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1.
Biol Futur ; 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39278890

RESUMO

This study aimed to screen 10 medicinal plant extracts on zebrafish (Danio rerio), evaluating their impact on the complement system, immunoglobulin M (IgM) levels, lysozyme, and peroxidase activity, while also enhancing their efficacy through the gradual release using alginate-chitosan nanocapsules. The prepared methanolic extracts were combined with fish feed. The fish were divided into 12 groups, including 10 treatment groups, a positive and a negative control group. Results showed varying impacts of the extracts on the immune and antioxidant systems, with Cinnamon (Cinnamon cassia) and Hypericum (Hypericum perforatum) extracts demonstrating the most significant effects. Subsequently, Cinnamon and Hypericum extract were encapsulated in alginate-chitosan nanocapsules to assess their impact on zebrafish immune parameters, separately and synergistically. Gradual release of the extracts from the nanocapsules was observed, with slower release at pH 2 compared to pH 7. Overall, Cinnamon and Hypericum extracts exhibited substantial immune system enhancement, and their encapsulation in nanocapsules improved their effects on zebrafish immune parameters. These findings suggest using these encapsulated extracts to enhance immune responses in aquatic organisms.

2.
Clin Exp Pharmacol Physiol ; 50(4): 298-306, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36573522

RESUMO

The percutaneous bioavailability of naproxen is low and several technologies have been utilized to overcome the problem. Although, some studies have reported the permeation-enhancing properties of natural essential oils, no research has reflected the effectiveness of Lavandula angustifolia essential oil (LAEO) on increasing the percutaneous absorption of naproxen sodium from a topical gel. Therefore, the present study was designed to investigate whether LAEO increased the percutaneous absorption and the analgesic effects of naproxen sodium topical gel. In the present study, naproxen topical gel was formulated using carbopol 940 (a gelling agent) and several vehicles such as PEG 400, ethanol, and water and the properties of gels were measured. Percutaneous absorption-enhancing properties of LAEO were measured too. Based on our data, the essential oil-containing formulation of naproxen represented greater penetration into (222.19 ± 24.87 vs. 107.65 ± 6.38 µg/cm2 ), and also across (22.07 ± 4.42 vs. 13.14 ± 2.87 µg/cm2 ) skin layers compared to the naproxen gel. Additionally, a significant analgesic property was observed in the naproxen topical gel containing 0.5% essential oil during both first and late phases of formalin test, as well as the late phase of tail-flick test. It could be concluded that LAEO significantly enhanced naproxen percutaneous absorption and also its analgesic effects.


Assuntos
Lavandula , Óleos Voláteis , Absorção Cutânea , Naproxeno , Óleos Voláteis/farmacologia , Géis
3.
J Complement Integr Med ; 19(2): 203-211, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33964199

RESUMO

OBJECTIVES: The neem (Azadirachta indica) have been used in herbal medicine for the treatment of multiple diseases, particularly cancer. The mechanism of anti-cancer properties of neem are far from clear. However, it is well accepted that anti-cancer effects of neem is mediated via its hepatic anti-oxidant activity. In the present review, we are going to classify in vitro and in vivo studies about anti-cancer activity of neem via its hepatic anti-oxidant activity. We also summarize its active ingredients and some therapeutic and toxic dosage forms. METHODS: A systematic search in the literature was performed in PubMed, Scopus, Embase, Cochrane Library, Web of Science, as well as Google Scholar pre-print database using all available MeSH terms for neem, A. indica, anti-cancer, anti-tumor, carcinogen, liver, antioxidant activity, neem ingredients, and glutathione. Electronic database searches combined and duplicates were removed. RESULTS: The neem plant have been used in herbal medicine for the treatment of various diseases, particularly cancer. The mechanisms of anti-cancer effects of neem are far from clear. Cancerous cells growth can induce imbalance the oxidant and anti-oxidant activity in various organs particularly in the liver. Therefore, it seems that neem have anti-cancer effects via restore of the antioxidant disturbances close to the control ones in the liver. Additionally, administration of neem extract can induce oncostatic potential via several mechanism including; suppression of the NF-κß pathway, increased expression of tumor suppressor (such as p53 and pTEN), decreased expression of oncogenes (such as c-Myc), and increased apoptosis in cancerous cells. The median lethal dose (LD50) value for extracts of neem was higher than 2,500 mg/kg. CONCLUSIONS: It is suggested that neem plays pivotal role in the prevention and treatment of cancer via its hepatic antioxidant activity. Indeed, application of neem extract can decreased tumor growth via restore of the antioxidant disturbances close to the control ones in the liver.


Assuntos
Azadirachta , Neoplasias , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Biofarmácia , Humanos , Fígado , Neoplasias/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Folhas de Planta
4.
Braz. arch. biol. technol ; Braz. arch. biol. technol;65: e22210268, 2022. tab
Artigo em Inglês | LILACS | ID: biblio-1364472

RESUMO

Abstract: Sulfur mustard is one of the chemical warfare agent. It rapidly reacts with the cutaneous tissues and other tissues, leading to various devastating long-term effects on human health. Mustard-exposed veterans suffer from its chronic skin problems, including itching, burning sensation, and eczema. We aimed to evaluate the protective effects of Myrtus communis L. (myrtle) on chronic skin lesions and quality of life of sulfur mustard-exposed veterans. In this randomized, double-blind clinical trial, 60 sulfur mustard-exposed patients were evaluated. Thirty patients received myrtle essence 5% cream (case group) and 30 patients received Eucerin cream (placebo group) twice in a day for one month. Then, We assessed the chronic skin problems and itching-related parameters (such as the itching time, severity, distribution, frequency, and calculated itching score), duration of sleep, number of waking up at night, and quality of life in the both groups. Our analysis of data revealed that application of myrtle cream effectively decreased skin problems including; itching and burning sensation. Additionally, myrtle markedly decreased skin lesion symptoms such as excoriation in the case group as compared with before treatment. Noticeably, myrtle cream significantly improved quality of life of the patients in the case group. The present study provides more in-depth information regarding the protective role of myrtle on the sulfur mustard-induces skin complication. Also, myrtle effectively improved quality of life of the sulfur mustard-exposed veterans.


Assuntos
Humanos , Pessoa de Meia-Idade , Dermatopatias/induzido quimicamente , Extratos Vegetais/uso terapêutico , Substâncias para a Guerra Química/toxicidade , Myrtus communis/uso terapêutico , Fitoterapia , Gás de Mostarda/toxicidade , Prurido/induzido quimicamente , Qualidade de Vida , Veteranos , Indicadores de Qualidade de Vida , Eczema/induzido quimicamente , Exposição à Guerra/efeitos adversos , Irã (Geográfico)
5.
J Complement Integr Med ; 18(4): 701-710, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33962501

RESUMO

OBJECTIVES: Resveratrol as a natural polyphenolic agent can alleviate neuropathic pain symptoms. The mechanism of analgesic activity of resveratrol is far from clear. The current study examine whether analgesic activity of resveratrol is mediated by its neuroprotective and anti-oxidant activity in the neuropathic pain. We further examine whether analgesic activity of resveratrol is mediated by ß-adrenoceptors in the brain. METHODS: Neuropathic pain induced by L5 spinal nerve ligation (SNL). Male Wistar rats assigned into sham, SNL, SNL + resveratrol (40 µg/5 µL), and SNL + resveratrol + propranolol (a non-selective ß-adrenoceptor antagonist, 30 µg/5 µL) groups. Drugs injected intracerebroventricular (ICV) at day SNL surgery and daily for 6 days following SNL. Thermal allodynia and anxiety examined on days of -1, 2, 4, and 6 following SNL. Electrophysiological study performed on day 6 following SNL for evaluation of resveratrol effects on sciatic nerve conduction velocity (NCV). The activity of catalase (Cat) and superoxide dismutase (SOD) enzymes in the brain assessed on days 6 following SNL. RESULTS: Resveratrol significantly decreased thermal allodynia (and not anxiety) in all experimental days. Additionally, resveratrol significantly increased NCV, and also normalized the disrupted Cat and SOD activities following neuropathic pain. Furthermore, propranolol significantly blocked the analgesic and neuroprotective effects of resveratrol. CONCLUSIONS: It is suggested that the analgesic effects of resveratrol is mediated by its neuroprotective and antioxidant activities in the neuropathic rats. Furthermore, propranolol blocked the analgesic and neuroprotective effects of resveratrol.


Assuntos
Fármacos Neuroprotetores , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Animais , Modelos Animais de Doenças , Hiperalgesia/tratamento farmacológico , Ligadura , Masculino , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Propranolol/farmacologia , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Resveratrol , Nervos Espinhais
6.
Biochem Mol Biol Educ ; 49(4): 509-517, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33847452

RESUMO

Western blot (WB) or immunoblot is a workhorse method. It is commonly used by biologists for study of different aspects of protein biomolecules. In addition, it has been widely used in disease diagnosis. Despite some limitations such as long time, different applications of WB have not been limited. In the present review, we have summarized scientific and clinical applications of WB. In addition, we described some new generation of WB techniques.


Assuntos
Western Blotting/métodos , Western Blotting/normas , Proteínas/análise , Proteínas/metabolismo , Pesquisa Translacional Biomédica , Humanos , Proteínas/isolamento & purificação
7.
Curr Comput Aided Drug Des ; 17(2): 235-243, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32065093

RESUMO

OBJECTIVE: Azole antifungal agents, which are widely used as antifungal antibiotics, inhibit cytochrome P450 sterol 14α-demethylase (CYP51). Nearly all azole antifungal agents are Nsubstituted azoles. In addition, an azolylphenalkyl pharmacophore is uniquely shared by all azole antifungals. Due to the importance of nitrogen atom of azoles (N-3 of imidazole and N-4 of triazole) in coordination with heme in the binding site of the enzyme, here a group of N- un-substituted azoles in which both nitrogen are un-substituted was reported. MATERIALS AND METHODS: Designed compounds were synthesized by the reaction of imidazole-4- carboxaldehyde with appropriate arylamines and subsequently reduced to desired amine derivatives. Antifungal activity against Candida albicans and Saccharomyces cervisiae was done using a broth micro-dilution assay. Docking studies were done using AutoDock. RESULTS: Antimicrobial evaluation revealed that some of these compounds exhibited moderate antimicrobial activities against tested pathogenic fungi, wherein compounds 3, 7, and 8 were potent. Docking studies propose that all of the prepared azoles interacted with 14α-DM, wherein azoleheme coordination played the main role in drug-receptor interaction. CONCLUSION: Our results offer some useful references for molecular design performance or modification of this series of compounds as a lead compound to discover new and potent antimicrobial agents.


Assuntos
Inibidores de 14-alfa Desmetilase/síntese química , Antifúngicos/síntese química , Azóis/síntese química , Desenho de Fármacos/métodos , Simulação de Acoplamento Molecular/métodos , Inibidores de 14-alfa Desmetilase/farmacologia , Antifúngicos/farmacologia , Azóis/farmacologia , Candida albicans/efeitos dos fármacos , Candida albicans/fisiologia , Humanos , Testes de Sensibilidade Microbiana/métodos , Estrutura Molecular
8.
Colloids Surf B Biointerfaces ; 185: 110619, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31707227

RESUMO

In the present study, the dual function of interleukin-23 (IL-23) Aptamer to suppress brain inflammation via attachment to macrophage stimulating 1 (MST1) kinase and IL-23, was introduced. Also, the anti-inflammatory property of IL-23 Aptamer has been investigated. This study showed that IL-23 Aptamer could reduce the clinical development of brain inflammation induced by Parathion, as an important organophosphate toxin. Both immunostaining and H&E staining indicated that the total inflammatory infiltration foci were remarkably decreased in IL-23 Aptamer-treated mice. Moreover, this study showed that IL-23 Aptamer reduced both absolute and relative numbers of MST1+CD4 + Th1 cells and IL-23-producing cells. Analysis of the Hippo signaling genes showed a sharp decrease of MST1 kinase compared with other genes (P < 0.001). Moreover, computer-assisted molecular docking demonstrated that both MST1 kinase and IL-23 could tightly attach to IL-23 Aptamer, and maybe block it. Taken together, IL-23 Aptamer coud decrease brain inflammation via suppressing MST1 kinase and IL-23.


Assuntos
Aptâmeros de Peptídeos/metabolismo , Encefalite/metabolismo , Interleucina-23/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Animais , Doenças Desmielinizantes/patologia , Encefalite/patologia , Feminino , Regulação da Expressão Gênica , Macrófagos/metabolismo , Camundongos , Simulação de Acoplamento Molecular
9.
Mikrochim Acta ; 186(9): 641, 2019 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-31444649

RESUMO

A nanocomposite was prepared with reduced graphene oxide, gold nanoparticles and an electropolymerized film made from 2-amino-5-mercapto-1,3,4-thiadiazole. An electrochemical sensor for doxorubicin (DOX) was constructed by modifying a glassy carbon electrode (GCE) with the nanocomposite. The modified GCE was studied by electrochemical techniques which showed it to enable highly sensitive sensing of DOX. Response (typically measured at a typical working potential of -0.56 V vs. Ag/AgCl) is linear in the 30 pM to 30 nM and 30 nM to 30 µM DOX concentration ranges, with a limit of detection (LOD) of 9 pM (at an S/N ratio of 3). The method was applied to the determination of DOX in serum and gave recoveries that ranged between 92 and 108%. Graphical abstract A combination of materials consisting of reduced graphene oxide (rGO), gold nanoparticles (AuNPs) and an electropolymerized film of 2-amino-5-mercapto-1,3,4-thiadiazole (poly-AMT, PAMT) is described. The nanocomposite was placed on a glassy carbon elkectrode (GCE) in order to fabricate an electrochemical sensor for doxorubicin (DOX).


Assuntos
Antibióticos Antineoplásicos/análise , Técnicas Biossensoriais , Doxorrubicina/análise , Técnicas Eletroquímicas , Nanocompostos/química , Ouro/química , Grafite/química , Nanopartículas Metálicas/química , Conformação Molecular , Oxirredução , Tamanho da Partícula , Polímeros/química , Propriedades de Superfície , Tiadiazóis/química
10.
Open Access Maced J Med Sci ; 7(7): 1067-1070, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-31049082

RESUMO

BACKGROUND: Candida species are the most common opportunistic fungal infections. Today, cinnamon plants have been considered for anti-Candida properties. AIM: This study aimed to investigate the effectiveness of cinnamaldehyde extract (from cinnamon derivatives) on Candida albicans and Candida glabrata species and comparison with nystatin. MATERIAL AND METHODS: In this study, cinnamaldehyde and nystatin were used. The specimens included Candida albicans and Candida glabrata. Minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) were measured for each one by the microdilution method. This experiment was repeated three times. RESULTS: Cinnamaldehyde extract at a concentration of 62.5 µl/ml was able to prevent the growth of Candida albicans, at a concentration of 93.7 µl/ml, causing Candida albicans to disappear, at 48.8 µl/ml, to prevent the growth of Candida glabrata, and in the concentration of 62.5 µl/ml, causes the loss of Candida glabrata. In comparison, nystatin at 0.5 µg/ml concentration prevented the growth of Candida albicans, at concentrations of 1 µg/ml causing Candida albicans to be destroyed, at 4 µg/ml concentration to prevent the growth of Candida glabrata, and at a concentration of 8 µg/ml causes the loss of Candida glabrata. The results were the same every three times. CONCLUSIONS: Although cinnamaldehyde extract had an effect on fungal growth in both Candida albicans and Candida glabrata with a fatal effect; the effect on these two species was lower than nystatin.

11.
J Neuroimmunol ; 326: 79-83, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30544018

RESUMO

The purpose of this study was to evaluate the anti-inflammatory property of gelatin hydrogel containing cerium oxide nanoparticles coated with interleukin-17 Aptemer ([CeON@IL-17]). Here, the brain inflammation model was induced by both proteolipid protein (PLP) and parathion. Then, the expression of some inflammatory genes and the serum level of related interleukins were evaluated. This study showed that the expression of IL-17, IL-10, and IL-6 genes and their serum levels were significantly decreased (P < .05) by administration of gelatin hydrogel containing [CeON@IL-17].


Assuntos
Anti-Inflamatórios/farmacologia , Encéfalo/efeitos dos fármacos , Portadores de Fármacos , Interleucina-17 , Animais , Aptâmeros de Peptídeos , Cério , Inibidores da Colinesterase/toxicidade , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Encefalite/induzido quimicamente , Feminino , Hidrogéis , Inflamação/induzido quimicamente , Camundongos , Camundongos Endogâmicos C57BL , Nanopartículas , Paration/toxicidade
12.
Iran J Pharm Res ; 17(3): 896-905, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30127813

RESUMO

Anticonvulsant activity of phthalimide was discovered in 2000 by molecular hybridization of thalidomide and ameltolide. In our present research we report some new 4-substituted derivatives of phthalimide with good activity against the tonic and clonic seizures. A series of novel 4-flurophthalimides designed using bioisosteric replacement were synthesized by condensation of 4-flurophthalic anhydride with appropriate arylamines. The purity of these compounds was determined by TLC and the chemical structures were confirmed by IR and 1H-NMR spectroscopy. Anticonvulsant activity of prepared compounds was evaluated using MES and PTZ models. Some of the designed compounds significantly protected mice against the PTZ-induced seizure among which, compound 10 with lipophilic and flexible aromatic moiety was more potent than the reference drug phenytoin and was the most potent in this series of phthalimide derivatives. In the MES model, the prepared phthalimide did not show efficient activity. The prepared compounds are active in clonic seizure.

13.
Recent Pat Anticancer Drug Discov ; 13(3): 378-385, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29769012

RESUMO

BACKGROUND: Hydroxyurea (HU) is used to treat cancer. HU has a short half-life due to its small molecular weight and high polarity, therefore a high dosage of the drug should be used which introduces side effects and more rapid development of resistance. OBJECTIVE: The objective of the current study is to design new lipophilic analogues of hydroxyurea with higher stability and better cell penetration. The designed compounds were synthesized and then evaluated in terms of their cytostatic activities against two human cell lines. METHODS: The synthesis of designed ligands was achieved via two-step procedure. Detail of the synthesis and chemical characterization of the analogs are described. The cytotoxic activity of the designed ligands was evaluated in vitro against two different cancer cell lines at 24 and 48h using MTT test. RESULTS: Based on the IC50 values, all the designed and prepared compounds were more potent than hydroxyurea at 24 and 48h on both cell lines that the cytostatic activity at 48h was more than 24h. Drug-receptor interactions study indicated compound 7 as the most potent ligand, tightly bonded to surrounding amino acids in the active site of receptor via two strong hydrogen bonds and some hydrophobic interactions. CONCLUSION: Compound 7 with the suitable volume, log p and shape is the most active ligand against both cell lines. It is concluded or suggested that the size, shape and hydrophobic character of substituents strongly affect the pharmacodynamics and pharmacokinetics of these type of ligands.


Assuntos
Simulação por Computador , Citostáticos/síntese química , Hidroxiureia/síntese química , Lipídeos/síntese química , Citostáticos/metabolismo , Células HeLa , Humanos , Hidroxiureia/metabolismo , Metabolismo dos Lipídeos/fisiologia , Simulação de Acoplamento Molecular/métodos
14.
Recent Pat Anticancer Drug Discov ; 13(2): 255-264, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29468983

RESUMO

BACKGROUND: P-glycoprotein (P-gp) causes the efflux of cancer chemotherapy drugs from tumor cells, so its inhibition can be one target for designing and synthesis of new anticancer drugs. OBJECTIVE: In this study, new compounds of 1,4-dihydropyridine (DHP) were recommended as inhibitors of P-gp. METHODS: We synthesized new symmetrical DHP with 36% - 43% yield by the reaction of new reactants. In biological studies, these compounds have high lipophilicity, and thus low water solubility. Four reactants I with different reactivity was computed and compared using DFT study. The LUMO-map was differently distributed on each reactant. Amine intermediate underwent tautomerism as a transition state and it seems to play important role in reaction progress. Calculations were performed to select suitable reactants. RESULTS: Two different reactants I, including one polar group and a non-polar group, were used to produce asymmetric compounds with 49% - 60% yield. These asymmetric DHPs were more soluble than symmetric DHPs. In the final step, another selected symmetric product (by the elimination of chlorine atom) was synthesized in high yield (74%) by using DFT study. CONCLUSION: In this study, selected reactants by DFT calculation have increased the yield of reaction from 36% to 74% without any catalyst. The diversity of products is a noticeable topic. Racemic asymmetric compounds with R and S enantiomers have the potential for enantiomeric separation. Each of these enantiomers could have a different physiological effect.


Assuntos
Subfamília B de Transportador de Cassetes de Ligação de ATP/antagonistas & inibidores , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Química Farmacêutica/métodos , Di-Hidropiridinas/síntese química , Di-Hidropiridinas/farmacologia , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Humanos , Estereoisomerismo
15.
Iran J Pharm Res ; 16(3): 880-892, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29201079

RESUMO

Acetylcholinesterase has important role in synaptic cleft. It breaks down the acetylcholineat cholinergic synapsesand terminates the cholinergic effects. Some chemical agents like organophosphorus compounds (OPCs) including nerve agents and pesticides react with acetylcholinesteraseirreversibly. They inhibit normal biological enzyme action and result in accumulation of acetylcholineand show toxic effects andcholinergic symptoms. The process of Acetylcholinesterase (AChE) inhibition can be reversed by a nucleophilic agent to dephosphorylate and reactivate the enzyme. In this study, design and docking studies of 15 novel nitrone based onoximes as reactivators were performed by using AutoDock program. Then, more effective reactivatorsoximes in terms of binding energy and orientation within the active site were synthesized and evaluated in-vitro on human AChE (hAChE) inhibited by paraoxon and compared to standard hAChE reactivators (2-PAM and obidoxime). Our results used to design new derivatives of Oxim with better efficacy than 2-PAM and obidoxime. Syntheses of some selected bis-pyridiniumoximes based on the nitrones are underway.

16.
Bull Emerg Trauma ; 5(4): 240-248, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29177170

RESUMO

OBJECTIVE: To determine the effects of chitosan-zinc oxide nanocomposite conduit on transected sciatic nerve in animal model of rat. METHODS: Sixty male White Wistar rats were used in this study. A 10-mm sciatic nerve defect was bridged using a chitosan-zinc oxide nanocomposite conduit (CZON) filled with phosphate buffered saline. In chitosan group (CHIT) the chitosan conduit was filled with phosphate buffered saline solution. In sham-operated group (SHAM), sciatic nerve was exposed and manipulated. In transected group (TC), left sciatic nerve was transected and nerve cut ends were fixed in the adjacent muscle. The regenerated fibers were studied within 12 weeks after surgery. RESULTS: The behavioral and functional tests confirmed faster recovery of the regenerated axons in CZON group compared to Chitosan group (p<0.05). The mean ratios of gastrocnemius muscles weight were measured. There was statistically significant difference between the muscle weight ratios of CZON and Chitosan groups (p<0.05). Morphometric indices of regenerated fibers showed number and diameter of the myelinated fibers were significantly higher in CZON than in Chitosan. In immuohistochemistry, the location of reactions to S-100 in CZON was clearly more positive than Chitosan group. CONCLUSION: Chitosan-zinc oxide nanocomposite conduit resulted in acceleration of functional recovery and quantitative morphometric indices of sciatic nerve.

17.
Expert Rev Clin Immunol ; 13(12): 1173-1188, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28994328

RESUMO

INTRODUCTION: Sulfur mustard (SM) is an extremely toxic gas used in chemical warfare to cause massive lung injury and death. Victims exposed to SM gas acutely present with inhalational lung injury, but among those who survive, some develop obstructive airway diseases referred to as SM-lung syndrome. Pathophysiologically, SM-lung shares many characteristics with smoking-induced chronic obstructive pulmonary disease (COPD), including airway remodeling, goblet cell metaplasia, and obstructive ventilation defect. Some of the hallmarks of COPD pathogenesis, which include dysregulated lung inflammation, neutrophilia, recruitment of interleukin 17A (IL -17A) expressing CD4+T cells (Th17), and the paucity of lung regulatory T cells (Tregs), have also been described in SM-lung. Areas covered: A literature search was performed using the MEDLINE, EMBASE, and Web of Science databases inclusive of all literature prior to and including May 2017. Expert commentary: Here we review some of the recent findings that suggest a role for Th17 cell-mediated inflammatory changes associated with pulmonary complications in SM-lung and suggest new therapeutic approaches that could potentially alter disease progression with immune modulating biologics that can restore the lung Th17/Treg balance.


Assuntos
Células Caliciformes/patologia , Imunoterapia/métodos , Pneumopatias/imunologia , Doença Pulmonar Obstrutiva Crônica/imunologia , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Obstrução das Vias Respiratórias , Remodelação das Vias Aéreas , Animais , Guerra Química , Humanos , Imunomodulação , Inflamação , Pneumopatias/induzido quimicamente , Pneumopatias/terapia , Metaplasia , Gás de Mostarda/toxicidade
18.
Iran J Basic Med Sci ; 20(4): 430-437, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28804613

RESUMO

OBJECTIVES: Phthalimide-based derivatives have anticonvulsant activity like as phenytoin by inhibition of sodium channel. In our previously research we mentioned about some phthalimide derivatives as potent anticonvulsant agents. MATERIALS AND METHODS: Fourteen analogs of 2-substituted phthalimide pharmacophore were synthesized and then were evaluated for the anticonvulsant activities in pentylenetetrazole-induced seizures (PTZ) and maximal electroshock seizure (MES) models. RESULTS: The in vivo screening results showed that all the analogs have the ability to protect against the maximal electroshock and PTZ. The compounds 3 and 9 elevated clonic seizure thresholds at 30 min which were more active than the standard medicine phenytoin. Compounds 3, 6, 7, 11, 13 and 14 with 100% protection were the most potent ones in tonic seizure. The most potent compound in the both PTZ and MES models was compound 3. Using a model of the open pore of sodium channel, all of the compounds were docked. Results of docking showed that the ligands interacted mainly with residues II-S6 of NaV1.2 by making hydrogen bonds and have additional hydrophobic interactions with other domains in the channel's inner pore. CONCLUSION: Some of these compounds are more potent than phenytoin simultaneously in the clonic and tonic seizures.

19.
Molecules ; 22(8)2017 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-28805729

RESUMO

Microbial remediation of nitroaromatic compounds (NACs) is a promising environmentally friendly and cost-effective approach to the removal of these life-threating agents. Escherichia coli (E. coli) has shown remarkable capability for the biotransformation of 2,4,6-trinitro-toluene (TNT). Efforts to develop E. coli as an efficient TNT degrading biocatalyst will benefit from holistic flux-level description of interactions between multiple TNT transforming pathways operating in the strain. To gain such an insight, we extended the genome-scale constraint-based model of E. coli to account for a curated version of major TNT transformation pathways known or evidently hypothesized to be active in E. coli in present of TNT. Using constraint-based analysis (CBA) methods, we then performed several series of in silico experiments to elucidate the contribution of these pathways individually or in combination to the E. coli TNT transformation capacity. Results of our analyses were validated by replicating several experimentally observed TNT degradation phenotypes in E. coli cultures. We further used the extended model to explore the influence of process parameters, including aeration regime, TNT concentration, cell density, and carbon source on TNT degradation efficiency. We also conducted an in silico metabolic engineering study to design a series of E. coli mutants capable of degrading TNT at higher yield compared with the wild-type strain. Our study, therefore, extends the application of CBA to bioremediation of nitroaromatics and demonstrates the usefulness of this approach to inform bioremediation research.


Assuntos
Engenharia Metabólica/métodos , Trinitrotolueno/química , Trinitrotolueno/metabolismo , Biodegradação Ambiental , Biotransformação , Catálise , Técnicas de Cultura de Células , Escherichia coli , Cinética , Modelos Biológicos , Fenótipo , Biologia de Sistemas
20.
Artigo em Inglês | MEDLINE | ID: mdl-28630182

RESUMO

1,2-Distigmasterylhemisuccinoyl-sn-glycero-3-phosphocholine (DSHemsPC) is a new lipid in which two molecules of stigmasterol (an inexpensive plant sterol) are covalently linked via a succinic acid to glycerophosphocholine. Our previous study revealed that liposome (Lip)-intercalated amphotericin B (AMB) prepared from DSHemsPC (DSHemsPC-AMB-Lip) possesses excellent colloidal properties and in vitro antifungal and antileishmanial activities similar to those of the liposomal AMB preparation AmBisome. The aim of this study was to determine the biodistribution and evaluate the antileishmanial effects of DSHemsPC-AMB-Lip in Leishmania major-infected BALB/c mice. The serum profile and tissue concentrations of AMB were similar in DSHemsPC-AMB-Lip- and AmBisome-treated mice after intravenous (i.v.) injection. Multiple i.v. doses of the micellar formulation of AMB (Fungizone; 1 mg/kg of body weight), DSHemsPC-AMB-Lip (5 mg/kg), and AmBisome (5 mg/kg) were used in L. major-infected BALB/c mouse models of early and established lesions. In a model of the early lesions of cutaneous leishmaniasis (CL), the results indicated that the level of footpad inflammation was significantly (P < 0.001) lower in mice treated with DSHemsPC-AMB-Lip and AmBisome than mice treated with empty liposomes or 5% dextrose. The splenic and footpad parasite load was also significantly (P < 0.001) lower in these groups of mice than in control mice that received 5% DW or free liposome. The in vivo activity of DSHemsPC-AMB-Lip was comparable to that of AmBisome, and both provided improved results compared to those achieved with Fungizone at the designated doses. The results suggest that systemic DSHemsPC-AMB-Lip administration may be useful for the treatment of leishmaniasis, and because it costs less to produce DSHemsPC-AMB-Lip than AmBisome, DSHemsPC-AMB-Lip merits further investigation.


Assuntos
Anfotericina B/farmacocinética , Anfotericina B/uso terapêutico , Antiprotozoários/uso terapêutico , Leishmania major/efeitos dos fármacos , Leishmaniose Cutânea/tratamento farmacológico , Fosfatidilcolinas/farmacocinética , Fosfatidilcolinas/uso terapêutico , Estigmasterol/análogos & derivados , Animais , Antiprotozoários/farmacocinética , Modelos Animais de Doenças , Vias de Administração de Medicamentos , Portadores de Fármacos/uso terapêutico , Feminino , Leishmania major/patogenicidade , Leishmaniose Cutânea/parasitologia , Lipossomos/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Carga Parasitária , Baço/parasitologia , Estigmasterol/farmacocinética , Estigmasterol/uso terapêutico
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