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GSK'872, but not Ac-IETD-CHO, reduced the ALN-induced release of NLRP3, but not ASC, into culture supernatants, and reduced ALN-induced cell death, but not ALN-induced LDH release. Antibodies against NLRP3 and ASC upregulated caspase-11 expression in the cytosol by inhibiting ALN-induced cell death. However, pretreating cells with an antibody against ASC, but not NLRP3, before ALN addition also inhibited lipid A-induced IL-1α release. Pretreating cells with an antibody against caspase-11 before the addition of ALN or lipid A did not downregulate lipid A-induced production of IL-1α. Taken together, our findings suggest that ALN augments lipid A-induced IL-1α release via activation of ASC, but not caspase-11.Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation in the joints. Although methotrexate (MX) is the first-line treatment, side effects are common. This study aimed to investigate the effects of quercetin (QT) and/or MX on inflammation and systemic toxicity in a rat model of RA. Male Wistar rats were divided into control (C), RA, QT, MX, and QT + MX groups (n=6). The RA induction consisted of three intra-articular injections of methylated bovine serum albumin (1×/week) in the temporomandibular joint (TMJ). QT (25 mg/kg) and/or MX (0.75 mg) administration occurred by oral gavage daily. We performed mechanical hyperalgesia in TMJ, leukocyte recruitment in synovial fluid, histopathology, and immunohistochemistry (TNF-α, IL-17, and IL-10) in synovial membrane and toxicity parameters. The RA showed a reduction in the nociceptive threshold (p0.05). QT has potential to support MX therapy, showing anti-inflammatory and hepatoprotective effects in this model.Baicalin has been reported to have ameliorative effects on nerve-induced hypoxic ischemia injury; however, its role in the NLRP3 inflammasome-dependent inflammatory response during cerebral ischemia-reperfusion remains unclear. To investigate the molecular mechanisms involved in baicalin alleviating cerebral ischemia-reperfusion injury, we investigated the AMPK signaling pathway which regulates NLRP3 inflammasome activity. SD rats were treated with baicalin at doses of 100 mg/kg and 200 mg/kg, respectively, after middle cerebral artery occlusion at 2 h and reperfusion for 24 h (MCAO/R). MCAO/R treatment significantly increased cerebral infarct volume, changed the ultrastructure of nerve cells, and activated the NLRP3 inflammasome, manifesting as significantly increased expression of NLRP3, ASC, cleaved caspase-1, IL-1β, and IL-18. Our results demonstrated that baicalin treatment effectively reversed these phenomena in a dose-dependent manner. Additionally, inhibition of NLRP3 expression was found to promote the neuroprotective effects of baicalin on cortical neurons. Furthermore, baicalin remarkably increased the expression of p-AMPK following oxygen glucose deprivation/reperfusion (OGD/R). The expression of the NLRP3 inflammasome was also increased when the AMPK pathway was blocked by compound C. Taken together, our findings reveal that baicalin reduces the activity of the NLRP3 inflammasome and consequently inhibits cerebral ischemia-reperfusion injury through activation of the AMPK signaling pathway.Background Since 2015, NHS England has facilitated the recruitment of pharmacists in general practice (GP) to reduce workload of general practitioners. The role of pharmacists is therefore expected to become more clinical and patient oriented. However, little is known about the current roles performed and the integration of GP pharmacists. Objective To assess the role performed by GP pharmacists and their integration into practice exploring facilitators and barriers to integration. Setting A cross-sectional survey of GP pharmacists in England. Method This study used both online and paper-based questionnaires for a period of six months. Survey items included demographics, roles performed, integration including available support and practice environment. Quantitative data were analysed using descriptive statistics and 95% confidence intervals. Open comments were analysed thematically to identify pharmacists' perceptions of barriers and facilitators to their integration into practice. Main outcome measure Current role and integration of pharmacists into GP. Results 195 participants completed the questionnaire. Three quarters of pharmacists (76%) had only been in GP since 2015. Most pharmacists (81%) were independent prescribers (PIPs). The most reported pharmacists' roles were medicine reconciliation (95%), telephone support for patients (95%) and face-to-face medication review (91%). 82% (95% CI 76% to 86.8%) were satisfied with their overall integration into practice. Half of pharmacists (45%) were working in a shared office or at a hot desk and 9% had no designated workspace. PIPs had more access to a convenient workplace (p = 0.016) compared to non-IPs. Conclusion Practice pharmacists are fulfilling a wide range of clinical and non-clinical roles in England. Findings highlight relatively a satisfactory level of pharmacists' integration into practice and shed the light on their integration issues. These findings could be significant for the development of future roles of pharmacists in GP.Background Tobacco use is one of the major causes of morbidity and mortality. An intensive pharmacist-delivered smoking cessation program was implemented in eight primary care pharmacies in Qatar. Objective This study aimed to qualitatively explore the perspectives of pharmacists and patients regarding their experiences in the program and their recommendations for improving it. Setting Primary care in Doha, Qatar. Method This study used a qualitative case study approach with semi-structured interviews of a sample of patients and pharmacists who participated in the program. Interviews were conducted between October 2016 and June 2017, were audio-recorded and transcribed verbatim. Selleck Deucravacitinib A thematic approach for data analysis was used. Main outcome measures Perspectives of pharmacists and patients. Results Pharmacists who delivered the program (n = 17) and patients who completed the program's outcomes assessment (n = 68) were invited through telephone call or email. Eight pharmacists and 22 patients were interviewed. Seven themes emerged (1) both pharmacists and patients had positive experiences and both considered pharmacists as among the most suitable healthcare providers to provide smoking cessation interventions (2) both pharmacist and patient participants indicated that the program provided successful services (3) pharmacists identified several challenges for implementing the program including difficulty in motivating and in following-up patients, workplace barriers, communication and cultural barriers, (4) both pharmacists and patients perceived several barriers for quitting including lack of motivation to quit or to commit to the plan, high nicotine dependence, stress and personal problems (5) both pharmacists and patients considered several patient-related facilitators for quitting including development of smoking related complications, religious beliefs and external support; (6) use of smoking cessation medications was considered a program-related facilitator for quitting by patients whereas behavioral therapy was perceived to be a facilitator by pharmacists (7) pharmacists and patients proposed strategies for program improvement including enhancing pharmacist training and patient recruitment.
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