Mechanistic modelling of targeted pulmonary delivery of dactinomycin iron oxide-loaded nanoparticles for lung cancer therapy.

With the increase in respiratory conditions including lung cancer post covid-19 pandemic, drug-loaded nanoparticulate dry powder inhalers (DPIs) can facilitate targeted lung delivery as a patient-friendly, non-invasive method. The aim of this work was to synthesise and optimise iron oxide nanoparticles (IONPs) containing dactinomycin as a model drug, using Quality by Design principles. Chitosan and sodium alginate were investigated as polymeric coatings. The mass median aerodynamic diameter (MMAD), fine particle fraction (FPF), burst-effect (BE), entrapment-efficiency and the emitted-dose (ED) were investigated in initial screening studies and outcomes used to set up a Design of Experiments. Results revealed that chitosan IONPs were superior to that of sodium alginate in delivering DPI with optimal properties [ED (89.9%), FPF (59.7%), MMAD (1.59 µm) and BE (12.7%)]. Design space for targeted IONPs included formulations containing 2.1-2.5% dactinomycin and 0.5-0.9% chitosan. Differential scanning calorimetry and X-ray diffraction and SEM-EDS analysis revealed effective formation of IONPs, and TEM images revealed the production of spherical IONPs with particle size of 4.4 ± 0.77 nm. This work overcame the light sensitivity of dactinomycin to potentially target the high molecular weight drugs to the lungs, with controlled delivery based on a reduced burst effect.

Anti_spike and anti_nucleocapsid IgG responses to SARS-CoV-2 in children of Jordan.

Background: It is proven that children have significantly milder COVID-19 disease compared to adults. Various immunological characteristics influence this age-related difference in protection against COVID-19. Pediatric COVID-19 in Jordan is extremely under reported. Objectives: The primary goal of this work is to identify the anti_S and anti_N antibody responses in a random group of children in Jordan and compare it to that of naturally infected-unvaccinated adults. Methods: 151 unvaccinated children, 4 days to 18 years old, were screened for anti_S and anti_N antibodies. History of COVID-19 infection or exposure to infection and symptom severity were reported by parents on a special questionnaire. Results: 78.9 % and 65.3 % of participants were seropositive for anti_S IgG and anti_N Abs, respectively. There was a remarkable association between age and anti_S IgG and anti_N IgG antibody titers, as children aged 12 years or older had increased anti_S IgG titers (mean = 19.3 BAU/mL) compared to younger groups (means of 10.15, 9.24, 7.91 BAU/mL for age groups 6-12, 1-6, less than 1 year, respectively). Gender did not show a statistically important role in anti_S and anti_N IgG seropositivity rates or titers. Children displayed significantly elevated anti_S titers (mean = 13.23 BAU/mL) compared to naturally infected adults (mean = 9.72 BAU/mL), in contrast, adults' anti_N titers (mean = 39.64 U/mL) were significantly higher compared to those of children (mean = 10.77 U/mL). Conclusions: The current work provides evidence of distinctly robust and persistent humoral immunity displayed by high anti_S and anti_N IgG in children, even >12 months post-infection. Age was the only factor that had a significant statistical impact on anti_S and anti_N Ab levels among the pediatric group in this study. Children exhibited significantly higher anti_S titers than naturally infected adults. In contrast, adults' anti_N titers were significantly higher. Such information can assist direct pediatric SARS-CoV-2 immunization programs, with implications for creating age-targeted strategies for diagnostic and population protection measures.

Awareness and knowledge of physicians and residents on the non-sexual routes of human papilloma virus (HPV) infection and their perspectives on anti-HPV vaccination in Jordan.

BACKGROUND AND OBJECTIVES: Although penetrative sex is the most common route of HPV infection, there is strong evidence of non-sexual modes of transmission. As the first of its kind, this study aimed to investigate the knowledge and awareness of Jordanian physicians on such routes. METHODS: A questionnaire was conducted among a national Jordanian sample of physicians from Jordanian health sectors. The survey included questions assessing participants' knowledge on HPV, non-sexual routes of infection and HPV vaccines. Physicians' attitudes towards HPV screening and vaccination were covered. Statistical analysis was carried out using SAS 9.4, ANOVA, post-hoc Tukey-Honest test and Kruskal-Wallis test. All significant differences were set at α = 0.05. RESULTS: A total of 412 participants completed the survey. Physicians showed a huge deficit in knowledge on nonsexual routes of HPV transmission. They agreed that the most and least common routes of non-sexual transmission are skin to mucosa (64%) and contaminated water (15%), respectively. Females showed significantly better knowledge in all aspects of HPV transmission and vaccination (p<0.0001) and more positive attitudes towards HPV screening and vaccination compared to males (p = 0.03). Age group ≤ 25 and academic physicians demonstrated higher knowledge on HPV vaccines compared to their counterparts in non-academic places (p = 0.002). Specialty and experience seemed to have no impact on knowledge or attitudes of participants. Higher knowledge physicians had more positive attitude towards vaccination and screening compared to lower knowledge fellows (p<0.001). CONCLUSIONS: The noteworthy findings of this study is the extremely low level of knowledge on non-sexual routes of HPV infection among Jordanian physicians. Increasing the level of awareness of physicians and healthcare workers on these routes and their association with cervical and other cancers through university curricula and other reliable sources is strongly recommended.

Changes in Lactate Production, Lactate Dehydrogenase Genes Expression and DNA Methylation in Response to Tamoxifen Resistance Development in MCF-7 Cell Line.

Lactate dehydrogenase (LDH) is a key enzyme in the last step of glycolysis, playing a role in the pyruvate-to-lactate reaction. It is associated with the prognosis and metastasis of many cancers, including breast cancer. In this study, we investigated the changes in LDH gene expression and lactate concentrations in the culture media during tamoxifen resistance development in the MCF-7 cell line, and examined LDHB promoter methylation levels. An upregulation of 2.9 times of LDHB gene expression was observed around the IC50 concentration of tamoxifen in treated cells, while fluctuation in LDHA gene expression levels was found. Furthermore, morphological changes in the cell shape accompanied the changes in gene expression. Bisulfate treatment followed by sequencing of the LDHB promoter was performed to track any change in methylation levels; hypomethylation of CpG areas was found, suggesting that gene expression upregulation could be due to methylation level changes. Changes in LDHA and LDHB gene expression were correlated with the increase in lactate concentration in the culture media of treated MCF-7 cells.