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1.
Pak J Pharm Sci ; 32(4): 1509-1518, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31608869

RESUMO

Stimulation of C-type lectin domain of human dectin-1 receptor by fungal ß-glucans causes conformational changes in its cytoplasmic domain which initiates various cellular responses mediated by downstream signaling components. We aimed to build the three-dimensional structures of the cytoplasmic domain as well as C-type lectin domain of human Dectin-1along with their potential ligands through homology modeling.The overall three-dimensional fold of cytoplasmic domain was found to consist of mixed ß-sheet whereas,in case of C-type lectin domain antiparallel ß-sheets flanked by α-helices were observed. Protein-protein docking strategy was utilized to monitorkey interactions between cytoplasmic domainof dectin-1 receptor and PKCδ, as a prime regulator of Dectin-1 signaling. The interface was observed to have both hydrophilic and hydrophobic amino acid residues maintaining crucial contacts between the two proteins. The given three dimensional structural information can be implicated in structure-based drug designing to discover potential immunomodulators that can interfere with the immune responses and phagocytosis during inflammatory and infectious conditions.


Assuntos
Lectinas Tipo C/química , Humanos , Lectinas Tipo C/metabolismo , Modelos Moleculares , Simulação de Acoplamento Molecular , Conformação Proteica , Proteína Quinase C-delta/química , Proteína Quinase C-delta/metabolismo , Análise de Sequência de Proteína , Homologia Estrutural de Proteína , beta-Glucanas/química , beta-Glucanas/metabolismo
2.
J Community Health ; 44(6): 1098-1110, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31267293

RESUMO

To assess the effectiveness of intervention in improving knowledge, attitude and perception regarding smokeless tobacco (SLT) use and its harmful effects and intention to quit SLT among school going adolescents. A school-based cluster randomized control trial was carried out in 18 secondary schools targeting male and female students from grades 6 to 10 in Karachi. Primary outcome was knowledge about hazards of smokeless tobacco (SLT) and secondary outcomes were attitude and Perception about hazards of SLT, and intention to quit SLT. We enrolled 738 participants in intervention group and 589 in the control group. Mean score of knowledge significantly improved in intervention as compared to control group (P value < 0.01). Intention to quit was found to be proportionately higher (33%) in the intervention group as compared to control group. Generalized estimating equations were used to assess the association of factors with knowledge regarding harmful effects of SLT use. Significant predictors of increase in knowledge score were found in children: who had seen any anti SLT messages on social media in the past 30 days, who were getting information regarding harmful effects of SLT use in school or textbooks and who had friends using SLT. A school-based intervention was effective in increasing knowledge regarding the harmful effects of SLT use and intention to quit SLT use among school adolescents. Introduction of such educational programmes on a regular basis in schools or as part of school curriculum can have an impact on reducing prevalence of SLT use.Trial Registration NCT03418506. https://register.clinicaltrials.gov/NCT03418506 .

3.
Biomed Pharmacother ; 112: 108624, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30784921

RESUMO

Rheumatoid arthritis (RA) is a chronic autoimmune disease of synovial inflammation and joint destruction. This study reports anti-arthritic potential of opuntioside-I opuntiol, and its gold and silver nanoparticles (NPs) against Complete Freund's Adjuvant (CFA)-induced arthritic rats. The mechanistic studies were performed targeting TLRs (TLR-2 and TLR-4) and cytokines (IL-1ß and TNF-α) expressions to validate their anti-inflammatory and immuno-modulatory response. The nano-formulations were successfully characterized employing Atomic Force Microscopy (AFM) and Dynamic Light Scattering (DLS) analysis. Opuntiol and opuntioside (OP and OPG: 10, 50 and 100 mg/kg) and opuntiol-coated silver and gold NPs (OP-AgNPs and OP-AuNPs: 0.5, 1 and 3 mg/kg) treatments in arthritic rat have shown minimal arthritic score exhibiting mild to moderate articular changes and tissue swelling in ankle joints. Radiographic examination reveals significant reduction in synovitis with improvement in joints degenarative changes in the presence of aforementioned treatments. Likewise, histology of rat ankle joints depicted comparatively lesser influx of inflammatory cells and diminished granulamatous inflammation. Moreover, treatment groups suppressed protein and mRNA expressions of TLRs (TLR-2 and TLR-4) and cytokines (IL-1ß and TNF-α) levels were also significantly declined in the presence of OPG, OP and its NPs comparing to arthritic control. This investigation concludes, the tested compounds and nano-formulations successfully restored the disease progression in CFA-induced arthritic rat owing to their immunomodulatory and anti-inflammatory potentials and can be considered for RA targeted therapy to address the utmost challenges of the disease.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Experimental/tratamento farmacológico , Ácidos Cumáricos/uso terapêutico , Nanopartículas Metálicas/uso terapêutico , Monossacarídeos/uso terapêutico , Receptor 2 Toll-Like/antagonistas & inibidores , Receptor 4 Toll-Like/antagonistas & inibidores , Animais , Antirreumáticos/administração & dosagem , Antirreumáticos/química , Artrite Experimental/imunologia , Artrite Experimental/metabolismo , Ácidos Cumáricos/administração & dosagem , Ácidos Cumáricos/química , Feminino , Adjuvante de Freund , Ouro/química , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/química , Monossacarídeos/administração & dosagem , Monossacarídeos/química , Ratos Wistar , Prata/química
4.
Artif Cells Nanomed Biotechnol ; 46(sup1): 597-607, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29381085

RESUMO

Nanomedicines anticipate drug delivery to inflamed tissues in rheumatoid arthritis (RA) with greater efficacy and lesser side effects. This study investigates the anti-arthritic potentials of Hesperidin (HP) loaded in gum acacia (GA) stabilized green silver nanoparticles (AgNPs). Synthesized GA-AgNPs were characterized through UV-vis spectrophotometer, zetasizer and atomic force microscope (AFM). The HP and its loaded NPs were tested for RA in Complete Freund's adjuvant (CFA) induced arthritis model. GA-AgNPs were found in nano-range size with negative charge, spherical shape and loaded increased HP amount. HP loaded GA-AgNPs showed minimal arthritic score exhibiting mild to moderate tissue swelling, reduced degenerative changes along with mild articular changes. Histopathological analysis revealed comparatively lesser influx of inflammatory cells and diminished granulamatous inflammation in ankle joints tissues in the presence of HP loaded GA-AgNPs. RT-PCR revealed that HP loaded GA-AgNPs significantly reduced the TLRs mRNA expression. Results validate GA stabilized green AgNPs as stable nano-cargos for targeted delivery of HP for restoring the progression of RA.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Portadores de Fármacos/química , Goma Arábica/química , Hesperidina/química , Hesperidina/uso terapêutico , Nanopartículas Metálicas/química , Prata/química , Adjuvantes Imunológicos/efeitos adversos , Animais , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/genética , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Ratos , Ratos Wistar , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/genética
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