ABSTRACT
This study assessed the physicochemical and antibiofilm properties of white mineral trioxide aggregate (MTA) associated with 1 or 2% of farnesol. Setting time was evaluated based on ISO 6876/2012. Radiopacity was evaluated by radiographic analysis. pH was assessed after time intervals of 1, 3, 7, 14, 21, and 28 days. Solubility (% mass loss) and volumetric change (by micro-CT) of the cements were evaluated after immersion in distilled water. The presence of voids inside the materials was assessed by using micro-CT. Antibiofilm activity against Enterococcus faecalis was evaluated by crystal violet assay and the modified direct contact test performed with biofilm previously formed on bovine root dentin for 14 days. Data were submitted to ANOVA/Tukey tests with 5% significance level. The incorporation of farnesol into MTA increased its setting time, but decreased its solubility at 30 days and its volumetric loss in all periods (p < 0.05). Radiopacity and solubility after 7 days were similar among the materials (p > 0.05). The association of farnesol showed the highest pH value after 1 and 3 days (p < 0.05). The association of farnesol with MTA promoted a decrease in the presence of voids, and increased the antimicrobial activity on biofilm biomass of E. faecalis (p < 0.05). In conclusion, the addition of farnesol can be suggested to improve the antimicrobial properties and the consistency of MTA.
Subject(s)
Aluminum Compounds , Biofilms , Calcium Compounds , Drug Combinations , Enterococcus faecalis , Farnesol , Materials Testing , Oxides , Root Canal Filling Materials , Silicates , Solubility , Silicates/pharmacology , Silicates/chemistry , Oxides/pharmacology , Oxides/chemistry , Biofilms/drug effects , Calcium Compounds/pharmacology , Calcium Compounds/chemistry , Enterococcus faecalis/drug effects , Aluminum Compounds/pharmacology , Aluminum Compounds/chemistry , Farnesol/pharmacology , Farnesol/chemistry , Hydrogen-Ion Concentration , Time Factors , Cattle , Root Canal Filling Materials/pharmacology , Root Canal Filling Materials/chemistry , Animals , Analysis of Variance , Reproducibility of Results , Dentin/drug effects , Reference Values , Surface Properties/drug effectsABSTRACT
BACKGROUND: Biotechnology provides a cost-effective way to produce nanomaterials such as silver oxide nanoparticles (Ag2ONPs), which have emerged as versatile entities with diverse applications. This study investigated the ability of endophytic bacteria to biosynthesize Ag2ONPs. RESULTS: A novel endophytic bacterial strain, Neobacillus niacini AUMC-B524, was isolated from Lycium shawii Roem. & Schult leaves and used to synthesize Ag2ONPS extracellularly. Plackett-Burman design and response surface approach was carried out to optimize the biosynthesis of Ag2ONPs (Bio-Ag2ONPs). Comprehensive characterization techniques, including UV-vis spectral analysis, Fourier transform infrared spectroscopy, transmission electron microscopy, X-ray diffraction, dynamic light scattering analysis, Raman microscopy, and energy dispersive X-ray analysis, confirmed the precise composition of the Ag2ONPS. Bio-Ag2ONPs were effective against multidrug-resistant wound pathogens, with minimum inhibitory concentrations (1-25 µg mL-1). Notably, Bio-Ag2ONPs demonstrated no cytotoxic effects on human skin fibroblasts (HSF) in vitro, while effectively suppressing the proliferation of human epidermoid skin carcinoma (A-431) cells, inducing apoptosis and modulating the key apoptotic genes including Bcl-2 associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), Caspase-3 (Cas-3), and guardian of the genome (P53). CONCLUSIONS: These findings highlight the therapeutic potential of Bio-Ag2ONPs synthesized by endophytic N. niacini AUMC-B524, underscoring their antibacterial efficacy, anticancer activity, and biocompatibility, paving the way for novel therapeutic strategies.
Subject(s)
Anti-Bacterial Agents , Metal Nanoparticles , Silver Compounds , Humans , Metal Nanoparticles/chemistry , Silver Compounds/pharmacology , Silver Compounds/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/biosynthesis , Microbial Sensitivity Tests , Bacillaceae/metabolism , Oxides/pharmacology , Oxides/chemistry , Fibroblasts/drug effects , Apoptosis/drug effectsABSTRACT
Background: Azathioprine is one of the earliest immunosuppressants prescribed for several autoimmune diseases. Yet there is a lack of research on the impact of azathioprine on pulp healing following the pulp capping procedure. Aim: This study aimed to investigate the effect of azathioprine on the healing ability of mechanically exposed dogs' dental pulps following direct pulp capping with mineral trioxide aggregate (MTA), bio-aggregates (BA), and Calcium hydroxide (Ca(OH)2). Methods: Four mongrel dogs were randomly assigned to two groups (two dogs/30 teeth in each group): immunosuppressed (group I) and control (group II). Group I received azathioprine for two months before surgical treatments and until the dogs were euthanized. Fifteen class V buccal cavities were performed in each dog. Each group was randomly divided into three subgroups (10 teeth each) based on the pulp capping substance. The pulps in subgroups A, B, and C were immediately capped with MTA, BA, and Ca(OH)2, respectively. Inflammation and dentine bridge development were histopathologically evaluated and scored at one and two months. The data were statistically analyzed. Results: The immunosuppressed group exhibited statistically greater inflammatory cell count and decreased dentine bridge thickness, compared to the control group in all subgroups (p < 0.05). Conclusion: Azathioprine has an adverse effect on the healing of exposed dogs' dental pulp following direct pulp capping with MTA, BA, and Ca(OH)2. Therefore, patients using azathioprine as an immunosuppressive medication may experience delayed healing of mechanically exposed pulps following capping with MTA, BA, or Ca(OH)2.
Subject(s)
Azathioprine , Calcium Compounds , Calcium Hydroxide , Dental Pulp Capping , Immunosuppressive Agents , Oxides , Silicates , Animals , Dogs , Azathioprine/pharmacology , Azathioprine/therapeutic use , Dental Pulp Capping/veterinary , Oxides/pharmacology , Immunosuppressive Agents/therapeutic use , Immunosuppressive Agents/pharmacology , Silicates/pharmacology , Calcium Compounds/pharmacology , Calcium Hydroxide/pharmacology , Calcium Hydroxide/therapeutic use , Dog Diseases/drug therapy , Aluminum Compounds/pharmacology , Dental Pulp/drug effects , Drug Combinations , Male , Wound Healing/drug effects , Pulp Capping and Pulpectomy Agents/pharmacology , FemaleABSTRACT
This study aims to investigate the effect of Mineral Trioxide Aggregate (MTA), a bioactive endodontic cement, and Concentrated Growth Factor (CGF), a second-generation autologous growth factor, on pulpotomy-induced pulp inflammation. The study utilized the maxillary anterior central teeth of thirty-six young male Sprague Dawley rats. Forty-eight teeth were randomly assigned to two groups (12 rats/group; 24 teeth/group) based on the capping material (MTA or CGF). Subsequently, two subgroups (MTAG and CGFG) were formed per group (12 teeth/group) based on the time following pulpotomy (2-weeks and 4-weeks). The central teeth of the 12 animals assigned to the control group (CG) were not manipulated in any way, both in the 2-week group and in the 4-week group. Tissue samples extracted from rats at the end of the experiment were stained with H&E for histopathological analysis. For immunohistochemical analysis, primary antibodies for TNF-α and NF-kß/65 were incubated. Data obtained from semi-quantitative analysis were assessed for normal distribution using Skewness-Kurtosis values, Q-Q plot, Levene's test, and the Shapiro-Wilk test on statistical software. A P value < 0.05 was considered significant. When compared with the control group, both MTAG and CGFG showed increased edematous and inflammatory areas. In MTAG, edematous and inflammatory areas decreased significantly from the 2nd week (2(2-2), 2(1-2)) to the 4th week (1(1-1), 1(0-1)), while in CGFG, edematous areas decreased (2(2-3), 1.5(1-2)), and inflammatory areas increased significantly (2(2-3), 3(2-2.5)). When compared with the control group, TNF-α and NF-kß/p65 positivity were higher in both MTAG and CGFG. In MTAG, TNF-α [2(1.5-2)] and NF-kß/p65 [1.5(1-2)] positivity decreased significantly from the 2nd week to the 4th week [TNF-α: 1(1-1), NF-kß/p65: 1(1-2)], while no significant change was observed in CGFG. In conclusion, this study revealed a reduction in cells showing TNF-α and NF-kß/p65 positivity in the MTA treatment group compared to the CGF group. Although MTA demonstrated more favorable results than CGF in mitigating pulpal inflammation within the scope of this study, further experimental and clinical investigations are warranted to obtain comprehensive data regarding CGF.
Subject(s)
Aluminum Compounds , Calcium Compounds , Oxides , Pulpotomy , Silicates , Animals , Male , Rats , Aluminum Compounds/pharmacology , Calcium Compounds/pharmacology , Calcium Compounds/therapeutic use , Drug Combinations , Intercellular Signaling Peptides and Proteins , NF-kappa B/metabolism , Oxides/pharmacology , Pulpitis/pathology , Pulpitis/metabolism , Pulpotomy/methods , Random Allocation , Rats, Sprague-Dawley , Silicates/pharmacology , Transcription Factor RelA/metabolism , Tumor Necrosis Factor-alpha/metabolismABSTRACT
A four-step synthesis of the natural product pseudane IX, starting from 3-oxododecanoic acid phenylamide and including only one chromatographic purification, was accomplished with an overall yield of 52%. The same synthetic sequence, but with a controlled partial reduction of a nitro group in the penultimate intermediate, led to the N-oxide of pseudane IX (NQNO). A shortened three-step variation of the synthesis allowed for the preparation of novel carboxamide analogs of the natural product. An agar diffusion assay against six different bacterial strains revealed significant antibacterial activity of the novel analogs against S. aureus at a concentration of 100 µg/mL. One of the novel compounds showed a remarkably broad spectrum of antibacterial activity, comparable to that of the positive control NQNO.
Subject(s)
Anti-Bacterial Agents , Microbial Sensitivity Tests , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Staphylococcus aureus/drug effects , Molecular Structure , Amides/chemistry , Amides/pharmacology , Amides/chemical synthesis , Oxides/chemistry , Oxides/pharmacologyABSTRACT
This study investigates the effects of chlorine dioxide (ClO2) disinfection on the community structure, regrowth potential, and metabolic product secretion of disinfection-residual bacteria (DRB) in secondary effluent (SE), denitrification filter effluent (DFE), and ultrafiltration effluent (UE). Results show that ClO2 effectively reduces bacteria in SE and UE, achieving log removal values exceeding 3 at 1 mg/L within 30 min. A salient positive correlation (R2 > 0.95) exists between changes in total fluorescence intensity and disinfection efficacy. Post-treatment, Acinetobacter abundance increased in SE, while Pseudomonas decreased in DFE and UE. At lower ClO2 concentrations, Staphylococcus, Mycobacterium, Aeromonas, and Lactobacillus increased in DFE, but decreased at higher concentrations. After storage, bacterial counts in disinfected samples exceeded those in the control group, surpassing 105 CFU/mL. Despite an initial decline, species richness and evenness partially recovered but remained lower than control levels. Culturing DRB for 72 h showed elevated extracellular polymeric substances (EPS) secretion, quantified as total organic carbon (TOC), ranging from 5 to 27 mg/L, with significantly higher EPS in the disinfection group. Parallel factor analysis with self-organizing maps (PARAFAC-SOM) effectively differentiated water sample types and EPS fluorescent substances, underscoring the potential of three-dimensional fluorescence as an indirect measure of ClO2 disinfection efficacy.
Subject(s)
Bacteria , Chlorine Compounds , Disinfectants , Disinfection , Oxides , Water Purification , Chlorine Compounds/pharmacology , Oxides/pharmacology , Disinfection/methods , Disinfectants/pharmacology , Bacteria/drug effects , Bacteria/growth & development , Bacteria/metabolism , Water Purification/methods , Water MicrobiologyABSTRACT
The heterogeneity of hepatocellular carcinoma (HCC) can prevent effective treatment, emphasizing the need for more effective therapies. Herein, we employed arsenene nanosheets coated with manganese dioxide and polyethylene glycol (AMPNs) for the degradation of Pin1, which is universally overexpressed in HCC. By employing an "AND gate", AMPNs exhibited responsiveness toward excessive glutathione and hydrogen peroxide within the tumor microenvironment, thereby selectively releasing AsxOy to mitigate potential side effects of As2O3. Notably, AMPNs induced the suppressing Pin1 expression while simultaneously upregulation PD-L1, thereby eliciting a robust antitumor immune response and enhancing the efficacy of anti-PD-1/anti-PD-L1 therapy. The combination of AMPNs and anti-PD-1 synergistically enhanced tumor suppression and effectively induced long-lasting immune memory. This approach did not reveal As2O3-associated toxicity, indicating that arsenene-based nanotherapeutic could be employed to amplify the response rate of anti-PD-1/anti-PD-L1 therapy to improve the clinical outcomes of HCC patients and potentially other solid tumors (e.g., breast cancer) that are refractory to anti-PD-1/anti-PD-L1 therapy.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Manganese Compounds , NIMA-Interacting Peptidylprolyl Isomerase , Oxides , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Oxides/chemistry , Oxides/pharmacology , Humans , NIMA-Interacting Peptidylprolyl Isomerase/antagonists & inhibitors , NIMA-Interacting Peptidylprolyl Isomerase/metabolism , Manganese Compounds/chemistry , Manganese Compounds/pharmacology , Nanostructures/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Arsenicals/chemistry , Arsenicals/pharmacology , Arsenicals/therapeutic use , Mice , Animals , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Cell Line, Tumor , Polyethylene Glycols/chemistryABSTRACT
Nitric oxide (NO) and reactive oxygen species (ROS) embody excellent potential in cancer therapy. However, as a small molecule, their targeted delivery and precise, controllable release are urgently needed to achieve accurate cancer therapy. In this paper, a novel US-responsive bifunctional molecule (SD) and hyaluronic acid-modified MnO2 nanocarrier was developed, and a US-responsive NO and ROS controlled released nanoplatform was constructed. US can trigger SD to release ROS and NO simultaneously at the tumor site. Thus, SD served as acoustic sensitizer for sonodynamic therapy and NO donor for gas therapy. In the tumor microenvironment, the MnO2 nanocarrier can effectively deplete the highly expressed GSH, and the released Mn2+ can make H2O2 to produce .OH by Fenton-like reaction, which exhibited a strong chemodynamic effect. The high concentration of ROS and NO in cancer cell can induce cancer cell apoptosis ultimately. In addition, toxic ONOO-, which was generated by the reaction of NO and ROS, can effectively cause mitochondrial dysfunction, which induced the apoptosis of tumor cells. The 131I was labeled on the nanoplatform, which exhibited internal radiation therapy for tumor therapy. In -vitro and -vivo experiments showed that the nanoplatform has enhanced biocompatibility, and efficient anti-tumor potential, and it achieves synergistic sonodynamic/NO/chemodynamic/radionuclide therapy for cancer.
Subject(s)
Iodine Radioisotopes , Manganese Compounds , Nitric Oxide , Oxides , Reactive Oxygen Species , Nitric Oxide/chemistry , Nitric Oxide/metabolism , Reactive Oxygen Species/metabolism , Humans , Animals , Manganese Compounds/chemistry , Manganese Compounds/pharmacology , Oxides/chemistry , Oxides/pharmacology , Iodine Radioisotopes/chemistry , Apoptosis/drug effects , Nanoparticles/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Mice , Drug Screening Assays, Antitumor , Cell Proliferation/drug effects , Molecular Structure , Mice, Inbred BALB C , Ultrasonic Therapy , Cell Survival/drug effects , Dose-Response Relationship, Drug , Ultrasonic Waves , Cell Line, TumorABSTRACT
AIMS: This study aimed to assess the effects of chlorine dioxide (ClO2) in water on whiteleg shrimp Penaeus vannamei, evaluating its impact on the stomach microbiota, gill transcriptome, and pathogens. METHODS AND RESULTS: ClO2 was added to the aquarium tanks containing the shrimp. The application of ClO2 to rearing water was lethal to shrimp at concentrations above 1.2 ppm. On the other hand, most of the shrimp survived at 1.0 ppm of ClO2. Microbiome analysis showed that ClO2 administration at 1.0 ppm significantly reduced the α-diversity of bacterial community composition in the shrimp stomach, and this condition persisted for at least 7 days. Transcriptome analysis of shrimp gill revealed that ClO2 treatment caused massive change of the gene expression profile, including stress response genes. However, after 7 days of the treatment, the gene expression profile was similar to that of shrimp in the untreated control group, suggesting a recovery to the normal state. This 1.0-ppm ClO2 significantly reduced shrimp mortality in artificial challenges with an acute hepatopancreatic necrosis disease-causing Vibrio parahaemolyticus and white spot syndrome virus, which were added to rearing water. CONCLUSIONS: The use of ClO2 at appropriate concentrations effectively eliminates a significant portion of the bacteria in the shrimp stomach and pathogens in the water. The results of this study provide fundamental knowledge on the disinfection of pathogens in water using ClO2 and the creation of semi germ-free shrimp, which has significantly decreased microbiome in the stomach.
Subject(s)
Chlorine Compounds , Gills , Oxides , Penaeidae , Transcriptome , Chlorine Compounds/pharmacology , Animals , Penaeidae/microbiology , Oxides/pharmacology , Gills/microbiology , Gastrointestinal Microbiome/drug effects , Disinfectants/pharmacology , Aquaculture , Vibrio parahaemolyticus/drug effectsABSTRACT
Sanitizer spray and brush roller treatments have been documented as an effective means of reducing Salmonella on the surface of produce. The purpose of this study was to evaluate the efficacy of chlorine (NaOCl), peroxyacetic acid (PAA), and chlorine dioxide (ClO2) sprays to reduce Salmonella populations on the surface of mangoes during washing with brush or polyvinyl chloride (PVC) rollers. Whole mangoes were spot inoculated with 100 µL of a rifampicin-resistant Salmonella (8 log CFU/mL) cocktail at the equator and dried for 1 h. Mangoes were washed with a lab-scale roller system with either ground water (control), or sanitizers (100 ppm NaOCl, 80 ppm PAA, or 5 ppm ClO2) for 0, 5, 15, 30, or 60 s (n = 15 mangoes). Dey/Engley buffer (100 mL) was used to rinse mangoes before plating on media supplemented with rifampicin. NaOCl, PAA, and ClO2 spray (except for ClO2 at 30 s) had significantly higher reduction on Salmonella population than water spray at all treatment times (P ≤ 0.05) when brush rollers were used. All tested sanitizers also achieved a significantly higher reduction than water at 5 s when PVC rollers were used (P ≤ 0.05). Salmonella reductions achieved by brush and PVC rollers was not statistically different (P > 0.05). After a 5 s treatment on brush and PVC rollers, NaOCl, PAA, and ClO2 spray had ca. 3.03 and 3.45 log, 3.96 and 3.28 log, and 2.54 and 2.00 log CFU/mango reductions, respectively, whereas water spray achieved 1.75 and 0.98 log CFU/mango reduction. Addition of sanitizers to spray water used during brush or PVC washing in mango packinghouses can reduce Salmonella on mango surfaces.
Subject(s)
Chlorine Compounds , Colony Count, Microbial , Disinfectants , Mangifera , Oxides , Peracetic Acid , Polyvinyl Chloride , Salmonella , Sodium Hypochlorite , Mangifera/microbiology , Chlorine Compounds/pharmacology , Salmonella/drug effects , Disinfectants/pharmacology , Oxides/pharmacology , Peracetic Acid/pharmacology , Sodium Hypochlorite/pharmacology , Food Handling/methods , Food MicrobiologyABSTRACT
Water pollution and antimicrobial resistance (AMR) have become two global threats; 80% of diseases and 50% of child deaths are due to poor water quality. In this study, hydrothermal processing was employed to manufacture manganese oxide nanorods. Silver dopant was deposited on the surface of manganese oxide. XRD diffractogram confirmed the facile synthesis of Ag/Mn2O3 nanocomposite. XPS survey analysis demonstrated silver content of 9.43 atom %. Photocatalytic measurements demonstrated the outstanding efficiency of the Ag-Mn2O3 compared to virgin oxide particles under visible radiation. Degradation efficiencies Mn2O3 and Ag/Mn2O3 on methyl orange (MO) dye was found to be 53% and 85% under visible spectrum. Silver dopant was found to decrease the binding energy of valence electrons; this action could support electron-hole pair generation under visible spectrum and could promote catalytic performance. Ag/Mn2O3 NPs demonstrated most effective performance (95% removal efficiency) at pH 3; this could be ascribed to the electrostatic attraction between positively charged catalyst and the negatively charged MO. Ag/Mn2O3 demonstrated enhanced antibacterial activity against Gram-positive Staphylococcus aureus (S. aureus) (19 mm ZOI), and Gram-negative Escherichia coli (E. coli) (22 mm ZOI) respectively; the developed nanocomposite demonstrated advanced anti-film activity with inhibition percentage of 95.5% against E. coli followed by 89.5% against S. aureus.
Subject(s)
Escherichia coli , Manganese Compounds , Nanocomposites , Oxides , Silver , Staphylococcus aureus , Manganese Compounds/chemistry , Manganese Compounds/pharmacology , Oxides/chemistry , Oxides/pharmacology , Silver/chemistry , Silver/pharmacology , Nanocomposites/chemistry , Catalysis , Escherichia coli/drug effects , Staphylococcus aureus/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Light , Azo Compounds/chemistry , Azo Compounds/pharmacology , Microbial Sensitivity Tests , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Anti-Infective Agents/chemical synthesis , Photochemical ProcessesABSTRACT
BACKGROUND: Preservation of primary teeth in children is highly important. Pulpotomy is a commonly performed treatment procedure for primary teeth with extensive caries. Thus, biocompatibility of pulpotomy agents is highly important. Biodentine, calcium enriched mixture (CEM) cement, ferric sulfate, and mineral trioxide aggregate (MTA) Angelus are commonly used for this purpose. Thus, this study aimed to assess the apoptotic effects of Biodentine, CEM cement, ferric sulfate, and MTA on stem cells isolated from the human pulp of exfoliated deciduous teeth. METHODS: In this in-vitro, experimental study, stem cells isolated from the human pulp of exfoliated deciduous teeth were exposed to three different concentrations of Biodentine, CEM cement, ferric sulfate, and MTA for different time periods. The cytotoxicity of the materials was evaluated by flow cytometry using the annexin propidium iodide (PI) kit. Data were analyzed by ANOVA and Tukey's test at P<0.05 level of significance. RESULTS: All four tested materials induced significantly greater apoptosis compared with the control group. The difference in cell apoptosis caused by the first concentration of ferric sulfate and MTA was not significant at 24 hours. In other comparisons, the cytotoxicity of ferric sulfate was significantly lower than that of other materials. Biodentine showed higher cytotoxicity than MTA at first; but this difference faded over time. The cytotoxicity of CEM cement was comparable to that of MTA. The highest cell viability was noted at 24 hours in presence of the minimum concentration of ferric sulfate. The lowest cell viability was noted at 72 hours in presence of the maximum concentration of CEM cement. CONCLUSIONS: In comparison with other materials, ferric sulfate showed minimum cytotoxicity; the cytotoxicity of the three cements was comparable. It appears that the concentration of ferric sulfate and the composition of cements are responsible for different levels of cytotoxicity.
Subject(s)
Aluminum Compounds , Apoptosis , Calcium Compounds , Dental Pulp , Drug Combinations , Ferric Compounds , Mesenchymal Stem Cells , Oxides , Silicates , Tooth, Deciduous , Humans , Calcium Compounds/pharmacology , Silicates/pharmacology , Aluminum Compounds/pharmacology , Aluminum Compounds/toxicity , Oxides/pharmacology , Tooth, Deciduous/drug effects , Tooth, Deciduous/cytology , Ferric Compounds/pharmacology , Apoptosis/drug effects , Mesenchymal Stem Cells/drug effects , Dental Pulp/cytology , Dental Pulp/drug effects , Dental Cements/pharmacology , Dental Cements/toxicity , Materials Testing , In Vitro Techniques , Flow Cytometry/methodsABSTRACT
Anaerobic fermentation has emerged as a promising method of transforming waste activated sludge into high-value products (e.g., volatile fatty acids (VFAs)). This work developed sodium citrate (SC)-calcium oxide (CaO) pretreatment to accelerate the production of VFAs by enhancing sludge solubilization and disintegration of extracellular polymeric substances. The results showed that co-pretreatment with 0.25 g/g TSS of SC and 0.05 g/g TSS of CaO effectively boosted VFAs accumulation (5823.3 mg COD/L), which was 12.2 times higher than the Control group. SC-CaO pretreatment enhanced hydrolysis and acidogenesis by providing ample organic substrates, thereby promoting the growth of hydrolytic and acidogenic bacteria. Additionally, the fermentation broth resulting from co-pretreatment exhibited lower phosphorus concentration and higher biodegradability. Economic analysis confirmed that the combined pretreatment is cost-effective. This work provides a viable strategy for enhancing high-value product recovery from sludge.
Subject(s)
Calcium Compounds , Citrates , Fatty Acids, Volatile , Oxides , Sewage , Sodium Citrate , Calcium Compounds/pharmacology , Calcium Compounds/chemistry , Oxides/pharmacology , Oxides/chemistry , Hydrolysis , Sodium Citrate/pharmacology , Fermentation , Biodegradation, Environmental , Biological Oxygen Demand AnalysisABSTRACT
The widespread use of antibiotics often increases bacterial resistance. Herein, we reported a silver peroxide-incorporated carbon dots (defined as Ag2O2-CDs) with high photothermal conversion efficiency viain situoxidation process. The prepared Ag2O2-CDs exhibited ultra-small size of 2.0 nm and hybrid phase structure. Meanwhile, the Ag2O2-CDs were of a similar optical performance comparing with traditional carbon dots (CDs). Importantly, the incorporation of Ag2O2into CDs significantly enhanced photothermal conversion efficiency from 3.8% to 28.5%. By combining silver ion toxicity and photothermal ablation, the Ag2O2-CDs were capable of destroying gram-positive and gram-negative bacterium effectively. These findings demonstrated that the Ag2O2-CDs could be served as a potential antibacterial agent for clinical applications.
Subject(s)
Anti-Bacterial Agents , Carbon , Quantum Dots , Silver Compounds , Carbon/chemistry , Quantum Dots/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Silver Compounds/chemistry , Silver Compounds/pharmacology , Oxides/chemistry , Oxides/pharmacology , Peroxides/chemistry , Peroxides/pharmacology , Silver/chemistry , Silver/pharmacology , Microbial Sensitivity Tests , Escherichia coli/drug effectsABSTRACT
Background: Vital pulp therapy (VPT) is considered a conservative treatment for preserving pulp viability in caries and trauma-induced pulpitis. However, Mineral trioxide aggregate (MTA) as the most frequently used repair material, exhibits limited efficacy under inflammatory conditions. This study introduces an innovative nanocomposite hydrogel, tailored to simultaneously target anti-inflammation and dentin mineralization, aiming to efficiently preserve vital pulp tissue. Methods: The L-(CaP-ZnP)/SA nanocomposite hydrogel was designed by combining L-Arginine modified calcium phosphate/zinc phosphate nanoparticles (L-(CaP-ZnP) NPs) with sodium alginate (SA), and was characterized with TEM, SEM, FTIR, EDX, ICP-AES, and Zeta potential. In vitro, we evaluated the cytotoxicity and anti-inflammatory properties. Human dental pulp stem cells (hDPSCs) were cultured with lipopolysaccharide (LPS) to induce an inflammatory response, and the cell odontogenic differentiation was measured and possible signaling pathways were explored by alkaline phosphatase (ALP)/alizarin red S (ARS) staining, qRT-PCR, immunofluorescence staining, and Western blotting, respectively. In vivo, a pulpitis model was utilized to explore the potential of the L-(CaP-ZnP)/SA nanocomposite hydrogel in controlling pulp inflammation and enhancing dentin mineralization by Hematoxylin and eosin (HE) staining and immunohistochemistry staining. Results: In vitro experiments revealed that the nanocomposite hydrogel was synthesized successfully and presented desirable biocompatibility. Under inflammatory conditions, compared to MTA, the L-(CaP-ZnP)/SA nanocomposite hydrogel demonstrated superior anti-inflammatory and pro-odontogenesis effects. Furthermore, the nanocomposite hydrogel significantly augmented p38 phosphorylation, implicating the involvement of the p38 signaling pathway in pulp repair. Significantly, in a rat pulpitis model, the L-(CaP-ZnP)/SA nanocomposite hydrogel downregulated inflammatory markers while upregulating mineralization-related markers, thereby stimulating the formation of robust reparative dentin. Conclusion: The L-(CaP-ZnP)/SA nanocomposite hydrogel with good biocompatibility efficiently promoted inflammation resolution and enhanced dentin mineralization by activating p38 signal pathway, as a pulp-capping material, offering a promising and advanced solution for treatment of pulpitis.
Subject(s)
Alginates , Anti-Inflammatory Agents , Dental Pulp , Hydrogels , Nanocomposites , Dental Pulp/cytology , Dental Pulp/drug effects , Humans , Hydrogels/chemistry , Hydrogels/pharmacology , Nanocomposites/chemistry , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Alginates/chemistry , Alginates/pharmacology , Pulpitis/therapy , Stem Cells/drug effects , Stem Cells/cytology , Calcium Phosphates/chemistry , Calcium Phosphates/pharmacology , Silicates/chemistry , Silicates/pharmacology , Rats , Cell Differentiation/drug effects , Calcium Compounds/chemistry , Calcium Compounds/pharmacology , Cells, Cultured , Aluminum Compounds/chemistry , Aluminum Compounds/pharmacology , Arginine/chemistry , Arginine/pharmacology , Rats, Sprague-Dawley , Drug Combinations , Male , Oxides/chemistry , Oxides/pharmacologyABSTRACT
Managing chronic non-healing wounds presents a significant clinical challenge due to their frequent bacterial infections. Mesoporous silica-based materials possess robust wound-healing capabilities attributed to their renowned antimicrobial properties. The current study details the advancement of mesoporous silicon-loaded MnO and CaO molecules (HMn-Ca) against bacterial infections and chronic non-healing wounds. HMn-Ca was synthesized by reducing manganese chloride and calcium chloride by urotropine solution with mesoporous silicon as the template, thereby transforming the manganese and calcium ions on the framework of mesoporous silicon. The developed HMn-Ca was investigated using scanning electron microscopy (SEM), transmission electron microscope (TEM), ultraviolet-visible (UV-visible), and visible spectrophotometry, followed by the determination of Zeta potential. The production of reactive oxygen species (ROS) was determined by using the 3,3,5,5-tetramethylbenzidine (TMB) oxidation reaction. The wound healing effectiveness of the synthesized HMn-Ca is evaluated in a bacterial-infected mouse model. The loading of MnO and CaO inside mesoporous silicon enhanced the generation of ROS and the capacity of bacterial capture, subsequently decomposing the bacterial membrane, leading to the puncturing of the bacterial membrane, followed by cellular demise. As a result, treatment with HMn-Ca could improve the healing of the bacterial-infected wound, illustrating a straightforward yet potent method for engineering nanozymes tailored for antibacterial therapy.
Subject(s)
Manganese Compounds , Nanoparticles , Oxides , Reactive Oxygen Species , Wound Healing , Wound Healing/drug effects , Animals , Mice , Nanoparticles/chemistry , Oxides/chemistry , Oxides/pharmacology , Manganese Compounds/chemistry , Manganese Compounds/pharmacology , Porosity , Reactive Oxygen Species/metabolism , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Calcium Compounds/chemistry , Calcium Compounds/pharmacology , Oxidation-Reduction , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Manganese/chemistry , Manganese/pharmacology , Microbial Sensitivity TestsABSTRACT
Arsenic trioxide (ATO) is expected to be a chemical drug with antitumor activity against acute promyelocytic leukemia (APL), a type of acute myeloid leukemia. In Japan, its antitumor effects were confirmed in clinical trials for APL, and it has been approved in various countries around the world. However, there have been no reports on ATO's antitumor effects on radioresistant leukemia cells, which can be developed during radiotherapy and in combination with therapeutic radiation beams. The present study sought to clarify the antitumor effect of ATO on APL cells with radiation resistance and determine its efficacy when combined with ionizing radiation (IR). The radiationresistant HL60 (ResHL60) cell line was generated by subjecting the native cells to 4Gy irradiation every week for 4 weeks. The halfmaximal inhibitory concentration (IC50) for cell proliferation by ATO on native cell was 0.87 µM (R2=0.67), while the IC50 for cell proliferation by ATO on ResHL60 was 2.24 µM (R2=0.91). IR exposure increased the subG1 and G2/M phase ratios in both cell lines. The addition of ATO resulted in a higher population of G2/M after 24 h rather than 48 h. When the rate of change in the subG1 phase was examined in greater detail, the subG1 phase in both control cells without ATO significantly increased by exposure to IR at 24 h, but only under the condition of 2 Gy irradiation, it had continued to increase at 48 h. ResHL60 supplemented with ATO showed a higher rate of subG1 change at 24 h; however, 2 Gy irradiation resulted in a decrease compared with the control. There was a significant increase in the ratio of the G2/M phase in cells after incubation with ATO for 24 h, and exposure to 2 Gy irradiation caused an even greater increase. To determine whether the inhibition of cell proliferation and cell cycle disruptions is related to reactive oxygen species (ROS) activity, intracellular ROS levels were measured with a flow cytometric assay. Although the ROS levels of ResHL60 were higher than those of native cells in the absence of irradiation, they did not change after 0.5 or 2 Gy irradiation. Furthermore, adding ATO to ResHL60 reduced intracellular ROS levels. These findings provide important information that radioresistant leukemia cells respond differently to the antitumor effect of ATO and the combined effect of IR.
Subject(s)
Arsenic Trioxide , Arsenicals , Cell Proliferation , Leukemia, Promyelocytic, Acute , Oxides , Radiation, Ionizing , Humans , Arsenic Trioxide/pharmacology , Leukemia, Promyelocytic, Acute/drug therapy , Leukemia, Promyelocytic, Acute/pathology , Leukemia, Promyelocytic, Acute/radiotherapy , Cell Proliferation/drug effects , Cell Proliferation/radiation effects , HL-60 Cells , Arsenicals/pharmacology , Oxides/pharmacology , Apoptosis/drug effects , Apoptosis/radiation effects , Radiation Tolerance/drug effects , Antineoplastic Agents/pharmacology , Reactive Oxygen Species/metabolismABSTRACT
Alzheimer disease (AD) is the cause of dementia and accounts for 60-80% cases. Tumor Necrosis Factor-alpha (TNF-α) is a multifunctional cytokine that provides resistance to infections, inflammation, and cancer. It developed as a prospective therapeutic target against multiple autoimmune and inflammatory disorders. Cholinergic insufficiency is linked to Alzheimer's disease, and several cholinesterase inhibitors have been created to treat it, including naturally produced inhibitors, synthetic analogs, and hybrids. In the current study, we tried to prepared compounds may also support the discovery and development of novel therapeutic and preventative drugs for Alzheimer's using manganese tetroxide nanoparticles (Mn3O4-NPs) as a catalyst to generate compounds with excellent reaction conditions. The Biginelli synthesis yields 4-(4-cyanophenyl)-6-oxo-2-thioxohexahydropyrimidine-5-carbonitrile when the 4-cyanobenzaldehyde, ethyl cyanoacetate, and thiourea were coupled with Mn3O4-NPs to produce compound 1. This multi-component method is non-toxic, safe, and environmentally friendly. The new approach reduced the amount of chemicals used and preserved time. Compound 1 underwent reactions with methyl iodide, acrylonitrile, chloroacetone, ethyl chloroacetate, and chloroacetic acid/benzaldehyde, each of the synthetized compounds was docked with TNF-α converting enzyme. These compounds may also support the discovery and development of novel therapeutic and preventative drugs for Alzheimer's disease. The majority of the produced compounds demonstrated pharmacokinetic features, making them potentially attractive therapeutic candidates for Alzheimer's disease treatment.
Subject(s)
Alzheimer Disease , Manganese Compounds , Molecular Docking Simulation , Nanoparticles , Oxides , Pyrimidines , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Pyrimidines/chemistry , Pyrimidines/pharmacology , Pyrimidines/pharmacokinetics , Manganese Compounds/chemistry , Manganese Compounds/pharmacology , Animals , Nanoparticles/chemistry , Oxides/chemistry , Oxides/pharmacology , Humans , Rats , MaleABSTRACT
Reactive oxygen species (ROS)-associated anticancer approaches usually suffer from two limitations, i.e., insufficient ROS level and short ROS half-life. Nevertheless, no report has synchronously addressed both concerns yet. Herein, a multichannel actions-enabled nanotherapeutic platform using hollow manganese dioxide (H-MnO2) carriers to load chlorin e6 (Ce6) sonosensitizer and CO donor (e.g., Mn2(CO)10) has been constructed to maximumly elevate ROS level and trigger cascade catalysis to produce CO. Therein, intratumoral H2O2 and ultrasound as endogenous and exogeneous triggers stimulate H-MnO2 and Ce6 to produce â¢OH and 1O2, respectively. The further cascade reaction between ROS and Mn2(CO)10 proceeds to release CO, converting short-lived ROS into long-lived CO. Contributed by them, such a maximumly-elevated ROS accumulation and long-lived CO release successfully suppresses the progression, recurrence and metastasis of lung cancer with a prolonged survival rate. More significantly, proteomic and genomic investigations uncover that the CO-induced activation of AKT signaling pathway, NRF-2 phosphorylation and HMOX-1 overexpression induce mitochondrial dysfunction to boost anti-tumor consequences. Thus, this cascade catalysis strategy can behave as a general means to enrich ROS and trigger CO release against refractory cancers.
Subject(s)
Carbon Monoxide , Lung Neoplasms , Manganese Compounds , Oxides , Porphyrins , Reactive Oxygen Species , Reactive Oxygen Species/metabolism , Lung Neoplasms/metabolism , Lung Neoplasms/drug therapy , Humans , Carbon Monoxide/pharmacology , Carbon Monoxide/metabolism , Carbon Monoxide/chemistry , Animals , Manganese Compounds/chemistry , Manganese Compounds/pharmacology , Oxides/chemistry , Oxides/pharmacology , Mice , Porphyrins/chemistry , Porphyrins/pharmacology , Chlorophyllides , Cell Line, Tumor , Mice, Inbred BALB C , Hydrogen Peroxide/metabolism , Mice, Nude , A549 CellsABSTRACT
Triple negative breast cancer (TNBC) has the characteristics of low immune cell infiltration, high expression of tumor programmed death ligand 1 (PD-L1), and abundant cancer stem cells. Systemic toxicity of traditional chemotherapy drugs due to poor drug selectivity, and chemotherapy failure due to tumor drug resistance and other problems, so it is particularly important to find new cancer treatment strategies for TNBC with limited treatment options. Both the anti-tumor natural drugs curcumin and ginsenoside Rg3 can exert anti-tumor effects by inducing immunogenic cell death (ICD) of tumor cells, reducing PD-L1 expression, and reducing cancer stem cells. However, they have the disadvantages of poor water solubility, low bioavailability, and weak anti-tumor effect of single agents. We used vinyl ether bonds to link curcumin (Cur) with N-O type zwitterionic polymers and at the same time encapsulated ginsenoside Rg3 to obtain hyperbranched zwitterionic drug-loaded micelles OPDEA-PGED-5HA@Cur@Rg3 (PPH@CR) with pH response. In vitro cell experiments and in vivo animal experiments have proved that PPH@CR could not only promote the maturation of dendritic cells (DCs) and increase the CD4+ T cells and CD8+ T cells by inducing ICD in tumor cells but also reduce the expression of PD-L1 in tumor tissues, and reduce cancer stem cells and showed better anti-tumor effects and good biological safety compared with free double drugs, which is a promising cancer treatment strategy.