Multimodal modulation of hepatic ischemia/reperfusion-induced injury by phytochemical agents: A mechanistic evaluation of hepatoprotective potential and safety profiles.

BACKGROUND: Hepatic ischemia-reperfusion (I/R) injury is a clinically fundamental phenomenon that occurs through liver resection surgery, trauma, shock, and transplantation. AIMS OF THE REVIEW: This review article affords an expanded and comprehensive overview of various natural herbal ingredients that have demonstrated hepatoprotective effects against I/R injury through preclinical studies in animal models. MATERIALS AND METHODS: For the objective of this investigation, an extensive examination was carried out utilizing diverse scientific databases involving PubMed, Google Scholar, Science Direct, Egyptian Knowledge Bank (EKB), and Research Gate. The investigation was conducted based on specific identifiable terms, such as hepatic ischemia/reperfusion injury, liver resection and transplantation, cytokines, inflammation, NF-kB, interleukins, herbs, plants, natural ingredients, phenolic extract, and aqueous extract. RESULTS: Bioactive ingredients derived from ginseng, curcumin, resveratrol, epigallocatechin gallate, quercetin, lycopene, punicalagin, crocin, celastrol, andrographolide, silymarin, and others and their effects on hepatic IRI were discussed. The specific mechanisms of action, signaling pathways, and clinical relevance for attenuation of liver enzymes, cytokine production, immune cell infiltration, oxidative damage, and cell death signaling in rodent studies are analyzed in depth. Their complex molecular actions involve modulation of pathways like TLR4, NF-κB, Nrf2, Bcl-2 family proteins, and others. CONCLUSION: The natural ingredients have promising values in the protection and treatment of various chronic aggressive clinical conditions, and that need to be evaluated on humans by clinical studies.

Use of K-Y Jelly on Throat Packs for Postoperative Sore Throat after Nasal Surgery: A Randomized Controlled Trial.

Introduction Postoperative sore throat (POST) is a fairly common side effect of general anesthesia. The K-Y jelly is a well-known lubricant used in many medical procedures. Objective In this randomized study, we evaluated the use of throat packs soaked with K-Y jelly for POST outcomes in patients submitted to nasal surgery. Methods The present double-blinded, randomized, controlled study included 140 ASA I-II patients undergoing nasal surgery under general anesthesia. Patients received either or K-Y jelly or water-soaked X-ray detectable throat packs fully inserted into the mouth to occlude the oropharynx. Results Comparison between the studied groups regarding the severity of POST assessed by visual analog scale revealed significantly lower POST levels in the K-Y jelly group on recovery from anesthesia, and at 2, 4, and 6 hours postoperatively. Conclusions The use of K-Y jelly-soaked throat packs was associated with less severe POST after nasal surgery.

Sodium alginate films incorporated with Lepidium sativum (Garden cress) extract as a novel method to enhancement the oxidative stability of edible oil.

This study addresses the growing interest in bio-based active food packaging by infusing Lepidium sativum (Garden cress) seeds extract (GRCE) into sodium alginate (SALG) films at varying concentrations (1, 3, and 5 %). The GRCE extract revealed six phenolic compounds, with gallic and chlorogenic acids being prominent, showcasing substantial total phenolic content (TPC) of 139.36 µg GAE/mg and total flavonoid content (TFC) of 26.46 µg RE/mg. The integration into SALG films significantly increased TPC, reaching 30.73 mg GAE/g in the film with 5 % GRCE. This enhancement extended to DPPH and ABTS activities, with notable rises to 66.47 and 70.12 %, respectively. Physical properties, including tensile strength, thickness, solubility, and moisture content, were positively affected. A reduction in water vapor permeability (WVP) was reported in the film enriched with 5 % GRCE (1.389 × 10-10 g H2O/m s p.a.). FT-IR analysis revealed bands indicating GRCE's physical interaction with the SALG matrix, with thermal stability of the films decreasing upon GRCE integration. SALG/GRCE5 effectively lowered the peroxide value (PV) of sunflower oil after four weeks at 50 °C compared to the control, with direct film-oil contact enhancing this reduction. Similar trends were observed in the K232 and K270 values.

Use of K-Y Jelly on Throat Packs for Postoperative Sore Throat after Nasal Surgery: A Randomized Controlled Trial

Abstract Introduction Postoperative sore throat (POST) is a fairly common side effect of general anesthesia. The K-Y jelly is a well-known lubricant used in many medical procedures. Objective In this randomized study, we evaluated the use of throat packs soaked with K-Y jelly for POST outcomes in patients submitted to nasal surgery. Methods The present double-blinded, randomized, controlled study included 140 ASA I-II patients undergoing nasal surgery under general anesthesia. Patients received either or K-Y jelly or water-soaked X-ray detectable throat packs fully inserted into the mouth to occlude the oropharynx. Results Comparison between the studied groups regarding the severity of POST assessed by visual analog scale revealed significantly lower POST levels in the K-Y jelly group on recovery from anesthesia, and at 2, 4, and 6 hours postoperatively. Conclusions The use of K-Y jelly-soaked throat packs was associated with less severe POST after nasal surgery.

Synthesis, Physicochemical Characterization using a Facile Validated HPLC Quantitation Analysis Method of 4-Chloro-phenylcarbamoyl-methyl Ciprofloxacin and Its Biological Investigations.

A novel derivative of ciprofloxacin (Cpx) was synthesized and characterized using various analytical techniques, including FT-IR spectroscopy, UV-Vis spectroscopy, TEM and SEM analysis, 1H NMR, 13C NMR, and HPLC analysis. The newly prepared Cpx derivative (Cpx-Drv) exhibited significantly enhanced antibacterial properties compared to Cpx itself. In particular, Cpx-Drv demonstrated a 51% increase in antibacterial activity against S. aureus and a 30% improvement against B. subtilis. It displayed potent inhibitory effects on topoisomerases II (DNA gyrase and topoisomerase IV) as potential molecular targets, with IC50 values of 6.754 and 1.913 µg/mL, respectively, in contrast to Cpx, which had IC50 values of 2.125 and 0.821 µg/mL, respectively. Docking studies further supported these findings, showing that Cpx-Drv exhibited stronger binding interactions with the gyrase enzyme (PDB ID: 2XCT) compared to the parent Cpx, with binding affinities of -10.3349 and -7.7506 kcal/mole, respectively.

Anti-Tumor Activity of Orally Administered Gefitinib-Loaded Nanosized Cubosomes against Colon Cancer.

Gefitinib (GFT) is a tyrosine kinase inhibitor drug used as a first-line treatment for patients with advanced or metastatic non-small cell lung, colon, and breast cancer. GFT exhibits low solubility and hence low oral bioavailability, which restricts its clinical application. One of the most important trends in overcoming such problems is the use of a vesicular system. Cubosomes are considered one of the most important vesicular systems used to improve solubility and oral bioavailability. In this study, GFT cubosomal nanoparticles (GFT-CNPs) were prepared by the emulsification method. The selected formulation variables were analyzed and optimized by full factorial design and response surface methodology. Drug entrapment efficiency (EE%), transmission electron microscopy, particle size, polydispersity index, in vitro release and its kinetics, and the effect of storage studies were estimated. The chosen GFT-CNPs were subjected to further investigations as gene expression levels of tissue inhibitors of metalloproteinases-1 (TIMP-1) and matrix metalloproteinases-7 (MMP-7), colon biomarkers, and histopathological examination of colon tissues. The prepared GFT-CNPs were semi-cubic in shape, with high EE%, smaller vesicle size, and higher zeta potential values. The in vivo data showed a significant decrease in the serum level of embryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), and gene expression level of TIMP-1 and MMP-7. Histopathological examination showed enhancement in cancer tissue and highly decreased focal infiltration in the lamina propria after treatment with GFT-CNPs.

Transcervical pharyngeal pouch stapling.

BACKGROUND: Pharyngeal pouches are generally treated with surgery, via either an endoscopic or an external approach. Large pouches extending to the mediastinum carry an increased risk of post-operative mediastinitis in the event of a leak following external approach surgery, and may not always be amenable to endoscopic stapling. METHODS: Transcervical stapling is a newly described technique that uses the endoluminal stapling approach but in which the diverticuloscope is inserted into the pharynx via a neck incision. CONCLUSIONS: This technique has been used successfully on three patients with large pharyngeal pouches, where endoscopic stapling was not possible due to access limitations.

A Novel C@Fe@Cu Nanocomposite Loaded with Doxorubicin Tailored for the Treatment of Hepatocellular Carcinoma.

High mortality and morbidity rates are related to hepatocellular carcinoma (HCC), which is the most prevalent type of liver cancer. A new vision for cancer treatment and cancer cell targeting has emerged with the application of nanotechnology, which reduces the systemic toxicity and adverse effects of chemotherapy medications while increasing their effectiveness. It was the goal of the proposed work to create and investigate an anticancer C@Fe@Cu nanocomposite (NC) loaded with Doxorubicin (DOX) for the treatment of HCC. Scanning and transmission electron microscopes (SEM and TEM) were used to examine the morphology of the produced NC. The formulation variables (DOX content, C@Fe@Cu NC weight, and stirring speed) were analyzed and optimized using Box-Behnken Design (BBD) and Response Surface Methodology (RSM). Additionally, X-ray diffraction patterns (XRD) and Fourier Transform Infrared (FTIR) were investigated. Doxorubicin and DOX- loaded C@Fe@Cu NC (DOX-C@Fe@Cu NC) were also assessed against HEPG2 cells for anticancer efficacy (Hepatic cancer cell line). The results revealed the formation of C@Fe@Cu NC with a mean size of 7.8 nm. A D-R model with a mean size of 24.1 nm best fits the adsorption behavior of DOX onto the C@Fe@Cu NC surface. DOX-C@Fe@Cu NC has also been demonstrated to have a considerably lower IC50 and higher cytotoxicity than DOX alone in an in vitro investigation. Therefore, DOX-C@Fe@Cu NC is a promising DOX delivery vehicle for the full recovery of HCC.

CYP11A1­derived vitamin D hydroxyderivatives as candidates for therapy of basal and squamous cell carcinomas.

Hydroxyderivatives of vitamin D3, including classical 1,25(OH)2D3 and novel CYP11A1­derived hydroxyderivatives, exert their biological activity by acting as agonists on the vitamin D receptor (VDR) and inverse agonists on retinoid­related orphan receptors (ROR)α and γ. The anticancer activities of CYP11A1­derived hydroxyderivatives were tested using cell biology, tumor biology and molecular biology methods in human A431 and SCC13 squamous (SCC)­ and murine ASZ001 basal (BCC)­cell carcinomas, in comparison with classical 1,25(OH)2D3. Vitamin D3­hydroxyderivatives with or without a C1α(OH) inhibited cell proliferation in a dose­dependent manner. While all the compounds tested had similar effects on spheroid formation by A431 and SCC13 cells, those with a C1α(OH) group were more potent in inhibiting colony and spheroid formation in the BCC line. Potent anti­tumorigenic activity against the BCC line was exerted by 1,25(OH)2D3, 1,20(OH)2D3, 1,20,23(OH)3D3, 1,20,24(OH)3D3, 1,20,25(OH)3D3 and 1,20,26(OH)3D3, with smaller effects seen for 25(OH)D3, 20(OH)D3 and 20,23(OH)2D3. 1,25(OH)2D3, 1,20(OH)2D3 and 20(OH)D3 inhibited the expression of GLI1 and ß­catenin in ASZ001 cells. In A431 cells, these compounds also decreased the expression of GLI1 and stimulated involucrin expression. VDR, RORγ, RORα and CYP27B1 were detected in A431, SCC13 and ASZ001 lines, however, with different expression patterns. Immunohistochemistry performed on human skin with SCC and BCC showed nuclear expression of all three of these receptors, as well as megalin (transmembrane receptor for vitamin D­binding protein), the level of which was dependent on the type of cancer and antigen tested in comparison with normal epidermis. Classical and CYP11A1­derived vitamin D3­derivatives exhibited anticancer­activities on skin cancer cell lines and inhibited GLI1 and ß­catenin signaling in a manner that was dependent on the position of hydroxyl groups. The observed expression of VDR, RORγ, RORα and megalin in human SCC and BCC suggested that they might provide targets for endogenously produced or exogenously applied vitamin D hydroxyderivatives and provide excellent candidates for anti­cancer therapy.

Bayesian network meta-analysis comparing cryoablation, radiofrequency ablation, and antiarrhythmic drugs as initial therapies for atrial fibrillation.

BACKGROUND: Antiarrhythmic drugs (AADs) and catheter ablation are first line treatments of paroxysmal atrial fibrillation (PAF), however, there exists a paucity of data regarding the potential benefit of different catheter ablation technologies versus AADs as an early rhythm strategy. OBJECTIVE: To assess the safety and efficacy of cryoablation versus radiofrequency ablation (RFA) versus AADs as a first line therapy of PAF. METHODS: MEDLINE, Embase, Scopus and CENTRAL were searched to retrieve randomized clinical trials (RCTs) comparing cryoablation, RFA or AADs to one another as first line therapies for atrial fibrillation (AF). The primary outcome was overall freedom from arrhythmia recurrence (AF, atrial flutter [AFL], atrial tachycardia). Secondary outcomes included freedom from symptomatic arrhythmia recurrence, hospitalization, and serious adverse events. A random-effects Bayesian network meta-analysis was used to calculate odds ratios (OR) and 95% credible intervals (CrI). RESULTS: Six RCTs (N = 1212) met the inclusion criteria (605 AADs, 365 Cryoablation, and 245 RFA). Compared with AADs, overall recurrence was reduced with RFA (OR: 0.31; 95% CrI: 0.10-0.71) and cryoablation (OR: 0.39; 95% CrI: 0.16-1.00). Comparing ablation (cryoablation and RFA) with AADs in respect to freedom from symptomatic AF recurrence, neither cryoablation (OR: 0.35; 95% CrI: 0.06-1.96) nor RFA (OR: 0.34; 95% CrI: 0.07-1.27) resulted in statistically significant reductions individually compared to AADs, though pooled ablation with both technologies showed lower odds of arrhythmia recurrence (OR: 0.35; 95% CrI: 0.13-0.79). In terms of serious adverse events rates, neither cryoablation (OR: 0.77; 95% CrI: 0.44-1.39) nor RFA (OR: 1.45; 95% CrI: 0.67-3.23) were significantly different to AADs. RFA resulted in a statistically significant reduction in hospitalizations compared to AAD (OR: 0.08; 95% CrI: 0.01-0.99), whereas cryoablation did not (OR: 0.77; 95% CrI: 0.44-1.39). The surface under the cumulative ranking curve showed RFA to be the most effective treatment at reducing overall rates of recurrence, symptomatic recurrence and hospitalizations; whereas cryoablation was most likely to reduce serious adverse events. CONCLUSION: Cryoablation and RFA are both effective and safe first line therapies for AF compared to AADs, with RFA being the most effective at reducing recurrences.

Prognostic indicators in clinically node-negative malignant primary salivary tumours of the parotid: A multicentre experience.

OBJECTIVES: Nodal metastasis is an important prognosticator in primary parotid cancers. The management of the clinically node-negative neck is an area lacking consensus. This study investigates the occult nodal metastasis rate, and prognostic indicators in primary parotid cancers. MATERIALS AND METHODS: We performed a multicentre retrospective case note review of patients diagnosed and treated surgically with curative intent between 1997 and 2020. Demographic, clinic-pathological and follow-up data was recorded. RESULTS: After exclusions, 334 patients were included for analysis, with a median follow-up of 48 months. The overall rate of occult lymph node metastasis amongst patients undergoing elective neck dissection was 22.4%, with older age, high-grade and more advanced primary tumours being associated with higher rates. On multivariable analysis, age ≥ 60 years (HR = 2.69, p = 0.004), high-grade tumours (HR = 2.70, p = 0.005) and advanced primary tumours (pT3-4, HR = 2.06, p = 0.038) were associated with worse overall survival. Occult nodal metastasis on final pathology was associated with a close-to-significant reduction in regional recurrence free survival (HR = 3.18, p = 0.076). CONCLUSION: This large series confirms the significant occult lymph node metastasis rate in primary parotid cancer, and demonstrates the importance of primary histology, tumour grade and stage in predicting survival outcome. This data supports the use of elective neck dissection in patients with high-risk tumours.

Design and Optimization of Orally Administered Luteolin Nanoethosomes to Enhance Its Anti-Tumor Activity against Hepatocellular Carcinoma.

Luteolin (LUT) is a natural flavonoid with low oral bioavailability with restricted clinical applications due to its low solubility. LUT shows significant anti-tumor activity in many cancer cells, including hepatocellular carcinoma (HCC). The most recent trend in pharmaceutical innovations is the application of phospholipid vesicles to improve the solubility of such hydrophobic drugs. Ethosomes are one of the most powerful phospholipid vesicles used to achieve that that target. In this study, LUT-loaded ethosomal nanoparticles (LUT-ENPs) were prepared by the cold method. Full factorial design and response surface methodology were used to analyze and optimize the selected formulation variables. Drug entrapment efficiency, vesicle size, zeta potential, Fourier transform infra-red spectroscopy, scanning electron microscopy, and cumulative percent drug released was estimated. The selected LUT-ENPs were subjected to further investigations as estimation of hepatic gene expression levels of GPC3, liver biomarkers, and oxidative stress biomarkers. The prepared LUT-ENPs were semi-spherical in shape with high entrapment efficiency. The prepared LUT-ENPs have a small particle size with high zeta potential values. The in vitro liver biomarkers assay revealed a significant decrease in the hepatic tissue nitric oxide (NO), malondialdehyde (MDA) content, and the expression of the GPC3 gene. Results showed a high increase in the hepatic tissue levels of glutathione (GSH) and superoxide dismutase (SOD). Histopathological examination showed a small number of hepatic adenomas and a significant decrease of neoplastic hepatic lesions after treatment with LUT-ENPs. Our results firmly suggest the distinctive anti-proliferative activity of LUT-ENPs as an oral drug delivery system for the treatment of HCC.

Novel Green Biosynthesis of 5-Fluorouracil Chromium Nanoparticles Using Harpullia pendula Extract for Treatment of Colorectal Cancer.

Colorectal cancer (CRC) is the third highest major cause of morbidity and mortality worldwide. Hence, many strategies and approaches have been widely developed for cancer treatment. This work prepared and evaluated the antitumor activity of 5-Fluorouracil (5-Fu) loaded chromium nanoparticles (5-FuCrNPs). The green biosynthesis approach using Harpullia (H) pendula aqueous extract was used for CrNPs preparation, which was further loaded with 5-Fu. The prepared NPs were characterized for morphology using scanning and transmission electron microscopes (SEM and TEM). The results revealed the formation of uniform, mono-dispersive, and highly stable CrNPs with a mean size of 23 nm. Encapsulation of 5-Fu over CrNPs, with a higher drug loading efficiency, was successful with a mean size of 29 nm being produced. In addition, Fourier transform infrared (FTIR) and X-ray diffraction pattern (XRD) were also used for the investigation. The drug 5-Fu was adsorbed on the surface of biosynthesized CrNPs in order to overcome its clinical resistance and increase its activity against CRC cells. Box-Behnken Design (BBD) and response surface methodology (RSM) were used to characterize and optimize the formulation factors (5-Fu concentration, CrNP weight, and temperature). Furthermore, the antitumor activity of the prepared 5-FuCrNPs was tested against CRC cells (CACO-2). This in vitro antitumor study demonstrated that 5-Fu-loaded CrNPs markedly decreased the IC50 of 5-Fu and exerted more cytotoxicity at nearly all concentrations than 5-Fu alone. In conclusion, 5-FuCrNPs is a promising drug delivery system for the effective treatment of CRC.

Additive Manufacturing Technologies for Drug Delivery Applications.

Patient to patient variability is one of the issues when administering medications to individuals with different health conditions, pharmacokinetic, age, fitness, gender, and race. This requires introducing smart and personalised drug delivery systems with controlled release profile manufactured using novel approaches. Additive manufacturing (AM) provides opportunities such as full customisation, design freedom, and on-site manufacturing, and materials recycling. As a result, the academic and industrial demand for additive manufacturing for drug delivery has been continuously increasing and showing impressive results for a wide range of products. This paper provides an extensive overview of AM technologies and their applications for drug delivery. The review discusses AM technologies including their working principles, processed materials, as well as current progress in drug delivery to produce personalized dosages for every patient with controlled release profile. AM potentials, industrial scale, and challenges are investigated with regards to practice and industrial applications. The paper covers novel possibilities of AM technologies and their pharmaceuticals applications, which indicate a promising healthcare future.

Controlled release alginate-chitosan microspheres of tolmetin sodium prepared by internal gelation technique and characterized by response surface modeling

Tolmetin sodium (TS) is a powerful non-steroidal mitigating drug for the treatment of rheumatoid joint inflammation, osteoarthritis, and adolescent rheumatoid joint pain. In addition to its gastrointestinal (GIT) problems, TS has a short biological half-life (1 hr). In a trial to overcome these side effects and control the rate of (TS) release, chitosan coated alginate microspheres are recommended. A Box-Behnken experimental design was employed to produce controlled release microspheres of TS in the sodium alginate and chitosan copolymers (Alg-Ch) by emulsification internal gelation methodology. The effect of critical formulation variables namely, drug to polymer ratio (D:P ratio), speed of rotation and span 80% on drug encapsulation efficiency (% EE), drug release at the end of 2 hours (Rel2) and drug release at the end of 8 hours (Rel8) were analyzed using response surface modeling. The parameters were assessed using the F test and mathematical models containing only the significant terms were generated for each parameter using multiple linear regression analysis. The produced microspheres were spherical in shape with extensive pores at D:P ratio 1:1 and small pores at a drug to polymer ratio (D:P ratio) 1:3. Differential scanning calorimetry (DSC) affirmed the steady character of TS in microspheres and revealed their crystalline form. All formulation variables examined exerted a significant influence on the drug release, whereas the speed emerged as a lone factor significantly influencing % EE. Increasing the D: P ratio decreases the release of the drug after two and 8 hours. The increase in speed results in an increase in drug release after two and eight hours. The drug release from the microspheres followed zero order kinetics. TS Alg-Ch microspheres exhibited a significant anti-inflammatory effect on incited rat paw edema after eight hours. These results revealed that the internal gelation technique is a promising method to control TS release and eradicate GIT side effects using Alg-Ch copolymers.

Design And Characterisation Of Novel Sorafenib-Loaded Carbon Nanotubes With Distinct Tumour-Suppressive Activity In Hepatocellular Carcinoma.

PURPOSE: Over the past 30 years, no consistent survival benefits have been recorded for anticancer agents of advanced hepatocellular carcinoma (HCC), except for the multikinase inhibitor sorafenib (Nexavar®), which clinically achieves only ~3 months overall survival benefit. This modest benefit is attributed to limited aqueous solubility, slow dissolution rate and, consequently, limited absorption from the gastrointestinal tract. Thus, novel formulation modalities are in demand to improve the bioavailability of the drug to attack HCC in a more efficient manner. In the current study, we aimed to design a novel sorafenib-loaded carbon nanotubes (CNTs) formula that is able to improve the therapeutic efficacy of carried cargo against HCC and subsequently investigate the antitumour activity of this formula. MATERIALS AND METHODS: Sorafenib was loaded on functionalized CNTs through physical adsorption, and an alginate-based method was subsequently applied to microcapsulate the drug-loaded CNTs (CNTs-SFN). The therapeutic efficacy of the new formula was estimated and compared to that of conventional sorafenib, both in vitro (against HepG2 cells) and in vivo (in a DENA-induced HCC rat model). RESULTS: The in vitro MTT anti-proliferative assay revealed that the drug-loaded CNTs formula was at least two-fold more cytotoxic towards HepG2 cells than was sorafenib itself. Moreover, the in vivo animal experiments proved that our innovative formula was superior to conventional sorafenib at all assessed end points. Circulating AFP-L3% was significantly decreased in the CNTs-SFN-MCs-treated group (14.0%) in comparison to that of the DENA (40.3%) and sorafenib (38.8%) groups. This superiority was further confirmed by Western blot analysis and immunofluorescence assessment of some HCC-relevant biomarkers. CONCLUSION: Our results firmly suggest the distinctive cancer-suppressive nature of CNTs-SFN-MCs, both against HepG2 cells in vitro and in a DENA-induced HCC rat model in vivo, with a preferential superiority over conventional sorafenib.

Modified Spraying Technique and Response Surface Methodology for the Preparation and Optimization of Propolis Liposomes of Enhanced Anti-Proliferative Activity against Human Melanoma Cell Line A375.

Propolis is a honeybee product that contains a mixture of natural substances with a broad spectrum of biological activities. However, the clinical application of propolis is limited due to the presence of a myriad of constituents with different physicochemical properties, low bioavailability and lack of appropriate formulations. In this study, a modified injection technique (spraying technique) has been developed for the encapsulation of the Egyptian propolis within liposomal formulation. The effects of three variables (lipid molar concentration, drug loading and cholesterol percentage) on the particle size and poly dispersity index (PDI) were studied using response surface methodology and the Box-Behnken design. Response surface diagrams were used to develop an optimized liposomal formulation of the Egyptian propolis. A comparative study between the optimized liposomal formulation prepared either by the typical ethanol injection method (TEIM) or the spraying method in terms of particle size, PDI and the in-vitro anti-proliferative effect against human melanoma cell line A375 was carried out. The spraying method resulted in the formation of smaller propolis-loaded liposomes compared to TEIM (particle sizes of 90 ± 6.2 nm, and 170 ± 14.7 nm, respectively). Furthermore, the IC50 values against A375 cells were found to be 3.04 ± 0.14, 4.5 ± 0.09, and 18.06 ± 0.75 for spray-prepared propolis liposomes (PP-Lip), TEIM PP-Lip, and propolis extract (PE), respectively. The encapsulation of PE into liposomes is expected to improve its cellular uptake by endocytosis. Moreover, smaller and more uniform liposomes obtained by spraying can be expected to achieve higher cellular uptake, as the ratio of liposomes or liposomal aggregates that fall above the capacity of cell membrane to "wrap" them will be minimized.

Synthesis of Novel Thiophene, Thiazole and Coumarin Derivatives Based on Benzimidazole Nucleus and Their Cytotoxicity and Toxicity Evaluations.

The reactivity of compounds 2-(1-(2-chloroacetyl)-1H-benzo[d]imidazol-2-yl)acetonitrile 2 and 3-(1-(2-chloroacetyl)-1H-benzo[d]imidazol-2-yl)-2H-chromen-2-one 8 towards different chemical reagents were studied and a series of novel benzimidazole derivatives were obtained (2-6a-d and 8-12a-d). Moreover, in vitro growth inhibitory effect of the newly synthesized compounds were evaluated in term of [IC50 µM] against the six cancer cell lines, human lung carcinoma (A549), lung cancer (H460), human colorectal (HT29), gasteric cancer cell (MKN-45), glioma cell line (U87MG) and cellosaurus cell line (SMMC-7721) where foretinib was used as standard reference. The results showed that compounds 2 (only for A549 cell line), 3a, 4, 6c, 6d, 8, 9a, 9e and 9f were the most active compounds towards the six cancer cell lines. On the other hand, the toxicity of these most potent compounds against shrimp larvae indicated that compounds 3a, 4, 6d, 9e and 9f were non toxic while compounds 6c and 8 were very toxic and compounds 2 and 9a were harmful against the tested organisms.

The effect of parental education on child health: Quasi-experimental evidence from a reduction in the length of primary schooling in Egypt.

This paper examines the impact of parental education on child health using a reduction in the length of primary schooling in Egypt. We use a fuzzy regression discontinuity design to compare the health outcomes of children whose parents were exposed to different schooling requirements because they were born either side of a threshold date. Using data from the Demographic and Health Survey (1992-2014), we find no effect of maternal education on child mortality or nutritional status. There is some evidence, although not entirely robust, that father's education reduces the likelihood of child stunting. We find, however, that father's education has no impact on child mortality or other measures of nutritional status. We provide suggestive evidence that, given the low levels of parental education in Egypt accompanied with the inferior quality of primary schooling, education has little effect on intermediate outcomes-literacy and utilization of antenatal care-that may improve the health of offspring.