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INTRODUCTION: Community pharmacies, as unique and accessible healthcare venues, are ideal locations to implement interventions aiming to improve patient care. However, these interventions may increase workload or disrupt workflow for community pharmacists, technicians, and other staff members, threatening long-term sustainment. There are growing calls from the field of implementation science to design for intervention sustainment and maintenance by maximizing innovation fit. Senior Safe™, an intervention to facilitate safer over-the-counter (OTC) product selection by older adults, serves as a case study to examine the congruence between Innovation Factors and community pharmacy Inner Context constructs and their implications for workload and sustainment. METHODS: Using the Exploration, Preparation, Implementation, Sustainment (EPIS) framework, this qualitative study identified factors surrounding Senior Safe implementation. Semi-structured interviews were conducted with staff from pharmacies where Senior Safe was implemented. Two coders independently analyzed interview transcripts using deductive analysis based on EPIS constructs. Thematic analysis was used to generate three themes that encapsulated innovation fit. RESULTS: Nineteen pharmacy staff members participated, with the majority reporting no significant change in their workload or workflow due to Senior Safe. Interview feedback supported a pre-existing culture of the healthcare system to engage patients, of leadership commitment to patient safety initiatives, and of an amplified role of pharmacy technicians. DISCUSSION AND CONCLUSION: Pharmacy staff interviews revealed congruence between Innovation Factors and Inner Context that likely yielded intervention workload neutrality. This study highlighted the importance for researchers to consider maintenance and sustainability when designing and implementing an intervention and the critical influence of culture and leadership support during this process.
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BACKGROUND: Nauclea officinalis (Pierre ex Pit.) Merr. & Chun (Rubiaceae) is widely used to treat respiratory diseases in China. Strictosamide is its main active component and has significant anti-inflammatory activity. However, the effects and molecular mechanisms of strictosamide in the treatment of acute lung injury (ALI) remain largely unknown. PURPOSE: This study aimed to examine the regulatory effects of strictosamide on T helper 17 cells (Th17 cells)/Regulatory T cells (Treg cells) and gut microbiota in ALI-affected mice. MATERIALS AND METHODS: The ALI model was induced using lipopolysaccharide (LPS) intraperitoneal injection. Hematoxylin-eosin (H&E) staining, the number of inflammatory cells in broncho-alveolar lavage fluid (BALF), the Wet/Dry (W/D) ratio, and myeloperoxidase (MPO) activity were utilized as evaluation indices for the therapeutic efficacy of strictosamide on ALI. Flow cytometry (FCM), enzyme-linked immune sorbent assay (ELISA), quantitative reverse transcription polymerase chain reaction (qRT-PCR), and western blotting were used to determine the regulation of strictosamide on the Th17/Treg cells and the STAT3/STAT5 signaling pathway. The analysis of gut microbiota was conducted using 16S rDNA sequencing. The verification of the relationship between the gut microbiome and immune function was conducted using Spearman analysis. RESULTS: Strictosamide attenuated inflammation on ALI induced by LPS, which reduced the levels of Th17-related factors interleukin (IL)-6 and IL-17 and increased Treg-related factors IL-10 and transforming growth factor (TGF)-ß. In the spleens and whole blood, strictosamide reduced the proportion of Th17 cells and increased the proportion of Treg cells. Furthermore, strictosamide increased Forkhead/winged helix transcription factor 3 (Foxp3) and p-STAT5 protein expression while inhibiting Retinoid-related orphan nuclear receptors-γt (RORγt) and p-STAT3 expression. Moreover, strictosamide reshaped the diversity and structure of the gut microbiota, and influence the associations between immune parameters and gut microbiota in ALI mice. CONCLUSIONS: In summary, the results of the current investigation showed that strictosamide has a therapeutic impact on LPS-induced ALI. The mechanism of action of this effect may be associated with the modulation of Th17 and Treg cells differentiation via the SATA signaling pathway, as well as the impact of the gut microbiota.
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Lesión Pulmonar Aguda , Microbioma Gastrointestinal , Lipopolisacáridos , Factor de Transcripción STAT3 , Linfocitos T Reguladores , Células Th17 , Animales , Lesión Pulmonar Aguda/tratamiento farmacológico , Linfocitos T Reguladores/efectos de los fármacos , Microbioma Gastrointestinal/efectos de los fármacos , Células Th17/efectos de los fármacos , Masculino , Ratones , Factor de Transcripción STAT3/metabolismo , Modelos Animales de Enfermedad , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Antiinflamatorios/farmacología , Líquido del Lavado Bronquioalveolar/citologíaRESUMEN
BACKGROUND: Acute lung injury (ALI) is a severe inflammatory disease, underscoring the urgent need for novel treatments. Nauclea officinalis Pierre ex Pitard (Danmu in Chinese, DM) is effective in treating inflammatory respiratory diseases. However, there is still no evidence of its protective effect against ALI. METHODS: Metabolomics was applied to identify the potential biomarkers and pathways in ALI treated with DM. Further, network pharmacology was introduced to predict the key targets of DM against ALI. Then, the potential pathways and key targets were further verified by immunohistochemistry and western blot assays. RESULTS: DM significantly improved lung histopathological characteristics and inflammatory response in LPS-induced ALI. Metabolomics analysis showed that 16 and 19 differential metabolites were identified in plasma and lung tissue, respectively, and most of these metabolites tended to recover after DM treatment. Network pharmacology analysis revealed that the PI3K/Akt pathway may be the main signaling pathway of DM against ALI. The integrated analysis of metabolomics and network pharmacology identified 10 key genes. These genes are closely related to inflammatory response and cell apoptosis of lipopolysaccharide (LPS)-induced ALI in mice. Furthermore, immunohistochemistry and western blot verified that DM could regulate inflammatory response and cell apoptosis by affecting the PI3K/Akt pathway, and expression changes in Bax and Bcl-2 were also triggered. CONCLUSION: This study first integrated metabolomics, network pharmacology and biological verification to investigate the potential mechanism of DM in treating ALI, which is related to the regulation of inflammatory response and cell apoptosis. And the integrated analysis can provide new strategies and ideas for the study of traditional Chinese medicines in the treatment of ALI.
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A new indole alkaloid, namely naucleofficine H (1), was obtained from the aqueous extract of Nauclea officinalis, together with four known alkaloids, vincosamide (2), strictosamide (3), angustoline (4) and pumiloside (5). Their structures were characterized by analyzing their physicochemical data including NMR, and HRMS. In addition, five compounds were tested for their proliferation activities. The expression of vascular endothelial growth factor (VEGF), extra-cellular signal-regulated protein kinase 1 and 2 (ERK) and phosphorylation of ERK 1/2 (p-ERK) were also detected in HUVEC treated withbioactive compounds using western blotting. The result showed that these compounds could promote HUVEC cell proliferation. Compounds 3 and 5 could up-regulate VEGF and p-ERK in HUVEC.
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Proliferación Celular/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Alcaloides Indólicos/farmacología , Rubiaceae , Humanos , Alcaloides Indólicos/aislamiento & purificación , Proteína Quinasa 1 Activada por Mitógenos , Proteína Quinasa 3 Activada por Mitógenos , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Rubiaceae/química , Factor A de Crecimiento Endotelial VascularRESUMEN
The compounds of N-Methylanhydrotetrahydroberberrubine A, dictamnine and eudesmin were the primary bioactive components in the roots of Zanthoxylum armatum DC (Z. armatum). To clarify the pharmacokinetics and distribution of these three compounds, an ultra-fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) was employed to determine the contents of these three compounds in rat plasma and seven tissues. The separation was achieved on a Kinetex XB-C18 100A column (2.1â¯×â¯50â¯mm, 2.6⯵m, Phenomenex). The optimized mobile phase system was set with 0.1 formic acid aqueous solution (A) and acetonitrile (containing 0.1 formic acid) (B) with a programmed elution of 0.00 to 0.50â¯min, 2% B; 0.51-4.00â¯min, 30%-60% B; and 4.01-5.00â¯min, 2% B. All analytes were measured with optimized multiple reaction monitoring (MRM) in the positive ion ESI mode. Berberine hydrochloride was selected as the internal standard (IS). The MS/MS transitions of N-Methylanhydrotetrahydroberberrubine A, dictamnine, eudesmin and IS were 339.9135.1, 200.1â¯ââ¯129.1, 387.4â¯ââ¯369.0 and 337.1â¯ââ¯321.1, respectively. The lower limits quantification (LLOQ) of the three analytes was 0.5-20â¯ng/ml. The linear ranges were 0.5-400â¯ng/ml for N-Methylanhydrotetrahydroberberrubine A and dictamnine and 20-4000â¯ng/ml for eudesmin. The present analysis showed that the two alkaloids were quickly absorbed, with Tmax in 0.167-0.292â¯h, and eudesmin was absorbed in 2.5â¯h. Moreover, all compounds were found at high concentrations in the gastrointestinal track. These results are helpful for further investigation of the clinical application of Z. armatum.