The clinical importance of IFN-γ and human epididymis protein 4 in Egyptian patients with epithelial ovarian cancer combined with HPV infection.

BACKGROUND: High-grade Epithelial Ovarian Cancer (HGEOC) is an aggressive disease that usually presents at an advanced stage. Thus, detecting the circulating cytokines (IFNγ and TNF-α) may serve as a biomarker to identify malignancy and manage therapeutic decisions. OBJECTIVES: Assessing the clinical importance of inflammatory mediators and tumor markers in EOC Egyptian patients compared with benign cases. Moreover, identifying the distinct inflammatory mediators in EOC patients combined with HPV infection. METHODS: This study was conducted on 61 Egyptian patients, divided into 25 patients with HGEOC, 22 patients with LGEOC, and 14 benign ovarian tumor cases. Measurements of serum HE4, CA125, CEA, and CA19-9 were determined by Roche Elecsys immunoassays. Serum levels of TNF-α and IFN-γ were measured using quantitative sandwich ELISA. Quantitative genotyping of HPV DNA types 16, 18, and 45 was assessed for the HPV DNA-positive samples. RESULTS: HPV DNA was detected in 25.53 % of malignant cases, HPV 16 was detected in 50 % of HPV-positive cases, and only 1 case of HPV 18 was detected out of 12 positive cases. The Human Epididymis protein 4 (HE4) was statistically different between patients with EOC and benign cases (p-value = 0.007) and between HPV DNA positive and HPV DNA negative cases (p-value = 0.008). The serum levels of IFN- γ were statistically different between HGEOC and LGEOC (p-value < 0.001), while the serum levels of TNF-α didn't differ statistically between the two groups. CONCLUSION: IFN-γ could be used as a biomarker to discriminate HGEOC and LGEOC. Initial evidence for the possible association between HE4 and the progression of HPV-associated EOC was speculated.

Realizing time-staggered expression of nucleic acid-encoded proteins by co-delivery of messenger RNA and plasmid DNA on a single nanocarrier.

Co-delivery of different protein-encoding polynucleotide species with varying expression kinetics of their therapeutic product will become a prominent requirement in the realm of combined nucleic acid(NA)-based therapies in the upcoming years. The current study explores the capacity for time-staggered expression of encoded proteins by simultaneous delivery of plasmid DNA (pDNA) in the core and mRNA on the shell of the same nanocarrier. The core is based on a Gelatin Type A-pDNA coacervate, thermally stabilized to form an irreversible nanogel stable enough for the deposition of cationic coats namely, protamine sulfate or LNP-related lipid mixtures. Only the protamine-coated nanocarriers remained colloidally stable following mRNA loading and could successfully co-transfect murine dendritic cell line DC2.4 with fluorescent reporter mRNA(mCherry) and pDNA (pAmCyan1). Further investigation of the protamine-coated nanosystem only, the transfection efficiency (percentage of transfected cells) and level of protein expression (mean fluorescence intensity, MFI) of mRNA and pDNA, simultaneously delivered by the same nanocarrier, were compared and kinetically assessed over 48 h in DC2.4 using flow cytometry. The onset of transfection for both nucleotides was initially delayed, with levels < 5% at 6 h. Thereafter, mRNA transfection reached 90% after 24 h and continued to slightly increase until 48 h. In contrast, pDNA transfection was clearly slower, reaching approximately 40% after 24 h, but continuing to increase to reach 94% at 48 h. The time course of protein expression (represented by MFI) for both NAs essentially followed that of transfection. Model-independent as well as model-dependent kinetic parameters applied to the data further confirmed such time-staggered expression of the two NA's where mRNA's rate of transfection and protein expression initially exceeded those of pDNA in the first 24 h of the experiment whereas the opposite was true during the second 24 h of the experiment where pDNA displayed the higher response rates. We expect that innovative nanocarriers capable of time-staggered co-delivery of different nucleotides could open new perspectives for multi-dosing, pulsatile or sustained expression of nucleic acid-based therapeutics in protein replacement, vaccination, and CRISPR-mediated gene editing scenarios.

Cumulative pulse methylprednisolone and its relation to disease activity, damage and mortality in systemic lupus erythematosus patients: A post hoc analysis of COMOSLE-EGYPT study.

OBJECTIVE: To investigate the relation between cumulative intravenous methylprednisolone dose and disease activity, damage, and mortality among a group of Egyptian SLE patients. PATIENTS AND METHODS: This is a post hoc analysis of a retrospective multicenter COMOSLE study. Cumulative pulse methylprednisolone dose was abstracted from COMOSLE database. Patients with cumulative pulse dose of ≤ 3.0 g (median dose) were compared to those with cumulative dose of > 3.0 g regarding demographic data, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and The Systemic Lupus International Collaborating Clinics/ACR Damage Index (SLICC) score as well as treatment received. Additionally, at 1.5, 3, 6, and 9 g of cumulative methylprednisolone, patients were compared regarding SLICC score and risk of mortality. RESULTS: Patients who received > 3 g of methylprednisolone were statistically significantly younger at disease onset, had longer disease duration, higher SLEDAI score at last visit, and higher SLICC score (p = 003, p = 0.002, p = 0.004 and p = < 0.001, respectively). Additionally, with every gram increase in the cumulative methylprednisolone, there was a significant increase in SLICC score by 0.169 (B = 0.169, CI = 0.122-0.216, p-value = < 0.001) and an increased risk of mortality by 13.5% (hazard ratio (HR) = 1.135, CI = 1.091-1.180, p-value = 0.001). The best cutoff value of methylprednisolone dose at which damage may occur, ranged between 2.75 (with sensitivity of 81.4% and specificity of 33.9%) and 3.25 g (with sensitivity of 48.3% and specificity of 71.5%). CONCLUSION: With every gram increase in the cumulative methylprednisolone, there may be increase in damage and mortality, especially in doses exceeding the range of 2.75-3.25 g. Key Points • Treatment of systemic lupus erythematosus should be with the least possible dose of steroids to decrease the risk of damage and mortality. • With every gram increase in the cumulative intravenous methylprednisolone there may be increase in damage and mortality.

Targeting average length of hospital stay as a control measure to decrease COVID-19 hospital-acquired infection in surgical cancer patients.

BACKGROUND: The global spread of coronaviruses had a great impact on the economic and social situation of most countries. As the backbone of any society, the health sector made a significant contribution through applying emergency risk management plans in order to control the pandemic. Monitoring the average length of hospital stay (ALOS) was an effective way to release the capacity of the health system during this time. The aim was to evaluate the effect of applying risk assessment/management strategies on ALOS and the impact of this ALOS on COVID-19 infection rates among cancer patients. METHODS: This is a prospective cohort study. All admitted cancer patients in 6 surgical departments from January to June 2021 were included. RESULTS: A total of 1287 patients were admitted to 6 surgical departments during the selected period. About 46% of them had surgery (n = 578), while 54% did not have surgery (n = 700). Among surgical patients, admission rates were highest in February and head and neck department (24% and 22.1%, respectively), and lowest in April and chest department (12.4% and 8%, respectively). ALOS was significantly different across the 6 months (p value < 0.001) with lower ALOS in (April, May, and June) than in (January-February, and March). No significant difference was found across the 6 surgical departments (p value = 0.423). Twenty-eight patients became COVID-19 positive after admission, 25 of them (89%) were infected from March to June-during the time of the third wave-and a significant decreasing linear trend (p value = 0.009) was found. CONCLUSION: ALOS had significantly reduced with commitment to infection control (IC) interventions and recommendations. The significant decreasing trend of COVID-19 infection from March to June (unlike the rising curve of the 3rd COVID-19 wave by that time) could be explained by improvement in ALOS.

Co-Delivery of mRNA and pDNA Using Thermally Stabilized Coacervate-Based Core-Shell Nanosystems.

Co-delivery of different species of protein-encoding polynucleotides, e.g., messenger RNA (mRNA) and plasmid DNA (pDNA), using the same nanocarrier is an interesting topic that remains scarcely researched in the field of nucleic acid delivery. The current study hence aims to explore the possibility of the simultaneous delivery of mRNA (mCherry) and pDNA (pAmCyan) using a single nanocarrier. The latter is based on gelatin type A, a biocompatible, and biodegradable biopolymer of broad pharmaceutical application. A core-shell nanostructure is designed with a thermally stabilized gelatin-pDNA coacervate in its center. Thermal stabilization enhances the core's colloidal stability and pDNA shielding effect against nucleases as confirmed by nanoparticle tracking analysis and gel electrophoresis, respectively. The stabilized, pDNA-loaded core is coated with the cationic peptide protamine sulfate to enable additional surface-loading with mRNA. The dual-loaded core-shell system transfects murine dendritic cell line DC2.4 with both fluorescent reporter mRNA and pDNA simultaneously, showing a transfection efficiency of 61.4 ± 21.6% for mRNA and 37.6 ± 19.45% for pDNA, 48 h post-treatment, whereas established commercial, experimental, and clinical transfection reagents fail. Hence, the unique co-transfectional capacity and the negligible cytotoxicity of the reported system may hold prospects for vaccination among other downstream applications.

Pitfalls in scientific research: critical appraisal of articles published in one of the international journals in Egypt.

BACKGROUND: To identify and report flaws of Internet-published articles in the Journal of the Egyptian National Cancer Institute (JENCI), Cairo University, through a retrospective documentary study on articles published during the period from 2011 to 2016. All sections were reviewed against a collective checklist. Articles were grouped by publication year into 2 intervals: early (from 2011 to 2013) and recent (from 2014 to 2016) to identify changes in study characteristics over time. RESULTS: The study included 139 original articles. Half of the titles represented aim and 9.4% represented study design. Abstracts were concise, clear, with structured writing format in 98.6%, 93.5%, and 35.3%, respectively. Most introductions included the study aim, while 41% had a rationale. Study timing was reported in 59.0%, while the study design was reported in 25.9%. Inclusion and exclusion criteria were clearly reported in 43.1% and 40.1%, respectively. Statistical methods were mentioned in 80.6%, complete in 30.4%, and appropriate in 85.7%. Four studies reported sample size estimation. Only 52.5% and 58.3% of results were exhaustive and answer the research question, respectively. Incorrect statistical calculations occurred in 41.0%, inappropriate statistical tests or descriptive parameter selection in 26.6%, while inappropriate test application occurred in 49.1%. About 60% of discussions did not completely cover results, 31.7% fully justified the findings, 56.1% followed a logical flow, and 36.7% had contradiction within the text. Conclusions were mostly linked to aim, imprecise, and extrapolating beyond results. On comparing both periods, only a significant less misuse of statistical terms, more reporting conflict of interest, more missing references for cited texts in the recent period, and more participation of NCI over other institutes in the early period were found. CONCLUSION: Articles published in JENCI (from 2011 to 2016) had many methodological and reporting defects and some points of strength. Using the collective checklist developed by this study, continuous training of researchers, involving epidemiologists throughout the whole research process, and applying strict journal reporting and publication rules should be encouraged.

Mesoporous silica nanoparticles, a safe option for silymarin delivery: preparation, characterization, and in vivo evaluation.

The present work aimed to prepare silymarin-loaded mesoporous silica nanoparticles (MSNs) and to assess the system's dissolution enhancement ability on the pharmacodynamic performance of silymarin as a hepatoprotective agent. For this purpose, a soft-templating technique was used to prepare silymarin-loaded MSNs. The loaded MSNs were further characterized for their particle size, zeta potential, surface properties, and in vitro drug dissolution testing. In addition, differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) were also carried out. DSC and specific surface area data confirmed deposition of silymarin in an amorphous state in MSNs' pores. In vitro drug dissolution testing displayed enhanced dissolution rate of silymarin upon loading on MSNs compared with the free drug. Paracetamol-induced rat model of liver injury was used for the in vivo study. Plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), total proteins, liver homogenate content of thiobarbituric acid reactive species (TBARS), or lactate dehydrogenase (LDH) were assessed for all animal groups, treated and control ones. Based on parameters indicative of liver function, our results showed that the oral use of silymarin loaded onto MSNs at a dose of 250 mg/kg is significantly superior to free silymarin. Moreover, prolonged administration of the formulation had no evident toxicity on rats.