Significant Antibacterial Effect Research Articles

Thermo-sensitive Poloxamer based antibacterial anti-inflammatory and photothermal conductive multifunctional hydrogel as injectable, in situ curable and adjustable intraocular lens

Cataract patients look forwards to fewer postoperative complications and higher vision quality after surgery. However, the current intraocular lens (IOL) implanted after cataract surgery neither can adjust focal length in response to ciliary muscle contraction as natural lens nor have the ability to prevent postoperative complications. Herein, a thermosensitve Poloxamer based hybrid hydrogel with antibacterial anti-inflammatory and photothermal functional elements doping was designed and used as injectable, in situ curable, and adjustable IOL (FHTAB IOL). The FHTAB IOL was composed of thermosensitve triblock-polymer F127DA and a small amount of HAMA, combined with BP NS, TA, and Ag NPs. FHTAB IOL can be injected into the empty lens capsule after cataract surgery via an injectable thermos-gel under NIR illumination and then be rapidly cured to form a full-size IOL under short-time blue light irradiation. The designed injectable FHTAB IOL possesses high transparency and transmittance, with a refractive index similar to the natural lens and adjustable properties. It was stabilized as a refractive medium without any leakage in the eye. In addition, the TA and Ag NPs loaded in the FHTAB IOL displayed significant antibacterial and anti-inflammatory effects in vitro and vivo. This study presents a potentially effective new strategy for the development of multifunctional adjustable IOLs.

Synthesis and evaluation of antibacterial and antioxidant effects of propolis nanoparticles and cinnamon nanostructures in preventive dentistry: Experimental and theoretical approaches.

Natural products such as green propolis and cinnamon have been used traditionally in medicine due to their medicinal value. Recently, interest has grown in developing nanotechnology-based approaches to enhance the biological activity of these compounds. This study evaluated the antioxidant and antibacterial properties of macro-sized and nanostructured forms of green propolis and cinnamon against Streptococcus mutans (S.mutans) and the 2,2-diphenyl-2-picrylhydrazyl (DPPH) assay. The sonochemical method was used to synthesize green propolis nanoparticles (PNPs) and cinnamon nanoparticles (CNPs). Their size was confirmed by scanning electron microscopy (SEM) and dynamic light scattering measurements, while they were compared with propolis (P) and cinnamon (C). The antioxidant activity was measured using the DPPH assay, while the minimum inhibitory concentration (MIC) test determined the antibacterial activity against S.mutans. One-way analysis of variance (ANOVA) and Tukey's post hoc tests (α = 0.05) were conducted to analyze the data. Furthermore, docking calculations were carried out to examine the potential of incorporating any new supplements or therapies into your routine. The MIC were 5.46, 21.87, 21.87, and 175 g/L for PNPs, P, CNPs, and C groups, respectively. The PNPs exhibited the most significant antibacterial effect while C was weakest. About antioxidant activity, PNPs and P exhibited significant differences from other groups (P = 0.000 and 0.001, respectively), while CNPs and C showed no significant difference between each other (P = 0.07). The docking calculations revealed a strong interaction between both nanoparticles and S.mutans. The binding energy of dihydroflavonols on propolis nanoparticles was -6.83 kcal/mol, indicating a stable connection.

Synthesis and antibacterial effects of silver nanoparticles (AgNPs) against multi-drug resistant bacteria.

The emergence of the global problem of multi-drug resistant bacteria (MDR) is closely related to the improper use of antibiotics, which gives birth to an urgent need for antimicrobial innovation in the medical and health field. Silver nanoparticles (AgNPs) show significant antibacterial potential because of their unique physical and chemical properties. By accurately regulating the morphology, size and surface properties of AgNPs, the antibacterial properties of AgNPs can be effectively enhanced and become a next generation antibacterial material with great development potential. The detection of the inhibitory effect of AgNPs on MDR provides more possibilities for the research and development of new antimicrobial agents. Promote the formation of AgNPs by redox reaction; determine the minimum inhibitory concentration (MIC) of AgNPs to bacteria by broth microdilution method; evaluate the killing efficacy of AgNPs against multi-drug-resistant bacteria by plate counting; evaluate the inhibitory effect of AgNPs on biofilm construction by crystal violet staining; study the drug resistance of bacteria by gradually increasing the concentration of AgNPs; and detect the toxicity of AgNPs to cells by CCK-8 method. AgNPs has a significant bactericidal effect on a variety of drug-resistant bacteria. After exposure to AgNPs solution for 12 hours, the number of E. coli decreased sharply, and S. aureus was basically eliminated after 16 hours. In particular, AgNPs showed stronger inhibition against Gram-negative bacteria. In addition, AgNPs can effectively hinder the formation of bacterial biofilm, and its inhibitory effect increases with the increase of AgNPs solution concentration. When AgNPs is used for a long time, the development of bacterial resistance to it is slow. From the point of view of safety, AgNPs has no harmful effects on organisms and has biosafety. AgNPs can inhibit MDR, and the bacteriostatic ability of Gram-negative bacteria is higher than that of Gram-positive bacteria. It can also inhibit the formation of bacterial biofilm, avoid drug resistance and reduce cytotoxicity.

Enriched advanced platelet-rich fibrin plus gold nanoparticles against Enterococcus faecalis for its potential use in revascularization for necrotic immature permanent teeth

Background: Regenerative endodontic procedures allow reinforcement of root canal wall and continuation of root development, opening new therapeutic possibilities. The root canal system of infected teeth is colonized by a variety of microorganisms, which hinder the regenerative process, leading to treatment failure if not adequately addressed, thereby requiring careful attention to microbial control. Aim and Objective: The aim of the study was to assess the antimicrobial activity of advanced platelet-rich fibrin (A-PRF) and gold nanoparticles (AuNps) against Enterococcus faecalis. Materials and Methods: Intravenous blood (5–6 ml) was drawn from four healthy individuals, and A-PRF was prepared through centrifugation at 1500 revolutions per minute (rpm) for 14 min. A-PRF was doped with 3 µl of AuNps and centrifuged at 1000 rpm for 1 min. Antimicrobial activity was assessed using disk diffusion; inhibition zones were measured. For minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), A-PRF + AuNps were added to the microbial broth at varying concentrations to determine growth inhibition and microbial death. Results: Disk diffusion assays revealed significant antibacterial effects against E. faecalis. Norfloxacin displayed the highest mean zone of inhibition (20.33 ± 1.53 mm), followed by the Test group (A-PRF + AuNPs) (19.33 ± 0.58 mm). Multiple comparisons indicated significant differences (P < 0.001). MIC of A-PRF + AuNPs against E. faecalis was 0.031 mg/ml, with MBC at 0.015 mg/ml. Conclusion: The addition of AuNPs to A-PRF offers the potential for sustained growth factor release while maintaining the sterility of the canal, leading to successful revitalization and regeneration. The combined use of A-PRF + AuNps shows promise for enhancing revascularization in necrotic immature permanent teeth.

Design and Application of an In Situ Traceable Nitric OxideDonor for Promoting the Healing of Wound Infections.

Therapies for wound infections require medications with antibacterial and wound-healing functions. However, it remains a challenge to produce a single drug that can perform dual functions. Nitric oxide (NO), with its antibacterial and wound-healing activities, is an ideal solution to address this challenge. However, many controlled-release strategies for NO rely on external probes for tracing the release in situ, making it difficult to precisely assess the location and magnitude. To address this issue, this study describes a novel NO donor, DHU-NO1, capable of efficiently releasing NO under mild conditions (450nm illumination). Simultaneously, DHU-NO1 generates the fluorophore Azure B (AZB), which enables direct, non-consumptive tracing of the NO release by monitoring the fluorescence and absorption changes in AZB. Given that NO can be conveniently traced, the amount of released NO can be controlled during biological applications, thereby allowing both functions of NO to be performed. When applied to the affected area, DHU-NO1, illuminated by both a simple light-emitting diode (LED) light source and natural light, achieves significant antibacterial effects against wound infections and promotes wound healing in mice. This study offers a novel and effective approach for treating wound infections.

Synthesis of acylated derivatives of alginate oligosaccharides and evaluation of their potential antibacterial activities against Staphylococcus aureus

Alginate oligosaccharides (AOS) are crucial carbohydrate-based biomaterial used in the synthesis of potential drugs and biological agents, but their antibacterial activities are not significant. In this study, AOS acylated derivatives were synthesized by grafting maleic anhydride (MA) onto AOS at varying ratios. Additionally, their inhibitory effects against Staphylococcus aureus were thoroughly investigated. Characterization of the AOS acylated derivatives (AOS-MA-x, where x = 1, 5, 10, and 20) was conducted using Fourier-transformed infrared spectroscopy, 1H nuclear magnetic resonance spectroscopy, and X-ray diffraction, which confirmed the successful synthesis of these derivatives. The bacteriostatic activity of the AOS-MA derivatives was assessed using growth curves and plate coating method, demonstrating significant antibacterial effects against S. aureus, as compared with AOS. Among these derivatives, AOS-MA-20 exhibited the most potent bacteriostatic activity and was selected for further investigation of its inhibitory mechanism. Scanning electron microscopy analysis revealed that treatment with AOS-MA-20 led to the lysis and rupture of S. aureus cells, expelling their intracellular contents. Moreover, AOS-MA-20 disrupted the integrity of cell wall and cell membrane, impacted ATPase activity, and inhibited the formation of biofilm to some extent, ultimately resulting in bacterial death. These findings lay a foundational framework for the development of environmentally friendly antimicrobial agents.

Gallium-based metal–organic frameworks with antibacterial and anti-inflammatory properties for oral health protection

The fascial space of the oral and maxillofacial region contains loose connective tissues, which possess weak anti-infection ability and are often prone to infection, leading to acute suppurative inflammation and sepsis through blood. Although antibiotic use can reduce the probability of bacterial infections, owing to the emergence of antibiotic-resistant bacteria, the search for new antimicrobial drugs is imminent. Herein, we report a metal–organic framework (MOF) antibacterial material designed and synthesized with gallium (Ga) as the central atom, which possesses significant antibacterial, anti-inflammatory, and antioxidant effects. Our data suggested that GA-based MOFs (Ga–MOFs; 1 μg/mL) could sufficiently kill Porphyromonas gingivalis, Streptococcus pyogenes, and Staphylococcus aureus. Ga–MOFs exhibited a bactericidal effect against these three pathogens by disrupting biofilm formation, exopolysaccharide production, and bacterial membrane integrity. In addition, we found that 1 μg/mL of Ga–MOFs was not cytotoxic to human oral epithelial cell (HOEC) lines and it significantly reduced the adhesion of the three pathogens to HOEC. Ga–MOFs protect macrophages from excessive oxidative stress by scavenging excess intracellular reactive oxygen species and upregulating antioxidant gene levels, thereby enhancing cellular antioxidant defense. In addition, Ga–MOFs can promote the transformation of macrophages from the proinflammatory phenotype to the anti-inflammatory phenotype, thereby protecting oral health. Herein, novel Ga–MOF materials were chemically synthesized for therapeutic applications in oral infections, which provides new ideas for the development of novel nonantibiotic drugs to accelerate patient recovery.

Hibiscus Sabdariffa L. Extract as a Natural Additive in Food Packaging Biodegradable Films to Improve Antioxidant, Antimicrobial, and Physicochemical Properties.

In this study, biodegradable active films were prepared from potato starch and polyvinyl alcohol at different proportions, mixed with acetone extract of Hibiscus sabdariffa L. (HS) and using glycerol as a plasticizer. Functional properties, antimicrobial, and antioxidant capacity were evaluated. Potato starch films with a proportion of polyvinyl alcohol up to 50% and HS extract had significant antioxidant capacity and antibacterial effect against most of the analyzed strains. Adding polyvinyl alcohol (PVOH) and HS extract improved the mechanical performance and reduced water vapor permeability of the materials. The active biobased films with HS extract presented good physicochemical, antimicrobial, and antioxidant properties. These materials are considered as suitable for food packaging, and the active compounds in the roselle extract are a natural antibacterial option for the food area. The materials based entirely on biodegradable products are an excellent alternative when developing and marketing biobased materials, minimizing the environmental impact of food packaging.

In-situ forming carboxymethyl chitosan hydrogel containing Paeonia suffruticosa Andr. leaf extract for mixed infectious vaginitis treatment by reshaping the micro-biota

Mixed infectious vaginitis poses a serious threat to female reproductive health due to complex pathogenic factors, a long course and easy recurrence. Currently, antibiotic-based treatment methods are facing a crisis of drug resistance and secondary dysbiosis. Exploring effective drugs for the treatment of mixed vaginitis from Paeonia suffruticosa Andr., a natural traditional Chinese medicine with a long history of medicinal use, is a feasible treatment strategy. P. suffruticosa Andr. leaf extract (PLE) has significant anti-bacterial effects due to its rich content of polyphenols and flavonoids. The polyphenols in peony leaves have the potential to make carboxymethyl chitosan form in situ gel. In the current study, PLE and carboxymethyl chitosan were combined to develop another type of natural anti-bacterial anti-oxidant hydrogel for the treatment of mixed infectious vaginitis. Through a series of characterisations, CP had a three-dimensional network porous structure with good mechanical properties, high water absorption, long retention and a slow-release drug effect. The mixed infectious vaginitis mouse model induced by a mixture of pathogenic bacteria was used to investigate the therapeutic effects of CP in vivo. The appearance of the vagina, H&E colouring of the tissue and inflammatory factors (TNF-α, IL-6) confirm the good anti-vaginal effect of CP. Therefore, CP was expected to become an ideal effective strategy to improve mixed infection vaginitis due to its excellent hydrogel performance and remarkable ability to regulate flora.

Diacetylcurcumin: a novel strategy against Enterococcus faecalis biofilm in root canal disinfection.

Aim: We evaluated Diacetylcurcumin (DAC), a derivative of curcumin, for its antibacterial and antibiofilm properties against Enterococcus faecalis. Methods: Minimum inhibitory concentration (MIC) and minimum bactericidal concentration were determined, along with antibiofilm potential and toxicity in Galleria mellonella. Additionally, in silico computational analysis was performed to understand its mechanisms of action. Results & conclusion: DAC demonstrated significant antibacterial effects, with MIC and MBC values of 15.6 and 31.25μg/ml, respectively, and reduced biofilm formation. A synergistic effect, reducing biofilm by 77%, was observed when combined with calcium hydroxide. G. mellonella toxicity tests confirmed DAC's safety at tested concentrations, suggesting its potential for use in root canal disinfection products.

Biological Evaluation of Oral Care Products Using 3D Tissue-Engineered In Vitro Models of Plaque-Induced Gingivitis.

The aim of this study was to investigate and visualize the anti-inflammatory and anti-bacterial effects of different oral care products using an infected and inflamed 3D tissue-engineered gingival mucosal model. A 3D full-thickness oral mucosal model was engineered inside tissue culture inserts using collagen hydrogels populated with human gingival fibroblasts and THP-1 monocytes and layered with oral epithelial cell lines. Oral saliva bacteria were cultured and added to the surface of the models and inflammation was further simulated with lipopolysaccharide (LPS) of Escherichia coli. The 3D models were exposed to three different types of toothpastes, a chlorhexidine antiseptic mouthwash, different antibiotics, and a mechanical rinse with phosphate-buffered saline (PBS) prior to biological evaluation using the PrestoBlue tissue viability assay, histology, optical coherence tomography (OCT), confocal microscopy, and measurement of the release of the inflammatory markers IL-1β, IL-6, and IL-8 with ELISA. Multiple-endpoint analyses of the infected oral mucosal models treated with different anti-bacterial agents showed consistent outcomes in terms of tissue viability, histology, OCT, and confocal microscopy findings. In terms of anti-inflammatory testings, the positive control group showed the highest level of inflammation compared with all other groups. Depending on the anti-bacterial and anti-inflammatory potential of the test groups, different levels of inflammation were observed in the test groups. The inflamed 3D oral mucosal model developed in this study has the potential to be used as a suitable in vitro model for testing the biocompatibility, anti-inflammatory, and anti-bacterial properties of oral care products including mouthwashes and toothpastes. The results of this study indicate that the chlorhexidine mouthwash has both anti-bacterial and cytotoxic effects on the 3D oral mucosal model. Hyaluronic-acid-containing toothpaste has significant anti-bacterial and anti-inflammatory effects on the 3D oral mucosal model.

Evaluation of the effect of active essential oil components added to pickled-based marinade on beef stored under vacuum packaging: Insight into physicochemical and microbiological quality

This research aimed to evaluate the effects of the addition of active essential oil components (linalool and/or eugenol) to a pickle-based marinade on controlling spoilage and extending the shelf life of fresh beef stored under vacuum packaging at 4 °C. Linalool and eugenol were used either separately at a concentration of 0.2 % (w/w) or together (1:1 ratio) to preserve marinated beef under vacuum packaging for 15 days. Samples were assessed for pH, color, texture, oxidative degradation, and microbiological parameters. All marinades exhibited significantly lower TBARS values than the control sample. The addition of linalool or eugenol to the marinate showed a significant antibacterial effect on total aerobic mesophilic bacteria (TAMB), lactic acid bacteria (LAB), Pseudomonas spp., and total coliform, and the reductions in microbial counts are as follows: TAMB: 1.563 log CFU/g and 1.46 log CFU/g; Pseudomonas spp.: 1.303 log CFU/g and 1.08 log CFU/g; LAB: 0.323 log CFU/g and 0.357 log CFU/g. Marinated beef with linalool and/or eugenol was found to be effective against the growth of yeast and mold. The use of eugenol presented the most effective inhibition activity against yeast and mold by reducing the number of yeast and molds to an uncountable level on the 12th and 15th days of storage. Physicochemical analysis also showed that the addition of active essential oils to marinade did not cause any undesirable effects on the color and texture properties of beef samples. Therefore, the findings revealed that eugenol and linalool could be suitable alternatives for beef marination.

Serratia plymuthica HK9-3 enhances tomato resistance against Phytophthora capsici by modulating antioxidant defense systems and rhizosphere micro-ecological condition.

Tomatoes are frequently challenged by various pathogens, among which Phytophthora capsici (P. capsici) is a destructive soil-borne pathogen that seriously threatens the safe production of tomatoes. Plant growth-promoting rhizobacteria (PGPR) positively induced plant resistance against multiple pathogens. However, little is known about the role and regulatory mechanism of PGPR in tomato resistance to P. capsici. Here, we identified a new strain Serratia plymuthica (S. plymuthica), HK9-3, which has a significant antibacterial effect on P. capsici infection. Meanwhile, stable colonization in roots by HK9-3, even under P. capsici infection, improved tomato growth parameters, root system architecture, photosynthetic capacity, and boosted biomass. Importantly, HK9-3 colonization significantly alleviated the damage caused by P. capsici infection through enhancing ROS scavenger ability and inducing antioxidant defense system and pathogenesis-related (PR) proteins in leaves, as evidenced by elevating the activities of peroxidase (POD), superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), phenylalanine ammonia lyase (PAL), polyphenol oxidase (PPO), and chitinase, β-1,3-glucanase, and increasing the transcripts of POD, SOD, CAT, APX1, PAL1, PAL2, PAL5, PPO2, CHI17 and β-1,3-glucanase genes. Notably, HK9-3 colonization not only effectively improved soil microecology and soil fertility, but also significantly enhanced fruit yield by 44.6% and improved quality. Our study presents HK9-3 as a promising and effective solution for controlling P. capsici infection in tomato cultivation while simultaneously promoting plant growth and increasing yield, which may have implications for P. capsici control in vegetable production.

Effect of 5-aminolevulinic acid-mediated photodynamic therapy against Fusobacterium nucleatum in periodontitis prevention

Periodontitis, a chronic infectious disease leading to gingival atrophy and potential tooth loss through alveolar bone resorption, is closely linked to the oral microbiome. Fusobacterium nucleatum, known to facilitate late-stage bacterial colonization in the oral microbiome, plays a crucial role in the onset of periodontitis. Controlling F. nucleatum abundance is vital for preventing and treating periodontal disease. Photodynamic therapy combined with 5-aminolevulinic acid (ALA-PDT) has been reported to be bactericidal against Pseudomonas aeruginosa and Staphylococcus aureus. We aimed to investigate the bactericidal potential of ALA-PDT against F. nucleatum, which was evaluated by examining the impact of varying 5-ALA concentrations, culture time, and light intensity. After ALA-PDT treatment, DNA was extracted from interdental plaque samples collected from 10 volunteers and sequenced using the Illumina MiSeq platform. To further elucidate the bactericidal mechanism of ALA-PDT, porphyrins were extracted from F. nucleatum following cultivation with 5-ALA and subsequently analyzed using fluorescence spectra. ALA-PDT showed a significant bactericidal effect against F. nucleatum. Its bactericidal activity demonstrated a positive correlation with culture time and light intensity. Microbiota analysis revealed no significant alteration in α-diversity within the ALA-PDT group, although there was a noteworthy reduction in the proportion of the genus Fusobacterium. Furthermore, fluorescence spectral analysis indicated that F. nucleatum produced an excitable photosensitive substance following the addition of 5-ALA. Overall, if further studies confirm these results, this combined therapy could be an effective strategy for reducing the prevalence of periodontitis.

Enhancing Escherichia coli Inactivation: Synergistic Mechanism of Ultraviolet Light and High-Voltage Electric Field.

This study investigated the bactericidal effects of ultraviolet (UV) radiation, a high-voltage electric field (HVEF), and their combination on Escherichia coli. The results indicated that UV and combined disinfection were more effective with longer exposure, leading to significant reductions in microbial activity. Specifically, the single UV disinfection alone reduced activity by 3.3 log after 5 min, while combined disinfection achieved a 4.2 log reduction. In contrast, short-term HVEF treatment did not exhibit significant bactericidal effects, only achieving a reduction of 0.17 log in 5 min. Furthermore, prolonged exposure to both UV disinfection and an HVEF was found to damage cell membranes, ultimately causing cell death, while shorter durations did not. Despite rapid cell count decreases, flow cytometry did not detect apoptotic or necrotic cells, likely due to rapid cell rupture. This study suggests that combining UV radiation and an HVEF could be a promising approach for inhibiting bacterial reproduction, with HVEF enhancing UV effects. These findings provide insights for using combined HVEF and UV disinfection in food safety and preservation.

Gut bacterium Burkholderia cepacia (BsNLG8) and immune gene Defensin A contribute to the resistance against Nicotine-induced stress in Nilaparvata lugens (Stål)

Nicotine, a naturally occurring alkaloid found in tobacco, is a potent neurotoxin extensively used to control Nilaparvata lugens (Stål), a destructive insect pest of rice crops. The insect gut harbors a wide array of resident microorganisms that profoundly influence several biological processes, including host immunity. Maintaining an optimal gut microbiota and immune homeostasis requires a complex network of reciprocal regulatory interactions. However, the underlying molecular mechanisms driving these symbiotic exchanges, particularly between specific gut microbe and immunity, remain largely unknown in insects. Our previous investigations identified and isolated a nicotine-degrading Burkholderia cepacia strain (BsNLG8) with antifungal properties. Building on those findings, we found that nicotine intake significantly increased the abundance of a symbiotic bacteria BsNLG8, induced a stronger bacteriostatic effect in hemolymph, and enhanced the nicotine tolerance of N. lugens. Additionally, nicotine-induced antimicrobial peptides (AMPs) exhibited significant antibacterial effects against Staphylococcus aureus. We adopted RNA-seq to explore the underlying immunological mechanisms in nicotine-stressed N. lugens. Bioinformatic analyses identified numerous differentially expressed immune genes, including recognition/immune activation (GRPs and Toll) and AMPs (i.e., Defensin, Lugensin, lysozyme). Temporal expression profiling (12, 24, and 48 hours) of immune genes revealed pattern recognition proteins and immune effectors as primary responders to nicotine-induced stress. Defensin A, a broad-spectrum immunomodulatory cationic peptide, exhibited significantly high expression. RNA interference-mediated silencing of Defensin A reduced the survival, enhanced nicotine sensitivity of N. lugens to nicotine, and decreased the abundance of BsNLG8. The reintroduction of BsNLG8 improved the expression of immune genes, aiding nicotine resistance of N. lugens. Our findings indicate a potential reciprocal immunomodulatory interaction between Defensin A and BsNLG8 under nicotine stress. Moreover, this study offers novel and valuable insights for future research into enhancing nicotine-based pest management programs and developing alternative biocontrol methods involving the implication of insect symbionts.

Structure-based drug design of DNA minor groove binders and evaluation of their antibacterial and anticancer properties

Antimicrobial and chemotherapy resistance are escalating medical problem of paramount importance. Yet, research for novel antimicrobial and anticancer agents remains lagging behind. With their reported medical applications, DNA minor groove binders (MGBs) are worthy of exploration. In this study, the approach of structure-based drug design was implemented to generate 11 MGB compounds including a novel class of bioactive alkyne-linked MGBs. The NCI screening protocol was utilized to evaluate the antitumor activity of the target MGBs. Furthermore, a variety of bactericidal, cytopathogenicity, MIC90, and cytotoxicity assays were carried out using these MGBs against 6 medically relevant bacteria: Salmonella enterica, Escherichia coli, Serratia marcescens, Bacillus cereus, Streptococcus pneumoniae and Streptococcus pyogenes. Moreover, molecular docking, molecular dynamic simulations, DNA melting, and isothermal titration calorimetry (ITC) analyses were utilized to explore the binding mode and interactions between the most potent MGBs and the DNA duplex d(CGACTAGTCG)2. NCI results showed that alkyne-linked MGBs (26 & 28) displayed the most significant growth inhibition among the NCI-60 panel. In addition, compounds MGB3, MGB4, MGB28, and MGB32 showed significant bactericidal effects, inhibited B. cereus and S. enterica-mediated cytopathogenicity, and exhibited low cytotoxicity. MGB28 and MGB32 demonstrated significant inhibition of S. pyogenes, whereas MGB28 notably inhibited S. marcescens and all four minor groove binders significantly inhibited B. cereus. The ability of these compounds to bind with DNA and distort its groove dimensions provides the molecular basis for the allosteric perturbation of proteins-DNA interactions by MGBs. This study shed light on the mechanism of action of MGBs and revealed the important structural features for their antitumor and antibacterial activities, which are important to guide future development of MGB derivatives as novel antibacterial and anticancer agents.

Elimination of E. faecalis with NaOCl versus chlorhexidine gluconate from primary molar root canal systems: an ex vivo model study

ObjectivesThis ex vivo human study aimed to evaluate the efficacy of NaOCl and chlorhexidine gluconate (CHG) irrigations in eliminating Enterococcus faecalis from the RCS of primary molars.Materials and methodsDisinfected extracted primary molars were inoculated with E. faecalis for 24 h. Then, the RCS samples were then irrigated with either 2.5% NaOCl, 0.2% and 2% CHG, or sham saline. The samples were collected immediately after irrigation; and 24 h later, the bacterial viability and counts were measured using blood agar and qRT-PCR, respectively. Histological sections were used to measure E. faecalis penetration and viability in dentin tubules using fluorescence microscopy.ResultsThe recovery of viable E. faecalis after the irrigation of the primary molars showed more significant bactericidal effects of NaOCl and 0.2% and 2% CHG than of saline. Immediately after the irrigation, the NaOCl group showed the greatest reduction in E. faecalis; and 24 h later, all the groups had lower viable E. faecalis than the saline control. The bacterial penetration was also lowest in the NaOCl group, although there was no difference in bacterial viability in the tubules between the groups.ConclusionIn primary teeth, NaOCl and CHG showed similar degrees of bacterial elimination efficacy in terms of E.faecalis.Clinical relevanceWithin the limitations of this study, NaOCl and CHG have the similar ability to perform endodontic irrigation of primary ex vivo teeth regarding the elimination of E.faecalis, but NaOCl penetrates dentin tubules better.

Multifunctional rare earth oxide/MBG composite microspheres as a carrier for bone tumor treatment

With the development of advanced composites, biomaterials have brought the field of tissue engineering and regeneration into a new era. Among them, composites of inorganic nonmetallic materials and rare earth oxides have unique structures and biochemical properties and have attracted widespread interest. In this work, rare earth oxides (CeO2)/inorganic nonmetallic materials (mesoporous bioactive glass, MBG) composite microspheres (CeO2/MBGs) were synthesized by a sol-gel method, and the in vitro biological effect of CeO2/MBGs was systematically studied. The filling of CeO2/MBGs in irregular bone tumor defects not only promoted osteogenic mineralization in MG63 cells but also had significant antibacterial effects on E. coli and S. aureus. CeO2 enters the MBG network as a network modifier, while doxorubicin (DOX) is adsorbed into the mesoporous structure through electrostatic interactions, which endows CeO2/MBGs with excellent bioactivity and controlled DOX release behavior. Moreover, the results of in vitro experiments showed that the proper addition of rare earth oxides had no toxic effect on normal cells, and the combination of rare earth oxides with antitumor drugs could slow the release of DOX through the use of an intelligent response design system, thus inducing the apoptosis of MG63 cells. This work suggested that combination chemotherapy and the design of a rare earth oxide/MBG composite microspheres may be potential therapeutic approaches for the postoperative repair of bone tumor defects. The construction of this multifunctional rare earth oxide/inorganic biocomposite provides a way to apply the material to bone tissue.

Enhanced bactericidal, antibiofilm and antioxidative response of Lawsonia inermis leaf extract synthesized ZnO NPs loaded with commercial antibiotic.

Globally, antibiotic resistance is a challenging issue in healthcare sector. The emergence of multiple drug-resistant bacteria has forced us to modify existing medicines and or formulate newer medicines that are effective and inexpensive. In this perspective, this study involves theformation of zinc oxide nanoparticles (ZnO NPs) by utilizing the Lawsonia inermis (Li) leaf extract. The prepared L. inermis leaf extract mediated ZnO NPs (Li-ZnO NPs) were bio-physically characterized. The antibacterial and radical scavenging effects of Li-ZnO NPs were evaluated. In addition, ZnO NPs were conjugated with standard antibiotic (ciprofloxacin) and its drug loading efficiency, drug release and antibacterial efficacy were tested and compared with non-drugloaded ZnO NPs. An absorbance peak at 340nm was noted for Li-ZnO NPs. After conjugation with the drug, two absorbance peaks- one at 242nm characteristic of ciprofloxacin and the other at 350nm characteristics of ZnO NPs were observed. The crystallite size was 18.7nm as determined by XRD. The antibacterial effect was higher on Gram-positive (S. aureus and S. pyogenes) than the Gram-negative pathogens (E. coli and K. pneumoniae). Inhibition of S. aureus and S. pyogenes biofilm at 100μgmL-1were, respectively, 97.5 and 92.6%. H2O2 free radicals was inhibited to 90% compared to the standard ascorbic acid at 100μgmL-1. After drug loading, the FTIR spectrum confirmed the existence of ciprofloxacin peaks at 965cm-1 and Zn-O bond at 492cm-1. The drug loading capacity of 15nm sized ZnO NPs was higher (58, 75, 90 and 95% at 1, 2.5, 5 and 10% drug concentrations, respectively) compared to 20nm. Similarly, the percentage of drug (ciprofloxacin) released from 15nm ZnO NPs were increased to 90% at 10% drug-loaded samples, respectively. Also, the antibiotic loaded ZnO NPs had significant antibacterial effects against tested bacteria compared to Li-ZnO NPs and ciprofloxacin alone. This revealed that the antibiotic loaded ZnO NPs offer a sustainable route to treat multi-drug-resistant bacterial infections.