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Ruthenium complexes incorporating 2,2':6',2''-terpyridine ligands have emerged as promising candidates due to their versatile biological activities including DNA-binding, anti-inflammatory, antimicrobial, and anticancer properties. In this study, three novel 4'-functionalized bis(terpyridine) ruthenium (II) complexes were synthesized. These complexes feature one ligand as 4-(2,2':6',2''-terpyridine-4'-yl) benzoic acid and the second ligand as either 4'-(2-thienyl)-2,2':6',2''-terpyridine, 4'-(3,4-dimethoxyphenyl)-2,2':6',2''-terpyridine, or 4'-(4-dimethylaminophenyl)-2,2':6',2''-terpyridine. Besides the chemical characterization by 1H and 13C NMR, mass spectrometry, and absorption and emission spectroscopy, the complexes were tested for their biological activity as anti-inflammatory, anticancer, and antimicrobial agents. Moreover, the toxicity of the Ru(II) complexes was assessed and benchmarked against diclofenac potassium and ibuprofen using a haemolysis assay. Biological evaluations demonstrate that these ruthenium complexes exhibit promising therapeutic potential with reduced haemolytic activity compared to standard drugs. They demonstrate substantial anti-inflammatory effects through inhibition of albumin denaturation along with moderate cytotoxicity against cancer cell lines and broad-spectrum antimicrobial activity. These findings highlight the multifaceted biomedical applications of 4'-functionalized bis(terpyridine) ruthenium (II) complexes, suggesting their potential for further development as effective and safe therapeutic agents., (© 2024 Wiley‐VCH GmbH.)

Background: Thoracoscopic sympathetic chain interruption is a definitive and effective therapy for severe primary palmar hyperhidrosis (PPH). Well-known methods include sympathectomy, sympathotomy, and clipping, but the occurrence of compensatory sweating offsets these methods. This study aims to report our experience with thoracoscopic sympathetic chain interruption in a large group of patients of age <18 years with PPH, focusing on surgical outcomes, complication rates, and patient satisfaction. Patients and Methods: This retrospective study included patients who underwent thoracoscopic sympathectomy, sympathotomy, or clipping for severe PPH between April 2008 and March 2023 at the Pediatric Surgery Department, Al-Azhar University Hospitals. Demographic and clinical data, operative steps, postoperative outcomes, complications, and patient satisfaction were reviewed from the patients' medical records. Results: During the 15-year study period, 420 children with PPH underwent bilateral thoracoscopic sympathetic chain interruption by either sympathectomy, sympathotomy, or clipping, with a sex ratio of 60% being females. The mean ages were 12 ± 3.48, 13 ± 2.45, and 13 ± 2.45 years, respectively. Sympathectomy was performed in 190 patients (45.2%), sympathotomy in 170 patients (40.5%), and clipping in 60 patients (14.3%). All patients had completed follow-up, with mean periods of ∼43 ± 5 months, 45 ± 3 months, and 42 ± 6 months, respectively. Complete palmar dryness was achieved in 405 patients (overall 96.4%) (97.8% after sympathectomy, 97.05% after sympathotomy, and 90% after clipping), whereas 2.1%, 2.9%, and 10% of patients experienced symptom recurrence, respectively, denoting significant statistical differences. Overall, 94 patients (22.4%) experienced compensatory sweating. Eventually, 409 patients (97.4%) were satisfied with the outcome, whereas 11 patients (2.6%) reported dissatisfaction, yet no significant differences found. Conclusion: The presented three modalities of thoracoscopic sympathetic chain interruption for PPH in children and adolescents are safe and effective, with overall very high postoperative satisfaction, despite a relatively high rate of compensatory sweating in sympathectomy group. Other major complications in this age population were scanty.

Quorum sensing (QS) is a bacterial cell-to-cell communication mechanism that plays an essential role in bacterial pathogenesis. QS governs bacterial behavior and controls biofilm formation, which in turn contributes to antibiotic resistance. Therefore, identifying and synthesizing novel compounds to overcome QS and inhibit biofilm formation are essential. Coumarins are important plant-derived natural products with wide-ranging bioactivities and extensive applications, including antibacterial, antifungal, anticoagulant, antioxidant, anticancer, and anti-inflammatory properties. Additionally, coumarins are capable of QS rewiring and biofilm formation inhibition, leading to higher susceptibility to antimicrobial agents and less antibiotic resistance. Therefore, in this review, we aim to provide an overview of QS and biofilm formation. This review also discusses the role of natural and synthesized coumarins in controlling QS, inhibiting biofilm formation, and inducing synergy in antibiotic-coumarin combinations. Hence, this review emphasizes the potential of coumarin compounds to act as antibacterial agents and demonstrates their ability to alleviate antibiotic resistance.

Inflammation serves as an intricate defense mechanism for tissue repair. However, overactivation of TLR4-mediated inflammation by lipopolysaccharide (LPS) can lead to detrimental outcomes such as sepsis, acute lung injury, and chronic inflammation, often associated with cancer and autoimmune diseases. This study delves into the anti-inflammatory properties of "Aspergillus unguis isolate SP51-EGY" on LPS-stimulated RAW 264.7 macrophages. Through real-time qPCR, we assessed the expression levels of pivotal inflammatory genes, including iNOS, COX-2, TNF-α, and IL-6. Remarkably, our fungal extracts significantly diminished NO production and showed noteworthy reductions in the mRNA expression levels of the aforementioned genes. Furthermore, while Nrf2 is typically associated with modulating inflammatory responses, our findings indicate that the anti-inflammatory effects of our extracts are not Nrf2-dependent. Moreover, the chemical diversity of the potent extract (B Sh F) was elucidated using Q-TOF LC-HRMS, identifying 54 compounds, some of which played vital roles in suppressing inflammation. Most notably, compounds like granisetron, fenofibrate, and umbelliprenin were found to downregulate TNF-α, IL-1β, and IL-6 through the NF-κB signaling pathway. In conclusion, "Aspergillus unguis isolate SP51-EGY", isolated from the Red Sea, Egypt, has been unveiled as a promising TLR4 inhibitor with significant anti-inflammatory potentials, presenting novel insights for their potential therapeutic use in inflammation., (© 2024. The Author(s).)

Date syrup is a very rich nutritional and medicinal product. It can be used alone or mixed with other food products. Now, it is widely used as a natural sweetener instead of harmful sugar in several food products. However, date syrup contains higher levels of 5-hydroxyl methyl furfural (5-HMF) (heat-induced toxicant). HMF is normally formed during processing via Maillard reaction as a result of heating. Thus, the present study aims at investigating the effect of gamma irradiation in reducing HMF content and improving the quality properties of date syrup. Date syrup samples (commercial) were irradiated at different doses (15, 20 and 25 kGy). HMF content was determined using the HPLC method. The obtained results showed that γ-irradiation reduced the toxic compound (HMF) in date syrup, where irradiation dose (20 kGy) recorded the lowest HMF level (1956.40 mg/kg) with a reduction percentage of 46.96% compared to the non-irradiated sample. While the non-irradiated sample revealed the highest level of HMF and bacterial growth. Therefore, γ-irradiation is considered an effective treatment that reduces HMF using a particular dose (20 kGy) and prevents microbial growth (20-25 KGy). Furthermore, it may increase the nutritional value by increasing minerals' bioavailability (15 kGy)., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

We developed and synthesized tetrahydropyrimidine derivatives as possible cytotoxic agents to inhibit EGFR and VEGFR-2 in the present study. Our study completely assesses the cytotoxic efficiency of pyrimidine-based derivatives 4-15 against various cancer cell lines, revealing derivatives 12 and 15 for their remarkable activity with GI 50 values of 37 and 35 nM, respectively, when compared to the reference erlotinib (33 nM). In vitro enzyme assays showed that target compounds, particularly 12 , 14 , and 15 , effectively inhibited EGFR and VEGFR-2. In vitro enzyme testing revealed that compound 15 was the most promising, with IC 50 values of 84 and 3.50 nM for EGFR and VEGFR-2, respectively. Additionally, an in vitro assessment of the novel targets' apoptotic potential revealed that both pro-apoptotic and antiapoptotic behaviors were promising, indicating that the apoptotic induction pathway is a strongly proposed action method for the newly developed targets. Finally, molecular docking experiments are elaborately discussed to corroborate the exact binding interactions of the most active hybrids 12 and 15 with the EGFR and VEGFR-2 active sites., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Novel coumarin derivatives were synthesised and tested for their cytotoxicity against human cancer cells (PC-3 and MDA-MB-231). Compounds 5 , 4b , and 4a possessed potent cytotoxic activity against PC-3 cells with IC 50 3.56, 8.99, and 10.22 µM, respectively. Compound 4c displayed cytotoxicity more than erlotinib in the MDA-MB-231 cells with IC 50 8.5 µM. Moreover, compound 5 exhibited potent inhibitory activity on EFGR with IC 50 0.1812 µM, as well as PI3Kβ inhibitory activity that was twofold higher than LY294002, suggesting that this compound has a dual EGFR and PI3Kβ inhibiting activity. Docking aligns with the in vitro results and sheds light on the molecular mechanisms underlying dual targeting. Furthermore, compound 5 decreased AKT and m-TOR expression in PC-3 cells, showing that it specifically targets these cells via the EGFR/PI3K/Akt/m-TOR signalling pathway. Simultaneously, compound 5 caused cell cycle arrest at S phase and induced activation of both intrinsic and extrinsic apoptotic pathways.

Benzimidazole scaffolds have potent anticancer activity due to their structure similarity to nucleoside. In addition, benzimidazoles could function as hydrogen donors or acceptors and bind to different drug targets that participate in cancer progression. The literature had many anticancer agents containing benzimidazole cores that gained much interest. Provoked by our endless interest in benzimidazoles as anticancer agents, we summarized the successful trials of the benzimidazole scaffolds in this concern. Moreover, we discuss the substantial opportunities in cancer treatment using benzimidazole-based drugs that may direct medicinal chemists for a compelling future design of more active chemotherapeutic agents with potential clinical applications. The uniqueness of this work lies in the highlighted benzimidazole scaffold hybridization with different molecules and benzimidazole-metal complexes, detailed mechanisms of action, and the IC 50 of the developed compounds determined by different laboratories after 2015., (© 2024. The Author(s).)

A new series of chromone and furochromone-based sulfonamide Schiff's base derivatives 3-12 were synthesized and evaluated for their antimicrobial activity against S. aureus, E. coli, C. albicans, and A. niger using agar diffusion method. Compound 3a demonstrated potent antimicrobial activities with MIC values of 9.76 and 19.53 μg/mL against S. aureus, E. coli and C. albicans, which is 2-fold and 4-fold more potent than neomycin (MIC = 19.53, 39.06 μg/mL respectively). To improve the effectiveness of 3a, it was encapsulated into chitosan nanoparticles (CS-3aNPs). The CS-3aNPs size was 32.01 nm, as observed by transmission electron microscope (TEM) images and the zeta potential value was 14.1 ± 3.07 mV. Encapsulation efficiency (EE) and loading capacity (LC) were 91.5 % and 1.6 %, respectively as indicated by spectral analysis. The CS-3aNPs extremely inhibited bacterial growth utilizing the colony-forming units (CFU). The ability of CS-3aNPs to protect skin wounds was evaluated in vivo. CS-3aNPs showed complete wound re-epithelialization, hyperplasia of the epidermis, well-organized granulation tissue formation, and reduced signs of wound infection, as seen through histological assessment which showed minimal inflammatory cells in comparison with untreated wound. Overall, these findings suggest that CS-3aNPs has a positive impact on protecting skin wounds from infection due to their antimicrobial activity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A novel series of dihydropyrimidine/sulphonamide hybrids 3a-j with anti-inflammatory properties have been developed and tested as dual mPGES-1/5-LOX inhibitors. In vitro assay, results showed that compounds 3c , 3e , 3h , and 3j were the most effective dual inhibitors of mPGES-1 and 5-LOX activities. Compound 3j was the most potent dual inhibitor with IC 50 values of 0.92 µM and 1.98 µM, respectively. In vivo, anti-inflammatory studies demonstrated that compounds 3c , 3e , 3h, and 3e had considerable anti-inflammatory activity, with EI% ranging from 29% to 71%. Compounds 3e and 3j were equivalent to celecoxib after the first hour but exhibited stronger anti-inflammatory effects than celecoxib after the third and fifth hours. Moreover, compounds 3e and 3j significantly reduced the levels of pro-inflammatory cytokines (PGE 2 , TNF-α, and IL-6) with gastrointestinal safety profiles. Molecular docking simulations explored the most potent derivatives' binding affinities and interaction patterns within mPGES-1 and 5-LOX active sites. This study disclosed that compound 3j is a promising anti-inflammatory lead with dual mPGES-1/5-LOX inhibition that deserves further preclinical investigation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Al-Wahaibi, Elshamsy, Ali, Youssif, Bräse, Abdel-Aziz and El-Koussi.)

Highly solid-state fluorescent dyes based on phenothiazine bearing sulfa-drug derivatives were successfully prepared and fully characterized by NMR, mass spectra, and elemental analysis. The prepared phenothiazine dyes bearing sulfadiazine and sulfathiazole 4-(((10-hexyl-10 H-phenothiazin-3-yl)methylene)amino)-N-(pyrimidin-2yl) benzenesulfonamide (PTZ-1) and 4-(((10-hexyl-10 H-phenothiazin-3-yl) methylene) amino)-N-(thiazol-2-yl)benzenesulfonamide (PTZ-2), showed strong emission in polycrystalline form, and significant emission in solution was observed. The quantum yield of the prepared dyes varied and decreased by increasing the solvent polarity, with the maximum recorded value being 0.63 and 0.6 in dioxane. Aggregation-induced emission (AIE) and the effect of the solvent polarity on absorption and emission spectra were investigated. The dyeing application of polyester fabrics using the prepared phenothiazine-based dyes was studied, showing very good affinity to dyed fabrics. The antibacterial affinity against gram-positive and gram-negative bacteria for the dye powder as well as the dyed PET fabric was investigated, with PTZ-2 showing better affinity against bacteria compared to PTZ-1. This multifunctional property highlights the potential uses of PTZ-1 and PTZ-2 for advanced applications in biomedicine and optoelectronics., (© 2024. The Author(s).)

Two new series of quinazoline-chalcone hybrids were designed, synthesized as histone deacetylase (HDAC)/epidermal growth factor receptor (EGFR) dual inhibitors, and screened in vitro against the NCI 60 human cancer cell line panel. The most potent derivative, compound 5e bearing a 3,4,5-trimethoxyphenyl chalcone moiety, showed the most effective growth inhibition value against the panel of NCI 60 human cancer cell lines. Thus, it was selected for further investigation for NCI 5 log doses. Interestingly, this trimethoxy-substituted analog inhibited the proliferation of Roswell Park Memorial Institute (RPMI)-8226 cells by 96%, at 10 µM with IC 50  = 9.09 ± 0.34 µM and selectivity index = 7.19 against normal blood cells. To confirm the selectivity of this compound, it was evaluated against a panel of tyrosine kinase enzymes. Mechanistically, it successfully and selectively inhibited HDAC6, HDAC8, and EGFR with IC 50  = 0.41 ± 0.015, 0.61 ± 0.027, and 0.09 ± 0.004 µM, respectively. Furthermore, the selected derivative induced apoptosis via the mitochondrial apoptotic pathway by raising the Bax/Bcl-2 ratio and activating caspases 3, 7, and 9. Also, the flow cytometry analysis of RPMI-8226 cells showed that the trimethoxy-substituted analog produced cell cycle arrest in the G1 and S phases at 55.82%. Finally, an in silico study was performed to explore the binding interaction of the most active compound within the zinc-containing binding site of HDAC6 and HDAC8., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

Coumarins are heterocycles of great interest in the development of valuable active structures in chemistry and biological domains. The ability of coumarins to inhibit biofilm formation of Gram positive bacterium (Staphylococcus aureus), Gram negative bacterium (Escherichia coli) as well as the methicillin-resistant S. aureus (MRSA) has been previously described. In the present work, new hybrid coumarin-heterocycles have been synthesized via the reaction of coumarin-6-sulfonyl chloride and 6-aminocoumarin with different small heterocycle moieties. The biological efficacy of the new compounds was evaluated towards their ability to inhibit biofilm formation and their anti-inflammatory properties. The antimicrobial activities of the newly synthesized compounds were tested against Gram positive bacterium (S. aureus ATCC 6538), Gram negative bacterium (E. coli ATCC 25922), yeast (Candida albicans ATCC 10231) and the fungus (Aspergillus niger NRRL-A326). Compounds 4d, 4e, 4f, 6a and 9 showed significant MIC and MBC values against S. aureus, E. coli, C. albicans, and methicillin-resistant S. aureus (MRSA) with especial incidence on compound 9 which surpasses all the other compounds giving MIC and MBC values of (4.88 and 9.76 µg/mL for S. aureus), (78.13 and 312.5 µg/mL for E. coli), (9.77 and 78.13 µg/mL for C. albicans), and (39.06 and 76.7 µg/mL for MRSA), respectively. With reference to the antibiofilm activity, compound 9 exhibited potent antibiofilm activity with IC 50 of 60, 133.32, and 19.67 µg/mL against S. aureus, E. coli, and MRSA, (respectively) considering the reference drug (neomycin). Out of all studied compounds, the anti-inflammatory results indicated that compound 4d effectively inhibited nitric oxide production in lipopolysaccharide-(LPS-) stimulated RAW264.7 macrophage cells, giving NO% inhibition of 70% compared to Sulindac (55.2%)., (© 2024. The Author(s).)

The relentless pursuit of novel therapeutic agents against cancer has led to the identification of multiple molecular targets, among which Sirtuin 2 (SIRT2) has garnered significant attention. This study presents an extensive SAR study of our reported trityl scaffold-based SIRT2 inhibitors. This study encompasses a range of different medicinal chemistry approaches to improve the activity of the lead compounds TH-3 and STCY1. The rationally designed and synthesized structures were confirmed using NMR and high-resolution mass spectroscopy before performing SIRT2 inhibition assay, NCI60 cytotoxicity test, and cell cycle analysis. Indeed, our strategies afforded hitherto unreported SIRT2 inhibitors with high activity, particularly 2a, 4a, 7c, and 7f. Remarkably, the presence of a lipophilic para substitution on the phenyl group of a freely rotating or a locked trityl moiety enhanced activity SIRT2 inhibition. Concomitantly, the synthesized compounds showed prominent activity against different cancer lines from the NCI60 assay. Of interest, compound 7c stands out as a potent and highly selective antiproliferative agent against leukemia and colon cancer panels. Furthermore, 7c treatment resulted in cell cycle arrest in MCF-7 cells at G2 phase and did not cause in vitro DNA cleavage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

The eradication of multifactorial diseases, such as cancer, requires the design of drug candidates that attack multiple targets that contribute to the progression and proliferation of such diseases. Here, 1,5-diarylpyrazole derivatives bearing vanillin or sulfanilamide are developed as potential dual inhibitors of epidermal growth factor receptor (EGFR)/c-Jun N-terminal kinase 2 (JNK-2) for possible anticancer activity. These derivatives inhibited the growths of DLD-1, HeLa, K-562, SUIT-2 and HepG2 cancer cell lines, with minimum concentration required to inhibit half of the cellular growth (IC 50 ) values of 2.7-63 μM. The tests confirmed that 5b and 5d were potent JNK-2 inhibitors, with IC 50 of 2.0 and 0.9 μM, respectively, whereas 6 h selectively inhibited EGFR protein kinase (EGFR-PK) (IC 50  = 1.7 μM). Notably, 6c inhibited both kinases, with IC 50 values of 2.7 and 3.0 μM against EGFR-PK and JNK-2, respectively, offering a reference for designing mutual inhibitors of EGFR/JNK-2. The docking studies revealed the ability of the pyrazole ring to bind to the hinge region of the ATP binding site, thereby supporting the experimental inhibitory results. Furthermore, the developed compounds could induce apoptosis and induce cell cycle arrest at different cell phases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This work aims to enhance the performance of the polyvinyl alcohol (PVA) composite by using cellulose nanocrystal (CNC) as reinforcement and copper nanoparticles (CuNPs)/reduced graphene oxide (rGO) as conducting and antimicrobial reagents. Firstly, rGO was loaded onto CuNPs using an eco-friendly microwave method. Different techniques characterized the components and prepared composites, which indicated the incorporation of cellulose nanocrystals and rGO@CuNPs within the polyvinyl alcohol matrix. Utilizing the clear zone of inhibition, the antibacterial test was quantified. Compared to the neat composite, the rGO@CuNPs loaded polyvinyl alcohol/ cellulose nanocrystal composites exhibited no bacterial growth against S. aureus, E. coli, and C. albicans. However, all composites did not have antifungal activity against A. niger. The combination of conductivity and interfacial polarization is the reason for the abrupt increase of permittivity with decreasing frequency. Besides, adding rGO@CuNPs improved the electrical conductivity. DC-Conductivity increased about a decade after adding cellulose nanocrystal to polyvinyl alcohol, then another decade after adding CuONPs. The electric loss modulus representation shows a systematic shift in the peak position towards higher frequencies, decreasing the so-called conductivity relaxation time. This is the main reason for the enhancement of conductivity. The systematic attenuation of peaks' height with increasing conductivity is still unclear., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Laccase-producing fungus (MY3) was successfully isolated from soil samples collected from Mansoura Governorate, Egypt. This fungal isolate has shown a high laccase production level over other isolated fungi. The identity of this isolate was determined by the molecular technique 18SrRNA as Curvularia lunata MY3. The enzyme purification was performed using ammonium sulfate precipitation followed by Sephacryl S-200 and DEAE-Sepharose column chromatography. The denatured enzyme using SDS-PAGE had a molar mass of 65 kDa. The purified laccase had an optimum temperature at 40 °C for enzyme activity with 57.3 kJ/mol activation energy for 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) oxidation. The enzyme had an optimum pH of 5.0, and it has shown a high stability at the acidic range (4.5 to 5.5). Mn 2+ and Mg 2+ ions enhanced the enzyme activity, while most of the enzyme activity was inhibited by Hg 2+ . Some compounds such as 2-mercaptoethanol, L-cysteine, and sodium azide at a concentration of 10 mmol/L had shown a high suppression effect on the enzyme activity. The enzyme strongly oxidized ABTS and syringaldazine and moderately oxidized DMP and guaiacol. The antimicrobial activity of the purified enzyme towards three pathogenic strains (Escherichia coli ATCC-25922, Staphylococcus aureus NRRLB-767, and Candida albicans ATCC-10231) was evaluated for the potential use as an antimicrobial therapeutic enzyme., (© 2023. The Author(s).)

A 42 day factorial trial (3x2) was designed to evaluate the effect of short-term starvation with different feeding frequencies on performance, feed utilization, physiological status and appetite responses of red hybrid tilapia fingerlings. Eighteen plastic tanks with a capacity of (55 L) were used to accomplish this work. Fingerlings with an average initial weight of 23 g ± 0.2 (SE) were randomly stocked at a rate of 8 fingerlings/aquarium. Six groups were designated as the following: II/ED: fish was fed twice every day; IV/ED: fish fed four times every day; II/EOD: fish fed twice every other day (alternate-day feeding or one day of feeding followed by another of fasting); IV/EOD: was fed four times every other day; II/EO3D: fish fed twice every other three days (three day of feeding followed by another of fasting) and IV/EO3D: fish fed four times every other three days. Fish were fed on commercial diets 30 % protein (4 % of biomass). Results showed insignificant differences between fish fed every other day and those fed every day in some growth indicators. In the same trend, the interaction between feed deprivation and feeding frequency cleared that fingerlings of IV/EOD did not significantly differ with those fed every day in growth indices. Moreover this treatment was the best in feed conversion efficiency and several physiological indicators., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

A new class of benzimidazole-based derivatives ( 4a - j , 5 , and 6 ) with potential dual inhibition of EGFR and BRAF V600E has been developed. The newly synthesized compounds were submitted for testing for antiproliferative activity against the NCI-60 cell line. All newly synthesized compounds 4a - j , 5 , and 6 were selected for testing against a panel of sixty cancer cell lines at a single concentration of 10 µM. Some compounds tested demonstrated remarkable antiproliferative activity against the cell lines tested. Compounds 4c , 4e , and 4g were chosen for five-dose testing against 60 human tumor cell lines. Compound 4c demonstrated strong selectivity against the leukemia subpanel, with a selectivity ratio of 5.96 at the GI 50 level. The most effective in vitro anti-cancer assay derivatives ( 4c , 4d , 4e , 4g , and 4h ) were tested for EGFR and BRAF V600E inhibition as potential targets for antiproliferative action. The results revealed that compounds 4c and 4e have significant antiproliferative activity as dual EGFR/BRAF V600E inhibitors. Compounds 4c and 4e induced apoptosis by increasing caspase-3, caspase-8, and Bax levels while decreasing the anti-apoptotic Bcl2 protein. Moreover, molecular docking studies confirmed the potential of compounds 4c and 4e to act as dual EGFR/BRAF V600E inhibitors.

A novel series of hybrid compounds comprising quinazolin-4-one and 3-cyanopyridin-2-one structures has been developed, with dual inhibitory actions on both EGFR and BRAF V600E . These hybrid compounds were tested in vitro against four different cancer cell lines. Compounds 8 , 9 , 18 , and 19 inhibited cell proliferation significantly in the four cancer cells, with GI 50 values ranging from 1.20 to 1.80 µM when compared to Doxorubicin (GI 50 = 1.10 µM). Within this group of hybrids, compounds 18 and 19 exhibited substantial inhibition of EGFR and BRAF V600E . Molecular docking investigations provided confirmation that compounds 18 and 19 possess the capability to inhibit EGFR and BRAF V600E . Moreover, computational ADMET prediction indicated that most of the newly synthesized hybrids have low toxicity and minimal side effects.

Aspergillus terreus has been reported to produce many bioactive metabolites that possess potential activities including anti-inflammatory, cytotoxic, and antimicrobial activities. In the present study, we report the isolation and identification of A. terreus from a collected soil sample. The metabolites existing in the microbial ethyl acetate extract were tentatively identified by HPLC/MS and chemically categorized into alkaloids, terpenoids, polyketides, γ-butyrolactones, quinones, and peptides. In addition, a new triglyceride (1) and a diketopiperazine derivative namely asterrine (4), together with two known butyrolactone (2-3) were purified from the extract. The chemical skeleton of the purified compounds was established by comprehensive analysis of their ESI/MS, 1 and 2D-NMR data. The extract and compounds 3,4 exhibited a strong inhibitory activity for the binding of ACE2 to SARS-CoV-2 spike-protein receptor with IC 50  7.4, 9.5, and 8.5 µg/mL, respectively. In addition, the extract, 1 and 2 displayed a potent anti-inflammatory effect with IC 50  51.31 and 37.25 pg/mL (Il-6) and 87.97, 68.22 pg/mL (TNF-α), respectively, in comparison to LPS control. In addition, the extract and compound 4 displayed an antimicrobial effect towards S. aureus by MIC 62.5 and 125 μg/mL, while the extract exhibited a potent effect against C. albicans (MIC of 125 μg/mL). Collectively, our data introduce novel bioactivities for the secondary metabolites produced by the terrestrial fungus Aspergillus terreus., (© 2023. Springer-Verlag GmbH Germany, part of Springer Nature.)

Histone deacetylase (HDAC) inhibitors are well-established multifaceted bioactive agents against tumors and neurodegenerative disorders. Pyrimidine and its fused and substituted derivatives were employed as a surface recognition moiety of HDAC inhibitors. De facto, the literature was loaded with different success stories of pyrimidine-based HDAC inhibitors that garnered much interest. Provoked by our continuous interest in HDAC inhibitors, we summarized and elaborated on the successful harnessing of the pyrimidine scaffold in this regard. Furthermore, we dissect our perspective that may guide medicinal chemists for an effective future design of more active chemotherapeutic agents with potential clinical applications., (© 2023 Deutsche Pharmazeutische Gesellschaft.)

Introduction: One of the most robust global challenges and difficulties in the 21st century is cancer. Treating cancer is a goal which continues to motivate researchers to innovate in design and development of new treatments to help battle the disease., Objectives: Our objective was developing new antiapoptotic hybrids based on biologically active heterocyclic motifs "benzimidazole?oxadiazole-chalcone hybrids'' that had shown promising ability to inhibit EGFR and induce apoptosis. We expected these scaffolds to display anticancer activity via inhibition of BRAF, EGFR, and Bcl-2 and induction of apoptosis through activation of caspases., Methods: The new hybrids 7a-x were evaluated for their anti-proliferative, EGFR & BRAF V600E inhibitory, and apoptosis induction activities were detected. Docking study & dynamic stimulation into EGFR and BRAF V600E were studied., Results: All hybrids exhibited remarkable cell growth inhibition on the four tested cell lines with IC 50 ranging from 0.95 μM to 12.50 μM. which was comparable to Doxorubicin. Compounds 7k-m had the most potent EGFR inhibitory activity. While, compounds 7e, 7g, 7k and 7l showed good inhibitory activities against BRAF V600E . Furthermore, Compounds 7k, 7l, and 7m increased Caspases 3,8 & 9, Cytochrome C and Bax levels and decreased Bcl-2 protein levels. Compounds 7k-m received the best binding scores and showed binding modes that were almost identical to each other and comparable with that of the co-crystalized Erlotinib in EGFR and BRAF active sites., Conclusion: Compounds 7k-m could be used as potential apoptotic anti-proliferative agents upon further optimization., (© 2023. Springer Nature Switzerland AG.)

BACKGROUND A central venous catheter (CVC) is an indwelling catheter that is inserted into a large central vein for different purposes, including hemodynamic monitoring and administration of fluids and medications. This report is of a 47-year-old woman with a retained CVC line guidewire presenting with a large right atrial thrombus requiring removal during open heart surgery. CVC insertion is one of the most frequently attempted procedures in intensive care units, emergency departments, and operation rooms, especially for critically ill patients. Possible complications range from failure to place the catheter to cardiac arrest. One of the rarest complications is missing the guidewire after insertion, which is usually discovered early after inserting it. CASE REPORT We report the case of a 47-year-old woman who had a CVC line inserted following complicated open cholecystectomy. A few years later, she developed shortness of breath, with an incidental finding of a huge right atrial thrombus and a wire shown on transthoracic echocardiography. The right atrial thrombus required open heart surgery to excise the thrombus and the wire, which was done successfully. The thrombus was histopathologically and clinically proven to be an organized right atrial thrombus formed around the CVC guidewire. CONCLUSIONS This case report presents a rare complication of CVC insertion. Because this procedure is increasingly used, clinicians should be aware of the potential complications of retained CVC lines. Moreover, this report outlines different techniques to prevent such fatal complications and emphasizes the significance of radiography after insertion.

A series of novel 3-cyanopyridone/pyrazoline hybrids ( 21-30 ) exhibiting dual inhibition against EGFR and BRAF V600E has been developed. The synthesized target compounds were tested in vitro against four cancer cell lines. Compounds 28 and 30 demonstrated remarkable antiproliferative activity, boasting GI 50 values of 27 nM and 25 nM, respectively. These hybrids exhibited dual inhibitory effects on both EGFR and BRAF V600E pathways. Compounds 28 and 30 , akin to Erlotinib, displayed promising anticancer potential. Compound 30 emerged as the most potent inhibitor against cancer cell proliferation and BRAF V600E . Notably, both compounds 28 and 30 induced apoptosis by elevating levels of caspase-3 and -8 and Bax, while downregulating the antiapoptotic Bcl2 protein. Molecular docking studies confirmed the potential of compounds 28 and 30 to act as dual EGFR/BRAF V600E inhibitors. Furthermore, in silico ADMET prediction indicated that most synthesized 3-cyanopyridone/pyrazoline hybrids exhibit low toxicity and minimal adverse effects.

New 1,5-diarylpyrazole oxime hybrid derivatives (scaffolds A and B ) were designed, synthesized, and then their purity was verified using a variety of spectroscopic methods. A panel of five cancer cell lines known to express EGFR and JNK-2, including human colorectal adenocarcinoma cell line DLD-1, human cervical cancer cell line Hela, human leukemia cell line K562, human pancreatic cell line SUIT-2, and human hepatocellular carcinoma cell line HepG2, were used to biologically evaluate for their in vitro cytotoxicity for all the synthesized compounds 7a - j , 8a - j , 9a - c , and 10a - c . The oxime containing compounds 8a-j and 10a-c were more active as antiproliferative agents than their non-oxime congeners 7a-j and 9a-c. Compounds 8d , 8g , 8i , and 10c inhibited EGFR with IC 50 values ranging from 8 to 21 µM when compared with sorafenib. Compound 8i inhibited JNK-2 as effectively as sorafenib, with an IC 50 of 1.0 µM. Furthermore, compound 8g showed cell cycle arrest at the G2/M phase in the cell cycle analysis of the Hela cell line, whereas compound 8i showed combined S phase and G2 phase arrest. According to docking studies, oxime hybrid compounds 8d , 8g , 8i , and 10c exhibited binding free energies ranging from -12.98 to 32.30 kcal/mol at the EGFR binding site whereas compounds 8d and 8i had binding free energies ranging from -9.16 to -12.00 kcal/mol at the JNK-2 binding site.

A feeding trial was conducted to investigate the effect of fermented soybean meal with Bacillus subtilis bacteria on growth performance, feed utilization, carcass composition, and hematological, and histological section of the liver and intestine of Nile tilapia Oreochromis niloticus fingerlings. Commercial soybean meal (SBM) containing 44% Crude Protein (CP) was fermented using the solid-state fermentation method which depended on autoclaving of SBM, then bacterial treatment injection by Bacillus subtilis , and finally incubation at 40C for 72 h then autoclaved to stop the growth of bacteria. Five isonitrogenous (25% crude protein) and isocaloric (4.4 kcal\g gross energy) experimental fish meal-free diets were formulated to compare with a common control diet containing fishmeal and unfermented soybean meal. Diets without fish meal contain fermented soybean meal (FSM) as a sole protein, FSM with corn gluten (CG), FSM with free amino acid methionine (Meth), FSM with corn gluten and methionine, and unfermented soybean meal. Eighteen glass aquaria, 80-L net volume, were used to stock 10 fingerlings (10.0 ± 0.1 g/fish) in each aquarium in the replicates group. The feed amount was given three times daily, six days a week throughout the 98 days experimental period. Fish were weighed biweekly and feed amounts were adjusted based on the new fish weight. Bacterial fermentation enhanced the protein content of commercial soybean meals by 6%. The crude protein of fermented soybean meal increased from 43.44% to 50.67%. Used of FSM as a sole dietary protein source resulted in a decrease in growth rate and feed utilization. However, the incorporation of FSM with corn gluten, and/or methionine amino acid led to an improvement in the performance of fish. Finally, the best final body weight, weight gain, specific growth rate, protein efficiency ratio, and protein productive value were recorded by a fish-fed mixed plant protein diet (FSM + CG + Meth). Also, Hematocrit and red blood cells were not significantly affected including the FSM., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.1-Herring2-Vitamin and mineral mixture kg−1of mixture contains: 40*105 I.U. Vit A, 10*105 IU cholecalciferol (vit. D), 13.3 g Vit E, 2 g Vit K, 10 mg Vit B12, 5.0 g Vit B2, 2 g Vit B6, 1 g Vit B1, 6.0 g Pantothenic acid, 20 g Nicotinic acid, 1000 mg Folic acid, 100 mg Biotin, 200 gm Choline, 4 g Copper, 0.4 g Iodine, 12 g Iron, 22 g Manganese, 22 g Zinc, 0.04 g Selenium. Folic acid, 1.2 mg; niacin, 12 mg; d-calcium pantothenate, 26 mg; pyridoxine. HCl, 6 mg; riboflavin, 7.2 mg; thiamin. HCl, 1.2 mg; sodium chloride (NaCl, 39% Na, 61% Cl), 3077 mg; ferrous sulfate (FeSO4·7H2O, 20% Fe), 65 mg; manganese sulfate (MnSO4, 36% Mn), 89 mg; zinc sulfate (ZnSO4·7H2O, 40% Zn), 150 mg; copper sulfate (CuSO4·5H2O, 25% Cu), 28 mg; potassium iodide (KI, 24%K, 76% I).3-Nitrogen free extract = 1- (%lipid + %moisture + %protein + %fiber + %ash).4-Gross energy calculated using gross calorific values of 23.63, 39.52 and 17.15 Kcal\g of protein, lipid and carbohydrate, respectively [59].5-Digestible energy calculated from standard physiological fuel values as 4,4 and 9 kcal\g of protein, carbohydrate and lipid respectively [60].1(SBM) Commercial soybean meal.2-(FSM) fermented soybean meal.3-Nitrogen-free extract = 100− (crude protein + crude lipid + ash + fiber).-Diets 1, 2.3, 4, 5 and 6 are control, fermented soybean meal FSM, FSM + corn gluten, FSM + methionine, and unfermented soy bean meal respectively.-Values are means ± SD (n = 3). Values with the same superscript within the same row are not significantly different (P < 0.05)., (© 2023 Published by Elsevier Ltd.)

Background: Although magnetic resonance imaging (MRI) is often the "gold standard" for diagnosing knee problems, it has many limitations. Therefore, ultrasonography has been suggested as an effective rapid alternative in many knee abnormalities, especially after injuries of the meniscus and collateral ligaments., Purpose: To determine the diagnostic accuracy of point-of-care ultrasound (POCUS) in detecting injuries of the meniscus and collateral ligament compared to MRI., Material and Methods: An observational cross-sectional blinded study was conducted of 60 patients with clinically suspicious meniscus and collateral ligament injuries who were planned for an arthroscopy and or operative procedure. These patients underwent both blinded POCUS and MRI of the knees before the intervention procedure and results of both imaging modalities were compared according to the operative and arthroscopic findings., Results: The preoperative reliability of POCUS compared to MRI for the assessment of meniscus injuries was sensitivity (92.9% vs. 90.5%), specificity (88.9% vs. 83.3%), positive predictive value (PPV; 95.1% vs. 92.7%), negative predictive value (NPV; 84.2% vs. 79%), and overall accuracy (91.7% vs. 88.3%). However, for diagnosing collateral ligament injures, POCUS versus MRI assessed sensitivity (92.3% vs. 88.5%), specificity (100% vs. 97.1%), PPV (100% vs. 95.8%), NPV (94.4% vs. 91.7%), and overall accuracy (96.7% vs. 93.3%)., Conclusion: Ultrasonography is a useful screening tool for the initial diagnosis of meniscal and collateral ligament pathology compared to or even with potential advantages over MRI, especially when MRI is unavailable or contraindicated. As newly advanced portable ultrasonography becomes available, it could be considered as a point-of-injury diagnostic modality.

The limited usage of chitosan as a dye adsorbent is attributed to its compact structure and low swelling ability, despite its exceptional properties. The present study aimed to prepare novel chitosan/pyrazole Schiff base (ChS) adsorbents enriched with greenly synthesized zinc oxide nanoparticles. The preparation of ZnO-NPs was carried out through a green approach using the Coriandrum sativum extract. The presence of ZnO-NPs at the nanoscale was validated through TEM, DLS and XRD analyses. FTIR and 1 H NMR confirmed the successful preparation of the Schiff base and its ZnO-NPs adsorbents. The incorporation of ZnO-NPs improved the thermal, swelling and antimicrobial properties of the chitosan Schiff base. In addition, a significant improvement in the adsorption of Maxilon Blue dye from its aqueous solution by the Schiff base/ZnO-NPs adsorbent was achived. The prepared ChS/ZnO-NPs adsorbent has the potential to be used as an alternative to conventional adsorbents for the removal of dyes from wastewater., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Lung cancer is the second most common cause of morbidity and mortality among cancer types worldwide, with non-small cell lung cancer (NSCLC) representing the majority of most cases. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) are among the most commonly used targeted therapy to treat NSCLC. Recent years have seen the evaluation of many synthetic EGFR TKIs, most of which showed therapeutic activity in pertinent models and were classified as first, second, and third-generation. The latest studies have concluded that their efficacy was also compromised by additional acquired mutations, including C797S. Because second- and third-generation EGFR TKIs are irreversible inhibitors, they are ineffective against C797S containing EGFR triple mutations (Del19/T790M/C797S and L858R/T790M/C797S). Therefore, there is an urgent unmet medical need to develop next-generation EGFR TKIs that selectively inhibit EGFR triple mutations via a non-irreversible mechanism. This review covers the fourth-generation EGFR-TKIs' most recent design with their essential binding interactions, the clinical difficulties, and the potential outcomes of treating patients with EGFR mutation C797S resistant to third-generation EGFR-TKIs was also discussed. Moreover, the utilization of various therapeutic strategies, including multi-targeting drugs and combination therapies, has also been reviewed., Competing Interests: The authors affirm that they have no known financial or interpersonal conflicts that would have appeared to impact the research presented in this paper., (This journal is © The Royal Society of Chemistry.)

Introduction: The main objective of this study was to assess the cost of prostate cancer over a 1-year period from a societal perspective., Methods: We constructed a cost-of-illness model to assess the cost of different health states of prostate cancer, metastatic or nonmetastatic, among Egyptian men. Population data and clinical parameters were extracted from the published literature. We relied on different clinical trials to extract clinical data. We considered all direct medical costs, including the costs of treatment and required monitoring, in addition to the indirect costs. The unit costs were captured from Nasr City Cancer Center and Egyptian Authority for Unified Procurement, Medical Supply, and Management of Medical Technology, and resource utilization were collected from clinical trials and validated by the Expert Panel. One-way sensitivity analysis was conducted to ensure model robustness., Results: The number of targeted patients with nonmetastatic hormone-sensitive prostate cancer, hormone-sensitive prostate cancer, and metastatic castration-resistant prostate cancer was 215,207, 263,032, and 116,732, respectively. The total costs, in Egyptian pounds (EGP) and US dollars (USD), for the targeted patients, including drug costs and nondrug costs over a time horizon of 1 year, were EGP 41.44 billion (USD 9.010 billion) for localized prostate cancer; for metastatic prostate cancer, they doubled to EGP 85.14 billion (USD 18.510 billion), which reflects a huge burden on the Egyptian healthcare system. The drug costs for localized and metastatic prostate cancer are EGP 41,155,038,137 (USD 8.946 billion) and EGP 81,384,796,471 (USD 17.692 billion), respectively. A significant difference in nondrug costs between localized and metastatic prostate cancer was demonstrated. Nondrug costs were estimated at EGP 293,187,203 (USD 0.063 billion) for localized prostate cancer and EGP 3,762,286,092 (USD 0.817 billion) for metastatic prostate cancer. This significant difference in nondrug costs highlights the importance of early treatment due to the increased costs of progression and the burden of follow-up and productivity loss associated with metastatic prostate cancer., Conclusion: Metastatic prostate cancer has a huge economic burden on the Egyptian healthcare system compared with localized prostate cancer owing to the increased costs of progression, follow-up, and productivity loss. This highlights the necessity of early treatment of these patients to save costs and lighten the burden of the disease on the patient, society, and economy., Competing Interests: Conflict of Interest: None.

Some new Bis-pyrazoline hybrids 8-17 with dual EGFR and BRAF V600E inhibitors have been developed. The target compounds were synthesized and tested in vitro against four cancer cell lines. Compounds 12 , 15 , and 17 demonstrated strong antiproliferative activity with GI 50 values of 1.05 µM, 1.50 µM, and 1.20 µM, respectively. Hybrids showed dual inhibition of EGFR and BRAF V600E . Compounds 12 , 15 , and 17 inhibited EGFR-like erlotinib and exhibited promising anticancer activity. Compound 12 is the most potent inhibitor of cancer cell proliferation and BRAF V600E . Compounds 12 and 17 induced apoptosis by increasing caspase 3, 8, and Bax levels, and resulted in the downregulation of the antiapoptotic Bcl2. The molecular docking studies verified that compounds 12 , 15 , and 17 have the potential to be dual EGFR/BRAF V600E inhibitors. Additionally, in silico ADMET prediction revealed that most synthesized bis-pyrazoline hybrids have low toxicity and adverse effects. DFT studies for the two most active compounds, 12 and 15 , were also carried out. The values of the HOMO and LUMO energies, as well as softness and hardness, were computationally investigated using the DFT method. These findings agreed well with those of the in vitro research and molecular docking study.

Microbial DNA gyrase is regarded as an outstanding microbial target. Hence, 15 new quinoline derivatives ( 5 - 14 ) were designed and synthesized. The antimicrobial activity of the afforded compounds was pursued via in vitro approaches. The investigated compounds displayed eligible MIC values, particularly against G-positive Staphylococcus aureus species. Consequently, an S. aureus DNA gyrase supercoiling assay was performed, using ciprofloxacin as a reference control. Obviously, compounds 6b and 10 unveiled IC 50 values of 33.64 and 8.45 μM, respectively. Alongside, ciprofloxacin exhibited an IC 50 value of 3.80 μM. Furthermore, a significant docking binding score was encountered by compound 6b (-7.73 kcal/mol), surpassing ciprofloxacin (-7.29 kcal/mol). Additionally, both compounds 6b and 10 revealed high GIT absorption without passing the blood brain barrier. Finally, the conducted structure-activity relationship study assured the usefulness of the hydrazine moiety as a molecular hybrid for activity either in cyclic or opened form., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

As dual EGFR and BRAF V600E inhibitors, 2-(3-cyano-4,6-bis(aryl)-2-oxo-1,2-dihydropyridine-1-yl)-N-(4-cinnamoylphenyl) acetamide derivatives 8-20 were developed. Compounds 8, 12, and 13 showed strong antiproliferative activity when the target compounds were synthesized and tested in vitro against four cancer cell lines. These hybrids have a dual inhibition activity on EGFR and BRAF V600E , according to in vitro studies. The EGFR was inhibited by compounds 8, 12, and 13 with IC 50 values between 89 and 110 nM, which were equivalent to those of erlotinib (IC 50  = 80 nm). Compound 13 was found to be an effective inhibitor of the proliferation of cancer cells (GI 50  = 0.72 µM) and demonstrated hopeful inhibitory activity of BRAF V600E (IC 50  = 58 nm), which is superior to erlotinib (IC 50  = 65 nm). Compound 13 caused apoptosis and showed cell cycle arrest in the G0/G1phase in a study on the MCF-7 cell line. The new compounds can fit tightly into the active sites of EGFR and BRAF V600E kinases, according to molecular docking analyses., (© 2022 Deutsche Pharmazeutische Gesellschaft.)

A series of new 1,3,4-oxadiazole-chalcone/benzimidazole hybrids 9a-o and 10a-k were designed and synthesized as potential antiproliferative agents. Hybrids 9a-o exhibited remarkable antiproliferative activities on different NCI-60 cell lines in a single-dose assay. The antiproliferative activities of the newly synthesized compounds were evaluated against a panel of four human cancer cell lines (A-549, MCF-7, Panc-1, and HT-29). Compounds 9g-i and their oxygen isosteres, 10f-h, exhibited promising antiproliferative activities with IC 50 values ranging from 0.80 to 2.27 µM compared to doxorubicin (IC 50 ranging from 0.90 to 1.41 µM). Furthermore, the inhibitory potency of these compounds against the epidermal growth factor receptor (EGFR) and BRAF V600E kinases was evaluated using erlotinib as a reference drug. Molecular modeling studies were done to investigate the binding mode of the most active hybrids in the ATP binding site of EGFR., (© 2022 Deutsche Pharmazeutische Gesellschaft.)

Background: Quinazolinone scaffolds have drawn international attention due to their potent anticancer activity and therapeutic applications. Furthermore, Chalcone and Oxime are special chemical templates with a wide range of biological activities, including anti-cancer activity. As a result, the purpose of this research is to synthesize and develop a new series of 2-thioxo-3-substituted quinazolin-4-one/chalcone analogues and 2-thioxo-3-substituted quinazolin-4-one/oximes analogues in order to obtain a new cytotoxic agent that can target epidermal growth factor (EGFR) and/or V-Raf Murine Sarcoma Viral Oncogene Homolog B (BRAF V600E ) oncogene., Objective: All synthesised compounds were tested for anticancer activity against four human cancer cell lines. The new hybrids' potential anti-cancer mechanism was evaluated using EGFR and BRAF enzymatic tests. The most active molecules within the target enzyme's active site were studied using molecular docking. Apoptosis and cell cycle analysis were also investigated., Methods: The target compounds 7a-j (series I) are obtained in high yields by alkylation of 2-mercapto-3-ethyl-(3H)- quinazolin-4-one 3a with acylated chalcones 6a-j. Alkylation of compounds 3b-c with N-(4-acetylphenyl)-2- bromoacetamide 8, the corresponding ketones intermediates 9b-c was produced in high yields. Compounds 7a-j, 9b-c, and 10b-c were tested for their antiproliferative activity against four human cancer cell lines using the MTT assay and doxorubicin as a control drug. The EGFR and BRAF assay tests were used to assess the inhibitory potency against EGFR and BRAF., Results: Compounds 7c, 7d, 7f and 10c exhibited high proliferative activity and inhibited EGFR, which could serve as a potential target for antiproliferative activity. The most active hybrid, 7c, primarily caused cell cycle arrest in G0/G1 phase and S phase as well as cell apoptosis. Finally, the most active hybrids were docked well to the EGFR active site., Conclusion: 2-thioxo-3-substituted quinazolin-4-one/chalcone derivatives have significant apoptotic and antiproliferative properties., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

A series of ciprofloxacin-uracil conjugates 5a-t were synthesized and identified by 1 H NMR, 13 C NMR, mass spectroscopy and elemental analyses. The antibacterial results revealed that the new derivatives exhibited better activity against Gram-positive than the Gram-negative strains; most of the target compounds exhibited good activities against S. aureus ATCC 6538. Compounds 5b and 5g possess the highest activities with MICs of 1.25 and 2.37 µM, respectively, which are more potent than the parent drug ciprofloxacin, MIC, 7.58 µM. In addition, they also exhibited potent activities against MRSA AUMC 261 with MICs, 0.031 and 0.046 µM respectively, higher than ciprofloxacin with MIC, 0.57 µM. Moreover, compounds 5b and 5g showed potent inhibitory activities against DNA gyrase (IC 50  = 1.72 and 5.72 µM) and topoisomerase IV (4.36 and 7.77 µM) compared to ciprofloxacin with IC 50 values 0.66 and 8.16 µM, respectively. The molecular docking study revealed that compounds 5b and 5g may formed stable interaction with the active sites of DNA gyrase and topoisomerase IV similar to ciprofloxacin. Hence, 5b and 5g are considered promising antibacterial candidated against MRSA AUMC 261 strains that requires further optimization., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Synthesis of thiazolidinone based on quinolone moiety was established starting from 4-hydroxyquinol-2-ones. The strategy started with the reaction of ethyl bromoacetate with 4-hydroxyquinoline to give the corresponding ethyl oxoquinolinyl acetates, which reacted with hydrazine hydrate to afford the hydrazide derivatives. Subsequently, hydrazides reacted with isothiocyanate derivatives to give the corresponding N , N -disubstituted thioureas. Finally, on subjecting the N , N -disubstituted thioureas with dialkyl acetylenedicarboxylates, cyclization occurred, and thiazolidinone derivatives were obtained in good yields. The two series based on quinolone moiety, one containing N , N -disubstituted thioureas and the other containing thiazolidinone functionalities, were screened for their in vitro urease inhibition properties using thiourea and acetohydroxamic acid as standard inhibitors. The inhibition values of the synthesized thioureas and thiazolidinones exhibited moderate to good inhibitory effects. The structure-activity relationship revealed that N -methyl quinolonyl moiety exhibited a superior effect, since it was proved to be the most potent inhibitor in the present series achieving (IC 50 = 1.83 ± 0.79 µM). The previous compound exhibited relatively much greater activity, being approximately 12-fold more potent than thiourea and acetohydroxamic acid as references. Molecular docking analysis showed a good protein-ligand interaction profile against the urease target (PDBID: 4UBP), emphasizing the electronic and geometric effect of N , N -disubstituted thiourea.

Prostate cancer (PCa) ranks as one of the most commonly diagnosed malignancies worldwide. Toxicity, lack of clinical efficacy, and development of resistance phenotypes are the main challenges in the control of prostate malignancies. Notably, castration-resistance prostate cancer (CRPCa) is a highly aggressive and metastatic phenotype of the disease with a poor prognosis and very limited therapeutic options. Herein, we report the isolation and genotypic identification of a soil-derived fungus Aspergillus neoniveus using the PCR-based internal transcribed spacer (ITS) region amplification approach. HPLC/MS investigation of the metabolic profile of the ethyl acetate extract from the fungal biomass revealed tentative identification of forty-five compounds belonging to various chemical classes including γ-butyrolactones, alkaloids, phenolics, and quinoids. Furthermore, the chromatographic purification of microbial extract enabled the identification of nervonic acid methyl ester ( 1 ) for the first time from endophytic fungi, as well as acetyl aszonalenin ( 2 ), and butyrolactone II ( 3 ) for the first time from A. neoniveus . The chemical frameworks of the isolated compounds were identified via extensive spectral analysis including 1 and 2D NMR and MS. The X-ray crystal structure and absolute configuration of acetyl aszonalenin ( 2 ) were also determined. Additionally, screening of in vitro anticancer activity of the fungal extract revealed its potential antiproliferative and anti-migratory activities against five different prostate cancer cells (PC3, PC-3M, DU-145, CWR-R1ca, and 22Rv1), including different cells with the castration-resistance phenotype. Moreover, the isolated metabolites significantly inhibited the proliferation, migration, and colonization of human prostate cancer cells at low micromolar levels, thus providing credence for future investigation of these metabolites in relevant anti-prostate cancer animal models. Furthermore, computational target prediction tools identified the cannabinoid G-protein coupled receptors type 1 (CB1) as a potential biological target mediating, at least in part, the anticancer effects of acetylaszonalenin ( 2 ). Moreover, molecular modeling and docking studies revealed a favorable binding pose at the CB1 receptor orthosteric ligand pocket aided by multiple polar and hydrophobic interactions with critical amino acids. In conclusion, the Aspergillus neoniveus- derived prenylated indole alkaloid acetylaszonalenin has promising anticancer activity and is amenable to further hit-to-lead optimization for the control of prostate malignancies via modulating CB1 receptors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fayek, Ebrahim, Elsayed, Abdel-Aziz, Kariuki and Moharram.)

Despite the outstanding characteristics of alginate, it suffers from bad UV-barrier, water barrier, and antimicrobial properties limiting its wide usage in food packaging. For this concern, Box-Behnken design (BBD) was applied to prepare an alginate-based edible coating of the best optimized UV-shielding properties upon the incorporation of both Aloe vera (AV) and zinc oxide nanoparticles (ZnO-NPs). The optimized minimum UV-transmittance was 4.96% when the optimized compositions of alginate (1.05 g), AV (2.95 g), and ZnO-NPs (4.93 wt%) were used. FTIR was used to verify the successful edible coating preparation while the wide-angle X-ray diffraction (XRD) was used to identify the interactions between the film's components. The incorporation of both AV and ZnO-NPs significantly improved alginate's thermal, water vapor permeability (WVP), mechanical and antimicrobial properties. In addition, the films incorporated with both AV and ZnO-NPs exhibited excellent UV-barrier properties compared with neat alginate. The optimized alginate film incorporated with both ZnO-NPs and AV significantly extended the shelf-life of tomato fruits up to 16 days without any defects. Due to the outstanding physical, UV-shielding, and antimicrobial properties of the optimized alginate/AV/ZnO-NPs film, it could be used potentially in food packaging industries., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Statement of Problem: Polyetheretherketone (PEEK) can be used as a framework material for removable and fixed dental prostheses. However, information about the use of PEEK as a post-and-core restoration is scarce., Purpose: The purpose of this in vitro study was to evaluate the effect of different surface treatments on the push-out bond strength of milled polyetheretherketone posts to resin cement., Material and Methods: Sixty intact human maxillary central incisors were selected and endodontically treated, and standardized post spaces were prepared. Sixty PEEK posts were milled from a prefabricated PEEK blank by using a computer-aided design and computer-aided manufacturing (CAD-CAM) system and divided into 3 groups (n=15) according to the surface treatment: acid etching by using 98% sulfuric acid (AE); airborne-particle abrasion by using 50-μm Al 2 O 3 (AA); nonthermal plasma treatment (NTP); in addition, PEEK posts (n=15) received no treatment (NT) and served as a control. All posts were bonded by using a self-adhesive resin cement. Three sections (coronal, middle, and apical) were obtained for each specimen. Push-out bond strength measurements (MPa) for each section were recorded by using a universal testing machine at a crosshead speed of 0.5 mm/min until failure occurred. The post-cement interfaces and failure modes were evaluated by using scanning electron microscopy. The data obtained were statistically analyzed by using 1-way ANOVA and the pair-wise Tukey (HSD) test to study the difference between group mean values (α=.05)., Results: The overall mean ±standard deviation of the push-out bond strength was 11 ±2 MPa for AE group, 6 ±1 MPa for AA group, 5 ±1 MPa for NTP group, and 3 ±1 MPa for NT group. A statistically significant difference was found among all groups subjected to different surface treatments as indicated by the ANOVA test (P<.001). The pair-wise Tukey honestly significant difference (HSD) test showed a significant difference among the AE group and all groups (P<.001); however, no significant difference was observed between the AA and NTP groups (P>.05). Moreover, a significant difference was observed among all root sections (P<.001)., Conclusions: Surface treatment of PEEK posts with 98% sulfuric acid for 60 seconds showed significantly higher bond strength values than those in other groups. The bond strength of PEEK posts to resin cement was significantly higher in the coronal section than that in other sections., (Copyright © 2020 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

The target of our current work was designed to prepare titanium oxide doped silver nanoparticles (Ag/TiO 2 NPs) and their impact on the functionalization of cotton fabrics. Additionally, the effect of Ag/TiO 2 NPs was compared with the individually prepared silver nanoparticles (AgNPs) and titanium oxide nanoparticles (TiO 2 NPs). In this work, AgNPs were prepared in the solid state using arabic gum as efficient stabilizing and reducing agent. Then, two concentrations of the as-synthesized nanoparticles were used to functionalize the cotton fabrics by pad-dry-cure treatment in the presence of fixing agent to increase the durability of treated cotton fabrics against vigorous washing cycles. The findings implied that the as-prepared nanoparticles were successfully synthesized in nano-size with spherical shape and homogeneity. The efficacy of the functionalized cotton fabrics with those nanoparticles were evaluated in terms of multifunctional properties including antimicrobial and ultraviolet protection factor (UPF) and the mechanical features before and after many washing cycles; 10, 15 and 20 times. The resultant also proved that Ag/TiO 2 NPs-treated cotton fabrics exhibited the greater values of both antimicrobial and UPF properties with enhancement in the tensile strength and elongation features. Thus, the combination between these two nanoparticles through doping reaction is suitable for imparting superior antimicrobial properties against the four tested microbial species (Staphylococcus aureus, Escherichia coli, Candida albicans, and Aspergillus niger) and good UPF properties. Depending on the promising obtained results of the multi-finishing fabrics, these nanoparticles of Ag/TiO 2 NPs can be applied for the production of an efficient medical clothes for doctors, nurses and bed sheets for patients in order to kill and prevent the spread of bacteria and then, reduce the transmission of infection to others., (© 2022 John Wiley & Sons Ltd.)

In the present study, nanocellulose was extracted from palm leaves to synthesize nanocellulose/chitosan nanocomposites for the removal of dyes from textile industrial wastewater. Nanocellulose is of interest in water purification technologies because of its high surface area and versatile surface chemistry. Following bleach, alkali, and acid treatments on palm leaves, nanocellulose is obtained as a white powder. The produced nanocellulose was investigated. The adsorption capacity of chitosan, nanocellulose, and novel synthetic nanocellulose/chitosan microbeads (CCMB) for direct blue 78 dye (DB78) removal was studied. A series of batch experiments were conducted in terms of adsorbent concentration, mixing time, pH, dye initial concentration, and nanocellulose concentration in synthetic microbeads. The CCMB was characterized by using physicochemical analysis, namely Brunauer-Emmett-Teller (BET), scanning electron microscope (SEM), zeta potential analysis, and Fourier-transform infrared spectroscopy (FTIR). It was found that the surface area of synthetic CCMB is 10.4 m 2 /g, with a positive net surface charge. The adsorption tests showed that the dye removal efficiency increases with an increasing adsorbent concentration. The maximum removal efficiencies were 91.5% and 88.4%, using 14 and 9 g/L of CCMB-0.25:1. The initial dye concentrations were 50 and 100 mg/L under acidic conditions (pH = 3.5) and an optimal mixing time of 120 min. The equilibrium studies for CCMB-0.25:1 showed that the equilibrium data were best fitted to Langmuir isothermal model with R 2 = 0.99. These results revealed that nanocellulose/chitosan microbeads are an effective eco-adsorbent for the removal of direct blue 78 dye and provide a new platform for dye removal.

The objective of this study was to prepare and evaluate Nystatin (NYS) loaded transfersomes to achieve better treatment of vulvovaginal candidiasis. Nystatin transferosomes were formulated utilizing thin film hydration method. A 3 2 full factorial design was employed to evaluate the effect of different formulation variables. Two independent variables were chosen; the ratio between lecithin surfactant (X 1 ) was set at three levels (10-40), and the type of surfactants (X 2 ) was set at three levels (Span 60, Span 85 and Pluronic F-127). The dependent responses were; entrapment efficiency (Y 1 : EE %), vesicles size (Y 2 : VS) and release rate (Y 3 : RR). Design Expert® software was utilized to statistically optimize formulation variables. The vesicles revealed high NYS encapsulation efficiency ranging from 97.35 ± 0.03 to 98.01 ± 0.20% whereas vesicle size ranged from 194.8 ± 20.42 to 400.8 ± 42.09 nm. High negative zeta potential values indicated good stability of the prepared formulations. NYS release from transfersomes was biphasic and the release pattern followed Higuchi's model. The optimized formulation (F7) exhibited spherical morphology under transmission electron microscopy (TEM). In-vitro and in-vivo antifungal efficiency studies revealed that the optimized formula F7 exhibited significant eradication of candida infestation in comparison to free NYS. The results revealed that the developed NYS transfersomes could be a promising drug delivery system to enhance antifungal efficacy of NYS., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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Schistosomosis is a worldwide tropical disease primarily caused by Schistosoma mansoni. Praziquantel is the only available drug for controlling schistosomosis, with many challenges. This study aims to evaluate the in vitro anti-Schistosoma effect of Ganoderma lucidum (G. lucidum) against adult and larval stages of Schistosoma based on the prediction of the binding activity of G. lucidum protein with proteins of various stages of S. mansoni by molecular docking to confirm its inhibitory potential through an insilico study. Results showed that Leu143, Ser165, Met214, and Asn213 were the primary crucial amino acids involved in the binding, with a promising large area of interactions between the two studied proteins. The in vitro study evaluated the motility and survival of adult and larval stages, compared to praziquantel and niclosamide, respectively. There was a significant reduction in the motility of adults after the two-hour incubation, with all concentrations and 100% death of all parasites with the minimal concentration (10 μg/ml) within 4 and 6 h of incubation (P<0.01). Regarding the cercariae, at a concentration of 10 μg/ml, all the cercariae (100%) died (P<0.01) after 15 min, and the miracidial complete mortality rate (100%) (P<0.01) occurred at a concentration of 10 μg/ml after 8 min. This study first predicted the binding activity of G. lucidum protein with proteins of S. mansoni at various stages and proved the anti-Schistosoma effect of G. lucidum in vitro, considered a promising treatment for schistosomosis.

Keratitis is a global health issue that claims the eye sight of millions of people every year. Dry eye, contact lens wearing and refractive surgeries are among the most common causes. The resistance rate among fluoroquinolone antibiotics is >30%. This study aims at formulating a newly synthesized ciprofloxacin derivative (2b) niosomes and Solulan C24-, sodium cholate- and deoxycholate-modified niosomes. The prepared niosomal dispersions were characterized macroscopically and microscopically (SEM) and by percentage entrapment efficiency, in vitro release and drug release kinetics. While the inclusion of Solulan C24 produced something discoidal-shaped with a larger diameter, both cholate and deoxycholate were unsuccessful in forming niosomes dispersions. Conventional niosomes and discomes (Solulan C24-modified niosomes) were selected for further investigation. A corneal ulcer model inoculated with colonies of Pseudomonas aeruginosa in rabbits was developed to evaluate the effectiveness of keratitis treatment of the 2b-loaded niosomes and 2b-loaded discomes compared with Ciprocin ® (ciprofloxacin) eye drops and control 2b suspension. The histological documentation and assessment of gene expression of the inflammatory markers (IL-6, IL1B, TNFα and NF-κB) indicated that both 2b niosomes and discomes were superior treatments and can be formulated at physiological pH 7.4 compatible with the ocular surface, compared to both 2b suspension and Ciprocin ® eye drops.

Heterocycles containing thienopyrimidine moieties have attracted attention due to their interesting biological and pharmacological activities. In this research article, we reported the synthesis of a series of new hybrid molecules through merging the structural features of chalcones and pyridothienopyrimidinones. Our results indicated that the synthesis of chalcone-thienopyrimidine derivatives from the corresponding thienopyrimidine and chalcones proceeded in a relatively short reaction time with good yields and high purity. Most of these novel compounds exhibited moderate to robust cytotoxicity against HepG2 and MCF-7 cancer cells similar to that of 5-fluorouracil (5-FU). The results indicated that IC 50 of the two compounds ( 3b and 3g ) showed more potent anticancer activities against HepG2 and MCF-7 than 5-FU. An MTT assay and flow cytometry showed that only 3b and 3g had anticancer activity and antiproliferative activities at the G1 phase against MCF-7 cells, while six compounds ( 3a - e and 3g ) had cytotoxicity and cell cycle arrest at different phases against HepG2 cells. Their cytotoxicity was achieved through downregulation of Bcl-2 and upregulation of Bax, caspase-3, and caspase-9. Although all tested compounds increased oxidative stress via increment of MDA levels and decrement of glutathione reductase (GR) activities compared to control, the 3a , 3b , and 3g in HepG2 and 3b and 3g in MCF-7 achieved the target results. Moreover, there was a positive correlation between cytotoxic efficacy of the compound and apoptosis in both HepG2 ( R 2 = 0.531; P = 0.001) and MCF-7 ( R 2 = 0.219; P = 0.349) cell lines. The results of molecular docking analysis of 3a-g into the binding groove of Bcl-2 revealed relatively moderate binding free energies compared to the selective Bcl-2 inhibitor, DRO. Like venetoclax, compounds 3a-g showed 2 violations from Lipinski's rule. However, the results of the ADME study also revealed higher drug-likeness scores for compounds 3a-g than for venetoclax. In conclusion, the tested newly synthesized chalcone-pyridothienopyrimidinone derivatives showed promising antiproliferative and apoptotic effects. Mechanistically, the compounds increased ROS production with concomitant cell cycle arrest and apoptosis. Therefore, regulation of the cell cycle and apoptosis are possible targets for anticancer therapy. The tested compounds could be potent anticancer agents to be tested in future clinical trials after extensive pharmacodynamic, pharmacokinetic, and toxicity profile investigations., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Ghada M. Safwat et al.)

Protein kinases have grown over the past few years as a crucial target for different cancer types. With the multifactorial nature of cancer, and the fast development of drug resistance for conventional chemotherapeutics, a strategy for designing multi-target agents was suggested to potentially increase drug efficacy, minimize side effects and retain the proper pharmacokinetic properties. Kinase inhibitors were used extensively in such strategy. Different kinase inhibitor agents which target EGFR, VEGFR, c-Met, CDK, PDK and other targets were merged into hybrids with conventional chemotherapeutics such as tubulin polymerization and topoisomerase inhibitors. Other hybrids were designed gathering kinase inhibitors with targeted cancer therapy such as HDAC, PARP, HSP 90 inhibitors. Nitric oxide donor molecules were also merged with kinase inhibitors for cancer therapy. The current review presents the hybrids designed in the past five years discussing their design principles, results and highlights their future perspectives., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)