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Abdallah E Abdallah,1 Reda R Mabrouk,1 Mohamed R Elnagar,2 Amel Mostafa Farrag,3 Mohamed H Kalaba,4 Mohamed H Sharaf,4 Esmail M El-Fakharany,5 Dina Abed Bakhotmah,6 Eslam B Elkaeed,7 Maged Mohammed Saleh Al Ward1 1Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, 11884, Egypt; 2Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Cairo, 11884, Egypt; 3Pharmaceutical Chemistry Department, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt; 4Botany and Microbiology Department, Faculty of Science, Al-Azhar University, Cairo, 11884, Egypt; 5Protein Research Department, Genetic Engineering and Biotechnology Research Institute, City of Scientific Research and Technological Applications, New Borg El Arab, Egypt; 6Chemistry Department, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia; 7Department of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, Riyadh, 13713, Saudi ArabiaCorrespondence: Abdallah E Abdallah; Maged Mohammed Saleh Al Ward, Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, 11884, Egypt, Email Abdulla_emara@azhar.edu.eg; majed1000ward@hotmail.comBackground: Cancer is still a major world health threat, causing a high rate of mortality. VEGFR-2 inhibitor anticancer agents are of great significance. However, they showed some serious side effects.Purpose: To discover new effective and safer anticancer agents, a new series of piperazinylquinoxaline-based derivatives was designed and synthesized on the basis of the pharmacophoric features of VEGFR-2 inhibitor drugs.Methods: The new candidates were evaluated against A549 lung cancer cells, HepG-2 hepatoma cells, Caco-2 colon cancer cells, MDA breast cancer cells, and VEGFR-2 kinase. Moreover, cell cycle kinetics and apoptosis rates were studied in HepG-2 cells treated with compound 11, which was the most promising candidate.Results: The new derivatives revealed better antitumor results (IC50 from 6.48 to 38.58 μM) against the aforementioned cancer cell lines than sorafenib. Also, the new candidates showed VEGFR-2 inhibition with IC50 values ranging from 0.19 to 0.60 μM compared to 0.08 μM for sorafenib. Compound 11, meanwhile, showed IC50 values equal to 10.61, 9.52, 12.45, 11.52, and 0.19 μM against the cancer cell lines and VEGFR-2, respectively. Moreover, compound 11 raised the apoptosis rate in HepG-2 cells from 5% to 44% and caused 4, 2.3, and 3-fold increases in BAX/Bcl-2 ratio, caspase-3 level, and P53 expression, respectively, compared to control untreated cells. Finally, the new derivatives displayed the correct binding mode into VEGFR-2 kinase pocket, giving interactions with the essential residues.Conclusion: This work suggests that compound 11 is a very significant anticancer candidate, and piperazinylquinoxaline is an important scaffold in the development of new potential effective and safer VEGFR-2 inhibitor agents.Keywords: anticancer, apoptosis, molecular modeling, piperazinylquinoxaline, VEGFR-2 kinase, Western blot

Samar A Salim,1,2 Elbadawy A Kamoun,1,3 Stephen Evans,4 Shahira H EL-Moslamy,5 Esmail M El-Fakharany,6 Mohamed M Elmazar,7 AF Abdel-Aziz,2 RH Abou-Saleh,8,9 Taher A Salaheldin10 1Nanotechnology Research Center (NTRC), The British University in Egypt (BUE), Cairo, 11837, Egypt; 2Biochemistry Group, Chemistry Dep., Faculty of Science, Mansoura University, Mansoura, Egypt; 3Polymeric Materials Research Dep., Advanced Technology and New Materials Research Institute (ATNMRI), City of Scientific Research and Technological Applications (SRTA-City), Alexandria, 21934, Egypt; 4Molecular and Nanoscale Physics Group, School of Physics and Astronomy, University of Leeds, Leeds, LS2 9JT, UK; 5Bioprocess Development Dep., GEBRI, City of Scientific Research and Technological Applications (SRTA-City), Alexandria, 21934, Egypt; 6Protein Research Dep. GEBRI, City of Scientific Research and Technological Applications (SRTA-City), Alexandria, 21934, Egypt; 7Faculty of Pharmacy, The British University in Egypt (BUE), Cairo, 11837, Egypt; 8Biophysics Group, Dep. of Physics, Faculty of Science, Mansoura University, Mansoura, Egypt; 9Nanoscience and Technology Program, Faculty of Advanced Basic Science, Galala University, Suez, Egypt; 10Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, NY, 12144, USACorrespondence: Elbadawy A Kamoun Email e-b.kamoun@tu-bs.de; badawykamoun@yahoo.comBackground: 6-Mercaptopurine (6-MP) is a potential anti-cancer agent which its therapeutic and limitation applicability due to its high toxicity.Objective: Herein, 6-MP was loaded into tri-layered sandwich nanofibrous scaffold (the top layer composed of poly methyl methacrylate/polycaprolactone (PMMA/PCL), the middle layer was PCL/PMMA/6-MP, and the bottom layer was PCL/PMMA to improve its bioactivity, adjusting the release-sustainability and reduce its toxicity.Methods: Electrospun tri-layered nanofibers composed of PCL/PMMA were utilized as nano-mats for controlling sustained drug release. Four groups of sandwich scaffold configurations were investigated with alteration of (PMMA: PCL) composition.Results: The sandwich scaffold composed of 2%PCL/4%PMMA/1%6-MP showed the best miscibility, good homogeneity and produced the smoothest nanofibers and low crystallinity. All fabricated 6-MP-loaded-PCL/PMMA scaffolds exhibited antimicrobial properties on the bacterial and fungal organisms, where the cytotoxicity evaluation proved the safety of scaffolds on normal cells, even at high concentration. Scaffolds provided a sustained-drug release profile that was strongly dependent on (PCL: PMMA). As (PCL: PMMA) decreased, the sustained 6-MP release from PCL/PMMA scaffolds increased. Results established that ∼ 18% and 20% of 6-MP were released after 23h from (4%PCL/4%PMMA/1%6-MP) and (2%PCL/4%PMMA/1%6-MP), respectively, where this release was maintained for more than 20 days. The anti-cancer activity of all fabricated scaffolds was also investigated using different cancerous cell lines (e.g., Caco-2, MDA, and HepG-2) results showed that 6-MP-loaded-nanofibrous mats have an anti-cancer effect, with a high selective index for breast cancer. We observed that viability of a cancer cell was dropped to about 10%, using nanofibers containing 2%PCL/4%PMMA/1%6-MP.Conclusion: Overall, the PCL: PMMA ratio and sandwich configuration imparts a tight control on long-term release profile and initial burst of 6-MP for anticancer treatment purposes.Keywords: sandwich scaffold, PCL/PMMA, 6-MP, sustained drug release, anticancer, 6-Mercaptopurine, polycaprolactone/poly methyl methacrylate

Hala M Helal,1 Wael M Samy,1 Elbadawy A Kamoun,2,3 Esmail M El-Fakharany,4 Doaa A Abdelmonsif,5,6 Rania G Aly,7 Sana M Mortada,1 Marwa A Sallam1 1Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt; 2Polymeric Materials Research Dep., Advanced Technology and New Materials Research Institute (ATNMRI), City of Scientific Research and Technological Applications (SRTA-City), New Borg Al-Arab City, Alexandria, 21934, Egypt; 3Nanotechnology Research Center (NTRC), The British University in Egypt (BUE), El- Sherouk City, Cairo, 11837, Egypt; 4Proteins Research Dep., Genetic Engineering and Biotechnology Research Institute (GEBRI), City of Scientific Research and Technological Applications (SRTA-City), New Borg Al-Arab City, Alexandria, 21934, Egypt; 5Department of Medical Biochemistry, Faculty of Medicine, Alexandria University, Alexandria, 21521, Egypt; 6Center of Excellence for Research in Regenerative Medicine and Applications (CERRMA), Faculty of Medicine, Alexandria University, Alexandria, 21521, Egypt; 7Department of Surgical Pathology, Faculty of Medicine, Alexandria University, Alexandria, 21521, EgyptCorrespondence: Marwa A SallamDepartment of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, EgyptTel +20 3 4868256Fax +20 3 4871668Email marwa.sallam@alexu.edu.egElbadawy A KamounPolymeric Materials Research Dep., Advanced Technology and New Materials Research Institute (ATNMRI), City of Scientific Research and Technological Applications (SRTA-City), New Borg Al-Arab City, Alexandria, 21934, EgyptTel +20 1283320302Email e-b.kamoun@tu-bs.deBackground: Tacrolimus (TAC) is a powerful immunosuppressive agent whose therapeutic applicability is confined owing to its systemic side effects.Objective: Herein, we harnessed a natural polymer based bioconjugate composed of maltodextrin and α-tocopherol (MD-α-TOC) to encapsulate TAC as an attempt to overcome its biological limitations while enhancing its therapeutic anti-rheumatic efficacy.Methods: The designed TAC loaded maltodextrin-α-tocopherol nano-micelles (TAC@MD-α-TOC) were assessed for their physical properties, safety, toxicological behavior, their ability to combat arthritis and assist bone/cartilage formation.Results: In vitro cell viability assay revealed enhanced safety profile of optimized TAC@MD-α-TOC with 1.6- to 2-fold increase in Vero cells viability compared with free TAC. Subacute toxicity study demonstrated a diminished nephro- and hepato-toxicity accompanied with optimized TAC@MD-α-TOC. TAC@MD-α-TOC also showed significantly enhanced anti-arthritic activity compared with free TAC, as reflected by improved clinical scores and decreased IL-6 and TNF-α levels in serum and synovial fluids. Unique bone formation criteria were proved with TAC@MD-α-TOC by elevated serum and synovial fluid levels of osteocalcin and osteopontin mRNA and proteins expression. Chondrogenic differentiation abilities of TAC@MD-α-TOC were proved by increased serum and synovial fluid levels of SOX9 mRNA and protein expression.Conclusion: Overall, our designed bioconjugate micelles offered an excellent approach for improved TAC safety profile with enhanced anti-arthritic activity and unique bone formation characteristics.Keywords: polymeric micelles, vitamin E, osteopontin, SOX9, rheumatoid

Sarah A El-Lakany,1 Ahmed I Abd-Elhamid,2 Elbadawy A Kamoun,3,4 Esmail M El-Fakharany,5 Wael M Samy,1 Nazik A Elgindy1 1Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; 2Nanotechnology and Composite Material Research Department, Advanced Technology and New Materials Research Institute, City of Scientific Research and Technological Applications (SRTA-City), Alexandria 21934, Egypt; 3Polymeric Materials Research Department, Advanced Technology and New Materials Research Institute, City of Scientific Research and Technological Applications (SRTA-City), Alexandria 21934, Egypt; 4Nanotechnology Research Center (NTRC), The British University in Egypt (BUE), El-Sherouk City, Cairo 11837, Egypt; 5Therapeutic and Protective Proteins Laboratory, Protein Research Department, Genetic Engineering and Biotechnology Research Institute, City of Scientific Research and Technological Applications (SRTA-City), Alexandria 21934, EgyptCorrespondence: Sarah A El-LakanyDepartment of Industrial Pharmacy Faculty of Pharmacy, Alexandria University, 1 El Khartoum Square, PO Box 21521, Alexandria, EgyptTel +20 3 1002828663Fax +20 3 4871668Email sarah.ellakany@alexu.edu.egObjectives: Novel α-bisabolol (BIS)-loaded citric acid cross-linked zein nanofibrous scaffolds (C-ZNFs) were proposed to serve as safe platforms for promoting wound repair in rats.Methods: ZNFs were synthesized using electrospinning technique, then NFs, with adequate water resistance, were produced using citric acid as a safe cross-linker.Results: Compared to the uncross-linked ZNFs, cross-linking with 7% w/w citric acid decreased swelling index by 3 folds, while the tensile strength and the contact angle were enhanced to 2.5 and 3.8 folds, respectively. SEM images showed beads-free homogeneous NFs with a fully inter-connected 3D-network, where the average diameter of optimized C-ZNFs was 181.7±50 nm. After 24 h, C-ZNFs exhibited a decreased BIS release rate (45.6%), compared to uncross-linked mats (84.9%). By increasing BIS concentration, the cell adhesion (WI38 fibroblasts) was improved which can be attributed mainly to BIS activation of transforming growth factor-beta (TGF-β1). The MTT-OD obtained values indicated that all tested zein scaffolds significantly enhanced the viability of WI38 fibroblasts, compared to the control after 48h of incubation which can be referred to the proliferative potential of zein by provoking cell spreading process. The scratch wound assay demonstrated that BIS-loaded ZNF scaffolds showed accelerated migration and proliferation of fibroblasts expressed by significantly higher wound closure rates compared to the control sample. BIS-loaded-C-ZNFs prominently accelerated tissue regeneration for wound closure demonstrated by entirely grown epithelium with normal keratinization and rapid wound contraction, compared to the control. Immunohistochemical results confirmed the superiority of BIS-loaded-C-ZNFs, where the observed reduced NF-κB and the elevated cytokeratin expressions confirmed the anti-inflammatory and proliferative effects of the scaffolds, respectively.Conclusion: In-vitro, optimized C-ZNFs offered a satisfactory cytocompatibility, adhesion and healing which were consistent with the in-vivo results. BIS-loaded-C-ZNFs could be regarded as a promising and effective biomaterial for tissue regeneration and for accelerating the wound healing process.Keywords: cell compatibility, electrospinning, German chamomile, fiber mats

The escalating interest in bacterial cellulose (BC) confronts a substantial obstacle due to its biologically inert properties. Hence, BC was modified with ethanolic mango peel extract (EEMP) for various industrial and medical applications of the novel nanocomposite (BC/EEMP). High-performance liquid chromatography (HPLC) delineated the phenolic composition of EEMP, revealing a repertoire of polyphenolic compounds, notably chlorogenic acid, gallic acid, catechin, and ellagic acid. EEMP exhibited broad-spectrum antimicrobial activity against Candida albicans and Staphylococcus aureus, with MIC of 0.018 mg/mL and 0.009 mg/mL, respectively. The removal mechanism of Pb 2+ and Ni 2+ by BC/EEMP nanocomposite membrane via SEM, EDX, FT-IR, and XRD was characterized, indicating deposition and aggregation of heavy metals with diminished porosity. Heavy metal removal optimization using the Box-Behnken design achieved maximal removal of 95.5 % and 90 % for Pb 2+ and Ni 2+ , respectively. Moreover, BC/EEMP nanocomposite demonstrated selective dose-dependent anticancer activity toward hepatoma (HepG-2, IC 50 of 208.8 μg/mL), skin carcinoma (A431, IC 50 of 216.7 μg/mL), and breast carcinoma (MDA, IC 50 of 197.5 μg/mL), attributed to the enhanced availability of biologically active polyphenolic compounds and physical characteristics of BC. This study underscores the remarkable potential of BC/EEMP nanocomposite for multifaceted industrial and biomedical applications, marking a pioneering contribution to the field., 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 article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Microbial enzymes are crucial catalysts in various industries due to their versatility and efficiency. The microbial enzymes market has recently expanded due to increased demand for many reasons. Among them are eco-friendly solutions, developing novel microbial strains with enhanced enzymes that perform under harsh conditions, providing sustainability, and raising awareness about the benefits of enzyme-based products. By 2030, the global enzyme market is expected to account for $525 billion, with a growth rate of 6.7 %. L-asparaginase and L-glutaminase are among the leading applied microbial enzymes in antitumor therapy, with a growing market share of 16.5 % and 9.5 %, respectively. The use of microbial enzymes has opened new opportunities to fight various tumors, including leukemia, lymphosarcoma, and breast cancer, which has increased their demand in the pharmaceutical and medicine sectors. Despite their promising applications, commercial use of microbial enzymes faces challenges such as short half-life, immunogenicity, toxicity, and other side effects. Therefore, this review explores the industrial production, purification, formulation, and commercial utilization of microbial enzymes, along with an overview of the global enzyme market. With ongoing discoveries of novel enzymes and their applications, enzyme technology offers promising avenues for cancer treatment and other therapeutic interventions., 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.)

The wide biological activity of the Moringa oleifera represents a potential opportunity for developing selective cancer treatment drugs. The bioactive phytochemicals in Moringa seed extract (MSE) indicated large numbers of phytochemicals (21 compounds) with dominant abundance for cycloisolongifolene, 8,9-dehydro-9-vinyl, and chamazulene accounting for 12.7% and 12.19% of the total detected compounds. The MSE showed a potent anticancer effect toward Caco-2, MDA, and HepG-2 cells with half-maximal inhibitory concentration (IC 50 ) values of 9.15 ± 1.18, 4.85 ± 0.11, and 7.36 ± 0.22 µg/mL, respectively, with higher safety (≥31-folds) toward normal human cells (IC 50 of 150.7 ± 11.11 µg/mL). It appears that MSE stimulates selective-dose-dependent cell shrinkage, and nuclear condensation in the tumor cells, which finally induces the apoptosis pathway to increase its anticancer action. Additionally, MSE showed a potent capability to stimulate cell cycle arrest in both main checkpoint phases (G0/G1 and G2/M) of cell population growth. The apoptotic death stimulation was confirmed through upregulation of tumor protein p53 (p53) and cyclin-dependent kinase inhibitor p21 (p21) expression by more than three- to sixfold and downregulation of B-cell lymphoma 2 expression (threefold) in MSE-treated cells compared to 5-fluorouracil (5-FU)-treated tumor cells. Furthermore, the MSE revealed strong anti-inflammatory activity with significant antioxidant activity by lowering nitric oxide levels and enhancing the superoxide dismutase activity. On the other hand, the MSE revealed broad-spectrum antibacterial activity in a dose-dependent manner against Staphylococcus aureus minimum inhibitory concentration (MIC of 1.25 mg/mL), followed by Salmonella typhimurium (MIC of 1.23 mg/mL), whereas Escherichia coli was the least sensitive to MSE activity (MIC of 22.5 mg/mL) with significant antibiofilm activity against sensitive pathogens., (© 2024 Institute of Food Technologists.)

Hyaluronidase (hyase) is an endoglycosidase enzyme that degrades hyaluronic acid (HA) and is mostly known to be found in the extracellular matrix of connective tissues. In the current study, eleven bacteria isolates and one actinomycete were isolated from a roaster comb and screened for hyase production. Seven isolates were positive for hyase, and the most potent isolate was selected based on the diameter of the transparent zone. Based on the morphological, physiological, and 16 S rRNA characteristics, the most potent isolate was identified as Brucella intermedia MEFS with accession number OR794010. The environmental conditions supporting the maximum production of hyase were optimized to be incubation at 30 ºC for 48 h and pH 7, which caused a 1.17-fold increase in hyase production with an activity of 84 U/mL. Hyase was purified using a standard protocol, including precipitation with ammonium sulphate, DEAE as ion exchange chromatography, and size exclusion chromatography using Sephacryle S100, with a specific activity of 9.3-fold compared with the crude enzyme. The results revealed that the molecular weight of hyase was 65 KDa, and the optimum conditions for hyase activity were at pH 7.0 and 37 °C for 30 min. The purified hyase showed potent anticancer activities against colon, lung, skin, and breast cancer cell lines with low toxicity against normal somatic cells. The cell viability of hyase-treated cancer cells was found to be in a dose dependent manner. Hyase also controlled the growth factor-induced cell cycle progression of breast cancer cells and caused relative changes in angiogenesis-related genes as well as suppressed many pro-inflammatory proteins in MDA cells compared with 5-fluorouracil, indicating the significant role of hyase as an anticancer agent. In addition, hyase recorded the highest DPPH scavenging activity of 65.49% and total antioxidant activity of 71.84% at a concentration of 200 µg/mL., (© 2024. The Author(s).)

The prevalent life-threatening microbial and cancer diseases and lack of effective pharmaceutical therapies created the need for new molecules with antimicrobial and anticancer potential. Bee venom (BV) was collected from honeybee workers, and melittin (NM) was extracted from BV and analyzed by urea-polyacrylamide gel electrophoresis (urea-PAGE). The isolated melittin was hydrolyzed with alcalase into new bioactive peptides and evaluated for their antimicrobial and anticancer activity. Gel filtration chromatography fractionated melittin hydrolysate (HM) into three significant fractions (F1, F2, and F3), that were characterized by electrospray ionization mass spectrometry (ESI-MS) and evaluated for their antimicrobial, anti-biofilm, antitumor, and anti-migration activities. All the tested peptides showed antimicrobial and anti-biofilm activities against Gram-positive and Gram-negative bacteria. Melittin and its fractions significantly inhibited the proliferation of two types of cancer cells (Huh-7 and HCT 116). Yet, melittin and its fractions did not affect the viability of normal human lung Wi-38 cells. The IC 50 and selectivity index data evidenced the superiority of melittin peptide fractions over intact melittin. Melittin enzymatic hydrolysate is a promising novel product with high potential as an antibacterial and anticancer agent., 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 El-Didamony, Kalaba, Sharaf, El-Fakharany, Osman, Sitohy and Sitohy.)

This study aimed to investigate the potential of cinnamon oil nanoemulsion (CONE) as an antibacterial agent against clinical strains of colistin-resistant Klebsiella pneumoniae and its anticancer activity. The prepared and characterized CONE was found to have a spherical shape with an average size of 70.6 ± 28.3 nm under TEM and a PDI value of 0.076 and zeta potential value of 6.9 mV using DLS analysis. The antibacterial activity of CONE against Klebsiella pneumoniae strains was investigated, and it was found to have higher inhibitory activity (18.3 ± 1.2-30.3 ± 0.8 mm) against the tested bacteria compared to bulk cinnamon oil (14.6 ± 0.88-20.6 ± 1.2) with MIC values ranging from 0.077 to 0.31 % v/v which equivalent to 0.2-0.82 ng/ml of CONE. CONE inhibited the growth of bacteria in a dose and time-dependent manner based on the time-kill assay in which Klebsiella pneumoniae B-9 was used as a model among the bacterial strains under investigation. The study also investigated the expression of the mcr-1 gene in the Klebsiella pneumoniae strains and found that all strains were positive for the gene expression and subsequently its presence. The level of mcr-1 gene expression among the B-2, B-4, B-9, and B-11 control strains and that treated with colistin was similar, but it was different in both B-5 and B-2. However, all strains exhibited a significant downregulation in gene expression (ranging from 3.97 to 8.7-fold) after their treatment with CONE. Additionally, the CONE-treated bacterial cells appeared with a great deformation compared with control cells under TEM. Finally, CONE exhibited selective toxicity against different cancer cell lines depending on comparison with the normal cell lines., Competing Interests: Declaration of competing interest We declare that we have no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Therapeutic proteins have been employed for centuries and reached approximately 50 % of all drugs investigated. By 2023, they represented one of the top 10 largest-selling pharma products ($387.03 billion) and are anticipated to reach around $653.35 billion by 2030. Growth hormones, insulin, and interferon (IFN α, γ, and β) are among the leading applied therapeutic proteins with a higher market share. Protein-based therapies have opened new opportunities to control various diseases, including metabolic disorders, tumors, and viral outbreaks. Advanced recombinant DNA biotechnology has offered the production of therapeutic proteins and peptides for vaccination, drugs, and diagnostic tools. Prokaryotic and eukaryotic expression host systems, including bacterial, fungal, animal, mammalian, and plant cells usually applied for recombinant therapeutic proteins large-scale production. However, several limitations face therapeutic protein production and applications at the commercial level, including immunogenicity, integrity concerns, protein stability, and protein degradation under different circumstances. In this regard, protein-engineering strategies such as PEGylation, glycol-engineering, Fc-fusion, albumin conjugation, and fusion, assist in increasing targeting, product purity, production yield, functionality, and the half-life of therapeutic protein circulation. Therefore, a comprehensive insight into therapeutic protein research and findings pave the way for their successful implementation, which will be discussed in the current review., 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.)

Several antiviral agents lost their efficacy due to their severe side effects and virus mutations. This study aimed to identify and optimize the conditions for exopolysaccharide (EPS) production from a newly isolated cyanobacterium, Acaryochloris Al-Azhar MNE ON864448.1, besides exploring its antiviral activity. The cyanobacterial EPS was purified through DEAE-52 cellulose column with a final yield of 83.75%. Different analysis instruments were applied for EPS identification, including Fourier-transform infrared (FT-IR) spectroscopy, thermogravimetric analysis (TGA), and gas chromatographic-mass spectrometry (GC-MS). Plackett-Burman's design demonstrated that working volume (X1), EDTA (X2), inoculum size (X3), CaCl 2 (X4), and NaCl (X5) are the most important variables influencing EPS production. Central composite design (CCD) exhibited maximum EPS yield (9.27 mg/mL) at a working volume of 300 mL in a 1 L volumetric flask, EDTA 0.002 g/L, inoculum size 7%, CaCl 2 0.046 g/L, and NaCl 20 g/L were applied. EPS showed potent antiviral activities at different stages of herpes simplex virus type-1 and 2 (HSV-1, HSV-2), adenovirus (ADV) and coxsackievirus (A16) infections. The highest half-maximal inhibitory concentration (IC 50 ) (6.477 µg/mL) was recorded during HSV-1 internalization mechanism, while the lowest IC 50 (0.005669 µg/mL) was recorded during coxsackievirus neutralization mechanism., (© 2024. The Author(s).)

This work aims to develop plant extract-loaded electrospun nanofiber as an effective wound dressing scaffolds for topical wound healing. Electrospun nanofibers were fabricated from Syzygium cumini leaf extract (SCLE), poly(lactic- co -glycolic acid) (PLGA), poly(methyl methacrylate) (PMMA), collagen and glycine. Electrospinning conditions were optimized to allow the formation of nanosized and uniform fibers that display smooth surface. Morphology and swelling behavior of the formed nanofibers were studied. In addition, the antibacterial activity of the nanofibers against multidrug-resistant and human pathogens was assessed by agar-well diffusion. Results showed that nanofibers containing Syzygium cumini extract at concentrations of 0.5 and 1% w/v exhibited greater antibacterial activity against the tested Gram-positive ( i.e. , Staphylococcus aureus , Candida albicans , Candida glabrata and Bacillus cereus ) and Gram-negative ( i.e. , Salmonella paratyphi and Escherichia coli ) pathogens compared to the same concentrations of the plain extract. Furthermore, in vivo wound healing was evaluated in Wistar rats over a period of 14 days. In vivo results demonstrated that nanofiber mats containing SCLE and collagen significantly improved wound healing within two weeks, compared to the control untreated group. These findings highlight the potential of fabricated nanofibers in accelerating wound healing and management of topical acute wounds., Competing Interests: The authors declare that they have no conflict of interest., (This journal is © The Royal Society of Chemistry.)

A new chitosan Schiff base was developed via the reaction of chitosan (CH) with 2-chloro-3-formyl-7-ethoxy quinoline (Q) derivative. The alteration in the chemical structure and morphology of CHQ derivative was confirmed by 1 H NMR, FT-IR spectroscopy and SEM analysis. The antibacterial activity was considerably promoted with increasing quinoline concentration up to 1 M with maximal inhibition reached 96 and 77% against Staphylococcus haemolyticus and Escherichia coli, respectively. Additionally, CHQ derivative afforded higher ABTS ·+ radical scavenging activity reached 59% compared to 13% for native chitosan, approving its acceptable antioxidant activity. Moreover, the developed CHQ derivative can stimulate the glucose uptake in HepG-2 and yeast cells, while better inhibition of α-amylase and α-glucosidase was accomplished with maximum values of 99.78 and 92.10%, respectively. Furthermore, the molecular docking simulation clarified the binding mode of CHQ derivative inside the active site of α-amylase and α-glucosidase, suggesting its potential use as diabetes mellitus drug. The DFT calculations indicated an improvement in the electronic properties of CHQ with a lower energy band gap reached 4.05eV compared to 5.94eV for CH. The cytotoxicity assay revealed the safety of CHQ towards normal HSF cells, hypothesizing its possible application as non-toxic antibacterial, antioxidant, and antidiabetic agent for biomedical applications., (© 2023. The Author(s).)

Background: CLA (conjugated linoleic acid)-mediated activation of the schistosome tegument-associated sphingomyelinase and consequent disruption of the outer membrane might allow host antibodies to access the apical membrane antigens. Here, we investigated a novel approach to enhance specific antibody delivery to concealed surface membrane antigens of Schistosoma mansoni utilising antibody-conjugated-CLA nanomicelle technology., Methodology/principal Findings: We invented and characterised an amphiphilic CLA-loaded whey protein co-polymer (CLA-W) as an IV injectable protein nanocarrier. Rabbit anti-Schistosoma mansoni infection (anti-SmI) and anti-Schistosoma mansoni alkaline phosphatase specific IgG antibodies were purified from rabbit sera and conjugated to the surface of CLA-W co-polymer to form antibody-conjugated-CLA-W nanomicelles (Ab-CLA-W). We investigated the schistosomicidal effects of CLA-W and Ab-CLA-W in a mouse model of Schistosoma mansoni against early and late stages of infection. Results showed that conjugation of nanomicelles with antibodies, namely anti-SmI, significantly enhanced the micelles' schistosomicidal and anti-pathology activities at both the schistosomula and adult worm stages of the infection resulting in 64.6%-89.9% reductions in worm number; 72.5-94% and 66.4-85.2% reductions in hepatic eggs and granulomas, respectively. Treatment induced overall improvement in liver histopathology, reducing granuloma size and fibrosis and significantly affecting egg viability. Indirect immunofluorescence confirmed CLA-W-mediated antigen exposure on the worm surface. Electron microscopy revealed extensive ultrastructural damage in worm tegument induced by anti-SmI-CLA-W., Conclusion/significance: The novel antibody-targeted nano-sized CLA delivery system offers great promise for treatment of Schistosoma mansoni infection and control of its transmission. Our in vivo observations confirm an immune-mediated enhanced effect of the schistosomicidal action of CLA and hints at the prospect of nanotechnology-based immunotherapy, not only for schistosomiasis, but also for other parasitic infections in which chemotherapy has been shown to be immune-dependent. The results propose that the immunodominant reactivity of the anti-SmI serum, Schistosoma mansoni fructose biphosphate aldolase, SmFBPA, merits serious attention as a therapeutic and vaccine candidate., Competing Interests: The authors have declared that no competing interests exist, (Copyright: © 2023 Amer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Cyanobacteria are a potential source of promising secondary metabolites with different biological activities, including antibacterial, antiviral, antifungal, antiprotozoal, and anticancer activities. To combat the emergence of antibiotic resistance, there is an urgent requirement for new drugs, and cyanobacteria metabolites can constitute alternative new antibacterial medication. The chemical complexity of their exopolysaccharides indicates that they have the potential to be bioactive molecules with many biological activities. The present study aimed to produce and optimise a novel alginate polymer from a newly isolated cyanobacterium, S. algini MNE ON864447, in addition to its promising antibacterial activity. We successfully isolated a new cyanobacterium strain, S. algini MNE ON864447 from the Nile River, which produces alginate as an extracellular polymeric substance. The isolated cyanobacterial alginate was identified using a set of tests, including FTIR, TLC, HPLC, GC-MS, and 1 H NMR. Plackett-Burman statistical design showed that working volume (X1), the incubation period (X2), and inoculum size (X3) are the most significant variables affecting the production of alginate. The highest alginate production (3.57 g/L) was obtained using 4% inoculum size in 400 mL medium/L conical flask after 20 days of the incubation period. The extracted alginate showed potent antibacterial activity against both Gram-negative and Gram-positive bacteria and Streptococcus mutants (NCTC10449) are the most sensitive tested pathogen for purified cyanobacterial alginate with inhibition zone diameters of 34 ± 0.1 mm at 10 mg/mL of purified alginate while Vibro cholera (NCTC 8021) the lowest sensitive one and showed inhibition zone diameters of 22.5 ± 0.05 mm at the same cyanobacterial alginate concentration. This antibacterial activity is a critical step in the development of antibacterial drugs and presents a new challenge to fight against multi-resistant bacteria., (© 2023. The Author(s).)

The ethanolic extract of Coleus forskohlii Briq leaves was employed in the green synthesis of zinc nanoparticles (Zn-NPs) by an immediate, one-step, and cost-effective method in the present study. Zn-NPs were coated with purified bovine lactoferrin (LF) and characterized through different instrumental analysis. The biosynthesized Zn-NPs were white in color revealing oval to spherical-shaped particles with an average size of 77 ± 5.50 nm, whereas LF-coated Zn-NPs (LF-Zn-NPs) revealed a larger particles size of up to 98 ± 6.40 nm. The biosynthesized Zn-NPs and LF-Zn-NPs revealed negatively charged surfaces with zeta-potentials of - 20.25 ± 0.35 and - 44.3 ± 3.25 mV, respectively. Interestingly, the LF-Zn-NPs showed potent in vitro retardation for SARS-CoV-2 entry to host cells by binding to the ACE2-receptor and spike protein receptor binding domain at IC 50 values of 59.66 and μg/mL, respectively. Additionally, the results indicated the ability of LF-Zn-NPs to inhibit SARS-CoV-2 replication by interfering with RNA-dependent RNA polymerase "RdRp" activity at IC 50 of 49.23 μg/mL. In vivo, the LF-Zn-NPs displayed a protective and therapeutic activity against induced pulmonary fibrosis in Bleomycin-treated male albino rats owing to its anti-inflammatory, antioxidant, and significant reduction in CRP, LDH, ferritin, and D-dimer levels. The obtained findings offer a promising route for biosynthesized Zn-NPs and LF-Zn-NPs as promising candidates against COVID-19., (© 2023. Springer Nature Limited.)

In this study, we aimed to develop hybrid antitumor compounds by synthesizing and characterizing novel N-substituted acrididine-1,8-dione derivatives, designed as hybrids of phthalimide and acridine-1,8-diones. We employed a three-step synthetic strategy and characterized all compounds using IR, 1 H NMR, 13 C NMR, and LC-MS. The cytotoxicity and antitumor activity of five compounds (8c, 8f, 8h, 8i, and 8L) against four cancer cell lines (H460, A431, A549, and MDA-MB-231) compared to human skin fibroblast cells were evaluated. Among the synthesized compounds, compound 8f showed promising activity against skin and lung cancers, with favorable IC 50 values and selectivity index. The relative changes in mRNA expression levels of four key genes (p53, TOP2B, p38, and EGFR) in A431 cells treated with the five synthesized compounds (8c, 8f, 8h, 8i, and 8L) were also investigated. Additionally, molecular docking studies revealed that compound 8f exhibited high binding affinity with TOP2B, p38, p53, and EGFR, suggesting its potential as a targeted anticancer therapy. The results obtained indicate that N-substituted acrididine-1,8-dione derivatives have the potential to be developed as novel antitumor agents with a dual mechanism of action, and compound 8f is a promising candidate for further investigation., (© 2023. Springer Nature Limited.)

Hepatocellular carcinoma (HCC) is one of the most lethal and prevalent cancers, closely associated with cirrhosis and fibrosis. This study aimed to assess the antitumor activity of oleic acid-liposomes (uncoated liposomes) upon coating with albumin against HCC. The in vitro studies revealed the high safety of the prepared uncoated and albumin-coated liposomes to normal HFB-4 cells (EC 100 of 35.57 ± 0.17 and 79.133 ± 2.92 µM, respectively) with significant anticancer activity against HepG-2 cells with IC 50 of 56.29 ± 0.91 and 26.74 ± 0.64 µM, respectively. The albumin-coated liposomes revealed superior apoptosis induction potential (80.7%) with significant upregulation of p53 gene expression ( > 7.0-fold), compared to OA. The in vivo study revealed that the administration of uncoated or albumin-coated liposomes (100 mg/kg) for six weeks markedly retarded the DENA-induced HCC in Wistar albino rates through regulating the liver enzymes, total bilirubin level, pro-inflammatory cytokines, and oxidative stress. Accordingly, the current study supports the in vitro and in vivo chemo-preventive feature of albumin-coated liposomes against HCC through modulation of apoptosis, improvement of the immune response, reduction of inflammation, and restoration of impaired oxidative stress, which is the first reported to the best of our knowledge.

Phycobiliproteins (PBPs) are a class of water-soluble pigments with a variety of biological functions that are present in red macroalgae and cyanobacterial species. The crude forms of phycocyanin (C-PC) from the blue green alga Arthrospira platensis and allophycocyanin (APC) from the red macroalga Corallina officinalis were extracted and purified by ammonium sulphate precipitation, anion exchange chromatography, and size exclusion chromatography methods, respectively. The obtained C-PC and APC from A. platensis and C. officinalis were 0.31 mg/mL and 0.08 mg/mL, respectively, with molecular masses of "17.0 KDa and 19.0 KDa" and "15.0 KDa and 17.0 KDa" corresponding to α and β subunits, respectively. FT-IR was used to characterize the purified APC and C-PC in order to look into their structures. Highly purified extracts (A620/A280 > 4.0) were obtained from subtractions' PC3 and PC4 that were tested for their biological activities. APC and C-PC crude extracts plus their fractions exhibited potent anti-oxidant in different ratios by using three techniques. PC1 showed high anti-inflammatory (75.99 and 74.55%) and anti-arthritic (78.89 and 76.92%) activities for C. officinalis and A. platensis, respectively compared with standard drugs (72.02 and 71.5%). The methanolic and water extracts of both species showed greater antibacterial efficacy against Gram +ve than Gram -ve marine bacteria. Our study shed light on the potential medical uses of C-PC and APC extracted from the tested species as natural substances in a variety of foods and drugs. Further investigations are required to explore the diverse chemical natures of distinct PBPs from different cyanobacteria and red algae because their amino acid sequences vary among different algal species., (© 2023. Springer Nature Limited.)

Colorectal cancer (CRC) is a malignant tumor recognized as a major cause of morbidity and mortality throughout the world. Therefore, novel liposomes of oleic acid coated with camel α-lactalbumin (α-LA coated liposomes) were developed for their potential antitumor activity against CRC, both in vitro and in DMH-induced CRC-modeled animal. In vitro results indicated the high safety of α-LA coated liposomes towards normal human cells with potent antitumor activity against Caco-2 cells at an IC 50 value of 57.01 ± 3.55 µM with selectivity index of 6.92 ± 0.48. This antitumor activity has been attributed to induction of the apoptotic mechanism, as demonstrated by nuclear condensation and arrest of Caco-2 cells in sub-G1 populations. α-LA coated liposomes also revealed a significant up-regulation of the p53 gene combined with a down-regulation of the Bcl2 gene. Moreover, in vivo results revealed that treatment of induced-CRC modeled animals with α-LA coated liposomes for six weeks markedly improved the CRC-disorders; this was achieved from the significant reduction in the values of AFP, CEA, CA19.9, TNF-α, IL-1β, MDA, and NO coupled with remarkable rise in SOD, GPx, GSH, CAT, and CD4+ levels. The histopathological findings asserted the therapeutic potential of α-LA coated liposomes in the treatment of CRC. Therefore, the present results proved the antitumor activity of α-LA coated liposomes against CRC through the restoration of impaired oxidative stress, improved immune response, and reduced inflammation.Communicated by Ramaswamy H. Sarma.

Severe acute respiratory syndrome 2019-new coronavirus (SARS-CoV-2) is a major global challenge caused by a pandemic disease, named 'COVID-19' with no effective and selective therapy available so far. COVID-19-associated mortality is directly related to the inability to suppress the viral infection and the uncontrolled inflammatory response. So, we investigated the antiviral efficiency of the nanofabricated and well-characterized lactoferrin-coated zinc nanoparticles (Lf-Zn-NPs) on SARS-CoV-2 replication and entry into host cells. Lf-Zn-NPs showed potent inhibition of the entry of SARS-CoV-2 into the host cells by inhibition of ACE2, the SARS-CoV-2 receptor. This inhibitory activity of Lf-Zn-NPs to target the interaction between the SARS-CoV-2 spike protein and the ACE2 receptor offers potent protection against COVID-19 outbreaks. Moreover, the administration of Lf-Zn-NPs markedly improved lung fibrosis disorders, as supported by histopathological findings and monitored by the significant reduction in the values of CRP, LDH, ferritin, and D-dimer, with a remarkable rise in CD4+, lung SOD, GPx, GSH, and CAT levels. Lf-Zn-NPs revealed therapeutic efficiency against lung fibrosis owing to their anti-inflammatory, antioxidant, and ACE2-inhibiting activities. These findings suggest a promising nanomedicine agent against COVID-19 and its complications, with improved antiviral and immunomodulatory properties as well as a safer mode of action., 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.)

Empagliflozin, a selective inhibitor of Na + -glucose cotransporter-2, has been reported to exert anti-inflammatory and anti-fibrotic effects in addition to autophagy modulation. Addressing the role of autophagy in allergic asthma revealed controversial results. The potential effect of empagliflozin treatment on airway inflammation and remodelling as well as autophagy modulation in a murine model of allergic asthma was investigated. Over a 7-week period, male BALB/c mice were sensitized and challenged by intraperitoneal injection and inhalation of ovalbumin, respectively. Animals were treated with empagliflozin (10 mg/kg; orally) and/or rapamycin (an autophagy inducer; 4 mg/kg; intraperitoneally) before every challenge. Methacholine-induced airway hyperresponsiveness was evaluated one day after the last challenge. After euthanasia, serum, bronchoalveolar lavage fluid, and lung tissues were collected for biochemical, histopathological, and immunohistochemical assessment. Results revealed that empagliflozin decreased airway hyperresponsiveness, serum ovalbumin-specific immunoglobulin E, and bronchoalveolar lavage total and differential leukocytic counts. Levels of inflammatory and profibrotic cytokines (IL-4, IL-5, IL-13, IL-17, and transforming growth factor-β1) were all inhibited. Moreover, empagliflozin preserved pulmonary microscopic architecture and alleviated bronchiolar epithelial thickening, goblet cell hyperplasia, fibrosis and smooth muscle hypertrophy. These effects were associated with inhibition of ovalbumin-activated autophagic flux, as demonstrated by decreased LC3B expression and LC3BII/I ratio, as well as increased P62 expression. However, the therapeutic potential of empagliflozin was inhibited when rapamycin was co-administered. In conclusion, this study demonstrates that empagliflozin has immunomodulatory, anti-inflammatory, and anti-remodelling properties in ovalbumin-induced allergic asthma and suggests that autophagic flux inhibition may play a role in empagliflozin's anti-asthmatic effects., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The present study aims to develop a novel nanocombination with high selectivity against several invasive cancer cells, sparing normal cells and tissues. Bovine lactoferrin (bLF) has recently captured the interest of numerous medical fields owing to its biological activities and well-known immunomodulatory effects. BLF is an ideal protein to be encapsulated or adsorbed into selenium nanocomposites (Se NPs) in order to produce stable nanocombinations with potent anticancer effects and improved immunological functions. The biosynthesis of the functionalized Se NPs was achieved using Rhodotorula sp. strain MZ312359 via a simultaneous bio-reduction approach to selenium sodium salts. The physicochemical properties of Se NPs using SEM, TEM, FTIR, UV Vis, XRD, and EDX confirmed the formation of uniform agglomerated spheres with a size of 18-40 nm. Se NPs were successfully embedded in apo-LF (ALF), forming a novel nanocombination of ALF-Se NPs with a spherical shape and an average nanosize of less than 200 nm. The developed ALF-Se NPs significantly displayed an effective anti-proliferation efficiency against many cancer cells, including MCF-7, HepG-2, and Caco-2 cell lines, as compared to Se NPs and ALF in free forms. ALF-Se NPs showed a significant selectivity impact (> 64) against all treated cancer cells at IC 50 63.10 ≤ μg/mL, as well as the strongest upregulation of p53 and suppression of Bcl-2, MMP-9, and VEGF genes. Besides, ALF-Se NPs were able to show the maximum activation of transcrition of key redox mediator (Nrf2) with suppression in reactive oxygen species (ROS) levels inside all treated cancer cells. This study demonstrates that this novel nanocombination of ALF-Se NPs has superior selectivity and apoptosis-mediating anticancer activity over free ALF or individual form of Se NPs., (© 2023. The Author(s).)

Pomegranate juice concentrate (PJC) is a rich source of polyphenols, which exhibit significant antioxidant activity and potential health benefits for disease prevention and therapy. In this study, the polyphenolic profile of PJC was investigated for the first time, and it was found that PJC can inhibit oxidative damage to bovine serum albumin (BSA) and deoxyribonucleic acid (DNA), as well as acetylcholinesterase, α-amylase, and tyrosinase activities. The primary polyphenols identified in PJC were 4-Hydroxy-3-Methoxybenzoate, epicatechin, catechin, rutin, ferulic acid, P-coumaric acid, and cinnamic acid. Additionally, PJC demonstrated potent antibacterial effects against human pathogens such as Streptococcus mutans and Aeromonas hydrophila and dose-dependently reduced the proliferation of colorectal, breast, and hepatic cancer cells via apoptosis. Furthermore, PJC blocked B-cell lymphoma 2 (BCl-2) and the expression of a potent cyclin-dependent kinase inhibitor (P21) and enhanced tumor protein (P53) expression, compared to both untreated cells and cells treated with fluoropyrimidine 5-fluorouracil (5-FU). As a result, PJC may be a beneficial ingredient in the formulation of emerging natural-compound-based chemotherapy and functional foods and could be utilized by the food, nutraceutical, and pharmaceutical industries.

Palm fruit pollen extract (PFPE) is a natural source of bioactive polyphenols. The primary aim of the study was to determine the antioxidant, antimicrobial, anticancer, enzyme inhibition, bovine serum albumin (BSA), and DNA-protective properties of PFPE and identify and quantify the phenolic compounds present in PFPE. The results demonstrated that PFPE exhibited potent antioxidant activity in various radical-scavenging assays, including (2,2-diphenyl-1-picrylhydrazyl) (DPPH • ), 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS • ), nitric oxide (NO), ferric-reducing/antioxidant power (FRAP), and total antioxidant capacity (TAC). PFPE also displayed antimicrobial activity against several pathogenic bacteria. Similarly, PFPE reduced acetylcholinesterase, tyrosinase, and α-amylase activities. PFPE has been proven to have an anticancer effect against colon carcinoma (Caco-2), hepatoma (HepG-2), and breast carcinoma (MDA) cancer cells. Apoptosis occurred in PFPE-treated cells in a dose-dependent manner, and cell cycle arrest was observed. Furthermore, in breast cancer cells, PFPE down-regulated Bcl-2 and p21 and up-regulated p53 and Caspase-9. These results show that PFPE constitutes a potential source of polyphenols for pharmaceutical, nutraceutical, and functional food applications.

Wound healing has grown to be a significant problem at a global scale. The lack of multifunctionality in most wound dressing-based biopolymers prevents them from meeting all clinical requirements. Therefore, a multifunctional biopolymer-based tri-layered hierarchically nanofibrous scaffold in wound dressing can contribute to skin regeneration. In this study, a multifunctional antibacterial biopolymer-based tri-layered hierarchically nanofibrous scaffold comprising three layers was constructed. The bottom and the top layers contain hydrophilic silk fibroin (SF) and fish skin collagen (COL), respectively, for accelerated healing, interspersed with a middle layer of hydrophobic poly-3-hydroxybutyrate (PHB) containing amoxicillin (AMX) as an antibacterial drug. The advantageous physicochemical properties of the nanofibrous scaffold were estimated by SEM, FTIR, fluid uptake, contact angle, porosity, and mechanical properties. Moreover, the in vitro cytotoxicity and cell healing were assessed by MTT assay and the cell scratching method, respectively, and revealed excellent biocompatibility. The nanofibrous scaffold exhibited significant antimicrobial activity against multiple pathogenic bacteria. Furthermore, the in vivo wound healing and histological studies demonstrated complete wound healing in wounded rats on day 14, along with an increase in the expression level of the transforming growth factor-β1 (TGF-β1) and a decrease in the expression level of interleukin-6 (IL-6). The results revealed that the fabricated nanofibrous scaffold is a potent wound dressing scaffold, and significantly accelerates full-thickness wound healing in a rat model.

The sustainable management of toner waste (T-raw) was performed via carbonization at 500 °C (T-500) and 600 °C (T-600) to produce iron oxide-nanographene nanohybrid (FeO-NG) for activating persulfate (PS) to efficiently degrade dyes (methylene blue, MB), antibiotics (sulfamethazine, SMZ), and pesticides (diazinon, DZN). Morphology, crystallinity, chemical structure, chemical composition, surface area, and pore size distribution of the synthesized materials were investigated using various analyses. High degradation ratios of MB were attained over a wide pH range (2-7), and the optimum operating conditions were determined. The FeO-NG/PS system was tested in different water matrices. MB degradation efficiency dropped from 80.13% to 78.56% after five succeeding experiments, proving the high stability of T-500. Trapping experiments proved the major role of sulfate radicals and the minor contribution of singlet oxygen. The toxicity evaluation of the treated and untreated MB solutions was conducted via measuring the cell viability, showing an increase in cell viability ratio after the degradation of MB. The degradation efficiencies of DZN and SMZ were 97.54% and 83.7%, respectively and the mineralization ratios were 74.08% and 60.37% at initial concentrations of sulfamethazine and diazinon of 50 and 100 mg/L, respectively. The high degradation efficiency of emerging micropollutants as well as the inexpensiveness, and facile synthesis of the catalyst boost the prospect of applying the proposed system on an industrial scale., 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 Inc. All rights reserved.)

Biologically active phytochemicals from pumpkin reveal versatile medical applications, though little is known about their antiviral activity. The fucose-rich polysaccharide extraction conditions were optimized through Box-Behnken design and purified by column chromatography. The purified fucose-rich polysaccharide was characterized through SEM, FT-IR, 1 H NMR, XRD, TGA, and GS-MS. The analysis results revealed an irregular and porous surface of the purified polysaccharide with high fucose, rhamnose, galactose, and glucose contents. The tested fucose-rich polysaccharides revealed significant antioxidant and anti-inflammatory activity at very low concentrations. The purified fucose-rich polysaccharides exerted a broad-spectrum antiviral activity against both DNA and RNA viruses, accompanied by high safety toward normal cells, where the maximum safe doses (EC 100 ) were estimated to be about 3-3.9 mg/mL for both Vero and PBMC cell lines. Treatment of HCV, ADV7, HSV1, and HIV viruses with the purified polysaccharides showed a potent dose-dependent inhibitory activity with IC 50 values of 95.475, 20.96, 5.213, and 461.75 μg/mL, respectively. This activity was hypothesized to be through inhibiting the viral entry in HCV infection and inhibiting the reverse transcriptase activity in HIV. The current study firstly reported the antioxidant, anti-inflammatory, and antiviral activities of Cucurbita maxima fucose-rich polysaccharide against several viral infections., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

In this study, we identified a suitable precursor and good cellular compartmentalization for enhancing bioactive metabolites to produce biosynthetic zinc oxide nanoparticles (ZnO NPs). An effective medium for cultivating endophytic Streptomyces albus strain E56 was selected using several optimized approaches in order to maximize the yield of biosynthetic ZnO NPs. The highest biosynthetic ZnO NPs yield (4.63 g/L) was obtained when pipetting the mixed cell-free fractions with 100 mM of zinc sulfate as a precursor. The generation of biosynthetic ZnO NPs was quickly verified using a colored solution (white color) and UV-Visible spectroscopy (maximum peak, at 320 nm). On a small scale, the Taguchi method was applied to improve the culture medium for culturing the strain E56. As a result, its cell-dry weight was 3.85 times that of the control condition. And then the biosynthesis of ZnO NPs (7.59 g/L) was increased by 1.6 times. Furthermore, by using the Plackett-Burman design to improve the utilized biogenesis pathway, the biosynthesis of ZnO NPs (18.76 g/L) was increased by 4.3 times. To find the best growth production line, we used batch and fed batch fermentation modes to gradually scale up biomass output. All kinetics of studied cell growth were evaluated during fed-batch fermentation as follows: biomass yield was 271.45 g/L, yield coefficient was 94.25 g/g, and ZnO NPs yield was 345.32 g/L. In vitro, the effects of various dosages of the controllable biosynthetic ZnO NPs as antimicrobial and anticancer agents were also investigated. The treatments with controllable biosynthetic ZnO NPs had a significant impact on all the examined multidrug-resistant human pathogens as well as cancer cells., (© 2023. The Author(s).)

Bacterial cellulose (BC) is currently among the most promising natural polymers. However, the production costs and biological inactivity are still challenges. The current study exploited the enzymatically hydrolyzed prickly pear peels (PPP) for BC production, which supported about 2.94 g/L as the sole production medium. The BC production was further optimized through a central composite design, where the maximum BC production was 6.01 g/L at 68 % PPPE at pH 4 after 11 days of incubation at 20 °C. The produced BC was characterized by FT-IR spectroscopy, XRD, and SEM analysis, and the results showed that PPPE is a promising carbon source for pure BC production. The BC membrane was separately loaded with several fruit byproduct extracts to enhance its biological activity for multiple applications. BC loaded with pomegranate peel extract (BC/PPE) revealed significant broad-spectrum antimicrobial activity, followed by BC loaded with pomegranate molasses (BC/PM). The BC/PPE membrane enhanced the shelf-life storage of strawberry fruits by about 5 days, with a reduction in the fruits' weight loss of 15 % compared to the uncovered group. The current study revealed the successful application of PPE for sustainable BC production with its packaging potential for enhancing strawberry shelf-life when loaded with PPE or PM., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The promising features of most bacterial celluloses (BC) promote the continuous mining for a cost-effective production approach toward wide and sustainable applications. Herein, cantaloupe peels (CP) were successfully implemented for sustainable BC production. Results indicated that the enzymatically hydrolyzed CP supported the maximum BC production of approximately 3.49 g/L when used as a sole fermentation media. The produced BC was fabricated with polyvinyl alcohol (PVA) and chitosan (Ch), and loaded with green synthesized copper oxide nanoparticles (CuO-NPs) to improve its biological activity. The novel composite showed an antimicrobial activity against several human pathogens such as Staphylococcus aureus, Streptococcus mutans, Salmonella typhimurium, Escherichia coli, and Pseudomonas fluorescens. Furthermore, the new composite revealed a significant in vitro anticancer activity against colon (Caco-2), hepatocellular (HepG-2), and breast (MDA) cancer cells, with low IC 50 of 0.48, 0.27, and 0.33 mg/mL for the three cell lines, respectively. On the other hand, the new composite was remarkably safe for human skin fibroblast (HSF) with IC 50 of 1.08 mg/mL. Interestingly, the composite membranes exhibited lethal effects against all stages of larval instar and pupal stage compared with the control. In this study, we first report the diverse potential applications of BC/PVA/Ch/CuO-NPs composites based on green synthesized CuO-NPs and sustainably produced BC membrane., (© 2022. The Author(s).)

This study identifies promising potential of a novel and safer nanocombination of bovine milk lactoperoxidase (LPO) and lactoferrin (LF) to target breast cancer in vitro and in adult female albino rat model. Favorable selective anticancer effects of the prepared nanocombination were observed, in a dose-dependent manner, against both MCF-7 and MDA cell lines, sparing normal HFB-4 cells. The administration of LPO + LFNPs markedly improved the induced-breast cancer disorders, prolonged survival and reduced the values of serum TNF-α, IL1β, CD4 + , ALAT, ASAT, urea, creatinine, cholesterol and triglycerides with remarkable elevation in mammary SOD and GPx activity and GSH level. Moreover, the histopathological findings showed that LPO + LFNPs succeeded in prevention of mammary gland tumorigenesis. Superior efficacy of LPO + LFNPs was observed against pro-inflammatory cytokines through their anti-inflammatory and immunomodulatory properties. The treatment of LPO + LFNPs more significantly modulated the apoptosis and enhanced the expression of cell cycle regulator genes, which demonstrates a successful tumor therapy in vitro and in vivo. Therefore, this study provided evidence that the chemo-preventive feature of LPO + LFNPs may offer a novel alternative therapy for the treatment of breast cancer through enhances apoptosis pathway, improvement of immune response, reduction of inflammation and restoration of the impaired oxidative stress., Competing Interests: Declaration of competing interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The prevalence of opportunistic human fungal pathogens is increasing worldwide, and antimicrobial resistance is one of the greatest medical challenges the world faces. Therefore, this study aimed to develop a novel agent to control fungal pathogens. The honeybee products (honey, royal jelly, propolis, bee bread, and bee venom) were screened against unicellular fungal (UCF) pathogens (Cryptococcus neoformans, Kodamaea ohmeri, and Candida albicans) and the bee venom was only exhibited an inhibitory effect against them. The protein contents of crude bee venom were separated using the gel filtration technique into eight fractions which were visualized on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) to confirm the presence of five bands with molecular weights of 65, 43, 21, 15, and 3 KDa. Bee venom (BV) of Apis mellifera loaded chitosan nanoparticles were prepared by the ionotropic gelation method. The encapsulation efficiency%, average size, zeta potentials, and surface appearance by Transmission electron microscope (TEM) were evaluated for the prepared nanoparticles. The minimum inhibitory concentration (MIC) of crude BV and BV loaded chitosan nanoparticles (BV-CNPs) was evaluated against the offer mentioned UCF where the MIC values of crude BV were 6.25, 3.12 & 6.25 while MIC values in the case of BV-CNPs were decreased to 3.12, 3.12 & 1.56 mg/ml against C. neoformans, K. ohmeri and C. albicans, respectively. Also, the results showed that BV-CNPs suppressed the biofilm formation as well as yeast to hyphal transition formed by the examined UCF. These results revealed that BV-CNPs are a promising natural compound for fungal pathogens treatment., (© 2022. The Author(s).)

Objectives: Colistin (polymyxin E) is a bactericidal antibiotic used to treat severe infections caused by multidrug-resistant Gram-negative bacteria. The product of the mcr1 gene generates transferable plasmid-mediated colistin resistance, which has arisen as a worldwide health-care problem. This study aimed to isolate and identify colistin-resistant bacteria, and evaluate the ability of essential oils in its fights., Methods: Twenty-seven bacterial isolates were collected from patients who were admitted to the National Cancer Institute, Cairo, Egypt, and processed using standard microbiological methods. Essential oils were purchased from AB Chem Company, Egypt, screened for antibacterial, cytotoxic activity, and (GC-MS) analysis., Results: A total of 5 bacterial isolates were resistant to colistin with minimum inhibitory concentration (MIC) ranging from 6.25->200 µg/ml. Cinnamon oil exhibited the highest activity against colistin-resistant strains followed by thyme and eucalyptus oil. The (MIC) of cinnamon oils against resistant strains ranged from 4.88 to 312.5 µg/ml. Moreover, mcr-1 gene expression was extremely down-regulated after the treatment of bacterial strains with cinnamon oil and decreased to 20-35-fold. Examination of treated bacterial cells with sub-inhibitory concentrations under transmission electron microscopy showed various abnormalities occurred in most of these cells., Conclusions: Cinnamon oil exhibits antibacterial activity against colistin-resistant strains, showing it as a promising natural alternative in clinical therapy.

<b>Background and Objective:</b> Epilepsy is one of the normal neurological problems that came about because of strange electrical movements and prompt serious and far-reaching cell misfortune in the mind. This study aimed to investigate if a nano-Chitosan formulation loaded with bovine milk lactoperoxidase (LPO) and lactoferrin (LF) could prevent Lithium Chloride/Pilocarpine-induced epilepsy in rats or not. <b>Materials and Methods:</b> Adult male rats (200-250 g) were partitioned into four groups (8 animals each) as follows: Group (1) Normal rats served as control group and received saline orally, group (2) Normal rats ingested with a daily oral dose of LPO and LF-NPS formulation at 50 mg kg<sup></sup><sup>1</sup>, group (3) Pilocarpine-induced epileptic rats and group (4) Epilepsy-modeled rats were treated with LPO+LF NPs (50 mg/kg/day, orally) for 6 weeks. <b>Results:</b> The results revealed that the administration of LPO+LF-NPs markedly improved the induced-epilepsy disorders, this was monitored from the significant reduction in the values of caspase-3, TNF-α, IL-1β, CD4<sup>+</sup>, MDA and NO coupled with remarkable raise in AchE-ase, dopamine, serotonin, SOD and GPx, CAT and GSH values in both brain regions. <b>Conclusion:</b> This study supported the anti-epilepsy features of LPO+LF-NPS against Lithium Chloride/Pilocarpine-induced epilepsy in rats through the improvement of the immune response, reduction of inflammation and restoration of the impaired oxidative stress status.

The healthy immune system eliminates pathogens and maintains tissue homeostasis through extraordinarily complex networks with feedback systems while avoiding potentially massive tissue destruction. Many parameters influence humoral and cellular vaccine responses, including intrinsic and extrinsic, environmental, and behavioral, nutritional, perinatal and administrative parameters. The relative contributions of persisting antibodies and immune memory as well as the determinants of immune memory induction, to protect against specific diseases are the main parameters of long-term vaccine efficacy. Natural and vaccine-induced immunity and monoclonal antibody immunotherapeutic, may be evaded by SARS-CoV-2 variants. Besides the complications of the production of COVID-19 vaccinations, there is no effective single treatment against COVID-19. However, administration of a combined treatment at different stages of COVID-19 infection may offer some cure assistance. Combination treatment of antiviral drugs and immunomodulatory drugs may reduce inflammation in critical COVID-19 patients with cytokine release syndrome. Molnupiravir, remdesivir and paxlovid are the approved antiviral agents that may reduce the recovery time. In addition, immunomodulatory drugs such as lactoferrin and monoclonal antibodies are used to control inflammatory responses in their respective auto-immune conditions. Therefore, the widespread occurrence of highly transmissible variants like Delta and Omicron indicates that there is still a lot of work to be done in designing efficient vaccines and medicines for COVID-19. In this review, we briefly discussed the immunological response against SARS-CoV-2 and the vaccines approved by the World Health Organization (WHO) for COVID-19, their mechanisms, and side effects. Moreover, we mentioned various treatment trials and strategies for COVID-19., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Date palm fruit seed ( Phoenix dactylifera L.) extract (DSE), an under-utilized resource, is a rich source of polyphenols with high potency for disease prevention and antioxidative activities. For the first time, the present study demonstrated that DSE inhibits labile iron activity and DNA and BSA damage and inhibits acetylcholinesterase and tyrosinase activities. Moreover, DSE reduces the proliferation of hepatic, colorectal, and breast cancer cells dose-dependently through apoptotic mechanisms. Furthermore, DSE significantly suppressed the expression of both BCl-2 and P21 genes and increased the P53 expression level when compared with the untreated cells and the 5-FU treated cells. These findings suggest a strong potential for DSE in protecting against the iron-catalyzed ferroptosis that results in programmed cell death. The results also confirm the efficacy of DSE against cancer cells. Therefore, DSE constitutes a valuable candidate for developing functional foods and for natural compound-based chemotherapy for the pharmaceutical and nutraceutical industries.

There is an urgent need in the medicinal fields to discover biocompatible nanoformulations with low cytotoxicity, which provide new strategies for promising therapies for several types of tumors. Bovine lactoperoxidase (LP) and lactoferrin (LF) have recently attracted attention in medicine for their antitumor activities with recognized safety pattern. Both LP and LF are suitable proteins to be coated or adsorbed to Cu and Fe nanometals for developing stable nanoformulations that boost immunity and strong anticancer effects. New nanometals of Cu and Fe NPs embedded in LP and LF forming novel nanocombinations of LP-CNPs and LF-FNPs had a spherical shape with an average nanosize of about 21 nm. The combination of LP-CNPs and LF-FNPs significantly exhibited the highest growth inhibitory efficacy, in terms of effectively lowering the half-maximal inhibitory concentration (IC 50 ) values, against Caco-2, HepG2 and MCF7 cells comparing to nanometals, LP, LF and individual nanoproteins (LP-CNPs or LF-FNPs). The highest apoptotic effect of this nanocombination (LP-CNPs and LF-FNPs) was confirmed by the highest percentages of annexin-stained apoptotic cells and G0 population with the strongest alteration in the expression of two well-characterized apoptosis guards (p53 and Bcl-2) and the maximum suppression in the proliferation marker (Ki-67). Also, the in silico analysis predicted that LP-CNPs and LF-FNPs enhanced AMP-activated protein kinase (AMPK, p53 activator) activity and inhibited cancer migration-related proteases (cathepsin B and matrix metalloproteinase (MMP)-9). Our results offer for the first time that these novel nanocombinations of LP and LF were superior in their selectivity and apoptosis-mediating anticancer activity to Cu and Fe nanometals as well as the free form of these proteins or their individual nanoforms., (© 2022. The Author(s).)

Grape seed extract from (Vitis vinifera) (VGSE) is an excellent source of various polyphenols that exhibit highly potent antioxidant and disease prevention properties. Although numerous biological activities, with potential for improving human health, have been reported for VGSE, there is a lack of data relating to the health benefits of VGSE on DNA damage, protein damage, labile iron activity, and enzyme inhibitory effects. This investigation demonstrated, for the first time, that VGSE inhibits DNA and BSA damage and labile iron activity in-vitro. Moreover, VGSE also inhibited in-vitro activities of AChE, tyrosinase, and α-amylase. VGSE treatment significantly reduced viability of MCF-7, Hep-G2, Caco-2, and Huh-7 cells after 48-h treatments. The results obtained provide additional support for the purported health benefits of VGSE and reinforce its potential in disease prevention and therapy, especially in relation to cancer., (© 2022. The Author(s).)

In our survey for a new antiviral agent, two types of lectin were purified from Nostoc muscorum using both ion-exchange and affinity columns chromatography. Nostoc muscorum lectins (NMLs) are categorized based on their carbohydrate preference. Nostoc muscorum lectin-1(NML-1) exhibited a strict binding specificity for complex glycoproteins without linked carbohydrates, and the other displayed specificity for α- glycosides mannose polymers (NML-2) and was classified as a glycoprotein with 16.8% linked carbohydrates. NML-1 displayed a single band of 166 kDa on native-PAGE and two bands of 81 kDa and 85 kDa on SDS-PAGE, which confirmed the heterodimeric nature of this lectin. While NML-2 is a 50 kDa glycoprotein composed of 25 kDa subunits. Physical characterization of NML-1 displayed its stability at a higher temperature of 90 °C for 5 min and over a wide pH range (4-9), while MNL-2 displayed stability up to a temperature of 80 °C for 25 min and a pH range of 5-8. NML-1 didn't require metal ions for agglutination activity, while the activity of NML-2 was doubled by manganese ions. The antiviral activity of two lectins was assessed against herpes simplex type-1 (HSV-1) using a plaque assay which revealed that NML-1 inhibited HSV-1 infection at an early stage in contrast to NML-2 which exerted its antiviral effect at the late stage of infection. These results suggest that Nostoc muscorum is a unique lead for antiviral drug discovery as it is a novel source for antiviral lectins with different modes of action., (Copyright © 2022 Elsevier B.V. All rights reserved.)

In this review, we focus on some interesting and recent examples of various applications of organic azides such as their intermolecular or intramolecular, under thermal, catalyzed, or noncatalyzed reaction conditions. The aforementioned reactions in the aim to prepare basic five-, six-, organometallic heterocyclic-membered systems and/or their fused analogs. This review article also provides a report on the developed methods describing the synthesis of various heterocycles from organic azides, especially those reported in recent papers (till 2020). At the outset, this review groups the synthetic methods of organic azides into different categories. Secondly, the review deals with the functionality of the azido group in chemical reactions. This is followed by a major section on the following: (1) the synthetic tools of various heterocycles from the corresponding organic azides by one-pot domino reaction; (2) the utility of the chosen catalysts in the chemoselectivity favoring C-H and C-N bonds; (3) one-pot procedures (i.e., Ugi four-component reaction); (4) nucleophilic addition, such as Aza-Michael addition; (5) cycloaddition reactions, such as [3+2] cycloaddition; (6) mixed addition/cyclization/oxygen; and (7) insertion reaction of C-H amination. The review also includes the synthetic procedures of fused heterocycles, such as quinazoline derivatives and organometal heterocycles (i.e., phosphorus-, boron- and aluminum-containing heterocycles). Due to many references that have dealt with the reactions of azides in heterocyclic synthesis (currently more than 32,000), we selected according to generality and timeliness. This is considered a recent review that focuses on selected interesting examples of various heterocycles from the mechanistic aspects of organic azides.

Herein, a distinctive dihydroxy ionic liquid ([Py-2OH]OAc) was straightforwardly assembled from the sonication of pyridine with 2-chloropropane-1,3-diol by employing sodium acetate as an ion exchanger. The efficiency of the ([Py-2OH]OAc as a promoter for the sono-synthesis of a novel library of condensed products through DABCO-catalyzed Knoevenagel condensation process of adequate active cyclic methylenes and ninhydrin was next investigated using ultimate greener conditions. All of the reactions studied went cleanly and smoothly, and the resulting Knoevenagel condensation compounds were recovered in high yields without detecting the aldol intermediates in the end products. Compared to traditional strategies, the suggested approach has numerous advantages including mild reaction conditions with no by-products, eco-friendly solvent, outstanding performance in many green metrics, and usability in gram-scale synthesis. The reusability of the ionic liquid was also studied, with an overall retrieved yield of around 97% for seven consecutive runs without any substantial reduction in the performance. The novel obtained compounds were further assessed for their in vitro antitumor potential toward three human tumor cell lines: Colo-205 (colon cancer), MCF-7 (breast cancer), and A549 (lung cancer) by employing the MTT assay, and the findings were evaluated with the reference Doxorubicin. The results demonstrated that the majority of the developed products had potent activities at very low doses. Compounds comprising rhodanine ( 5 ) or chromane ( 12 ) moieties exhibited the most promising cytotoxic effects toward three cell lines, particularly rhodanine carboxylic acid derivative ( 5c ), showing superior cytotoxic effects against the investigated cell lines compared to the reference drug. Furthermore, automated docking simulation studies were also performed to support the results obtained.

A novel lectin was purified from newly cyanobacterium isolate, Oscillatoria acuminate MHM-632 MK014210.1 using affinity chromatography with a molecular weight of 120 kDa under native-PAGE and 30 kDa on reducing-PAGE, represented tetramer nature of this lectin. Oscillatorial lectin showed stability at 60 °C for 30 min, pH-dependent, with the highest activities over the pH range of 6-8, and required zinc ions to express its full activity. Oscillatorial lectin is a glycan-binding protein with a neutral carbohydrate content of 7.0% as evaluated by the phenol-sulfuric acid method. Polyols and α- glycosides polymer of mannose sugar or sugars alcohol were completely inhibited oscillatorial lectin with MIC of 0.195 mM, while β-glycosides sugars did not show any inhibition effect. The oscillatorial lectin has anti-proliferative activity against Huh-7 and MCF-7 cancer cells and inhibited their proliferation with EC 50 values of 106.75 µg/ml and 254.14 µg/ml, respectively. Besides the anticancer effect, oscillatorial lectin also has potent antiviral activity against HSV-1 in a dose-dependent manner via virions neutralization and inhibition of viral replication with IC 50 values of 90.95 ng/ml and 131.3 ng/ml, respectively. The unique carbohydrate affinity of oscillatorial lectin provides insight into its use as a promising candidate in many biotechnological applications, like fighting viral infection and combating cancer disease.Communicated by Ramaswamy H. Sarma.

Cancer and microbial infections threaten human health. Currently, chemotherapeutic drugs for cancer lack selectivity between normal and cancer cells, exacerbating this problem. Effective anticancer drug encapsulation is the golden key to solving this issue. Disulfiram (DS), an anticancer drug, has low solubility and selectivity and to tackle this concern, cellulose acetate (CA) and poly (ethylene oxide) (PEO) was selected as a matrix to prepare nanofiber containing DS (DS@CA/PEO) via electrospinning technique. DS@CA/PEO nanofiber was characterized by SEM, FTIR, TGA, and X-rd patterns and the results confirmed DS incorporation in CA/PEO nanofiber. DS@CA/PEO nanofiber scaffold showed higher safety than DS-free on human normal cells (Wi-38) with revealing similar anticancer activity of DS-free against colon cancer line (Caco-2) and breast cancer line (MDA-MB 231). This higher selectivity of DS@CA/PEO towards cancer cells than normal cells was associated with maintaining apoptotic activity and aldehyde dehydrogenase-inhibitory potency of DS. The latter efficacy led to eradicating colon and breast cancer stem cells, as evidenced by flow cytometry. Moreover, DS@CA/PEO nanofiber scaffold showed potent antibacterial activity (in vitro) against both Gram-negative and Gram-positive bacteria. These results investigated that DS@CA/PEO nanofiber scaffold could be a potential dual candidate as a selective anticancer and antimicrobial agent., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Cyanobacteria are photosynthetic, Gram-negative bacteria that are considered one of the most morphologically diverse groups of prokaryotes with a chief role in the global nutrient cycle as they fixed gaseous carbon dioxide and nitrogen to organic materials. Cyanobacteria have significant adaptability to survive in harsh conditions due to they have different metabolic pathways with unique compounds, effective defensive mechanisms, and wide distribution in different habitats. Besides, they are successfully used to face different challenges in several fields, including industry, aquaculture, agriculture, food, dairy products, pollution control, bioenergy, and pharmaceutics. Analysis of 680 publications revealed that nearly 1630 cyanobacterial molecules belong to different families have a wide range of applications in several fields, including cosmetology, agriculture, pharmacology (immunosuppressant, anticancer, antibacterial, antiprotozoal, antifungal, anti-inflammatory, antimalarial, anticoagulant, anti-tuberculosis, antitumor, and antiviral activities) and food industry. In this review, we nearly mentioned 92 examples of cyanobacterial molecules that are considered the most relevant effects related to anti-inflammatory, antioxidant, antimicrobial, antiviral, and anticancer activities as well as their roles that can be used in various biotechnological fields. These cyanobacterial products might be promising candidates for fighting various diseases and can be used in managing viral and microbial infections.Communicated by Ramaswamy H. Sarma.

The current study was directed toward developing a new series of fused heterocycles incorporating indazolylthiazole moiety. The newly synthesized compounds were characterized through elemental analysis and spectral data (IR, 1H-NMR, 13C-NMR, and Mass Spectrometry). The cytotoxic effect of the newly synthesized compounds was evaluated against normal human cells (HFB-4) and cancer cell lines (HepG-2 and Caco-2). Among the synthesized compounds, derivatives 4, and 6 revealed a significant selective antitumor activity, in a dose-dependent manner, against both HepG-2 and Caco-2 cell lines, with lower risk toward HFB-4 cells (normal cells). Derivative 8 revealed the maximum antitumor activity toward both tumor cell lines, with an SI value of about 26 and IC50 value of about 5.9 μg/mL. The effect of these derivatives (8, 4, and 6) upon the expression of 5 tumor regulating genes was studied through quantitative real-time PCR, where its interaction with these genes was simulated through the molecular docking study. Furthermore, the antimicrobial activity results revealed that compounds 2, 7, 8, and 9 have a potential antimicrobial activity, with maximum broad-spectrum activity through compound 3 against the three tested pathogens: Streptococcus mutans, Pseudomonas aeruginosa, and Candida albicans. The newly prepared compounds also revealed anti-biofilm formation activity with maximum activity against Streptococcus mutans, Pseudomonas aeruginosa, and Candida albicans, respectively., (© 2022. The Author(s).)

Bacterial polymeric silk is produced by Bacillus sp. strain NE and is composed of two proteins, called fibroin and sericin, with several biomedical and biotechnological applications. In the current study and for the first time, the whole bacterial silk proteins were found capable of exerting antiviral effects against herpes simplex virus type-1 (HSV-1), adenovirus type 7 (AD7), and hepatitis C virus (HCV). The direct interaction between bacterial silk-like proteins and both HSV-1 and AD7 showed potent inhibitory activity against viral entry with IC 50 values determined to be 4.1 and 46.4 μg/mL of protein, respectively. The adsorption inhibitory activity of the bacterial silk proteins showed a blocking activity against HSV-1 and AD7 with IC 50 values determined to be 12.5 and 222.4 ± 1.0 μg/mL, respectively. However, the bacterial silk proteins exhibited an inhibitory effect on HSV-1 and AD7 replication inside infected cells with IC 50 values of 9.8 and 109.3 μg/mL, respectively. All these results were confirmed by the ability of the bacterial silk proteins to inhibit viral polymerases of HSV-1 and AD7 with IC 50 values of 164.1 and 11.8 μg/mL, respectively. Similarly, the inhibitory effect on HCV replication in peripheral blood monocytes (PBMCs) was determined to be 66.2% at concentrations of 100 μg/mL of the bacterial silk proteins. This antiviral activity against HCV was confirmed by the ability of the bacterial silk proteins to reduce the ROS generation inside the infected cells to be 50.6% instead of 87.9% inside untreated cells. The unique characteristics of the bacterial silk proteins such as production in large quantities via large-scale biofermenters, low costs of production, and sustainability of bacterial source offer insight into its use as a promising agent in fighting viral infection and combating viral outbreaks.

Bio sustainable hydrogels including tunable morphological and/or chemical cues currently offer a valid strategy of designing innovative systems to enhance healing/regeneration processes of damaged tissue areas. In this work, TEMPO-oxidized cellulose nanofibrils (T-CNFs) were embedded in alginate (Alg) and polyvinyl alcohol (PVA) solution to form a stable mineralized hydrogel. A calcium chloride reaction was optimized to trigger a crosslinking reaction of polymer chains and mutually promote in situ mineralization of calcium phosphates. FTIR, XRD, SEM/EDAX, and TEM were assessed to investigate the morphological, chemical, and physical properties of different mineralized hybrid hydrogels, confirming differences in the deposited crystalline nanostructures, i.e., dicalcium phosphate dehydrate (DCPDH) and hydroxyapatite, respectively, as a function of applied pH conditions (i.e., pH 4 or 8). Moreover, in vitro tests, in the presence of HFB-4 and HSF skin cells, confirmed a low cytotoxicity of the mineralized hybrid hydrogels, and also highlighted a significant increase in cell viability via MTT tests, preferentially, for the low concentration, crosslinked Alg/PVA/calcium phosphate hybrid materials (<1 mg/mL) in the presence of hydroxyapatite. These preliminary results suggest a promising use of mineralized hybrid hydrogels based on Alg/PVA/T-CNFs for bone and wound healing applications.