Immunomodulatory effects of tigecycline in Balb/c mice

Tigecycline is a glycylcycline antibiotic approved by the FDA for the treatment of complicated infections. Despite its effectiveness, the FDA announced a warning of increasing mortality associated with its use. There is, however, no clear explanation for this side effect. Previous reports found a possible effect of tigecycline on leukocyte proliferation and proinflammatory cytokine release. We therefore investigated the effect of tigecycline on the immune components and response in Balb/c mice in vivo and in vitro. It was found that tigecycline enhanced lymphocyte proliferation and significantly increased cellular infiltration within the footpad, as based on DTH testing, but reduced the hemagglutination titer. In splenocyte cultures, tigecycline suppressed splenocyte proliferation with IC50 3–5 mol L–1, significantly increased IL-2 secretion and reduced IL-17 secretion in a dose dependent mode. In conclusion, tigecycline is safe at therapeutic and sub-therapeutic doses, but it could still have an immunomodulatory effect at higher doses. Use of higher doses of tigecycline requires further investigation

Academic stress-induced changes in Th1- and Th2-cytokine response

Psychological stress stimulates physiological responses releasing catecholamines and corticoids, which act via corresponding receptors on immune cells, producing a shift in the cytokine balance. These responses are variable depending on the nature of stressors. The effect of the academic stress on the production of the Th1-cytokines (TNF-α, IFN-γ, IL-1β, IL-2, IL-6 and IL-8) and Th2-cytokines (IL-1ra, IL-4, IL-5 and IL-10) on 35 medical/health sciences students after completing their questionnaires was investigated. Blood samples were taken at three stages; baseline stage at the beginning, midterm and final academic examination stages. Plasma cortisol and cytokines were measured during the three stages. The last two stages were compared with the baseline non-stress period. Results of the stress induced during the final examination stage were the highest with a significant increase in cortisol release, IL-4, IL-5 and IL-1ra release with a shift in Th1:Th2 cytokines balance towards Th2. Whereby, the midterm stage did not show significant reduction in Th1-cytokines except for TNF-α, with an increase in IFN-γ level that was reduced in the third stage. Th2 cytokine, IL-1ra, had positive correlations with Th1 cytokines; IL-2 and IFN-γ in the second stage and IL-6 cytokine in the third stage. Cortisol was positively correlated with IL-8 in the last stage and heart rates had negative correlation with IL-10 in the first and last stages. Findings of this study indicate that exam stress down-regulates Th1 with a selective up-regulation of Th2-cytokines. In conclusion, Cortisol might have a role in suppressing the release of Th1- mediated cellular immune response which could increase the vulnerability among the students to infectious diseases. Keywords: Academic stress, Cortisol, Th1-cytokines, Th2-cytokines, Medical/health sciences student

Immunomodulatory Effects of Tigecycline in Balb/C Mice

Tigecycline is a glycylcycline antibiotic approved by the FDA for the treatment of complicated infections. Despite its effectiveness, the FDA announced a warning of increasing mortality associated with its use. There is, however, no clear explanation for this side effect. Previous reports found a possible effect of tigecycline on leukocyte proliferation and proinflammatory cytokine release. We t herefore i nvestigated the effect of tigecycline on the immune components and response in Balb/c mice in vivo and in vitro. It was found that tigecycline enhanced lymphocyte proliferation and significantly increased cellular infiltration within the footpad, as based on DTH testing, but reduced the hemagglutination titer. In splenocyte cultures, tigecycline suppressed splenocyte proliferation with IC50 3-5 mmol L-1, significantly increased IL-2 secretion and reduced IL-17 secretion in a dose dependent mode. In conclusion, tigecycline is safe at therapeutic and sub-therapeutic doses, but it could still have an immunomodulatory effect at higher doses. Use of higher doses of tigecycline requires further investigation

Attitude towards hpv vaccination and the intention to get vaccinated among female university students in health schools in jordan

Cervical cancer is a leading cause of morbidity and mortality in women worldwide. The availability of prophylactic vaccines for high-risk types of human papillomavirus (HPV) infection represents an important advancement in the prevention of cervical cancer. In Jordan, the availability of the HPV vaccination is restricted to individuals who are willing to pay. The aim of the current study was to evaluate the willingness and attitude of female university students in health schools/faculties in Jordan to get HPV vaccination and their knowledge about the virus. A self-administered online questionnaire was distributed in October 2021, which comprised 27 items to evaluate HPV knowledge, history of HPV vaccination, intentions to get the HPV vaccine, and the reason(s) behind vaccine refusal for those who rejected vaccination. The study sample comprised 836 participants: medical students (39.7%), pharmacy students (26.0%), dental students (21.2%), and nursing students (13.2%). Only 524 participants had heard of HPV prior to the study (62.7%), of which 48.7% knew about the availability of HPV vaccines. The lowest level of HPV knowledge was observed among nursing students. Only 19/524 students reported a history of HPV vaccination (3.6%). The overall willingness to receive HPV vaccination if provided freely was 75.0%, while only 16.0% were willing to pay for the vaccine. The most common reason for HPV vaccine rejection was the perceived low risk to get HPV infection. Significantly higher intentions to get HPV vaccination were found among older participants and medical students. The embrace of vaccine conspiracy beliefs was associated with a significantly less willingness to get the HPV vaccination (p < 0.001). Dependence on the internet/social media as the source of HPV knowledge was associated with a significantly lower intention to get HPV vaccination (p = 0.002). The coverage of the HPV vaccination among female university students in health schools in Jordan appeared extremely low; however, three-fourths of the students who had heard of HPV were willing to receive the HPV vaccination if provided freely. Complacency appeared as a major factor for HPV vaccine rejection. Increasing the levels of knowledge and awareness of HPV infection and its association with cervical cancer through reliable sources is recommended. This can be helpful for the individual benefit of the students besides the potentially positive role they can play in community education. Countering vaccine conspiracy beliefs with proper education and awareness programs can be helpful to appraise the role of HPV vaccines in cancer prevention

Synthesis, Crystal Study, and Anti-Proliferative Activity of Some 2-Benzimidazolylthioacetophenones towards Triple-Negative Breast Cancer MDA-MB-468 Cells as Apoptosis-Inducing Agents

On account of its poor prognosis and deficiency of therapeutic stratifications, triple negative breast cancer continues to form the causative platform of an incommensurate number of breast cancer deaths. Aiming at the development of potent anticancer agents as a continuum of our previous efforts, a novel series of 2-((benzimidazol-2-yl)thio)-1-arylethan-1-ones 5a–w was synthesized and evaluated for its anti-proliferative activity towards triple negative breast cancer (TNBC) MDA-MB-468 cells. Compound 5k was the most active analog against MDA-MB-468 (IC50 = 19.90 ± 1.37 µM), with 2.1-fold increased activity compared to 5-fluorouracil (IC50 = 41.26 ± 3.77 µM). Compound 5k was able to induce apoptosis in MDA-MB-468, as evidenced by the marked boosting in the percentage of florecsein isothiocyanate annexin V (Annexin V–FITC)-positive apoptotic cells (upper right (UR) + lower right (LR)) by 2.8-fold in comparison to control accompanied by significant increase in the proportion of cells at pre-G1 (the first gap phase) by 8.13-fold in the cell-cycle analysis. Moreover, a quantitative structure activity relationship (QSAR) model was established to investigate the structural requirements orchestrating the anti-proliferative activity. Finally, we established a theoretical kinetic study