A new modality in targeted delivery of epirubicin for tumor theranosis based on PEGylated silver nanoparticles: Design, radiolabeling and bioevaluation.

This work highlights boosting the tumor targeting efficiency of epirubicin through loading on a new radionanosystem, based on the effective role of silver nanoparticles (AgNPs). Accordingly, PEGylated silver nanoparticles (PEG/AgNPs) were prepared in a size of 20.2 ± 0.1 nm. Additionally, epirubicin was loaded on PEG/AgNPs with a loading efficiency of 63 ± 3 %. Furthermore, both of PEG/AgNPs and EPI/PEG/AgNPs were radiolabeled with 131I isotope with radiolabeling yields of 85 ± 0.2 % and 90.3 ± 1 %, respectively. The in-vivo distribution of 131I-PEG/AgNPs and 131I-EPI/PEG/AgNPs were examined in healthy and tumor bearing mice models. Excitingly, 131I-EPI/PEG/AgNPs revealed a reticuloendothelial system (RES) avoidance and prolonged circulating time. In addition, 131I-EPI/PEG/AgNPs showed fast targeting of tumor site by 25.1 ± 0.1 %ID/g within 0.5 h after intravenous injection. Subsequently, the outcomes provided 131I-EPI/PEG/AgNPs as a new potential system for enhancement of tumor targeting and theranosis (therapy and/or imaging).

The role of miRNAs in viral myocarditis, and its possible implication in induction of mRNA-based COVID-19 vaccines-induced myocarditis.

Background: Several reports of unheeded complications secondary to the current mass international rollout of SARS-COV-2 vaccines, one of which is myocarditis occurring with the FDA fully approved vaccine, Pfizer, and others. Main body of the abstract: Certain miRNAs (non-coding RNA sequences) are involved in the pathogenesis in viral myocarditis, and those miRNAs are interestingly upregulated in severe COVID-19. We hypothesize that the use of mRNA-based vaccines may be triggering the release of host miRNAs or that trigger the occurrence of myocarditis. This is based on the finding of altered host miRNA expression promoting virus-induced myocarditis. Short conclusion: In conclusion, miRNAs are likely implicated in myocarditis associated with mRNA vaccines. Our hypothesis suggests the use of miRNA as a biomarker for the diagnosis of mRNA vaccine-induced myocarditis. Additionally, the interplay between viral miRNA and the host immune system could alter inflammatory profiles, hence suggesting the use of therapeutic inhibition to prevent such complications.

A case report of interventricular hemorrhage in William-Beuren syndrome.

Background: Williams syndrome (WS) (also as known Williams-Beuren Syndrome) is a neurodevelopmental disorder caused by deletion of chromosomes 7q11.23. WS phenotype is very variable but usually it is associated with a distinctive pattern of cognitive abilities. Case presentation: 9-year-old female patient known case of developmental delay and precocious puberty presented to the emergency department with altered level of consciousness, elevated blood pressure of 230/160 with a provisional diagnosis of hypertensive encephalopathy. Conclusions: In our patient, the strongest indications for establishing the diagnosis included the classic elfin face and multisystemic involvement. Later on genetic analysis confirmed our diagnosis.

Two concomitant thrombotic microangiopathies in the background of systemic lupus erythematosus: A case report.

Introduction and importance: Lupus nephritis is particularly a very concerning occurrence due to the susceptibility for potential renal damage and ultimately renal failure. Cardiac involvement was present as well in the form of pericarditis. Our study reports a case of lupus nephritis that has had a very severe course of fluctuations between relapses and improvements which constantly necessitated an MDT interference at various points. Case presentation: We report a case of a 13-year-old female patient who presented with a 5-day history of fever, dizziness, joint pain, menorrhagia, convulsions, and visual disturbances. Essential diagnostic tests took place and a diagnosis of lupus nephritis was confirmed. Conclusion: In conclusion we found that a combination of various treatment modalities and flexibility in decision making in response to changes in the clinical course are vital to treatment success. Utilization of plasma exchange which resulted in an enormous drop in the percentage of fragmented red blood cells (RBCs) from 9.8% to 1.8%.

Improvement of doxorubicin radioiodination and in-vivo cancer suppression via loading in nanosilver system.

This study aimed at improving the radioiodination of doxorubicin (DOX) and its localization in cancer cell for theranostic purposes. To achieve this goal, a composite of DOX with polyvinyl pyrrolidone (PVP) and silver nanoparticles (AgNPs) was prepared. Both DOX and (DOX/PVP/AgNPs) were radiolabelled with iodine-125 [125I] and optimized using iodogen as a preferable oxidizing agent. The maximum obtained radiochemical yields for both systems were 79.9% and 96.6%, respectively. Interestingly, the biodistribution study revealed that [125I]DOX/PVP/AgNPs had an effective localization on tumors. Moreover, Target/control target (T/CT) ratio of [125I] DOX/PVP/AgNPs showed the highest value of 9.1 at 1 h post injection, suggesting that [125I]DOX/PVP/AgNPs has a great potential as a proposed tumor targeting agent.

Investigation for anticancer activity of the newly synthesized p-Methoxyphenyl maleanilic acid and the diagnostic property of its 99mTc-analogue.

PURPOSE: The limitations of the current chemotherapeutics are the main rational to develop and/or explore new anticancer agents and radiolabeled analogues for cancer early diagnosis. MATERIALS AND METHODS: The newly synthesized p-methoxyphenyl maleanilic acid (MPMA) was prepared, characterized and investigated for its anticancer activity. MPMA screened in-vitro against human hepatocellular carcinoma (HepG-2), human colon carcinoma (HCT-116) and human breast carcinoma (MCF-7) cell lines. Furthermore, the in-vivo screening was performed by radiolabeling of MPMA with technetium-99m (99mTc) and investigating its biological distribution in normal mice and solid tumor models. Moreover, MPMA and its radiolabeled analogue were docked to Y220C and Y220S mutants of p53 (p53Y220C and p53Y220S) in an effort to confirm their affinity to cancer as well as to investigate, virtually, the mechanism of action of MPMA. RESULTS: The results revealed significant potency of MPMA against HepG-2 cell line (IC50 = 56.2 ± 1.5 µg/mL) if compared to HCT-116 (IC50 = 89.9 ± 1.8 µg/mL) and MCF-7 (IC50 = 104 ± 2.7 µg/mL) cell lines. The radiolabeling yield was optimized to be 90.2 ± 2.1%. The radiolabeled MPMA showed a good localization in the site of solid tumor (15.1 ± 1.6%ID/g) at 2 h post intravenous administration to the tumor bearing mice. CONCLUSIONS: Collectively, the findings confirmed the potential anticancer activity of MPMA and the possible use of 99mTc-MPMA for cancer diagnosis and monitoring.

Removal of Methylene Blue and Congo Red Using Adsorptive Membrane Impregnated with Dried Ulva fasciata and Sargassum dentifolium.

Biosorption is a bioremediation approach for the removal of harmful dyes from industrial effluents using biological materials. This study investigated Methylene blue (M. blue) and Congo red (C. red) biosorption from model aqueous solutions by two marine macro-algae, Ulva fasciata and Sargassum dentifolium, incorporated within acrylic fiber waste to form composite membranes, Acrylic fiber-U. fasciata (AF-U) and Acrylic fiber-S. dentifolium (AF-S), respectively. The adsorption process was designed to more easily achieve the 3R process, i.e., removal, recovery, and reuse. The process of optimization was implemented through one factor at a time (OFAT) experiments, followed by a factorial design experiment to achieve the highest dye removal efficiency. Furthermore, isotherm and kinetics studies were undertaken to determine the reaction nature. FT-IR and SEM analyses were performed to investigate the properties of the membrane. The AF-U membrane showed a significant dye removal efficiency, of 88.9% for 100 ppm M. blue conc. and 79.6% for 50 ppm C. red conc. after 240 min sorption time. AF-S recorded a sorption capacity of 82.1% for 100 ppm M. blue conc. after 30 min sorption time and 85% for 100 ppm C. red conc. after 240 min contact time. The membranes were successfully applied in the 3Rs process, in which it was found that the membranes could be used for five cycles of the removal process with stable efficiency.

Green Synthesis of Zinc Oxide Nanoparticles (ZnO-NPs) Using Arthrospira platensis (Class: Cyanophyceae) and Evaluation of their Biomedical Activities.

In this study, zinc oxide nanoparticles (ZnO-NPs) were successfully fabricated through the harnessing of metabolites present in the cell filtrate of a newly isolated and identified microalga Arthrospira platensis (Class: Cyanophyceae). The formed ZnO-NPs were characterized by UV-Vis spectroscopy, Fourier transform infrared (FT-IR), transmission electron microscopy (TEM), energy-dispersive spectroscopy (EDX), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). Data showed the efficacy of cyanobacterial metabolites in fabricating spherical, crystallographic ZnO-NPs with a size ≈30.0 to 55.0 nm at a wavelength of 370 nm. Moreover, FT-IR analysis showed varied absorption peaks related to nanoparticle formation. XPS analysis confirms the presence of Zn(II)O at different varied bending energies. Data analyses exhibit that the activities of biosynthesized ZnO-NPs were dose-dependent. Their application as an antimicrobial agent was examined and formed clear zones, 24.1 ± 0.3, 21.1 ± 0.06, 19.1 ± 0.3, 19.9 ± 0.1, and 21.6 ± 0.6 mm, at 200 ppm against Bacillus subtilis, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Candida albicans, respectively, and these activities were reduced as the NPs concentration decreased. The minimum inhibitory concentration (MIC) values were determined as 50 ppm for S. aureus, 25 ppm for P. aeruginosa, and 12.5 ppm for B. subtilis, E. coli, and C. albicans. More interestingly, ZnO-NPs exhibit high in vitro cytotoxic efficacy against cancerous (Caco-2) (IC50 = 9.95 ppm) as compared with normal (WI38) cell line (IC50 = 53.34 ppm).

Biological Screening and Radiolabeling of Raptinal as a Potential Anticancer Novel Drug in Hepatocellular Carcinoma Model.

New synthetic compound Raptinal (RAP) was investigated on different biological levels for its potential anticancer activity. RAP showed higher antiproliferative activity on HepG2 cell line with IC50 0.62µM compared to MCF-7 and HCT-116 (4.03 and 92.3 µM) respectively. Moreover, RAP induces early stage of apoptosis in the most sensitive HepG2 treated cells after 24 hr with cell cycle arrest in both subG0-G1 and G0-G1 phases and minimal cell count in G2/M mitotic phase with apoptotic index 9.25-fold higher than to control. RAP induces over-expression of key apoptotic genes such as Fas receptor, Caspase-8, Caspase-9, Bax and P53. Western blotting confirm the observation on protein level via over-expression of Caspase-9, Cytochrome-C and higher ration of Bax/Bcl-2. In addition, RAP was radiolabeled using one of the most important diagnostic radioactive isotopes, technetium-99m (99mTc), with a radiochemical yield of 92.7 ± 0.41 %. Quality control and biological distribution of 99mTc-RAP in both healthy and HCC rat model were investigated. Biodistribution profile revealed the localization of RAP in liver tissues (20.5±2.6 %) of HCC models at half an hour post intravenous injection. Histopathological examination confirmed the biodistribution of RAP into liver tissue with induction of karyomegaly in the nuclei of hepatocytes as well as others that proceeded into apoptosis. Molecular docking suggested RAP binds in binding pocket of p53 cancer mutant Y220C making reactivation of the mutant form which is a promising strategy for further investigation on molecular level as a novel anticancer therapeutics. All the results support the use of RAP as a potential anticancer drug in HCC and its 99mTc complex as an imaging probe.

Obese communities among the best predictors of COVID-19-related deaths.

Coronavirus disease 2019 (COVID-19) is the largest outbreak to strike the world since the Spanish flu in 1918. Visual examination of the world map shows a wide variation of death tolls between countries. The main goal of our series is to determine the best predictors of such discrepancy. METHODS: This is a retrospective study in which the rate of COVID-19 deaths was correlated with each of the following independent variables: total tests per 1 million population, gross domestic product (GDP), average temperatures per country, ultraviolet index, median age, average BMI per country, food supply, Bacille Calmette-Guerin compulsory status, and passenger traffic. RESULTS: BMI per country proved to be the second best predictor of death rate with an R value of 0.43, and GDP being the best predictor with R = 0.65. CONCLUSION: This article shows a tight correlation between average BMI, food supply per country, and COVID-19-related deaths. Such predisposing factors might operate by upregulating the inflammation pathway in heavily struck countries, leading to easier triggering of the infamous cytokine storm syndrome. Obesity also increases cardiovascular and respiratory morbidities, which are coupled to increased ICU demand and deaths among infected cases.Video abstract: http://links.lww.com/CAEN/A25.

Enhancing Tumor Targeting Efficiency of Radiolabeled Uridine (via) Incorporation into Nanocubosomal Dispersions.

Background: Several nanosystems are currently being utilized to enhance the targeting efficiency of several cancer chemotherapeutic agents. This study was designed to improve tumor accumulation of iodine-125 (125I)-uridine via incorporation into a nanocubosomal preparation. Materials and Methods: Nanocubosomes were prepared with the aid of Glycerol mono-oleate and Pluronic F127. Each prepared nanocubosomal preparation was adequately characterized by testing their particle size, polydispersity index (PDI), ζ potential (ZP), and transmission electron microscopy. The radiolabeling of uridine with 125I was attempted using several oxidizing agents to achieve a high radiochemical yield, and the factors affecting the reaction yield were studied in detail. A comparative biodistribution study of free 125I-uridine and 125I-uridine loaded nanocubosomes was performed in normal and tumor bearing mice. The biodistribution was evaluated by intravenous injection of the sterile test solution, and animals were anesthetized and dissected at different time intervals postinjection (p.i.). Results: 125I-uridine was obtained in a high radiochemical yield (92.5% ± 0.8%). Afterward, 125I uridine was incorporated in a selected nanocubosome formulation, which showed nanosized cubic particles (178.6 ± 0.90 nm) with PDI (0.301 ± 0.04) and a ZP (34.35 ± 0.4). The biodistribution studies revealed that 125I-uridine nanocubosomes showed higher tumor localization (3.1 ± 0.4%IA/g at 2 h p.i. and a tumor/muscle ratio of 6.2) compared with the free 125I-uridine (2.7% ± 0.4%IA/g at 2 h p.i. and a tumor/muscle ratio of 3.3). Conclusion: The results of this study confirmed that 125I-uridine loaded nanocubosome had better efficiency in targeting the tumor site, which makes it an adequate targeting agent for tumor imaging.

Comparative study on radiolabeling and biodistribution of core-shell silver/polymeric nanoparticles-based theranostics for tumor targeting.

A simple and rapid method for radiolabeling of three types of Ag NPs has been performed using 125I isotope, with high labeling yields, >90% without disturbing the optical properties. All the factors affecting labeling yield were studied. In order to monitor the in-vivo tissue uptake of radiolabeled Ag NPs using γ-rays, Ag-based radioiodo-NPs with a maximum labeling yield were intravenously injected in normal and solid tumor bearing mice. The preliminary biodistribution study revealed that this new radioiodo-NPs have a high affinity to be localized in the tumor site for a long period of time. The reported highly efficient method provides new radiolabeled Ag-based NPs as tumor-specific agents for both diagnostic and therapeutic applications.

Antibacterial, cytotoxicity and anticoagulant activities from Hypnea esperi and Caulerpa prolifera marine algae.

Extracts from 2 algal species (Hypnea esperi and Caulerpa prolifera) from Suez Canal region, Egypt were screened for the production of antibacterial compounds against some pathogenic bacteria. The bacteria tested included Escherichia coli, Pseudomonas aeruginosa, Salmonella typhimurium, Aeromonas hydrophila, Bacillus subtilis and Staphylococcus aureus. Algal species displayed antibacterial activity. The methanolic extracts showed variable response by producing various zones of inhibition against studied bacteria. The tested Gram-negative bacteria were less affected by studied algal extracts than Gram-positive bacteria. We determined some biopotentials properties such as cytotoxicity and anticoagulant activity of most potent algal active extracts. The secondary metabolites of only Hypnea esperi algal extract effectively prevented the blood clotting to the extent of 120 seconds. Minimum inhibitory concentration (MIC) indicated that all potent tested algal extract C inhibits Bacillus subtilis and Staphylococcus aureus. Minimum bactericidal concentration (MBC) was between 1 and 1.4mg/ml. The algal isolates from Egypt have been found showing promising results against infectious bacteria instead of some synthetic antibiotics.