Knowledge, attitude, and practice of Egyptian medical students towards healthcare workers' recommended vaccines: a nationwide cross-sectional survey.

BACKGROUND: Vaccination of healthcare workers (HCWs) is pivotal in decreasing the incidence of contagious infections in hospital settings. In this study, we assessed the knowledge, attitude, and practice regarding HCWs' recommended vaccines among medical students and interns in Egypt. METHODS: A multicenter, cross-sectional study was conducted using a structured, pilot-tested, and self-administered questionnaire among Egyptian medical students and interns. We invited 1332 participants to our survey using a systematic random sampling that included participants across nine medical schools in Egypt during the 2021-2022 academic year. RESULTS: Out of 1332 participants, 1141 completed our questionnaire with a response rate of 85.7%. Overall, 43% of the participants had intermediate knowledge (knew 2-3 HCWs' recommended vaccines). Furthermore, 36.7% had received a booster dose of at least one of the HCWs' recommended vaccines over the last 10 years, with only 6.1% having received all recommended vaccines. Hepatitis B vaccine was the most widely known (71%) and received (66.7%). Interns were more likely to know, receive, and recommend HCWs' recommended vaccines. The majority (> 90%) agreed that vaccination is beneficial and safe, with a median score of eight (interquartile range [IQR: Q25-Q75]: 7-9) out of ten for vaccine efficacy and eight (IQR: 7-8) for safety. However, the median score for hesitancy was five (IQR: 2-7). The most common influential and limiting factors for vaccination were scientific facts (60.1%) and fear of vaccine side effects (44.9%). CONCLUSION: Although medical students in Egypt have good knowledge of and attitudes towards vaccination, there is a gap in their practices. Interventions are needed to improve vaccination uptake among medical students in Egypt.

Trivalent chromium versus baricitinib for rheumatoid arthritis treatment: first phase 2/3 randomized controlled trial, is trivalent chromium the upcoming immune-modulator?

BACKGROUND: Rheumatoid arthritis (RA) is a debilitating disease mainly treated by DMARDs. Baricitinib is one of the emerging DMARDs with strong anti-rheumatic effects but has serious side effects. Trivalent chromium (Cr III) is a natural element with anti-inflammatory properties. Trivalent chromium (Cr III) is introduced for the first time to study its effect and safety in treatment of RA patients and compared to those of baricitinib. METHODS: This is a phase 2/3 randomized controlled trial where RA patients were divided in a ratio of 2:1 according to the newly introduced medication either Cr (III) (group A) or baricitinib (group B). Patients attended three visits on day 0, after 3 weeks and 12 weeks, disease activity was scored. Hands ultrasound was done and reassessed. Side effects were monitored throughout the study. RESULTS: DAS28-CRP improved by 26.9% and 11.8% on third visit for Cr III and baricitinib, respectively (p = 0.001). DAS28-ESR improved by 25.6% and 7.74% on third visit for Cr III and baricitinib, respectively (p = < 0.001). ACR 50 was 18.8% for Cr III and 5.7% for baricitinib on second visit. ACR 70 was 25% for Cr III and 0% for baricitinib on third visit (P = < 0.001). Ultrasound GLOESS, SH, PDUS, joints effusions improved by 38.9%, 38.4%, 56.7% and 74.8% for Cr III, while by 10.5%, 3.75%, 59.6% and worsening of joints effusions happened with baricitinib on third visit. p = 0.022 and 0.002 between groups for GLOESS and SH improvement, respectively. CONCLUSIONS: Cr III has shown very promising fast clinical and sonographic results in treating RA patients which were surprisingly superior to baricitinib in most aspects. Furthermore, Cr III is potentially safe with evidently fewer side effects than baricitinib and other DMARDs, however, long-term safety is still not established. (IRB No.: 00012098- FWA No.: 00018699, Serial number: 040457) ClinicalTrials.gov ID: NCT05545020.

Could Osteopontin be a useful biomarker in the diagnosis and severity assessment of osteoarthritis? A systematic review and meta-analysis of recent evidence.

PURPOSE: Osteoarthritis (OA) patients demonstrated higher Osteopontin (OPN) plasma, serum, and synovial fluid concentrations than healthy individuals. In the present study, we aimed to investigate whether OPN could be used as a diagnostic or prognostic marker for OA symptom/disease severity. METHODS: Using Web of Science, PubMed, Scopus, and Embase, we conducted a systematic review and meta-analysis of studies that measured OPN levels in OA patients' plasma, serum, or synovial fluid. After setting the eligibility criteria, data extraction, and quality assessment of the identified studies, we performed statistical analysis using Revman 5.4 and Open Meta analyst. RESULTS: OPN has been found to be associated with advanced knee joint damage in OA patients. In addition, higher expression of OPN is thought to be associated with disease progression. Nevertheless, further studies should examine the role of other markers of chronic bone damage, such as leptin and sclerostin. This systematic review and meta-analysis included 14 studies with a total of 776 cases and 530 controls. OPN was significantly elevated in osteoarthritis patients' plasma, serum, and synovial fluid samples, with significant heterogeneity between studies. CONCLUSION: We recommend that OPN plasma and synovial fluid levels be measured as a diagnostic and prognostic marker to determine the severity of OA symptoms.

Recent Advances in Floating Photovoltaic Systems.

In recent years, floating photovoltaic (FPV) technologies have gained more importance as a key source of clean energy, particularly in the context of providing sustainable energy to buildings. The rise of land scarcity and the need to reduce carbon emissions have made FPV systems a cost-effective solution for generating electricity. This review article aims to explore the rapidly growing trend of floating PV systems, which can be a practical solution for regions with limited land areas. The article discusses the structure of the PV modules used in FPV plants and key factors that affect site suitability choice. Moreover, the article presents various techniques for cooling and cleaning FPV to keep optimal performance and discusses feasible trends and prospects for the technology. Finally, this paper proposes the potential integration of FPV systems with other technologies to enhance energy generation efficiency and discusses other research aimed at the advancement of the technology. By examining the various features of FPV systems, this review article contributes to understanding the advantages and challenges associated with using this sustainable energy technology in different regional contexts.

Echinochrome Ameliorates Physiological, Immunological, and Histopathological Alterations Induced by Ovalbumin in Asthmatic Mice by Modulating the Keap1/Nrf2 Signaling Pathway.

Asthma is a persistent inflammatory disease of the bronchi characterized by oxidative stress, airway remodeling, and inflammation. Echinochrome (Ech) is a dark-red pigment with antioxidant and anti-inflammatory activities. In this research, we aimed to investigate the effects of Ech against asthma-induced inflammation, oxidative stress, and histopathological alterations in the spleen, liver, and kidney in mice. Mice were divided into four groups (n = 8 for each): control, asthmatic, and asthmatic mice treated intraperitoneally with 0.1 and 1 mg/kg of Ech. In vitro, findings confirmed the antioxidant and anti-inflammatory activities of Ech. Ech showed antiasthmatic effects by lowering the serum levels of immunoglobulin E (IgE), interleukin 4 (IL-4), and interleukin 1ß (IL-1ß). It attenuated oxidative stress by lowering malondialdehyde (MDA) and nitric oxide (NO) contents and increasing reduced glutathione (GSH), superoxide dismutase (SOD), glutathione-s-transferase (GST), and catalase (CAT) in the liver, spleen, and kidney. Moreover, it protected asthma-induced kidney and liver functions by increasing total protein and albumin and decreasing aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, urea, and uric acid levels. Additionally, it ameliorated histopathological abnormalities in the lung, liver, spleen, and kidney. Additionally, molecular docking studies were used to examine the interactions between Ech and Kelch-like ECH-associated protein 1 (Keap1). PCR and Western blot analyses confirmed the association of Ech with Keap1 and, consequently, the regulatory role of Ech in the Keap1-(nuclear factor erythroid 2-related factor 2) Nrf2 signaling pathway in the liver, spleen, and kidney. According to our findings, Ech prevented asthma and its complications in the spleen, liver, and kidney. Inhibition of inflammation and oxidative stress are two of echinochrome's therapeutic actions in managing asthma by modulating the Keap1/Nrf2 signaling pathway.

Novel promising benzoxazole/benzothiazole-derived immunomodulatory agents: Design, synthesis, anticancer evaluation, and in silico ADMET analysis.

Eleven novel benzoxazole/benzothiazole-based thalidomide analogs were designed and synthesized to obtain new effective antitumor immunomodulatory agents. The synthesized compounds were evaluated for their cytotoxic activities against HepG-2, HCT-116, PC3, and MCF-7 cells. Generally, the open analogs with semicarbazide and thiosemicarbazide moieties (10, 13a-c, 14, and 17a,b) exhibited higher cytotoxic activities than derivatives with closed glutarimide moiety (8a-d). In particular, compound 13a (IC50 = 6.14, 5.79, 10.26, and 4.71 µM against HepG-2, HCT-116, PC3, and MCF-7, respectively) and 14 (IC50 = 7.93, 8.23, 12.37, and 5.43 µM, respectively) exhibited the highest anticancer activities against the four tested cell lines. The most active compounds 13a and 14 were further evaluated for their in vitro immunomodulatory activities on tumor necrosis factor-alpha (TNF-α), caspase-8 (CASP8), vascular endothelial growth factor (VEGF), and nuclear factor kappa-B p65 (NF-κB p65) in HCT-116 cells. Compounds 13a and 14 showed a remarkable and significant reduction in TNF-α. Furthermore, they showed significant elevation in CASP8 levels. Also, they significantly inhibited VEGF. In addition, compound 13a showed significant decreases in the level of NF-κB p65 while compound 14 demonstrated an insignificant decrease with respect to thalidomide. Moreover, our derivatives exhibited good in silico absorption, distribution, metabolism, elimination, toxicity (ADMET) profiles.

The influence of intra-aortic balloon counter pulsation on central venous blood oxygen saturation.

OBJECTIVES: We aim at identifying the changes in venous blood saturation values that associates intra-aortic balloon pump (IABP) in cardiac surgery patients with reduced left ventricular function (LVF). METHODS: A retrospective observational study was conducted in a cardiothoracic intensive care unit (CTICU) in a tertiary cardiac center over 5 years in Qatar. A total of 114 patients with at least moderate impairment of LVF with ejection fraction (EF) less than 40% were enrolled. According to the association of IABP, patients were segregated into two groups with and without IABP (groups 1, 40 patients and group 2, 74 patients). Sequential arterial and venous blood gases were analyzed. The primary outcome was to analyze the changes in the central venous saturation (ScvO2) in both groups and the secondary outcome was to analyze whether these changes affect the overall outcome in terms of intensive care unit (ICU) length of stay. RESULTS: There was no significant difference between both groups with regard to age, preoperative EF, hemoglobin, and arterial oxygen saturation (SaO2) in blood gases. Patients with IABP have a higher cScvO2 when compared to the other group (71.5 ± 12.5 vs 63.5 ± 9.3, 68.3 ± 12.6 vs 60.1 ± 9.5, 62.7 ± 10.8 vs 55.63 ± 8.1, and 60.6 ± 7.6 vs 54.9 ± 8.1; p = 0.04, 0.05, 0.03, and 0.5, respectively). However, generalized estimating equations (GEE) analysis showed that compared with the participants showing that there is a decreasing trend in mean levels within the groups during follow-ups, overall difference between both groups' mean levels was not statistically significant. CONCLUSIONS: In this study, we observed that after cardiac surgeries, patients with IABP had non-significant higher ScvO2 when compared with a corresponding group with moderate impairment of LVF. Further prospective studies are required to validate these findings.

Design, Synthesis, and Biological Evaluation of New Potential Unusual Modified Anticancer Immunomodulators for Possible Non-Teratogenic Quinazoline-Based Thalidomide Analogs.

Sixteen new thalidomide analogs were synthesized. The new candidates showed potent in vitro antiproliferative activities against three human cancer cell lines, namely hepatocellular carcinoma (HepG-2), prostate cancer (PC3), and breast cancer (MCF-7). It was found that compounds XII, XIIIa, XIIIb, XIIIc, XIIId, XIVa, XIVb, and XIVc showed IC50 values ranging from 2.03 to 13.39 µg/mL, exhibiting higher activities than thalidomide against all tested cancer cell lines. Compound XIIIa was the most potent candidate, with an IC50 of 2.03 ± 0.11, 2.51 ± 0.2, and 0.82 ± 0.02 µg/mL compared to 11.26 ± 0.54, 14.58 ± 0.57, and 16.87 ± 0.7 µg/mL for thalidomide against HepG-2, PC3, and MCF-7 cells, respectively. Furthermore, compound XIVc reduced the expression of NFκB P65 levels in HepG-2 cells from 278.1 pg/mL to 63.1 pg/mL compared to 110.5 pg/mL for thalidomide. Moreover, compound XIVc induced an eightfold increase in caspase-8 levels with a simultaneous decrease in TNF-α and VEGF levels in HepG-2 cells. Additionally, compound XIVc induced apoptosis and cell cycle arrest. Our results reveal that the new candidates are potential anticancer candidates, particularly XIIIa and XIVc. Consequently, they should be considered for further evaluation for the development of new anticancer drugs.

Placenta percreta in primigravida with unscarred uterus complicated by uterine rupture and sudden maternal and fetal death: an autopsy case report.

Placenta percreta is a rare, aggressive, and severe form of the placenta accreta spectrum. One of its most devastating effects is the sudden rupture of uterus. Uterine scarring is the leading risk factor for uterine rupture, although it can also happen, but rarely, in an unscarred uterus showing more severe repercussions. The present study reported a case of an Egyptian primigravida female, aged 29 years old, at 32 weeks of gestation who died suddenly due to uterine rupture complicating placenta percreta, the diagnosis of which was first settled during autopsy. There was no history of abdominal trauma. No medical history of significance was present. Autopsy denoted an intrauterine fetal death of 32 weeks gestational age. The fundus of the uterus had a laceration (rupture) of the uterine wall including the serosa and myometrium. The placenta has extensively infiltrated the fundus uterine wall and penetrated the myometrium and serosa. Histopathological examination of the ruptured site on the uterus confirms total invasion of the uterine wall by chorionic villi with the presence of hemorrhage and fibrin indicating placenta percreta. Uterine rupture due to placenta percreta may go unnoticed, especially when no associated high-risk factors exist. The current case depicts that placenta percreta is a rare but critical complication of pregnancy that may exist at any stage of pregnancy without any associated high-risk factors with unusual symptoms and leads to uterine rupture and sudden death.

Cleft posterior mitral valve leaflet: The added value of 3-dimensional echocardiography.

A 65-year-old female patient diagnosed with degenerative aortic valve disease and severe regurgitation on transthoracic echocardiography (TTE) also had severe mitral regurgitation (MR), but the exact mechanism of MR could not be determined. Transesophageal echocardiography (TEE) showed limited leaflet coaptation and a severe central MR jet. Further three-dimensional (3D) imaging revealed an indentation in the middle of P2 scallop almost reaching the annulus. This was consistent with the diagnosis of cleft posterior mitral valve leaflet. Unlike cleft anterior leaflet which can be clear on TTE short-axis images, cleft posterior leaflet may only be visible using 3D TEE. The identification of cleft posterior leaflet is essential in guiding surgical valve repair.

Synthesis, biological evaluation, and molecular docking of new series of antitumor and apoptosis inducers designed as VEGFR-2 inhibitors.

Based on quinazoline, quinoxaline, and nitrobenzene scaffolds and on pharmacophoric features of VEGFR-2 inhibitors, 17 novel compounds were designed and synthesised. VEGFR-2 IC50 values ranged from 60.00 to 123.85 nM for the new derivatives compared to 54.00 nM for sorafenib. Compounds 15a, 15b, and 15d showed IC50 from 17.39 to 47.10 µM against human cancer cell lines; hepatocellular carcinoma (HepG2), prostate cancer (PC3), and breast cancer (MCF-7). Meanwhile, the first in terms of VEGFR-2 inhibition was compound 15d which came second with regard to antitumor assay with IC50 = 24.10, 40.90, and 33.40 µM against aforementioned cell lines, respectively. Furthermore, Compound 15d increased apoptosis rate of HepG2 from 1.20 to 12.46% as it significantly increased levels of Caspase-3, BAX, and P53 from 49.6274, 40.62, and 42.84 to 561.427, 395.04, and 415.027 pg/mL, respectively. Moreover, 15d showed IC50 of 253 and 381 nM against HER2 and FGFR, respectively.

Therapeutic Potency of Ovothiol A on Ethanol-Induced Gastric Ulcers in Wistar Rats.

Peptic ulcer is a widespread disease, with a lifetime frequency of 5−10% among the general population and an annual incidence of 0.1−0.3%. Ovothiol A is naturally produced from sea urchin eggs with special antioxidant activity. Gastric ulcers were induced in rats by a single ethanol dose (5 mL/kg). The rats were divided into control, ulcer, and ulcer with 250 and 500 mg/kg ovothiol A doses. Molecular docking studies were used to examine the interactions between ovothiol A and the H+/K+ ATPase active site residues. Ovothiol A led to a significant decline (p < 0.05) in gastric juice volume, ulcer index, MDA, IL-6, and cytochrome c, while levels of gastric juice pH, GSH, CAT, GST, SOD, and NO increased. Histopathological investigation of stomach sections revealed architecture preservation of the gastric mucosa after ovothiol A administration. The anti-ulcerogenic activity of ovothiol A includes scavenging free radicals, inhibition of inflammation, regulation of apoptosis, and stabilization of fibroblast growth factors to promote gastric ulcers healing.

Interplay between personality traits and learning strategies: the missing link.

Students with varying personality traits are likely to employ diverse learning and study strategies. However, this relationship has never been explored in the medical education context. This study's aim was to explore the relationship between learning strategies and personality traits among medical students. This study was a cross-sectional study, and a quantitative approach was employed using two self-administered questionnaires: one to assess the personality traits from the Five-Factor Model (Conscientiousness, Neuroticism, Extraversion, Openness, and Agreeableness), and the other to assess 10 learning strategies (Anxiety, Attitude, Concentration, Information Processing, Motivation, Selecting Main Ideas, Self-Testing, Test Strategies, Time Management, and Using Academic Resources). A stratified random sampling technique was used to recruit medical students at Alfaisal University in the preclinical and clinical years (N = 309). Pearson correlation coefficient was used to measure the relationship between variables, and linear regression was used to evaluate how personality traits predicted learning strategy selection. Personality traits predicted the selection of learning strategies, especially Conscientiousness and Neuroticism. Conscientiousness showed a positive correlation with seven learning strategies and was the most important predictor of learning strategies students employ. Neuroticism correlations and predictions were negative. The other three traits showed weaker correlations. These correlations were between Extraversion and Using Academic Resources (r = 0.27), Information Processing (r = 0.23), and Attitude (r = 0.19); Openness and Information Processing (r = 0.29); and Agreeableness and Attitude (r = 0.29). All personality domains influence at least one learning strategy, especially Conscientiousness and Neuroticism. This study helps build a foundation for individualized coaching and mentorship in medical education.NEW & NOTEWORTHY This study aspires to build a foundation for individualized coaching and mentorship in medical education through utilizing personality traits to empower academic success. We demonstrate that all personality domains influence students' selection of at least one learning strategy, especially Conscientiousness and Neuroticism.

Tool Condition Monitoring for High-Performance Machining Systems-A Review.

In the era of the "Industry 4.0" revolution, self-adjusting and unmanned machining systems have gained considerable interest in high-value manufacturing industries to cope with the growing demand for high productivity, standardized part quality, and reduced cost. Tool condition monitoring (TCM) systems pave the way for automated machining through monitoring the state of the cutting tool, including the occurrences of wear, cracks, chipping, and breakage, with the aim of improving the efficiency and economics of the machining process. This article reviews the state-of-the-art TCM system components, namely, means of sensing, data acquisition, signal conditioning and processing, and monitoring models, found in the recent open literature. Special attention is given to analyzing the advantages and limitations of current practices in developing wireless tool-embedded sensor nodes, which enable seamless implementation and Industrial Internet of Things (IIOT) readiness of TCM systems. Additionally, a comprehensive review of the selection of dimensionality reduction techniques is provided due to the lack of clear recommendations and shortcomings of various techniques developed in the literature. Recent attempts for TCM systems' generalization and enhancement are discussed, along with recommendations for possible future research avenues to improve TCM systems accuracy, reliability, functionality, and integration.

Design, Synthesis, Molecular Modeling and Anti-Hyperglycemic Evaluation of Quinazoline-Sulfonylurea Hybrids as Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) and Sulfonylurea Receptor (SUR) Agonists.

New quinazoline-sulfonylurea hybrids were prepared and examined for their in vivo anti-hyperglycemic activities in STZ-induced hyperglycemic rats using glibenclamide as a reference drug. Compounds VI-6-a, V, IV-4, VI-4-c, IV-6, VI-2-a, IV-1, and IV-2 were more potent than the reference glibenclamide. They induced significant reduction in the blood glucose levels of diabetic rats: 78.2, 73.9, 71.4, 67.3, 62, 60.7, 58.4, and 55.9%, respectively, while the reference glibenclamide had 55.4%. Compounds IV-1, VI-2-a, IV-2, V, and IV-6 showed more prolonged antidiabetic activity than glibenclamide. Moreover, molecular docking and pharmacokinetic studies were performed to examine binding modes of the prepared compounds against peroxisome proliferator-activated receptor gamma (PPARγ). The highest active compounds exhibited good binding affinity with high free energy of binding against PPARγ. In silico absorption, distribution, metabolism, elimination and toxicity (ADMET) studies were performed to investigate pharmacokinetics and safety of the synthesized compounds. They showed considerable human intestinal absorption with low toxicity profile.

Discovery of New VEGFR-2 Inhibitors: Design, Synthesis, Anti-Proliferative Evaluation, Docking, and MD Simulation Studies.

Four new nicotinamide-based derivatives were designed as antiangiogenic VEGFR-2 inhibitors. The congeners were synthesized possessing the pharmacophoric essential features to bind correctly with the VEGFR-2 active pocket. All members were evaluated for their cytotoxic and VEGFR-2 inhibitory potentialities. Compound 6 was the most potent showingIC50 values of 9.3 ± 0.02 and 7.8 ± 0.025 µM against HCT-116 and HepG-2 cells, respectively, and IC50 of 60.83 nM regarding VEGFR-2 enzyme inhibition. Compound 6 arrested the growth of HCT-116 cells at the pre-G1 and G2-M phases. Further, it induced both early and late apoptosis. Additionally, compound 6 caused a significant decrease in TNF-α and IL6 by 66.42% and 57.34%, respectively. The considered compounds had similar docking performances to that of sorafenib against the VEGFR-2 (PDB ID: 2OH4). The correct binding of compound 6 with VEGFR-2 was validated using MD simulations, and MM-GPSA calculations.

Echinochrome Exhibits Antitumor Activity against Ehrlich Ascites Carcinoma in Swiss Albino Mice.

Background: Echinochrome (Ech) is a common pigment present in sea urchins, which has antioxidant, antimicrobial, antialgal, hypolipidemic and hypoglycemic activities.Purpose: The present investigation assessed the anticancer and antioxidant activities of Ech against the Ehrlich ascites carcinoma tumor model in mice.Methods: Forty female mice were divided into four groups (n = 10). All groups except the group I received EAC cells (5 × 106 cells/mouse i.p.). Group I, served as saline control (5 ml/kg 0.9% NaCl w/v p.o); group II served as EAC; groups III and IV received Ech (1 mg/kg body weight i.p.), and reference drug (5-Fu, 20 mg/kg body weight i.p.) respectively. Tumor markers, hematological parameters, liver functions, kidney functions and oxidative stress markers were analyzed in the present study.Results: A significant decrease (p < 0.05) were detected in the tumor volume, tumor cell counts, tumor cells viability, WBC count, MDA, urea, uric acid, AST, ALT, and ALP levels in Ech-treated mice. Furthermore, Ech-treated mice showed significant increases in RBCs count, Hb, Pt, GSH, CAT, and GST levels.Conclusion: The study results revealed that echinochrome suppresses tumor growth, decreases lipid peroxidation and improves the antioxidant status.

Design, synthesis and molecular modeling of new quinazolin-4(3H)-one based VEGFR-2 kinase inhibitors for potential anticancer evaluation.

Globally cancer is the second leading cause of death. So that this work is an attempt to develop new effective anti-cancer agents. In line with pharmacophoric features of VEGFR-2 kinase inhibitors, new nineteen quinazolin-4-one derivatives were designed, synthesized and biologically evaluated for their potential anticancer activity. All target compounds were evaluated in vitro for VEGFR-2 tyrosine kinase inhibition. Then, nine compounds of best results were further investigated by in vitro assay against three human cancer cell lines, namely HepG2, PC3 and MCF. N'-{2-](3-Ethyl-6-nitro-4-oxo-3,4-dihydroquinazoline-2-yl)thio[acetyl}benzohydrazide (36) was found to be the most potent candidate as it showed IC50 = 4.6 ± 0.06 µM against VEGFR-2 kinase. It also exhibited IC50 = 17.23 ± 1.5, 26.10 ± 2.2 and 30.85 ± 2.3 µg/mL against HepG2, PC3 and MCF, respectively. At the same time it showed IC50 = 145.93 ± 1.1 µg/mL against the normal human lung fibroblasts cell line (WI-38), indicating good selectivity index. Further investigation into HepG2 cell cycle showed the ability of compound 36 to induce apoptosis and arrest cell growth at G2/M phase. Moreover, docking studies demonstrated the ability of compound 36 to bind VEGFR-2 in a correct manner making three essential hydrogen bonds with the key residues Glu885, Asp1046 and Cys919. In sum, this work suggests that compound 36 can serve as a lead for development of effective anticancer agents targeting VEGFR-2.

Design, synthesis, and biological evaluation of new challenging thalidomide analogs as potential anticancer immunomodulatory agents.

Thalidomide and its analogs are immunomodulatory drugs that inhibit the production of certain inflammatory mediators associated with cancer. In the present work, a new series of thalidomide analogs was designed and synthesized to obtain new effective antitumor immunomodulatory agents. The synthesized compounds were evaluated for their cytotoxic activities against a panel of four cancer cell lines (HepG-2, HCT-116, PC3 and MCF-7). Compounds 33h, 33i, 42f and 42h showed strong potencies against all tested cell lines with IC50 values ranging from 14.63 to 49.90 µM comparable to that of thalidomide (IC50 values ranging from 32.12 to 76.91 µM). The most active compounds were further evaluated for their in vitro immunomodulatory activities via estimation of human tumor necrosis factor alpha (TNF-α), human caspase-8 (CASP8), human vascular endothelial growth factor (VEGF), and nuclear factor kappa-B P65 (NF-κB P65) in HCT-116 cells. Thalidomide was used as a positive control. Compounds 33h and 42f showed a significant reduction in TNF-α. Furthermore, compounds 33i and 42f exhibited significant elevation in CASP8 levels. Compounds 33i and 42f inhibited VEGF. In addition, compound 42f showed significant decrease in levels of NF-κB p65. Moreover, apoptosis and cell cycle tests of the most active compound 42f, were performed. The results indicated that compound 42f significantly induce apoptosis in HCT-116 cells and arrest cell cycle at the G2/M phase.

Freshwater Clam as a Potential Bioindicator for Silver/Saponin Nanocomposites Toxicity.

Despite the progress in using silver nano products in many fields, including medicine, food, and industry, their effects on the environment need more attention. Therefore, the current study aimed to assess the effect of silver/saponin nanocomposites (Ag/S NCs) for the first time on the aquatic environment by using freshwater clam, Caelatura aegyptiaca, as a fundamental bioindicator in the freshwater system. Following the preparation and characterization of Ag/S NCs by using atomic absorption spectrophotometer, UV-Vis spectrophotometer, X-ray diffraction, transmission electron microscopy, and acute toxicity study, we exposed the clam to three different doses of Ag/S NCs (12.5, 25 and 50 mg L-1) for consecutive 6 days. All Ag/S NCs concentrations caused a significant increase in malondialdehyde and nitric oxide while induced a notable decrease in glutathione and catalase levels in all studied organs. Moreover, the histological alternations were observed in gills, labial palp, and foot tissues, particularly at dose 50 mg L-1. From the results of our work, we concluded that toxicity of Ag/S NCs on freshwater clam leads to an oxidative stress response as well as histopathological changes. Besides, we assumed that Coelatura aegyptiaca could be used as a sensitive bioindicator for monitoring water pollution caused by different nanoparticles. Therefore, we do recommend performing further studies by using fresh clam to provide a better assessment for our aquatic environment to prevent water pollution locally and globally.