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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.)

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.)

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.)

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.)

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.)

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.)

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.)

For thousands of years, fungi have been a valuable and promising source of therapeutic agents for treatment of various diseases. Mushroom is a macrofungus which has been cultivated worldwide for its nutritional value and medicinal applications. Several bioactive molecules were extracted from mushroom such as polysaccharides, lectins and terpenoids. Lectins are carbohydrate-binding proteins with non-immunologic origin. Lectins were classified according to their structure, origin and sugar specificity. This protein has different binding specificity with surface glycan moiety which determines its activity and therapeutic applications. A wide range of medicinal activities such as antitumor, antiviral, antimicrobial, immunomodulatory and antidiabetic were reported from sugar-binding proteins. However, glycan-binding protein from mushroom is not well explored as antiviral agent. The discovery of novel antiviral agents is a public health emergency to overcome the current pandemic and be ready for the upcoming viral pandemics. The mechanism of action of lectin against viruses targets numerous steps in viral life cycle such as viral attachment, entry and replication. This review described the history, classification, purification techniques, structure-function relationship and different therapeutic applications of mushroom lectin. In addition, we focus on the antiviral activity, purification and physicochemical characteristics of some mushroom lectins., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest regarding the publication of this manuscript., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Lactoferrin is a glycoprotein with a molecular weight of 80 kDa, which produced in many mammalian excretions. LF is involved in various physiological processes and known to possess prominent biocidal activities, serving as an effective agent against a wide range of pathogens. This effective biocidal activity of LF in association with immune system response has made this protein an attractive therapeutic candidate. Interaction of proteins with nanoparticles (NPs) gives rise to the formation of a dynamic NP-protein complex and can induce conformational changes in the adsorbed proteins which may lead to the change in their function. With the recent advances in nanotechnology, NPs may provide the protection and stabilization of LF from hydrolysis by some proteases and increase their uptake by targeted cells. These nanoformulations of LF can be used as diagnosis, disease targeting and drug delivery tools. Owing to its multiple functionalities, LF is a promising active ingredient to be loaded or adsorbed to NPs for preparing a stable, controlled surface NPs. Thus, LF NPs can potentially empower the resulting nanocomplex with attracting functionalities and might be useful in many applications, e.g., to modify the optical or rheological properties of products, or to encapsulate and deliver bioactive ingredients., Competing Interests: Declaration of competing interest The author declares that there is no conflict of interest regarding the publication of this review manuscript., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Hyaluronic acid (HA) based nanofibers (NFs) represented a novel class of bioactive wound dressings that have a vital role in wound management due to their unique properties as an extracellular-matrix and accelerating wound healing. Novel L-arginine-loaded citric acid crosslinked PVA-HA NFs were fabricated by electrospinning and proposed for potential wound healing purposes. However, poor mechanical properties of HA NFs might limit its biological usage, thus this study aims to develop reinforced PVA/HA NFs by incorporation of cellulose nanocrystals (CNCs) as nanofiller and loading L-arginine as wound healing accelerator. Results revealed that incorporation of CNCs into PVA/HA significantly improved mechanical and swelling properties of NFs, compared to CNC-free NFs. Biological performance of NFs was evaluated on normal human skin melanocyte (HFB-4) and lung fibroblast (WI38) cell-lines. PVA/HA/CNC/L-arginine NFs exhibited excellent hemocompatibility, high protein adsorption, outstanding proliferative and adhesive potential on HFB-4 cells expressed by high wound gap-closure 99.9% after 48 h of exposure. Released arginine from PVA/HA/CNC NFs showed sustained release about 46.5% and ~90% after 24 h and 48 h, respectively. Briefly, PVA/HA/CNCs/L-arginine showed adequate antibacterial activity especially against Klebsiella pneumonia, as an acute popular pathogen causing a skin infection. These results indicate that PVA/HA/CNC/L-arginine could act as promising and multifunctional wound dressings., Competing Interests: Declaration of competing interest The authors declare no competing or financial interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In the present study, a novel lectin was purified from the newly isolated cyanobacterium, Lyngabya confervoides MK012409 and tested for its antiviral and anticancer activity. Out of 30 isolates, Mabroka-s isolate which identified as Lyngabya confervoides MK012409 showed the highest agglutination titer. Lyngabyal lectin showed the greatest haemagglutination activity with pigeon/rabbit erythrocytes with a minimum concentration of 2.4 μg/ml. Physical characterization of Lyngabyal lectin showed ability to keep the activity at a higher temperature up to 80 °C with stability over a wide pH range (4-8) as well as its stability toward chemical denaturants. Carbohydrate specificity test revealed that the sugar alcohols completely inhibited the lectin haemagglutination activity. The electrophoretic analysis revealed that the lyngabyal lectin is a 140 kDa composed of two 70 kDa subunits. Lyngabyal lectin was able to inhibit the proliferation of MCF-7 and Caco-2 cancer cell lines with IC 50 values of 246 ± 0.17 and 376.4 ± 0.34 μg/ml, respectively. Lyngabyal lectin also showed virucidal activity against HSV-1 with EC 50 of 167 ± 0.52 ng/ml and inhibited plaque formation in the HSV-1 infected Vero cells with EC 50 of 84.94 ± 0.34 ng/ml. These findings emphasize the ability of the lyngabyal lectin to fight breast and colon cancer besides it represents a promising antiviral agent., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Interpenetrating hydrogel membranes consisting of pH-sensitive hyaluronan (HA) and thermo-sensitive poly(N-isopropylacrylamide) (PNIPAAM) were synthesized using redox polymerization, followed by N,N-methylenebisacrylamide (BIS) and epichlorohydrin (EPI) were added as chemical crosslinkers. The interaction between membrane compositions has been characterized by FTIR spectroscopy and discussed intensively. The result indicates that HA incorporation in membranes increase the gel fraction, swelling uptake, and the flexibility/elasticity of crosslinked membranes, however it reduced oppositely the mechanical elongation of membranes. PNIPAAm-HA hydrogels responded to both temperature and pH changes and the stimuli-responsiveness was reversible. However, in vitro bioevaluation results revealed that the released ampicillin during the burst release time was sharply influenced and increased with increasing HA contents in membranes; afterwards it became sustainable. Whereas, high HA contents in hydrogels unexpectedly impacted negatively on the cells viability, owing to the viscosity of cell culture media changed. A big resistance was observed against microbial growth of Staphylococcus aureus, Salmonella typhi, and Candida albicans in case of pure PNIPAAm hydrogel membranes without HA or ampicillin. However, HA incorporation or the loaded ampicillin in membranes showed unexpected easily microbial growth. The fast release performance with dual pH-thermo-sensitive hydrogels were suggested as promising materials for quick drug carrier in the biomedical field., (Copyright © 2017 Elsevier B.V. All rights reserved.)