RESUMO
Rheumatoid arthritis (RA) is an autoimmune inflammatory disease, which is accompanied by progressive joint damage and disability. The intolerability of conventional antirheumatic drugs by some patients necessitates the search for effective antirheumatic agents having better tolerability. In the current work, we aimed to investigate the efficacy of cinnamaldehyde, tadalafil, and aliskiren as potential antirheumatic candidates and to explore their modulatory effects on joint destruction, inflammatory response, and intracellular signaling. Arthritis was induced in female Wistar rats by complete Freund's adjuvant (CFA) 0.4 ml s.c. on days 1, 4, and 7. Treated groups received their respective drugs, starting from day 13, daily for 3 weeks. Methotrexate and prednisolone were the standard antirheumatic drugs, while cinnamaldehyde, tadalafil, and aliskiren were the test agents. Treatment with cinnamaldehyde, tadalafil, or aliskiren reduced serum levels of rheumatoid factor, and pro-inflammatory cytokines; tumor necrosis factor-alpha and interleukin-6 (IL-6), along with elevated level of IL-10 which is an anti-inflammatory cytokine. Besides, cartilage and bone destruction biomarkers; matrix metalloproteinase-3 (MMP-3) and receptor activator of nuclear factor-kappa B ligand (RANKL); were significantly reduced after treatment with the test agents, which was further confirmed by histopathological investigation. The elevated protein expressions of phosphorylated-Janus kinase 2 (p-JAK2), phosphorylated-signal transducer and activator of transcription 3 (p-STAT3), and inducible nitric oxide synthase (iNOS) in articular tissue were markedly attenuated after treatment with cinnamaldehyde, tadalafil, or aliskiren, while that of endothelial nitric oxide synthase (eNOS) was greatly enhanced. In addition, oxidative stress and inflammatory markers such as malondialdehyde, nitric oxide, and myeloperoxidase were reduced in joint tissue after treatment with the test agents, while glutathione content was elevated. Furthermore, the renin inhibitor aliskiren produced effects close to those of the normal and methotrexate, the gold standard antirheumatic drug, in most of the measured parameters. Collectively, these findings led to the assumption that the downregulation of IL-6/JAK2/STAT3 signaling by cinnamaldehyde, tadalafil, and aliskiren could alleviate joint destruction by MMP-3 and RANKL, reduce iNOS, and enhance eNOS expressions. Moreover, aliskiren could be a promising therapeutic agent for RA, because of its ability to normalize most of the measured parameters after CFA-induced arthritis.
RESUMO
PURPOSE: Timely detection of breast cancer (BC) is important to reduce its related deaths. Hence, high awareness of its symptoms and risk factors is required. This study aimed to assess the awareness level of BC among females in Gaza. MATERIALS AND METHODS: A cross-sectional study was performed during September and October 2017 in Gaza, Palestine. Stratified sampling was used to recruit patients from four hospitals and seven high schools. The validated Breast Cancer Awareness Measure (BCAM) was used to assess confidence and behavior in relation to breast changes, awareness of BC symptoms and risk factors, barriers to seek medical help, and knowledge of BC screening. Women (age ≥ 18 years) visiting or admitted to any of the four hospitals, and female adolescents (age 15 to 17 years) in any of the seven schools, were recruited for face-to-face interviews to complete the BCAM. RESULTS: Of 3,055 women approached, 2,774 participants completed the BCAM questionnaire (response rate, 90.8%); 1,588 (57.2%) were adults, and 1,186 (42.8%) were adolescents. Of these, 1,781 (64.2%) rarely (or never) checked their breasts, and 909 (32.8%) were not confident to notice changes. In total, 1,675 (60.4%) were aware of the availability of BC screening programs. The overall mean ± standard deviation score for awareness of BC symptoms was 5.9 ± 2.9 of 11, and that of risk factors 7.5 ± 3.1 of 16. Feeling scared was the most reported barrier to seeking advice reported among women (n = 802; 50.2%), whereas feeling embarrassed was the most reported in adolescents (n = 745; 62.8%). CONCLUSION: Awareness of BC symptoms, risk factors, and screening programs is suboptimal in Gaza. Educational interventions are necessary to increase public awareness of BC and to train local female breast surgeons to address barriers to early detection.
