RESULTS: Twenty two of the top-ranked water-soluble compounds were selected for inhibitory screening against PAD4. Three compounds showed significant inhibition of PAD4 and their IC50 values were investigated. The structures of the three compounds show no resemblance with previously discovered PAD4 inhibitors, nor with existing drugs for RA treatment.
CONCLUSION: Three compounds were discovered as potential inhibitors of PAD4 by virtual screening. The compounds are commercially available and can be used as scaffolds to design more potent inhibitors against PAD4.
PURPOSE: This review article aims to recapitulate the therapeutic potential of berberine and its mechanism of action in treating musculoskeletal disorders.
METHODS: A wide range of literature illustrating the effects of berberine in ameliorating musculoskeletal disorders was retrieved from online electronic databases (PubMed and Medline) and reviewed.
RESULTS: Berberine may potentially retard the progression of osteoporosis, osteoarthritis and rheumatoid arthritis. Limited studies reported the effects of berberine in suppressing the proliferation of osteosarcoma cells. These beneficial properties of berberine are mediated in part through its ability to target multiple signaling pathways, including PKA, p38 MAPK, Wnt/β-catenin, AMPK, RANK/RANKL/OPG, PI3K/Akt, NFAT, NF-κB, Hedgehog, and oxidative stress signaling. In addition, berberine exhibited anti-apoptotic, anti-inflammatory, and immunosuppressive properties.
CONCLUSION: The current evidence indicates that berberine may be effective in preventing musculoskeletal disorders. However, findings from in vitro and in vivo investigations await further validation from human clinical trial.
METHODS/DESIGN: This is a randomized, single-blind, two-arm, controlled trial in patients with rheumatoid arthritis visiting outpatient rheumatology clinics in Karachi, Pakistan. We will enroll patients with established diagnosis of rheumatoid arthritis over 3 months. The patients would be randomized through a computer-generated list into the control group, i.e., usual care or into the intervention group, i.e., pharmaceutical care, in a ratio of 1:1, after providing signed written consent. The study will take place in two patient-visits over the course of 3 months. Patients in the intervention group would receive intervention from the pharmacist while those in the control group will receive usual care. Primary outcomes include change in mean score from baseline (week 0) and at follow up (week 12) in disease knowledge, adherence to medications and rehabilitation/physical therapy. The secondary outcomes include change in the mean direct cost of treatment, HRQoL and patient satisfaction with pharmacist counselling.
DISCUSSION: This is a novel study that evaluates the role of the pharmacist in improving treatment outcomes in patients with rheumatoid arthritis. The results of this trial could set the foundation for future delivery of care for this patient population in Pakistan. The results of this trial would be published in a peer-reviewed journal.
TRIAL REGISTRATION: ClinicalTrials.gov, NCT03827148 . Registered on February 2019.
MATERIALS AND METHODS: Data was collected using a self-administered pilot-tested questionnaire. Dentists awareness about link between oral and systemic link was assessed on five point likert scale. Data was entered and analysed using SPSS.
RESULTS: Of the 588 dentists, 500 completed the questionnaire (response rate 85.03%). About 93% of the participants (mean age 25.82 ± 4.21 years) agreed that oral health was associated with systemic health. Most dentists were aware of a connection between periodontal disease and diabetes (84.4%) and heart disease (70.2%). Similarly, 85.6% believed in the negative impact of oral disease on the quality of life of patients. More female than male dentists were aware of the relationship between periodontal disease and adverse pregnancy outcomes, diabetes, and rheumatoid arthritis (P < 0.001). Most dentists (97%) believed that more patients would seek oral care if they were aware of the oral-systemic link. After adjustments, private dentists were 4.65 times more likely than public dentists to believe in improving access to oral care with increased patient awareness of the oral-systemic connection (P = 0.011).
CONCLUSIONS: Most dentists were aware of the oral-systemic link. They believed that patients' access to oral care would improve if they were aware of a connection between oral and systemic health. Therefore, patients should be informed of the oral-systemic link to improve their oral health.