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Nanofibrous electrically conductive scaffolds based on gelatin, namely gelatin-grafted polythiophene (Gel-g-PTh) and gelatin-grafted polythiophene/poly(ε-caprolactone) (Gel-g-PTh/PCL), have been designed and fabricated using the electrospinning technique. The performances of the fabricated electrospun nanofibers as scaffolds in tissue engineering (TE) application were preliminarily investigated in terms of some physicochemical as well as biological features. The results revealed that both fabricated electrospun nanofibers have potential as scaffolds for use in TE applications that require electroactivity. It was found that the co-electrospinning of Gel-g-PTh with a small amount of PCL improves the nanofibers' uniformity as well as some biological characteristics of the resultant scaffold. [ABSTRACT FROM AUTHOR]

A novel multi-stimuli-responsive theranostic nanomedicine was designed and fabricated by the conjugation of a thiol end-capped poly(N-isopropylacrylamide-block-acrylic acid) (HS-PNIPAAm-b-PAA) onto Fe3O4@Au nanoparticles (NPs) followed by physical loading of doxorubicin hydrochloride (Dox) as a general anticancer drug. For this purpose, Fe3O4@Au NPs were fabricated through small Au nanolayer grown on larger magnetic NPs. A HS-PNIPAAm-b-PAA was synthesized through an atom transfer radical polymerization (ATRP) approach, and then conjugated with as-synthesized Fe3O4@Au NPs by Au-S bonding. The Dox loading capacity of the synthesized Fe3O4@Au/Polymer theranostic NPs was calculated to be 81%. The theranostic nanomedicine exhibited excellent in vitro drug release behavior under pH and thermal stimuli. The anticancer activity evaluation using MTT assay (against MCF7 cells) revealed that the fabricated Fe3O4@Au/Polymer has high potential as theranostic nanomedicine for cancer therapy of solid tumors. This nanosystem can also applied in photothermal therapy, hyperthermia therapy, and their combination with chemotherapy due to presence of gold and Fe3O4 nanomaterials in its structure. [ABSTRACT FROM AUTHOR]

Although several anticancer drugs have been introduced as chemotherapeutic agents, the effective treatment of cancer remains a challenge. Major limitations in the application of anticancer drugs include their nonspecificity, wide biodistribution, short half-life, low concentration in tumor tissue and systemic toxicity. Drug delivery to the tumor site has become feasible in recent years, and recent advances in the development of new drug delivery systems for controlled drug release in tumor tissues with reduced side effects show great promise. In this field, the use of biodegradable polymers as drug carriers has attracted the most attention. However, drug release is still difficult to control even when a polymeric drug carrier is used. The design of pharmaceutical polymers that respond to external stimuli (known as stimuli-responsive polymers) such as temperature, pH, electric or magnetic field, enzymes, ultrasound waves, etc. appears to be a successful approach. In these systems, drug release is triggered by different stimuli. The purpose of this review is to summarize different types of polymeric drug carriers and stimuli, in addition to the combination use of stimuli in order to achieve a better controlled drug release, and it discusses their potential strengths and applications. A survey of the recent literature on various stimuli-responsive drug delivery systems is also provided and perspectives on possible future developments in controlled drug release at tumor site have been discussed. [ABSTRACT FROM AUTHOR]

ABSTRACT In this article, we introduce a new method for preparing ultrasmall chitosan (CS)/succinyl β-cyclodextrin (SCD) nanoparticles (NPs) intended for loading bovine serum albumin (BSA) as a model protein. The proposed method is based on the complex coacervation technique followed by ionotropic gelation with tripolyphosphate. SCD, an anionic derivative of cyclodextrin, was synthesized and used in CS-based NPs to enhance the entrapment efficiency of BSA. The results show that with this approach, ultrasmall, compact, and neutralized NPs with a mean particle size near 30 nm were obtained. A high degree of protein entrapment in the NPs led to a significant improvement in the BSA release profile with a low initial burst release (ca. 3% w/v of the initially loaded BSA) and a sustained release over time. This enabled a suitable nanocarrier for long-term protein delivery (30% release over 120 h). © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 39648. [ABSTRACT FROM AUTHOR]

Hydrogels based on chitosan or alginate biopolymers are believed to be desirable for covering skin lesions. In this research, we explored the potential of a new composite hydrogels series of sodium alginate (Alg) filled with cross-linked chitosan to use as hydrogel wound dressings. Cross-linked chitosan (CSPN) was synthesized by Schiff-base reaction with aldehydated cyclophosphazene, and its Cu(II) complex was manufactured and identified. Then, their powder suspension and Alg were transformed into hydrogel via ion-crosslinking with Ca2+. The hydrogel constituents were investigated by using FTIR, XRD, rheological techniques, and thermal analysis including TGA (DTG) and DSC. Moreover, structure optimization calculations were performed with the Material Studio 2017 program based on DFT-D per Dmol3 module. Examination of Alg's interactions with CSPN and CSPN-Cu using this module demonstrated that Alg molecules can be well adsorbed to the particle's surface. By changing the dosage of CSPN and CSPN-Cu, the number and size of pores, swelling rate, degradation behavior, protein absorption rate, cytotoxicity and blood compatibility were changed significantly. Subsequently, we employed erythromycin as a model drug to assess the entrapment efficiency, loading capacity, and drug release rate. FITC staining was selected to verify the hydrogels' intracellular uptake. Assuring the cytocompatibility of Alg-based hydrogels was approved by assessing the survival rate of fibroblast cells using MTT assay. However, the presence of Cu(II) in the developed hydrogels caused a significant antibacterial effect, which was comparable to the antibiotic-containing hydrogels. Our findings predict these porous, biodegradable, and mechanically stable hydrogels potentially have a promising future in the wound healing as antibiotic-free antibacterial dressings. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a progressive disorder that belongs to a class of neurodegenerative disorders (NDs) called Synucleinopathies. It has characterized by the misfolding and aggregation of a-synuclein. Our understanding of PD continues to evolve, and so does our approach to treatment. including therapies aimed at delaying pathology, quitting neuronal loss, and shortening the course of the disease by selectively targeting essential proteins suspected to play a role in PD pathogenesis. One emerging approach that is generating significant interest is Targeted Protein Degradation (TPD). TPD is an innovative method that allows us to specifically break down certain proteins using specially designed molecules or peptides, like PROteolysis-TArgeting-Chimera (PROTACs). This approach holds great promise, particularly in the context of NDs. In this review, we will briefly explain PD and its pathogenesis, followed by discussing protein degradation systems and TPD strategy in PD by reviewing synthesized small molecules and peptides. Finally, future perspectives and challenges in the field are discussed. • Targeted protein degradation is a promising technique for treating Neurodegenerative Diseases. • α-synuclein, LRRK2, and tau proteins are used for Targeted Protein Degradation. • Autophagy plays a key role in Parkinson's Disease through misfolding of proteins. [ABSTRACT FROM AUTHOR]

As pivotal role of scaffold in tissue engineering (TE), the aim of present study was to design and development of extracellular matrix (ECM)-mimetic electrically conductive nanofibrous scaffolds composed of polyaniline- grafted tragacanth gum (TG- g -PANI) and poly(vinyl alcohol) (PVA) with different PANI content for skin tissue engineering (STE) application. The fabricated scaffolds were preliminary evaluated in terms of some physicochemical and biological properties. Cytocompatibility and cells proliferation properties of the scaffolds were examined with the well-known MTT assay, and it was found that the developed scaffolds have proper cytocompatibilities and can enhances the mouse fibroblast L929 cells adhesion as well as proliferation, which confirm their potential for STE applications. Hemocompatibility assay revealed that the hemolysis rate of the fabricated scaffolds were <2 % even at a relatively high concentration (200 μgmL−1) of samples, therefore, these scaffolds can be considered as safe. Human serum albumin (HSA) protein adsorption capacities of the fabricated scaffolds were quantified as 42 and 49 μgmg−1 that represent suitable values for a successful TE. Overall, the fabricated scaffold with 20 wt% of TG- g -PANI showed higher potential in both physicochemical and biological features than scaffold with 30 wt% of mentioned copolymer for STE application. Extracellular matrix (ECM)-mimetic electrically conductive nanofibrous scaffolds composed of polyaniline- grafted tragacanth gum (TG- g -PANI) and poly(vinyl alcohol) (PVA) with different PANI content was design and developed for skin tissue engineering application. [Display omitted] • Electroconductive nanofibrous scaffolds were fabricated based on TG- g -PANI and PVA • The scaffolds showed porous 3D interconnected morphology. • The performance of the scaffolds for skin TE was preliminary investigated. • Incorporation of PANI to the scaffolds improved the biological functions of fibroblast cells. • The scaffolds have potential for STE. [ABSTRACT FROM AUTHOR]

[Display omitted] • Fibrinogen, a vital protein involved in wound healing and blood clotting, requires stability for proper functioning. • Trehalose, an effective protein stabilizer, is capable of preserving fibrinogen's structure and functionality. • Through hydrogen bonding and van der Waals forces, trehalose binds to fibrinogen, causing compaction and stability. • Specifically, trehalose primarily attaches to the C-terminal and globular regions of fibrinogen's Bβ chain. • Fibrinogen-trehalose complex exhibited reduced toxicity compared to trehalose alone, highlighting its potential use as a safe and effective protein stabilizer. Trehalose, a remarkable substance, holds great importance in biomedicine for its anti-inflammatory properties and its capacity to hinder scar formation at wounds. This study aims to explore how trehalose interacts with fibrinogen, a crucial protein in wound healing, paying particular attention to their structural characteristics. An array of analytical methods, such as steady-state fluorescence, UV–Vis analysis, circular dichroism (CD), Zeta potential measurements, Dynamic light scattering (DLS), and Fourier-transform infrared spectroscopy (FT-IR), are employed to examine the influence of trehalose on fibrinogen. The findings demonstrate that trehalose induces structural alterations on the surface of fibrinogen, resulting in its compaction. Moreover, computational modeling approaches like docking and molecular dynamics simulations are utilized to enhance the understanding of the interactions between trehalose and fibrinogen. The findings indicate the establishment of a stable complex between the two entities, accompanied by slight modifications in the protein's structure due to their interaction. The main forces facilitating the bonding of trehalose (the ligand) and the protein are hydrogen bonds and van der Waals forces, resulting in an entropy-driven spontaneous bonding process. FT-IR data reveals the emergence of fresh bonds between fibrinogen and trehalose post their interaction, whereas Zeta potential investigations suggest that the engagement with trehalose enhances the stability of the protein structure. Tests assessing cytotoxicity on a typical fibroblast cell line demonstrated that the fibrinogen-trehalose compound displays lower toxicity levels compared to trehalose alone. This suggests a milder impact on cells from the compound. Moreover, molecular docking analysis supports these experimental results, indicating that trehalose molecules primarily bind to the C-terminal end of the coiled-coil segment and the globular area of the Bβ chain within the Dβ fragment. These outcomes highlight the promise of trehalose as a valuable material for wound dressing purposes. [ABSTRACT FROM AUTHOR]

[Display omitted] • Ultra-sensitive immunosensor for PSA is designed based on (Fe-Cu LDH/rGO) as a sensing platform. • The peak current of the immunosensor was proportional to the concentration of PSA from 100.0 to 10.0 µg/ml with aLOD of 63.24 fg/ml. • The immunosensor exhibited desirable results for determining PSA in human serum samples - comparable with ELISA method. Here, a label-free immunosensor has been developed to detect prostate specific antigen as a diagnostic biomarker for prostate cancer. A pencil graphite electrode (PGE) coated with nanocomposites of iron-copper layered double hydroxide (Fe-Cu LDH) and reduced graphene oxide (rGO) was utilized as a sensor platform to capture the monoclonal anti-PSA antibody. The LDH/rGO nanocomposite can boost the electrical conductivity and enhance the surface area of the fabricated electrode; accordingly, it can efficiently amplify the electrode response and sensitivity in PSA detection. Electrochemical properties of the constructed sensor have been conducted utilizing cyclic voltammetry (CV), and electrochemical impedance spectroscopy(EIS). The PSA concentration level in serum samples was measured by monitoring the current changes of the Cu oxidation peak which was through the formation of antibody-PSA complexes on the surface of the electrode. The current response of the label-free immunosensor has been correlated to the concentration of PSA in a linear manner ranging from 100.0 fg/ml to 10.0 µg/ml with a limit of detection (LOD) of 63.24 fg/ml (S/N = 3). The morphology and structure of the synthesized Fe-Cu LDH/rGO nanocomposite was characterized using various analytical techniques such as field-emission scanning electron microscopy (FESEM), energy dispersive X-ray analysis (EDX), X-ray diffraction (XRD)and Fourier transform infrared (FTIR). The suggested immunosensor was employed to accurately and sensitively determine PSA concentration in serum samples with satisfactory results consistent with those achieved by enzyme-linked immunosorbent assay (ELISA) as a reference method. Finally, the obtained results indicate the promising application of the fabricated immunosensor in premature prostate cancer diagnostics. [ABSTRACT FROM AUTHOR]

Targeted Protein Modification (TPM) is an umbrella term encompassing numerous tools and approaches that use bifunctional agents to induce a desired modification over the POI. The most well-known TPM mechanism is PROTAC-directed protein ubiquitination. PROTAC-based targeted degradation offers several advantages over conventional small-molecule inhibitors, has shifted the drug discovery paradigm, and is acquiring increasing interest as over ten PROTACs have entered clinical trials in the past few years. Targeting the protein of interest for proteasomal degradation by PROTACS was the pioneer of various toolboxes for selective protein degradation. Nowadays, the ever-increasing number of tools and strategies for modulating and modifying the POI has expanded far beyond protein degradation, which phosphorylation and de-phosphorylation of the protein of interest, targeted acetylation, and selective modification of protein O-GlcNAcylation are among them. These novel strategies have opened new avenues for achieving more precise outcomes while remaining feasible and minimizing side effects. This field, however, is still in its infancy and has a long way to precede widespread use and translation into clinical practice. Herein, we investigate the pros and cons of these novel strategies by exploring the latest advancements in this field. Ultimately, we briefly discuss the emerging potential applications of these innovations in cancer therapy, neurodegeneration, viral infections, and autoimmune and inflammatory diseases. [Display omitted] • TPM is an umbrella term that used to induce a desired modification over the POI. • The most well-known TPM mechanism is PROTAC-directed protein ubiquitination. • PROTAC-based targeted degradation offers several advantages over conventional small-molecule inhibitors. [ABSTRACT FROM AUTHOR]

The synthesis and characterization of metal complexes have garnered significant attention due to their versatile applications in scientific and biomedical fields. In this research, two novel copper (Cu) complexes, [Cu(L)(L')(H 2 O) 2 ] (1) and [Cu(L)(Im)H 2 O] (2), where L = pyridine-2,6-dicarboxylic acid, L' = 2,4-diamino-6-hydroxypyrimidine, and Im = imidazole, were investigated concerning their sonochemical synthesis, spectroscopic analysis, and biological activity. The complexes' structural characterization was achieved using analytical techniques, including single-crystal X-ray structure determination, FTIR, PXRD, TGA and DTA, SEM, TEM, and EDS. Complex (1) displayed a six-coordinated Cu 2+ ion, while complex (2) exhibited a five-coordinated Cu 2+ ion. The crystal structures revealed monoclinic (C2/c) and triclinic (P-1) space groups, respectively. Both complexes showcased zero-dimensional (0D) supramolecular networks, primarily driven by hydrogen bonding and π-π stacking interactions, which played pivotal roles in stabilizing the structures and shaping the unique supramolecular architecture. Both complexes demonstrated significant antioxidant activity, suggesting their capability to neutralize free radicals and mitigate oxidative stress-related diseases. Hemolysis percentages were less than 2%, per the ASTM F756-00 standard, indicating non-hemolytic behavior. Low cytotoxicity was observed against fibroblast and MCF-7 cell lines. They do not exhibit antibacterial activity against Escherichia coli and Staphylococcus aureus. These findings suggest that the synthesized Cu 2+ ‒complexes hold considerable promise for applications in drug delivery and cancer treatment. This research contributes to the advancement of supramolecular chemistry and the development of multifunctional materials for diverse scientific and medical applications., (© 2024. The Author(s).)

A new drug delivery system using an asymmetric polyethersulfone (PES) membrane modified by SBA-15 and glutamine-modified SBA-15 (SBA-Q) was prepared in this study by the aim of azithromycin delivery enhancement in both in vitro and ex vivo experiments. The research focused on optimizing membrane performance by adjusting critical parameters including drug concentration, membrane thickness, modifier percentage, polymer percentage, and pore maker percentage. To characterize the fabricated membranes, various techniques were employed, including scanning electron microscopy, water contact angle, and tensile strength assessments. Following optimization, membrane composition of 17% PES, 2% polyvinylpyrrolidone, 1% SBA-15, and 0.5% SBA-Q emerged as the most effective. The optimized membranes demonstrated a substantial increase in drug release (906 mg/L) compared to the unmodified membrane (440 mg/L). The unique membrane structure, with a dense top layer facilitating sustained drug release and a porous sub-layer acting as a drug reservoir, contributed to this improvement. Biocompatibility assessments, antibacterial activity analysis, blood compatibility tests, and post-diffusion tissue integrity evaluations confirmed the promising biocompatibility of the optimized membranes. Moreover, long-term performance evaluations involving ten repeated usages underscored the reusability of the optimized membrane, highlighting its potential for sustained and reliable drug delivery applications., (© 2024. The Author(s).)

This study investigates the probiotic and anti-cancer effects of 21 isolated Lactobacillus strains from cheese, milk, and yogurt in Kermanshah, Iran, on oral cancer cell lines KB and OSCC. Four selected isolates (Y33, M45, C5, and C28) displayed good viability and resistance to specific antibiotics. Notably, strains C28 and Y33 exhibited the best results, showing susceptibility or semi-susceptibility to five antibiotics. Y33, with high cell surface hydrophobicity (62%), demonstrated significant anti-pathogenic activity, inhibiting the growth of tested pathogens and displaying strong adhesion to human intestinal Caco-2 cells (52%). Further assessments, including acridine orange/ethidium bromide staining and mRNA expression analysis, revealed four isolates (C5, C28, M45, and Y33) with promising probiotic properties. Particularly, Y33's protein-based extract metabolites showed dose- and time-dependent inhibition of KB and OSCC cancer cell lines, inducing apoptosis without significant cytotoxic effects on normal cells. Y33 (Lactiplantibacillus plantarum) exhibited the strongest probiotic potential, surpassing conventional anti-cancer drugs, suggesting its therapeutic potential for preventing oral cancer cell proliferation and improving survival rates in oral cancer patients., (© 2024. The Author(s).)

A novel strategy was designed and developed based of horseradish peroxidase (HRP)-mediated crosslinking of tyramine-functionalized starch (Tyr-St), tannic acid (TA) and phenolated-magnetic nanoparticles (Fe 3 O 4 -PhOH NPs), and simultaneous loading of doxorubicin hydrochloride (Dox) to afford a pH-responsive magnetic hydrogel-based drug delivery system (DDS) for synergistic in vitro chemo/hyperthermia therapy of human breast cancer (MCF-7) cells. The developed St-g-PTA/Fe 3 O 4 magnetic hydrogel showed porous micro-structure with saturation magnetization (δ s ) value of 19.2 emu g -1 for Fe 3 O 4 NPs content of ∼7.4 wt%. The pore sizes of the St-g-PTA/Fe 3 O 4 hydrogel was calculated to be 2400 ± 200 nm -2 . In vitro drug release experiments exhibited the developed DDS has pH-dependent drug release behavior, while at physiological pH (7.4) released only 30 % of the loaded drug after 100 h. Human serum albumin (HSA) adsorption capacities of the synthesized St/Fe 3 O 4 and St-g-PTA/Fe 3 O 4 magnetic hydrogels were obtained as 86 ± 2.2 and 77 ± 1.9 μgmg -1 , respectively. The well-known MTT-assay approved the cytocompatibility of the developed St-g-PTA/Fe 3 O 4 hydrogel, while the Dox-loaded system exhibited higher anti-cancer activity than those of the free Dox as verified by MTT-assay, and optical as well as florescent microscopies imaging. The synergistic chemo/hyperthermia therapy effect was also verified for the developed St-g-PTA/Fe 3 O 4 -Dox via hot water approach., 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. Published by Elsevier B.V.)

Novel electrically conductive nanofibrous scaffolds were designed and fabricated through the grafting of aniline monomer onto a phenylamine-functionalized alginate (Alg-NH 2 ) followed by electrospinning with poly(vinyl alcohol) (PVA). Performance of the prepared scaffolds in bone tissue engineering (TE) were studied in terms of physicochemical (e.g., conductivity, electroactivity, morphology, hydrophilicity, water uptake, and mechanical) and biological (cytocompatibility, in vitro biodegradability, cells attachment and proliferation, hemolysis, and protein adsorption) properties. The contact angles of the scaffolds with water drop were obtained about 50 to 60° that confirmed their excellent hydrophilicities for TE applications. Three dimensional (3D), inter-connected and uniform porous structures of the scaffolds without any bead formation was confirmed by scanning electron microscopy (SEM). Electrical conductivities of the fabricated scaffolds were obtained as 1.5 × 10 -3 and 2.7 × 10 -3 Scm -1 . MTT assay results revealed that the scaffolds have acceptable cytocompatibilities and can enhance the cells adhesion as well as proliferation, which approved their potential for TE applications. Hemolysis rate of the developed scaffolds were quantified <2 % even at high concentration (200 μgmL -1 ) of samples that approved their hemocompatibilities. The scaffolds were also exhibited acceptable protein adsorption capacities (65 and 68 μgmg -1 ). As numerous experimental results, the developed scaffolds have acceptable potential for bone TE., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

Background: Heterocyclic compounds have always been used as a core portion in the development of anticancer drugs. However, there is a pressing need for developing inexpensive and simple alternatives to high-cost and complex chemical agents-based catalysts for large-scale production of heterocyclic compounds. Also, development of some smart platforms for cancer treatment based on nanoparticles (NPs) which facilitate Fenton reaction have been widely explored by different scientists. Magnetic NPs not only can serve as catalysts in the synthesis of heterocyclic compounds with potential anticancer properties, but also are widely used as smart agents in targeting cancer cells and inducing Fenton reactions., Aim of Review: Therefore, in this review we aim to present an updated summary of the reports related to the main clinical or basic application and research progress of magnetic NPs in cancer as well as their application in the synthesis of heterocyclic compounds as potential anticancer drugs. Afterwards, specific tumor microenvironment (TME)-responsive magnetic nanocatalysts for cancer treatment through triggering Fenton-like reactions were surveyed. Finally, some ignored factors in the design of magnetic nanocatalysts- triggered Fenton-like reaction, challenges and future perspective of magnetic nanocatalysts-assisted synthesis of heterocyclic compounds and selective cancer therapy were discussed. Key Scientific Concepts of Review: This review may pave the way for well-organized translation of magnetic nanocatalysts in cancer therapy from the bench to the bedside., Competing Interests: The authors have none to declare., (© 2021 The Authors. Published by Elsevier B.V. on behalf of Cairo University.)

A novel multi-stimuli-responsive theranostic nanomedicine was designed and fabricated by the conjugation of a thiol end-capped poly( N -isopropylacrylamide- block -acrylic acid) (HS-PNIPAAm- b -PAA) onto Fe 3 O 4 @Au nanoparticles (NPs) followed by physical loading of doxorubicin hydrochloride (Dox) as a general anticancer drug. For this purpose, Fe 3 O 4 @Au NPs were fabricated through small Au nanolayer grown on larger magnetic NPs. A HS-PNIPAAm- b -PAA was synthesized through an atom transfer radical polymerization (ATRP) approach, and then conjugated with as-synthesized Fe 3 O 4 @Au NPs by Au-S bonding. The Dox loading capacity of the synthesized Fe 3 O 4 @Au/Polymer theranostic NPs was calculated to be 81%. The theranostic nanomedicine exhibited excellent in vitro drug release behavior under pH and thermal stimuli. The anticancer activity evaluation using MTT assay (against MCF7 cells) revealed that the fabricated Fe 3 O 4 @Au/Polymer has high potential as theranostic nanomedicine for cancer therapy of solid tumors. This nanosystem can also applied in photothermal therapy, hyperthermia therapy, and their combination with chemotherapy due to presence of gold and Fe 3 O 4 nanomaterials in its structure.