Radiotherapy-sensitized cancer immunotherapy via cGAS-STING immune pathway by activatable nanocascade reaction.

Radiotherapy-induced immune activation holds great promise for optimizing cancer treatment efficacy. Here, we describe a clinically used radiosensitizer hafnium oxide (HfO2) that was core coated with a MnO2 shell followed by a glucose oxidase (GOx) doping nanoplatform (HfO2@MnO2@GOx, HMG) to trigger ferroptosis adjuvant effects by glutathione depletion and reactive oxygen species production. This ferroptosis cascade potentiation further sensitized radiotherapy by enhancing DNA damage in 4T1 breast cancer tumor cells. The combination of HMG nanoparticles and radiotherapy effectively activated the damaged DNA and Mn2+-mediated cGAS-STING immune pathway in vitro and in vivo. This process had significant inhibitory effects on cancer progression and initiating an anticancer systemic immune response to prevent distant tumor recurrence and achieve long-lasting tumor suppression of both primary and distant tumors. Furthermore, the as-prepared HMG nanoparticles "turned on" spectral computed tomography (CT)/magnetic resonance dual-modality imaging signals, and demonstrated favorable contrast enhancement capabilities activated by under the GSH tumor microenvironment. This result highlighted the potential of nanoparticles as a theranostic nanoplatform for achieving molecular imaging guided tumor radiotherapy sensitization induced by synergistic immunotherapy.

Sodium arsenite and arsenic trioxide differently affect the oxidative stress of lymphoblastoid cells: An intricate crosstalk between mitochondria, autophagy and cell death.

Although the toxicity of arsenic depends on its chemical forms, few studies have taken into account the ambiguous phenomenon that sodium arsenite (NaAsO2) acts as a potent carcinogen while arsenic trioxide (ATO, As2O3) serves as an effective therapeutic agent in lymphoma, suggesting that NaAsO2 and As2O3 may act via paradoxical ways to either promote or inhibit cancer pathogenesis. Here, we compared the cellular response of the two arsenical compounds, NaAsO2 and As2O3, on the Burkitt lymphoma cell model, the Epstein Barr Virus (EBV)-positive P3HR1 cells. Using flow cytometry and biochemistry analyses, we showed that a NaAsO2 treatment induces P3HR1 cell death, combined with drastic drops in ΔΨm, NAD(P)H and ATP levels. In contrast, As2O3-treated cells resist to cell death, with a moderate reduction of ΔΨm, NAD(P)H and ATP. While both compounds block cells in G2/M and affect their protein carbonylation and lipid peroxidation, As2O3 induces a milder increase in superoxide anions and H2O2 than NaAsO2, associated to a milder inhibition of antioxidant defenses. By electron microscopy, RT-qPCR and image cytometry analyses, we showed that As2O3-treated cells display an overall autophagic response, combined with mitophagy and an unfolded protein response, characteristics that were not observed following a NaAsO2 treatment. As previous works showed that As2O3 reactivates EBV in P3HR1 cells, we treated the EBV- Ramos-1 cells and showed that autophagy was not induced in these EBV- cells upon As2O3 treatment suggesting that the boost of autophagy observed in As2O3-treated P3HR1 cells could be due to the presence of EBV in these cells. Overall, our results suggest that As2O3 is an autophagic inducer which action is enhanced when EBV is present in the cells, in contrast to NaAsO2, which induces cell death. That's why As2O3 is combined with other chemicals, as all-trans retinoic acid, to better target cancer cells in therapeutic treatments.

Multifunctional Hydrogel of Recombinant Humanized Collagen Loaded with MSCs and MnO2 Accelerates Chronic Diabetic Wound Healing.

Chronic wound repair is a clinical treatment challenge. The development of multifunctional hydrogels is of great significance in the key aspects of treating chronic wounds, including reducing oxidative stress, promoting angiogenesis, and improving the natural remodeling of extracellular matrix and immune regulation. In this study, we prepared a composite hydrogel, sodium alginate (SA)@MnO2/recombinant humanized collagen III (RHC)/mesenchymal stem cells (MSCs), composed of SA, MnO2 nanoparticles, RHC, and MSCs. The hydrogel has high mechanical properties and good biocompatibility. In vitro, SA@MnO2/RHC/MSCs hydrogel effectively enhanced the formation of intricate tubular structures and angiogenesis and showed synergistic effects on cell proliferation and migration. In vivo, the SA@MnO2/RHC/MSCs hydrogel enhanced diabetes wound healing, rapid re-epithelization, favorable collagen deposition, and abundant wound angiogenesis. These findings demonstrated that the combined effects of SA, MnO2, RHC, and MSCs synergistically accelerate healing, resulting in a reduced healing time. These observed healing effects demonstrated the potential of this multifunctional hydrogel to transform chronic wound care and improve patient outcomes.

Tumor microenvironment-responsive size-changeable and biodegradable HA-CuS/MnO2 nanosheets for MR imaging and synergistic chemodynamic therapy/phototherapy.

Tumor microenvironment (TME)-responsive size-changeable and biodegradable nanoplatforms for multimodal therapy possess huge advantages in anti-tumor therapy. Hence, we developed a hyaluronic acid (HA) modified CuS/MnO2 nanosheets (HCMNs) as a multifunctional nanoplatform for synergistic chemodynamic therapy (CDT)/photothermal therapy (PTT)/photodynamic therapy (PDT). The prepared HCMNs exhibited significant NIR light absorption and photothermal conversion efficiency because of the densely deposited ultra-small sized CuS nanoparticles on the surface of MnO2 nanosheet. They could precisely target the tumor cells and rapidly decomposed into small sized nanostructures in the TME, and then efficiently promote intracellular ROS generation through a series of cascade reactions. Moreover, the local temperature elevation induced by photothermal effect also promote the PDT based on CuS nanoparticles and the Fenton-like reaction of Mn2+, thereby enhancing the therapeutic efficiency. Furthermore, the T1-weighted magnetic resonance (MR) imaging was significantly enhanced by the abundant Mn2+ ions from the decomposition process of HCMNs. In addition, the CDT/PTT/PDT synergistic therapy using a single NIR light source exhibited considerable anti-tumor effect via in vitro cell test. Therefore, the developed HCMNs will provide great potential for MR imaging and multimodal synergistic cancer therapy.

A multifunctional cascade enzyme system for enhanced starvation/chemodynamic combination therapy against hypoxic tumors.

Starvation therapy has shown promise as a cancer treatment, but its efficacy is often limited when used alone. In this work, a multifunctional nanoscale cascade enzyme system, named CaCO3@MnO2-NH2@GOx@PVP (CMGP), was fabricated for enhanced starvation/chemodynamic combination cancer therapy. CMGP is composed of CaCO3 nanoparticles wrapped in a MnO2 shell, with glucose oxidase (GOx) adsorbed and modified with polyvinylpyrrolidone (PVP). MnO2 decomposes H2O2 in cancer cells into O2, which enhances the efficiency of GOx-mediated starvation therapy. CaCO3 can be decomposed in the acidic cancer cell environment, causing Ca2+ overload in cancer cells and inhibiting mitochondrial metabolism. This synergizes with GOx to achieve more efficient starvation therapy. Additionally, the H2O2 and gluconic acid produced during glucose consumption by GOx are utilized by MnO2 with catalase-like activity to enhance O2 production and Mn2+ release. This process accelerates glucose consumption, reactive oxygen species (ROS) generation, and CaCO3 decomposition, promoting the Ca2+ release. CMGP can alleviate tumor hypoxia by cycling the enzymatic cascade reaction, which increases enzyme activity and combines with Ca2+ overload to achieve enhanced combined starvation/chemodynamic therapy. In vitro and in vivo studies demonstrate that CMGP has effective anticancer abilities and good biosafety. It represents a new strategy with great potential for combined cancer therapy.

Neuroprotective Assessment of Betaine against Copper Oxide Nanoparticle-Induced Neurotoxicity in the Brains of Albino Rats: A Histopathological, Neurochemical, and Molecular Investigation.

Copper oxide nanoparticles (CuO-NPs) are commonly used metal oxides. Betaine possesses antioxidant and neuroprotective activities. The current study aimed to investigate the neurotoxic effect of CuO-NPs on rats and the capability of betaine to mitigate neurotoxicity. Forty rats; 4 groups: group I a control, group II intraperitoneally CuO-NPs (0.5 mg/kg/day), group III orally betaine (250 mg/kg/day) and CuO-NPs, group IV orally betaine for 28 days. Rats were subjected to neurobehavioral assessments. Brain samples were processed for biochemical, molecular, histopathological, and immunohistochemical analyses. Behavioral performance of betaine demonstrated increasing locomotion and cognitive abilities. Group II exhibited significantly elevated malondialdehyde (MDA), overexpression of interleukin-1 beta (IL-1ß), and tumor necrosis factor-alpha (TNF-α). Significant decrease in glutathione (GSH), and downregulation of acetylcholine esterase (AChE), nuclear factor erythroid 2-like protein 2 (Nrf-2), and superoxide dismutase (SOD). Histopathological alterations; neuronal degeneration, pericellular spaces, and neuropillar vacuolation. Immunohistochemically, an intense immunoreactivity is observed against IL-1ß and glial fibrillary acidic protein (GFAP). Betaine partially neuroprotected against CuO-NPs associated alterations. A significant decrease at MDA, downregulation of IL-1ß, and TNF-α, a significant increase at GSH, and upregulation of AChE, Nrf-2, and SOD. Histopathological alterations partially ameliorated. Immunohistochemical intensity of IL-1ß and GFAP reduced. It is concluded that betaine neuroprotected against most of CuO-NP neurotoxic effects through antioxidant and cell redox system stimulating efficacy.

Bactericidal Effect and Cytotoxicity of Graphene Oxide/Silver Nanocomposites.

To tackle the proliferation of pathogenic microorganisms without relying on antibiotics, innovative materials boasting antimicrobial properties have been engineered. This study focuses on the development of graphene oxide/silver (GO/Ag) nanocomposites, derived from partially reduced graphene oxide adorned with silver nanoparticles. Various nanocomposites with different amounts of silver (GO/Ag-1, GO/Ag-2, GO/Ag-3, and GO/Ag-4) were synthesized, and their antibacterial efficacy was systematically studied. The silver nanoparticles were uniformly deposited on the partially reduced graphene oxide surface, exhibiting spherical morphologies with an average size of 25 nm. The nanocomposites displayed potent antibacterial properties against both gram-positive bacteria (S. aureus and B. subtilis) and gram-negative bacteria (E. coli and S. enterica) as confirmed by minimum inhibition concentration (MIC) studies and time-dependent experiments. The optimal MIC for Gram-positive bacteria was 62.5 µg/mL and for Gram-negative bacteria was 125 µg/mL for the GO/Ag nanocomposites. Bacterial cells that encountered the nanocomposite films exhibited significantly greater inhibitory effects compared to those exposed to conventional antibacterial materials. Furthermore, the cytotoxicity of these nanocomposites was assessed using human epithelial cells (HEC), revealing that GO/Ag-1 and GO/Ag-2 exhibited lower toxicity levels toward HEC and remained compatible even at higher dilution rates. This study underscores the potential of GO/Ag-based nanocomposites as versatile materials for antibacterial applications, particularly as biocompatible wound dressings, offering promising prospects for wound healing and infection control.

Amoebicidal effect of chlorine dioxide gas against pathogenic Naegleria fowleri and Acanthamoeba polyphaga.

The pathogenic free-living amoebae, Naegleria fowleri and Acanthamoeba polyphaga, are found in freshwater, soil, and unchlorinated or minimally chlorinated swimming pools. N. fowleri and A. polyphaga are becoming problematic as water leisure activities and drinking water are sources of infection. Chlorine dioxide (ClO2) gas is a potent disinfectant that is relatively harmless to humans at the concentration used for disinfection. In this study, we examined the amoebicidal effects of ClO2 gas on N. fowleri and A. polyphaga. These amoebae were exposed to ClO2 gas from a ready-to-use product (0.36 ppmv/h) for 12, 24, 36, and 48 h. Microscopic examination showed that the viability of N. fowleri and A. polyphaga was effectively inhibited by treatment with ClO2 gas in a time-dependent manner. The growth of N. fowleri and A. polyphaga exposed to ClO2 gas for 36 h was completely inhibited. In both cases, the mRNA levels of their respective actin genes were significantly reduced following treatment with ClO2 gas. ClO2 gas has an amoebicidal effect on N. fowleri and A. polyphaga. Therefore, ClO2 gas has been proposed as an effective agent for the prevention and control of pathogenic free-living amoeba contamination.

MnO2-based capacitive system enhances ozone inactivation of bacteria by disrupting cell membrane.

The application of ozone (O3) disinfection has been hindered by its low solubility in water and the formation of disinfection by-products (DBPs). In this study, capacitive disinfection is applied as a pre-treatment for O3 oxidation, in which manganese dioxide with a rambutan-like hollow spherical structure is used as the electrode to increase the charge density on the electrode surface. When a voltage is applied, the negative-charged microbes are attracted to the electrodes and killed by electrical interactions. The contact between microbes and capacitive electrodes leads to changes in cell permeability and burst of reactive oxygen species, thereby promoting the diffusion of O3 into the cells. After O3 penetrates the cell membrane, it can directly attack the cytoplasmic constituents, accelerating fatal and irreversible damage to pathogens. As a result, the performance of the capacitance-O3 process is proved better than the direct sum of the two individual process efficiencies. The design of capacitance-O3 system is beneficial to reduce the ozone dosage and DBPs with a broader inactivation spectrum, which is conducive to the application of ozone in primary water disinfection.

Facile synthesis of Fe2O3, Fe2O3@CuO and WO3 nanoparticles: characterization, structure determination and evaluation of their biological activity.

Due to their high specific surface area and its characteristic's functionalized nanomaterials have great potential in medical applications specialty, as an anticancer. Herein, functional nanoparticles (NPs) based on iron oxide Fe2O3, iron oxide modified with copper oxide Fe2O3@CuO, and tungsten oxide WO3 were facile synthesized for biomedical applications. The obtained nanomaterials have nanocrystal sizes of 35.5 nm for Fe2O3, 7 nm for Fe2O3@CuO, and 25.5 nm for WO3. In addition to octahedral and square nanoplates for Fe2O3, and WO3; respectively. Results revealed that Fe2O3, Fe2O3@CuO, and WO3 NPs showed remarked anticancer effects versus a safe effect on normal cells through cytotoxicity test using MTT-assay. Notably, synthesized NPs e.g. our result demonstrated that Fe2O3@CuO exhibited the lowest IC50 value on the MCF-7 cancer cell line at about 8.876 µg/ml, compared to Fe2O3 was 12.87 µg/ml and WO3 was 9.211 µg/ml which indicate that the modification NPs Fe2O3@CuO gave the highest antiproliferative effect against breast cancer. However, these NPs showed a safe mode toward the Vero normal cell line, where IC50 were monitored as 40.24 µg/ml for Fe2O3, 21.13 µg/ml for Fe2O3@CuO, and 25.41 µg/ml for WO3 NPs. For further evidence. The antiviral activity using virucidal and viral adsorption mechanisms gave practiced effect by viral adsorption mechanism and prevented the virus from replicating inside the cells. Fe2O3@CuO and WO3 NPs showed a complete reduction in the viral load synergistic effect of combinations between the tested two materials copper oxide instead of iron oxide alone. Interestingly, the antimicrobial efficiency of Fe2O3@CuO NPs, Fe2O3NPs, and WO3NPs was evaluated using E. coli, S. aureus, and C. albicans pathogens. The widest microbial inhibition zone (ca. 38.45 mm) was observed with 250 mg/ml of WO3 NPs against E. coli, whereas using 40 mg/ml of Fe2O3@CuO NPS could form microbial inhibition zone ca. 32.86 mm against S. aureus. Nevertheless, C. albicans was relatively resistant to all examined NPs. The superior biomedical activities of these nanostructures might be due to their unique features and accepted evaluations.

Asymmetric synthesis of P-stereogenic phosphindane oxides via kinetic resolution and their biological activity.

The importance of P-stereogenic heterocycles has been widely recognized with their extensive use as privileged chiral ligands and bioactive compounds. The catalytic asymmetric synthesis of P-stereogenic phosphindane derivatives, however, remains a challenging task. Herein, we report a catalytic kinetic resolution of phosphindole oxides via rhodium-catalyzed diastereo- and enantioselective conjugate addition to access enantiopure P-stereogenic phosphindane and phosphindole derivatives. This kinetic resolution method features high efficiency (s factor up to >1057), excellent stereoselectivities (all >20:1 dr, up to >99% ee), and a broad substrate scope. The obtained chiral phosphindane oxides exhibit promising therapeutic efficacy in autosomal dominant polycystic kidney disease (ADPKD), and compound 3az is found to significantly inhibit renal cyst growth both in vitro and in vivo, thus ushering in a promising scaffold for ADPKD drug discovery. This study will not only advance efforts towards the asymmetric synthesis of challenging P-stereogenic heterocycles, but also surely inspire further development of P-stereogenic entities for bioactive small-molecule discovery.

Enhancing Photothermal/Photodynamic Therapy for Glioblastoma by Tumor Hypoxia Alleviation and Heat Shock Protein Inhibition Using IR820-Conjugated Reduced Graphene Oxide Quantum Dots.

We use low-molecular-weight branched polyethylenimine (PEI) to produce cytocompatible reduced graphene oxide quantum dots (rGOQD) as a photothermal agent and covalently bind it with the photosensitizer IR-820. The rGOQD/IR820 shows high photothermal conversion efficiency and produces reactive oxygen species (ROS) after irradiation with near-infrared (NIR) light for photothermal/photodynamic therapy (PTT/PDT). To improve suspension stability, rGOQD/IR820 was PEGylated by anchoring with the DSPE hydrophobic tails in DSPE-PEG-Mal, leaving the maleimide (Mal) end group for covalent binding with manganese dioxide/bovine serum albumin (MnO2/BSA) and targeting ligand cell-penetrating peptide (CPP) to synthesize rGOQD/IR820/MnO2/CPP. As MnO2 can react with intracellular hydrogen peroxide to produce oxygen for alleviating the hypoxia condition in the acidic tumor microenvironment, the efficacy of PDT could be enhanced by generating more cytotoxic ROS with NIR light. Furthermore, quercetin (Q) was loaded to rGOQD through π-π interaction, which can be released in the endosomes and act as an inhibitor of heat shock protein 70 (HSP70). This sensitizes tumor cells to thermal stress and increases the efficacy of mild-temperature PTT with NIR irradiation. By simultaneously incorporating the HSP70 inhibitor (Q) and the in situ hypoxia alleviating agent (MnO2), the rGOQD/IR820/MnO2/Q/CPP can overcome the limitation of PTT/PDT and enhance the efficacy of targeted phototherapy in vitro. From in vivo study with an orthotopic brain tumor model, rGOQD/IR820/MnO2/Q/CPP administered through tail vein injection can cross the blood-brain barrier and accumulate in the intracranial tumor, after which NIR laser light irradiation can shrink the tumor and prolong the survival times of animals by simultaneously enhancing the efficacy of PTT/PDT to treat glioblastoma.

Reactive Oxygen Species Scavenging Injectable Hydrogel Potentiates the Therapeutic Potential of Mesenchymal Stem Cells in Skin Flap Regeneration.

Cell-based therapies offer tremendous potential for skin flap regeneration. However, the hostile microenvironment of the injured tissue adversely affects the longevity and paracrine effects of the implanted cells, severely reducing their therapeutic effectiveness. Here, an injectable hydrogel (nGk) with reactive oxygen species (ROS) scavenging capability, which can amplify the cell viability and functions of encapsulated mesenchymal stem cells (MSCs), is employed to promote skin flap repair. nGk is formulated by dispersing manganese dioxide nanoparticles (MnO2 NPs) in a gelatin/κ-carrageenan hydrogel, which exhibits satisfactory injectable properties and undergoes a sol-gel phase transition at around 40 °C, leading to the formation of a solid gel at physiological temperature. MnO2 NPs enhance the mechanical properties of the hydrogel and give it the ability to scavenge ROS, thus providing a cell-protective system for MSCs. Cell culture studies show that nGk can mitigate the oxidative stress, improve cell viability, and boost stem cell paracrine function to promote angiogenesis. Furthermore, MSC-loaded nGk (nGk@MSCs) can improve the survival of skin flaps by promoting angiogenesis, reducing inflammatory reactions, and attenuating necrosis, providing an effective approach for tissue regeneration. Collectively, injectable nGk has substantial potential to enhance the therapeutic benefits of MSCs, making it a valuable delivery system for cell-based therapies.

Composite of KLVFF-Transthyretin-Penetratin and Manganese Dioxide Nanoclusters: A Multifunctional Agent against Alzheimer's ß-Amyloid Fibrillogenesis.

Design of amyloid ß-protein (Aß) inhibitors is considered an effective strategy for the prevention and treatment of Alzheimer's disease (AD). However, the limited blood-brain barrier (BBB) penetration and poor Aß-targeting capability restricts the therapeutic efficiency of candidate drugs. Herein, we have proposed to engineer transthyretin (TTR) by fusion of the Aß-targeting peptide KLVFF and cell-penetrating peptide Penetratin to TTR, and derived a fusion protein, KLVFF-TTR-Penetratin (KTP). Moreover, to introduce the scavenging activity for reactive oxygen species (ROS), a nanocomposite of KTP and manganese dioxide nanoclusters (KTP@MnO2) was fabricated by biomineralization. Results revealed that KTP@MnO2 demonstrated significantly enhanced inhibition on Aß aggregation as compared to TTR. The inhibitory effect was increased from 18%, 33%, and 49% (10, 25, and 50 µg/mL TTR, respectively) to 52%, 81%, and 100% (10, 25, and 50 µg/mL KTP@MnO2). In addition, KTP@MnO2 could penetrate the BBB and target amyloid plaques. Moreover, multiple ROS, including hydroxyl radicals, superoxide radicals, hydrogen peroxide, and Aß-induced-ROS, which cannot be scavenged by TTR, were scavenged by KTP@MnO2, thus resulting in the mitigation of cellular oxidative damages. More importantly, cell culture and in vivo experiments with AD nematodes indicated that KTP@MnO2 at 50 µg/mL increased the viability of Aß-treated cells from 66% to more than 95%, and completely cleared amyloid plaques in AD nematodes and extended their lifespan by 7 d. Overall, despite critical aspects such as the stability, metabolic distribution, long-term biotoxicity, and immunogenicity of the nanocomposites in mammalian models remaining to be investigated, this work has demonstrated the multifunctionality of KTP@MnO2 for targeting Aß in vivo, and provided new insights into the design of multifunctional nanocomposites of protein-metal clusters against AD.

An antibacterial membrane based on Janus bacterial cellulose with nano-sized copper oxide through polydopamine conjugation for infectious wound healing.

Bacterial cellulose (BC) produced by Acetobacter xylinum has great advantages in wound dressing. However, the structural limitation under static culture, and lack of antibacterial properties restrict its application, especially for infectious wound healing. The present study reported an original wound dressing, which was composed of a Janus BC membrane with antibacterial nano-sized copper oxide (CuO) through polydopamine (PDA) conjugation to promote wound healing under infectious condition. The finished product (CuO/PDA/BC membrane) exhibited favorable air permeability, high hydrophilicity and good mechanical properties, as well as strong antibacterial effects by the sustained release of CuO and photothermal effect of CuO/PDA. Furthermore, CuO/PDA/BC membrane inhibited inflammatory response and promoted wound healing in an infectious wound model in vivo. These results suggested that our CuO/PDA/BC membrane had great potential as wound dressing for infectious wound healing.

Hard tissue formation in pulpotomized primary teeth in dogs with nanomaterials MCM-48 and MCM-48/hydroxyapatite: an in vivo animal study.

BACKGROUND: This animal study sought to evaluate two novel nanomaterials for pulpotomy of primary teeth and assess the short-term pulpal response and hard tissue formation in dogs. The results were compared with mineral trioxide aggregate (MTA). METHODS: This in vivo animal study on dogs evaluated 48 primary premolar teeth of 4 mongrel female dogs the age of 6-8 weeks, randomly divided into four groups (n = 12). The teeth underwent complete pulpotomy under general anesthesia. The pulp tissue was capped with MCM-48, MCM-48/Hydroxyapatite (HA), MTA (positive control), and gutta-percha (negative control), and the teeth were restored with intermediate restorative material (IRM) paste and amalgam. After 4-6 weeks, the teeth were extracted and histologically analyzed to assess the pulpal response to the pulpotomy agent. RESULTS: The data were analyzed using the Kruskal‒Wallis, Fisher's exact, Spearman's, and Mann‒Whitney tests. The four groups were not significantly different regarding the severity of inflammation (P = 0.53), extent of inflammation (P = 0.72), necrosis (P = 0.361), severity of edema (P = 0.52), extent of edema (P = 0.06), or connective tissue formation (P = 0.064). A significant correlation was noted between the severity and extent of inflammation (r = 0.954, P < 0.001). The four groups were significantly different regarding the frequency of bone formation (P = 0.012), extent of connective tissue formation (P = 0.047), severity of congestion (P = 0.02), and extent of congestion (P = 0.01). No bone formation was noted in the gutta-percha group. The type of newly formed bone was not significantly different among the three experimental groups (P = 0.320). CONCLUSION: MCM-48 and MCM-48/HA are bioactive nanomaterials that may serve as alternatives for pulpotomy of primary teeth due to their ability to induce hard tissue formation. The MCM-48 and MCM-48/HA mesoporous silica nanomaterials have the potential to induce osteogenesis and tertiary (reparative) dentin formation.

Biocompatibility and bioactive potential of NeoPUTTY calcium silicate-based cement: An in vivo study in rats.

AIM: To evaluate the inflammatory reaction and the ability to induce mineralization activity of a new repair material, NeoPUTTY (NPutty; NuSmile, USA), in comparison with Bio-C Repair (BC; Angelus, Brazil) and MTA Repair HP (MTA HP; Angelus, Brazil). METHODOLOGY: Polyethylene tubes were filled with materials or kept empty (control group, CG) and implanted in subcutaneous tissue of rats for 7, 15, 30, and 60 days (n = 6/group). Capsule thickness, number of inflammatory cells (ICs), fibroblasts, collagen content, and von Kossa analysis were performed. Unstained sections were evaluated under polarized light and by immunohistochemistry for osteocalcin (OCN). Data were submitted to two-way anova followed by Tukey's test (p ≤ .05), except for OCN. OCN data were submitted to Kruskal-Wallis and Dunn and Friedman post hoc tests followed by the Nemenyi test at a significance level of 5%. RESULTS: At 7, 15, and 30 days, thick capsules containing numerous ICs were seen around the materials. At 60 days, a moderate inflammatory reaction was observed for NPutty, BC while MTA HP presented thin capsules with moderate inflammatory cells. In all periods, NPutty specimens contained the highest values of ICs (p < .05). From 7 to 60 days, the number of ICs reduced significantly while an increase in the number of fibroblasts and birefringent collagen content was observed. At 7 and 15 days, no significant difference was observed in the immunoexpression of OCN (p > .05). At 30 and 60 days, NPutty showed the lowest values of OCN (p < .05). At 60 days, a similar immunoexpression was observed for BC and MTA HP (p > .05). In all time intervals, capsules around NPutty, BC, and MTA HP showed von Kossa-positive and birefringent structures. CONCLUSIONS: Despite the greater inflammatory reaction promoted by NeoPutty than BC and MTA HP, the reduction in the thickness of capsules, the increase in the number of fibroblasts, and the reduction in the number of ICs indicate that this bioceramic material is biocompatible Furthermore, NeoPutty presents the ability to induce mineralization activity.

Green synthesis of MnO2 NPs using Arabic gum: assessing its potential antiviral activity against influenza A/H1N1.

BACKGROUND: The antiviral properties of metal nanoparticles against various viruses, including those resistant to drugs, are currently a subject of intensive research. Recently, the green synthesis of nanoparticles and their anti-viral function have attracted a lot of attention. Previous studies have shown promising results in the use of Arabic gum for the green synthesis of nanoparticles with strong antiviral properties. In this study we aimed to investigate the antiviral effects of MnO2 nanoparticles (MnO2-NPs) synthesized using Arabic gum, particularly against the influenza virus. METHODS: Arabic gum was used as a natural polymer to extract and synthesize MnO2-NPs using a green chemistry approach. The synthesized MnO2-NPs were characterized using SEM and TEM. To evaluate virus titration, cytotoxicity, and antiviral activity, TCID50, MTT, and Hemagglutination assay (HA) were performed, respectively. Molecular docking studies were also performed to investigate the potential antiviral activity of the synthesized MnO2-NPs against the influenza virus. The molecular docking was carried out using AutoDock Vina software followed by an analysis with VMD software to investigate the interaction between Arabic gum and the hemagglutinin protein. RESULTS: Simultaneous combination treatment with the green-synthesized MnO2-NPs resulted in a 3.5 log HA decrement and 69.7% cellular protection, which demonstrated the most significant difference in cellular protection compared to the virus control group (p-value < 0.01). The docking results showed that binding affinities were between - 3.3 and - 5.8 kcal/mole relating with the interaction between target with MnO2 and beta-D-galactopyranuronic acid, respectively. CONCLUSION: The results of the study indicated that the MnO2-NPs synthesized with Arabic gum had significant antiviral effects against the influenza virus, highlighting their potential as a natural and effective treatment for inhibition of respiratory infections.

Gum Arabic assisted the biomass synthesis of bimetallic silver copper oxide nanoparticles using gamma-rays for improving bacterial and viral wound healing: Promising antimicrobial activity against foot and mouth disease.

In this work, gamma irradiation was used to create bimetallic silver­copper oxide nanoparticles (Ag-CuO NPs) in an ecologically acceptable way using gum Arabic (GA) polymer as a capping and reducing agent. Bimetallic Ag-CuO NPs were investigated through UV-Vis. spectroscopy, HR-TEM, SEM, DLS, and XRD examinations. The potency of antimicrobial and antibiofilm activities against a few bacterial isolates and Candida sp. had been investigated. Clinical investigations of 30 cows and 20 buffaloes from different sites in Egypt's Sharkia governorate found ulcerative lesions on the mouth and interdigital region. The cytotoxic assay of the generated NPs on BHK-21 was examined. The bimetallic Ag-CuO NPs had an average diameter of 25.58 nm, and the HR-TEM results showed that they were spherical. According to our results, Ag-CuO NPs exhibited the highest antibacterial efficacy against S. aureus (26.5 mm ZOI), K. pneumoniae (26.0 mm ZOI), and C. albicans (28.5 mm ZOI). The growth of biofilms was also successfully inhibited through the application of Ag-CuO NPs by 88.12 % against S. aureus, 87.08 % against C. albicans, and 74.0 % against B. subtilis. The ulcers on the mouth and foot of diseased animals healed in 4-5 days and 1 week, respectively, following topical application of bimetallic Ag-CuO NPs. The results examined the potential protective effects of a dosage of 3.57 µg/mL on cells before viral infection (cell control). According to our research, bimetallic Ag-CuO NPs limit the development of the virus that causes foot-and-mouth disease (FMD). The reduction of a specific FMD virus's cytopathic impact (CPE) on cell development represented the inhibitory effect when compared to identical circumstances without pretreatment with bimetallic Ag-CuO NPs. Their remarkable antibacterial properties at low concentration and continued-phase stability suggest that they may find widespread use in a variety of pharmacological and biological applications, especially in the wound-healing process.

Multi-functional bandage - bioactive glass/metal oxides/alginate composites based regenerative membrane facilitating re-epithelialization in diabetic wounds with sustained drug delivery and anti-bactericidal efficacy.

Chronic wounds, especially diabetic, foot and pressure ulcers are a major health problem affecting >10 % of the world's populace. Calcium phosphate materials, particularly, bioactive glasses (BG), used as a potential material for hard and soft tissue repair. This study combines nanostructured 45S5 BG with titania (TiO2) and alumina (Al2O3) into a composite via simple sol-gel method. Prepared composites with alginate (Alg) formed a bioactive nanocomposite hydrogel membrane via freezing method. X-ray diffraction revealed formation of two phases such as Na1.8Ca1.1Si6O14 and ß-Na2Ca4(PO4)2SiO4 in the silica network. Fourier transformed InfraRed spectroscopy confirmed the network formation and cross-linking between composite and alginate. <2 % hemolysis, optimal in vitro degradation and porosity was systematically evaluated up to 7 days, resulting in increasing membrane bioactivity. Significant cytocompatibility, cell migration and proliferation and a 3-4-fold increase in Collagen (Col) and Vascular Endothelial Growth Factor (VEGF) expression were obtained. Sustained delivery of 80 % Dox in 24 h and effective growth reduction of S. aureus and destruction of biofilm development against E. coli and S. aureus within 24 h. Anatomical fin regeneration, rapid re-epithelialization and wound closure were achieved within 14 days in both zebrafish and in streptozotocin (STZ) induced rat in vivo animal models with optimal blood glucose levels. Hence, the fabricated bioactive membrane can act as effective wound dressing material, for diabetic chronic infectious wounds.