractylis gummifera roots. A. gummifera is a thistle belonging to the Asteraceae family that produces the ent-kaurane diterpenoid glycoside atractyloside (ATR). ATR (1) was isolated and chemically modified to obtain its aglycone atractyligenin (2) and the methylated derivatives ATR-OMe (3) and genine-OMe (4). The compounds 1-5 were structurally characterised and evaluated against the intracellular amastigote, cultured within macrophages, and the extracellular promastigote of Leishmania donovani, the protozoan parasite responsible for the highly infective disease visceral leishmaniasis, which is fatal if untreated. The 2-furyl(phenyl)methanol 5 exhibited notable activity against the promastigote.


Assuntos
Antiprotozoários/farmacologia , Atractylis/química , Leishmania donovani/efeitos dos fármacos , Metanol/farmacologia , Animais , Antiprotozoários/isolamento & purificação , Itália , Macrófagos/parasitologia , Metanol/análogos & derivados , Metanol/isolamento & purificação , Camundongos Endogâmicos BALB C , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Extratos Vegetais , Rizoma/química
9.
Radiat Prot Dosimetry ; 186(2-3): 186-190, 2019 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-31812995

RESUMO

The influence of various hydroxyl radical scavengers such as methanol, ethanol and dimethyl sulfoxide on radiation sensitivity of prokaryotic cells (bacteria Escherichia coli) and eukaryotic cells (yeast Saccharomyces cerevisiae and V79 cells-Chinese hamster pulmonary fibroblasts) irradiated by 60Co gamma radiation was investigated. The dependence of radiation sensitivity on dose rate in range from 1.8 to 100 Gy h-1 was evaluated. Survival of cells irradiated by increasing dose rates was followed using clonogenic assay. Specific protective effect was found to be a nonmonotonous function of dose rate with typical maximum at the dose rate range from 50 to 55 Gy h-1 in all studied cell types.


Assuntos
Sequestradores de Radicais Livres/farmacologia , Radical Hidroxila , Protetores contra Radiação/farmacologia , Animais , Células CHO , Sobrevivência Celular/efeitos da radiação , Radioisótopos de Cobalto/farmacologia , Cricetulus , Dano ao DNA , Dimetil Sulfóxido/farmacologia , Relação Dose-Resposta à Radiação , Escherichia coli/efeitos dos fármacos , Escherichia coli/efeitos da radiação , Etanol/farmacologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/efeitos da radiação , Raios gama , Metanol/farmacologia , Proteção Radiológica , Tolerância a Radiação , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/efeitos da radiação
10.
Nucleic Acids Res ; 47(22): 11956-11962, 2019 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-31713635

RESUMO

There is increasing demand for single-stranded DNA (ssDNA) of lengths >200 nucleotides (nt) in synthetic biology, biological imaging and bionanotechnology. Existing methods to produce high-purity long ssDNA face limitations in scalability, complexity of protocol steps and/or yield. We present a rapid, high-yielding and user-friendly method for in vitro production of high-purity ssDNA with lengths up to at least seven kilobases. Polymerase chain reaction (PCR) with a forward primer bearing a methanol-responsive polymer generates a tagged amplicon that enables selective precipitation of the modified strand under denaturing conditions. We demonstrate that ssDNA is recoverable in ∼40-50 min (time after PCR) with >70% yield with respect to the input PCR amplicon, or up to 70 pmol per 100 µl PCR reaction. We demonstrate that the recovered ssDNA can be used for CRISPR/Cas9 homology directed repair in human cells, DNA-origami folding and fluorescent in-situ hybridization.


Assuntos
DNA de Cadeia Simples/síntese química , Reação em Cadeia da Polimerase/métodos , Sequência de Bases , Proteína 9 Associada à CRISPR/metabolismo , Reparo do DNA/efeitos dos fármacos , DNA de Cadeia Simples/química , Marcação de Genes/métodos , Células HEK293 , Humanos , Metanol/química , Metanol/farmacologia , Mutagênese Sítio-Dirigida/métodos , Polímeros/química , Fatores de Tempo
11.
Epilepsy Res ; 158: 106225, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31710948

RESUMO

PURPOSE: Epilepsy is a chronic neurological disorder characterized by spontaneous and recurrent seizures. The currently available synthetic antiepileptic drugs have a limited efficacy and are associated with a wide range of side effects. In Ayurveda, Anacyclus pyrethrum root (APR) has been used as a traditional antiepileptic remedy. The aim of the present study is to evaluate the anticonvulsive and neuroprotective effects of aqueous and methanol extracts of Anacyclus pyrethrum root (AEAPR and MEAPR) on experimental model of status epilepticus (SE). METHODS: Twenty four male mice were divided into four groups. The control and KA groups had free access to tap water for 5 days before the intraperitoneal injection of distillated water or kainic acid (KA; 30 mg/kg), respectively. In the treated groups, mice received extracts solutions MEAPR and AEAPR in drinking water at the concentration of 5 g/l for 5 days. At the fifth day, animals received intraperitoneal injection of KA. The behavioral changes latency of seizures, the number of wet dog shakes (WDS) and the mortality were observed over 6 h. Thereafter, the mice were sacrificed for immunohistochemical studies. RESULTS: Pretreatment with MEAPR and AEAPR decreases significantly the frequency of WDS (32.5% and 43.9%, p < 0.01; respectively), and increases considerably the latent period (77.9% and 91.9%, p<0.01; respectively) between the injection of the KA and the appearance of the SE as compared to the KA group. The duration and severity of seizure in the MEAPR or AEAPR-pretreated groups were significantly lower (p < 0.01 and p < 0.05 or p < 0.01; respectively) than those in the KA group. These behavioral results were confirmed by the immunohistochemical study at the level of the hippocampus, in which the c-FOS and GFAP expression of both MEAPR and AEAPR-treated animals largely reduced (p < 0.001) the number of labelled cells with respect to the group, which received the KA alone. CONCLUSION: Our results showed that the MEAPR and AEAPR have anticonvulsive effect and putative neuroprotective effect against seizures induced by KA. Further studies are required to identify its active ingredients responsible for the observed effects.


Assuntos
Anticonvulsivantes/farmacologia , Agonistas de Aminoácidos Excitatórios/farmacologia , Ácido Caínico/farmacologia , Fármacos Neuroprotetores/farmacologia , Animais , Chrysanthemum cinerariifolium/efeitos dos fármacos , Modelos Animais de Doenças , Metanol/farmacologia , Camundongos , Extratos Vegetais/farmacologia
12.
Curr Alzheimer Res ; 16(10): 963-973, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31660828

RESUMO

BACKGROUND: Cholinesterase inhibitors are routinely applied in the treatment of Alzheimer's disease, and seeking new cholinesterase inhibitors is a priority. OBJECTIVES: Twenty seven compounds were compared, including ones not previously tested. An attempt was undertaken to precisely describe the role of alcohol in the inhibitory activity. This paper underlines the role of a "false positive" blank sample in the routine analysis. METHODS: The inhibition of cholinesterase was measured using Ellman's colorimetric method with a few modifications designed by the authors (including the "false-positive" effect). The inhibitory role of ethanol and methanol was also carefully evaluated. The present and past results were compared taking the source of enzyme and alcohol content into consideration. RESULTS: For the first time, new inhibitors were identified, namely: methyl jasmonate, 1R-(-)-nopol ((anti-acetyl-(AChE) and butyrylcholinesterase (BChE) activity)) and 1,4-cineole, allo-aromadendrene, nerolidol, ß-ionone, and (R)-(+)-pulegone (anti-BChE activity). Oleanolic acid and (+)-ß-citronellene (not previously studied) proved to be inefficient inhibitors. For a number of well-known inhibitors (such as nerol, (-)-menthol, (+)-menthol, isoborneol, (-)-bornyl acetate, limonene, α-pinene, ß-pinene, α- ionone, and eugenol) some serious discrepancies were observed between our findings and the results of previous studies. Ethanol and methanol showed no anti-AChE activity up to 0.29% (v/v) and 0.23% (v/v), respectively. Similarly, ethanol up to 0.33% (v/v) and methanol up to 0.29% (v/v) did not inhibit the activity of BChE. CONCLUSION: It can be stated that the impact of alcohol should be precisely determined and that blank "false-positive" samples should be processed together with test samples. Furthermore, the effect of the enzyme origin on the result of this test must be taken into consideration.


Assuntos
Acetilcolinesterase/metabolismo , Butirilcolinesterase/metabolismo , Inibidores da Colinesterase/metabolismo , Fenilpropionatos/metabolismo , Terpenos/metabolismo , Animais , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/métodos , Electrophorus , Etanol/química , Etanol/metabolismo , Etanol/farmacologia , Cavalos , Metanol/química , Metanol/metabolismo , Metanol/farmacologia , Fenilpropionatos/química , Fenilpropionatos/farmacologia , Terpenos/química , Terpenos/farmacologia
13.
Tuberculosis (Edinb) ; 117: 52-55, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31378268

RESUMO

Pharmacokinetic/pharmacodynamic studies of anti-tuberculosis agents in animal models of tuberculosis are hampered by the frequent necessity to perform sample bioanalysis outside the biosafety level-3 environment. Thus, each specimen has to undergo tedious and time-consuming sample sterilization procedures that may also affect drug stability. Here, we tested treatment of Mycobacterium tuberculosis (Mtb) infected samples with methanol to sterilize samples while preserving drug integrity for further pharmacokinetic/pharmacodynamic evaluations. Tissue samples harvested from Mtb infected mice were homogenized, incubated in methanol, and tested for sterility. Once sterility was confirmed, the samples were used to determine concentrations of the anti-tuberculosis drug spectinamide-1599 in lung homogenates using liquid chromatography coupled with mass spectrometry. The results demonstrate that methanol sterilizes tissue samples harvested from Mtb infected mice without altering the integrity of the drug in the tissue.


Assuntos
Antituberculosos/farmacologia , Metanol/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Manejo de Espécimes/métodos , Esterilização/métodos , Tuberculose/microbiologia , Animais , Antituberculosos/análise , Contagem de Colônia Microbiana , Estudos de Viabilidade , Feminino , Infecção Laboratorial/prevenção & controle , Pulmão/microbiologia , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana/métodos , Viabilidade Microbiana/efeitos dos fármacos , Mycobacterium tuberculosis/fisiologia , Espectinomicina/análogos & derivados , Espectinomicina/análise , Espectinomicina/farmacologia , Células-Tronco/efeitos dos fármacos
14.
Appl Environ Microbiol ; 85(19)2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31375482

RESUMO

Schizochytrium is a promising source for the production of docosahexaenoic acid and astaxanthin. The effects of different methanol concentrations on astaxanthin, biomass, and production of the lipids, squalene, and total sterol in Schizochytrium limacinum B4D1 were investigated. Astaxanthin began to accumulate when the methanol concentration reached 3.2% and peaked at 5.6% methanol, with a 2,000-fold increase over that in the control. However, under cultivation with 5.6% methanol, the biomass, lipids, squalene, and total sterol decreased to various degrees. Transcriptomic analysis was performed to explore the effects of different methanol concentrations (0%, 3.2%, and 5.6%) on the expression profile of B4D1. Three key signaling pathways were found to play important roles in regulating cell growth and metabolism under cultivation with methanol. Five central carbon metabolism-associated genes were significantly downregulated in response to 5.6% methanol and thus were expected to result in less ATP and NADPH being available for cell growth and synthesis. High methanol conditions significantly downregulated three genes involved in fatty acid and squalene/sterol precursor biosynthesis but significantly upregulated geranylgeranyl diphosphate synthase, lycopene ß-cyclase, and ß-carotene 3-hydroxylase, which are involved in astaxanthin synthesis, thus resulting in an increase in the levels of precursors and the final production of astaxanthin. Additionally, the transcriptional levels of three stress response genes were upregulated. This study investigates gene expression profiles in the astaxanthin producer Schizochytrium when grown under various methanol concentrations. These results broaden current knowledge regarding genetic expression and provide important information for promoting astaxanthin biosynthesis in Schizochytrium IMPORTANCE Schizochytrium strains are usually studied as oil-producing strains, but they can also synthesize other secondary metabolites, such as astaxanthin. In this study, methanol was used as an inducer, and we explored its effects on the production of astaxanthin, a highly valuable substance in Schizochytrium Methanol induced Schizochytrium to synthesize large amounts of astaxanthin. Transcriptomic analysis was used to investigate the regulation of signaling and metabolic pathways (mainly relative gene expression) in Schizochytrium grown in the presence of various concentrations of methanol. These results contribute to the understanding of the underlying molecular mechanisms and may aid in the future optimization of Schizochytrium for astaxanthin biosynthesis.


Assuntos
Biomassa , Ácidos Graxos/biossíntese , Metanol/farmacologia , Estramenópilas/genética , Organismos Aquáticos/genética , Organismos Aquáticos/metabolismo , Perfilação da Expressão Gênica , Redes e Vias Metabólicas , Estramenópilas/metabolismo , Transcriptoma , Xantofilas/análise
15.
J Helminthol ; 94: e77, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31455460

RESUMO

This study assessed the in vitro anthelmintic (AH) activity of methanol and acetone:water leaf extracts from Annona squamosa, A. muricata and A. reticulata against Haemonchus contortus eggs. The egg hatch test was used to determine the effective concentrations required to inhibit 50% of eggs hatching (EC50). The role of polyphenols on AH activity was measured through bioassays with and without polyvinylpolypyrrolidone (PVPP). Methanolic extracts mainly caused the death of eggs at the morula stage (ovicidal activity). Meanwhile, acetone:water extracts caused egg-hatching failure of developed larvae (larvae failing eclosion (LFE) activity). The lowest EC50 values against H. contortus eggs were observed for the methanolic extracts from A. reticulata and A. muricata (274.2 and 382.9 µg/ml, respectively). From the six extracts evaluated, the methanolic extracts of A. muricata, A. reticulata and A. squamosa showed the highest ovicidal activity, resulting in 98.9%, 92.8% and 95.1% egg mortality, respectively. When the methanolic extract of A. squamosa was incubated with PVPP, its AH activity increased. Similarly, when acetone:water extracts of A. muriata and A. reticulata were incubated with PVPP, their LFE activity increased. Alkaloids were only evident in methanolic extracts, irrespective of PVPP incubation. The presence of acetogenins was not observed. In conclusion, methanolic extracts obtained from leaves of A. muricata, A. reticulata and A. squamosa showed ovicidal activity affecting the morula of H. contortus eggs, with minor LFE activity. Meanwhile, acetone:water extracts showed mostly LFE activity, with a lower proportion of ovicidal activity.


Assuntos
Annona/química , Anti-Helmínticos/farmacologia , Haemonchus/efeitos dos fármacos , Óvulo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Acetona/farmacologia , Animais , Annona/classificação , Haemonchus/fisiologia , Larva/efeitos dos fármacos , Metanol/farmacologia , Folhas de Planta/química , Polifenóis/farmacologia
16.
DNA Cell Biol ; 38(11): 1338-1345, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31464523

RESUMO

Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease, which often affects colon or rectum or both. It is now well recognized that sphingosine kinases-1/sphingosine-1-phosphate (S1P) signaling may have a very significant potential as targets for therapeutic intervention in UC. Compared with the pure dextran sodium sulfate group, administration of PF543 significantly reduced clinical symptoms with less weight loss, diarrhea, and shortening of the colon. The severity of colitis was improved with reduced disease activity index and degree of histological damage in colon. Moreover, treatment with PF543 not only decreased S1P but also inhibited mRNA expression of proinflammatory factors such as interleukin (IL)-1ß and IL-6. This suggests that PF543 might exhibit an anti-inflammatory function against colitis through inhibition of expression of proinflammatory factors.


Assuntos
Colite/patologia , Colo/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Metanol/análogos & derivados , Fosfotransferases (Aceptor do Grupo Álcool)/antagonistas & inibidores , Pirrolidinas/farmacologia , Animais , Colite/sangue , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colo/patologia , Sulfato de Dextrana , Modelos Animais de Doenças , Inibidores Enzimáticos/uso terapêutico , Lisofosfolipídeos/sangue , Masculino , Metanol/farmacologia , Metanol/uso terapêutico , Camundongos , Camundongos Endogâmicos C57BL , Tamanho do Órgão/efeitos dos fármacos , Pirrolidinas/uso terapêutico , Esfingosina/análogos & derivados , Esfingosina/sangue , Baço/efeitos dos fármacos , Baço/patologia , Especificidade por Substrato
17.
Niger J Physiol Sci ; 34(1): 83-90, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31449276

RESUMO

The present study examines the possible ameliorative effects of the hydromethanolic extract of Citrullus lanatus rind (HECL) on some reproductive function and oxidative indices of the testes in male Wistar rats following administration of nicotine. Twenty male rats were assigned into four groups: Group A to D of five rats each. Group A served as control and received 2ml/kg body weight of 10% extract vehicle; Group B received 1mg/kg body weight of nicotine; Group C were co-administered 1mg/kg body weight nicotine and 500 mg/kg body weight of HECL and Group D received only 500mg/kg body weight of HECL. The drugs and extracts were administered orally to the rats for 42days; blood samples were collected by direct cardiac puncture for determination of serum concentrations of testosterone, Follicle Stimulating Hormone and Luteinizing Hormone. The testes were also harvested for determination of semen parameters: motility, morphology, viability and count and testicular tissue processed for superoxide dismutase and malondialdehyde concentration. Compared to Group A control rats, administration of HECL significantly increased sperm count and reproductive hormone concentrations amongst Group B rats (p<0.05). Treatment with nicotine caused a significant reduction in the levels of all reproductive hormones with significant diminution of some sperm parameters: motility, morphology and viability; and decrease in superoxide dismutase and increase in malondialdehyde concentration amongst Group B rats compared to Group A control rats (p<0.05). Co-administration of HECL with nicotine to Group C rats apparently reversed the effects of nicotine resulting in significant increases in sperm count and the reproductive hormones concentration as compared to Group A control rats (p<0.05). Amongst Group D rats, the extract also caused a significant increase in superoxide dismutase concentration and a significant decrease in malondialdehyde concentration compared with the Group A control rats (p<0.05). The findings suggest that the hydromethanolic extract of Citrullus lanatus rind possibly ameliorates the deleterious effects of nicotine on some reproductive indices in male Wistar rats.


Assuntos
Citrullus , Hormônios Esteroides Gonadais/sangue , Nicotina/toxicidade , Extratos Vegetais/farmacologia , Sêmen/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Hormônios Esteroides Gonadais/antagonistas & inibidores , Masculino , Metanol/farmacologia , Nicotina/administração & dosagem , Agonistas Nicotínicos/administração & dosagem , Agonistas Nicotínicos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Ratos , Ratos Wistar , Sêmen/metabolismo , Testículo/metabolismo , Resultado do Tratamento
18.
Mol Biol Rep ; 46(5): 5131-5142, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31317456

RESUMO

Medicinal plants can be candidate as a common alternative for cancer treatment according to natural landscaping and native plants in each country. The aim of this study was the evaluations of cytotoxicity, apoptosis, and cell cycle arrest induction by using seven leaves extracts of Catharanthus roseus, Calystegia sepium, Berberis integerrima, Mahonia fortunei, Melia azedarach, Plantago major, Betula pendula and one bulb extract of Narcissus tazetta. Extracts were assessed on three cancer cell lines including MCF-7 breast cancer cells, A431 epidermal cell line, and U87-MG glioma cell line that were compared to HGF-1 as normal cells. According to analysis of MTT, methanolic extract of C. sepium leaves increased significantly the rate of cell death in all cancer cell lines when compared to HGF-1 as normal cells. Among different extracts, methanolic extract of C. roseus leaves and methanolic extract of C. sepium leaves indicated a crucial role in apoptosis of cancer cells according to evidences from MTT assay, cell cycle analysis, and apoptosis assay. Doxorubicin has been used as standard drug to compare with IC50 s of different extracts. In addition, the encapsulation of methanolic and ethanolic extracts in small unilamellar vesicles form (SUV) increased the cytotoxicity on cancer cell lines and normal cells. Our results indicated that different extracts can differently affect the cytotoxicity rate in variety of cancer cell lines.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias da Mama/genética , Glioblastoma/genética , Plantas Medicinais/química , Neoplasias Cutâneas/genética , Antineoplásicos Fitogênicos/química , Proteínas Reguladoras de Apoptose/genética , Neoplasias da Mama/tratamento farmacológico , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioblastoma/tratamento farmacológico , Humanos , Lipossomos , Células MCF-7 , Metanol/química , Metanol/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Neoplasias Cutâneas/tratamento farmacológico
19.
Biosci Biotechnol Biochem ; 83(11): 2163-2171, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31272289

RESUMO

Motile bacteria often exhibit chemotaxis toward favorable compounds. However, the diversity of bacteria that are attracted to a given substance is largely unknown. This study aimed to reveal the diversity of bacteria with natural chemotaxis towards methanol. We tried to enrich environmental chemotactic bacteria using a glass capillary that is half-filled with methanol solidified with agarose as a trap ("chemotaxis fishing"). The pilot experiment using methanol-chemotactic Methylobacterium aquaticum strain 22A enriched the cells by 46-fold. The method was then applied to bacterial suspensions from paddy water and plants. Depending on the isolation sources and the methods of motility induction, methylotrophic bacteria were enriched 1.2-330-fold. The fished isolates belong to 32 species in 18 genera, mainly containing Acinetobacter, Methylobacterium and Pseudomonas species. Our chemotaxis fishing unveiled a part of diversity of the bacteria with natural chemotaxis towards methanol.


Assuntos
Bactérias/citologia , Bactérias/efeitos dos fármacos , Quimiotaxia/efeitos dos fármacos , Metanol/farmacologia , Técnicas Microbiológicas/métodos , Plantas/microbiologia
20.
Biotechnol Prog ; 35(5): e2867, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31187591

RESUMO

The cyclodextrin glycosyltransferase (CGTase) is an important enzyme for cyclodextrin (CD) production, and is also widely used in the biotechnology, food, and pharmaceuticals industries. Secretory CGTase production by recombinant Komagataella phaffii using defined medium is a promising approach because of low cost, less impurity protein. It was found that no CGTase was expressed using traditional defined medium (basal salt medium [BSM]) because of pH value decreasing significantly. CGTase was expressed by recombinant K. phaffii through pH maintenance in range of 5.5-7.0. ß-CGTase activity increased to 122.0 U/mL after optimization of glycerol, phosphate buffer, pH value, ammonium sulfate, temperature, methanol, and additives based on BSM, establishing a modified defined medium. These results showed that it was necessary to establish recombinant K. phaffii-based special defined medium although the same host cell used for different heterologous protein expression.


Assuntos
Meios de Cultura , Glucosiltransferases/metabolismo , Proteínas Recombinantes/metabolismo , Saccharomycetales/metabolismo , Sulfato de Amônio/metabolismo , Sulfato de Amônio/farmacologia , Biotecnologia , Meios de Cultura/química , Meios de Cultura/metabolismo , Meios de Cultura/farmacologia , Glucosiltransferases/análise , Glucosiltransferases/genética , Glicerol/metabolismo , Glicerol/farmacologia , Concentração de Íons de Hidrogênio , Metanol/metabolismo , Metanol/farmacologia , Proteínas Recombinantes/análise , Proteínas Recombinantes/genética , Saccharomycetales/genética , Temperatura
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