Human-Derived Induced GABAergic Progenitor Cells Improve Cognitive Function in Mice and Inhibit Astrocyte Activation with Anti-Inflammatory Exosomes.

OBJECTIVE: The role of gamma-aminobutyric acid-ergic (GABAergic) neuron impairment in Alzheimer's disease (AD), and if and how transplantation of healthy GABAergic neurons can improve AD, remain unknown. METHODS: Human-derived medial ganglionic eminence progenitors (hiMGEs) differentiated from programmed induced neural precursor cells (hiNPCs) were injected into the dentate gyrus region of the hippocampus (HIP). RESULTS: We showed that grafts migrate to the whole brain and form functional synaptic connections in amyloid precursor protein gene/ presenilin-1 (APP/PS1) chimeric mice. Following transplantation of hiMGEs, behavioral deficits and AD-related pathology were alleviated and defective neurons were repaired. Notably, exosomes secreted from hiMGEs, which are rich in anti-inflammatory miRNA, inhibited astrocyte activation invitro and in vivo, and the mechanism was related to regulation of CD4+ Th1 cells mediated tumor necrosis factor (TNF) pathway. INTERPRETATION: Taken together, these findings support the hypothesis that hiMGEs transplantation is an alternative treatment for neuronal loss in AD and demonstrate that exosomes with anti-inflammatory activity derived from hiMGEs are important factors for graft survival. ANN NEUROL 2024;96:488-507.

Gelatin/carboxymethylcellulose composite film combined with photodynamic antibacterial: New prospect for fruit preservation.

Plastic packaging causes environmental pollution, and the development of simple and effective biodegradable active packaging remains a challenge. In this study, gelatin (G) and sodium carboxymethylcellulose (CMC) were used as film materials, with the addition of curcumin (Cur), a photosensitive substance, to investigate the changes in the physical and chemical properties of the film and its application in fruit preservation. The results demonstrated that Cur was compatible with the film. With the addition of Cur, the thickness of the film increased up to 1.3 times, while the moisture content was reduced to 12.10 %. The tensile strength (TS) and elongation at break (EAB) of the film can reach 8.84 MPa and 19.33 %, respectively. The photodynamic antibacterial experiment revealed that the film containing 0.5 % Cur exhibited the highest antibacterial rate, reaching 99.99 % against Staphylococcus aureus (S. aureus) and 95 % against Escherichia coli (E. coli). During storage, the grapes remained unspoiled for up to 9 days after being phototreated with the film and the microbial content of the skin was much lower than that of the control group. In addition, Cur provided antioxidant activity for the film, with a scavenging activity of 39.54 % against the 2,2-diphenyl-1-picrind radical (DPPH). Bananas exposed to the film-forming solution for a short period of time remained fresh for up to 6 days. During preservation, the weight of the treated bananas decreased more slowly than that of the control group. In addition, the activity of SOD on the 7th day was approximately 20 U/g higher than that of the control group, which helped to reduce oxidative stress during banana preservation. In summary, G-CMC/Cur film is an optional fruit-cling film that can be used in food packaging.

Photodynamic antibacterial application of TiO2/curcumin/hydroxypropyl-cyclodextrin and its konjac glucomannan composite films.

Although photodynamic therapy (PDT) has great advantages for the treatment of bacterial infections, photosensitizers (PSs) often have many disadvantages that limit their application. Improving the shortcomings of PSs and developing efficient PDT antimicrobial materials remain serious challenges. In this study, a nanocomposite drug (TiO2/curcumin/hydroxypropyl-cyclodextrin, TiO2/Cur/HPCD) was constructed and combined with konjac glucomannan to form composite films (TiO2/Cur/HPCD films, KTCHD films). The stabilities of TiO2 and Cur were improved in the presence of HPCD. The particle size of TiO2/Cur/HPCD was approximately 33.9 nm, and the addition of TiO2/Cur/HPCD enhanced the mechanical properties of the films. Furthermore, TiO2/Cur/HPCD and KTCHD films exhibited good biocompatibility and PDT antibacterial effects. The antibacterial rate of TiO2/Cur/HPCD was 74.46 % against MRSA at 500 µg/mL and 99.998 % against E. coli at 400 µg/mL, while it was adsorbed on the surface of bacteria to improve the effectiveness of the treatment. In addition, studies in mice confirmed that TiO2/Cur/HPCD and KTCHD films can treat bacterial infections and promote wound healing, with a highest wound healing rate of 84.6 % in the KTCHD-10 films + Light group on day 12. Overall, TiO2/Cur/HPCD is a promising nano-antibacterial agent and KTCHD films have the potential to be employed as antibacterial and environment-friendly trauma dressings.

Polydopamine-curcumin coating of titanium for remarkable antibacterial activity via synergistic photodynamic and photothermal properties.

Combined photothermal therapy (PTT) and photodynamic therapy (PDT) has emerged as a novel and effective antibacterial strategy. In order to endow titanium (Ti) with antibacterial properties, the Ti-PDA-Cur composite was prepared using the excellent adhesion properties of polydopamine (PDA) to load curcumin (Cur) on the surface of Ti. The Ti-PDA-Cur coating can produce singlet oxygen (1 O2 ) and heat under 405 + 808 nm light irradiation, which can effectively kill Staphylococcus aureus and Escherichia coli. Moreover, the cytotoxicity and hemolysis rate of Ti-PDA-Cur were low, indicating its good biocompatibility. Therefore, this study provided a new strategy for the development of new Ti implants.

Polydopamine/tannic acid/chitosan/poloxamer 407/188 thermosensitive hydrogel for antibacterial and wound healing.

The design and development of smart shape-adaptable wound dressings with superior antimicrobial ability remain a challenge in therapeutic and clinical application. Herein, polydopamine/tannic acid/chitosan/poloxamer 407/188 hydrogel (PTCPP) was prepared with the aim of developing an in situ-formed antibacterial wound dressing with temperature stimulation and near-infrared radiation (NIR) responsive ability. PTCPP possessed injectability, photothermal stability, sustained release properties and cytocompatibility. In vitro antibacterial results showed that the bactericidal rates of PTCPP against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) under NIR irradiation were 99.994 % and 99.91 %, respectively. In vivo experiments, PTCPP can adapt to shape of the wound, showing good adhesion, while promoting wound healing in bacterial infections. Therefore, PTCPP has potential application in the treatment of infectious wounds, and provides a strategic choice for developing antibacterial wound dressing combined with photothermal therapy.

Methylene Blue/Carbon Dots Composite with Photothermal and Photodynamic Properties: Synthesis, Characterization, and Antibacterial Application.

Photodynamic therapy and photothermal therapy provide new ways to combat antibiotic resistance. In this research, methylene blue (MB) as an effective photosensitizer was conjugated with carbon quantum dots (CQDs), the composite product not only possessed good antibacterial properties against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) due to excellent singlet oxygen (1 O2 ) production rate and light heat transfer performance, but also showed good biocompatibility. Combined with 808 nm and 660 nm laser irradiation, the minimum bactericidal concentration of CQDs-MB towards S. aureus and E. coli was 5 µm. Therefore, this study provides a potential candidate material based on CQDs for clinical applications.

Preparation of graphene oxide/polydopamine-curcumin composite nanomaterials and its antibacterial effect against Staphylococcus aureus induced by white light.

Curcumin (Cur) plays a key role in photodynamic antibacterial activity as a photosensitizer. On the other hand, the antimicrobial potential of graphene oxide (GO) has been reported controversially, and how to improve its antimicrobial ability has become an meaningful study. In this study, we prepared polydopamine-curcumin (PDA-Cur) by pi-pi stacking and loaded it onto the GO surface to obtain GO/PDA-Cur composite nanomaterials. GO/PDA-Cur was characterized by physical and optical means, and GO/PDA-Cur possessed good dispersion and stability in water. In vitro antibacterial results showed that GO/PDA-Cur mediated photodynamic therapy significantly reduced Gram-positive Staphylococcus aureus (S. aureus) by 4 orders of magnitude with a bactericidal rate of 99.99 %. The antibacterial mechanism stems from the fact that GO/PDA-Cur can generate reactive oxygen species (ROS) under white light irradiation (405-780 nm), which causes bacterial outer membrane breakage and cellular deformation. In addition, GO/PDA-Cur has good biocompatibility. The antibacterial ability of graphene oxide was significantly improved by combining it with PDA-Cur, which allows it to be used as a photodynamic antibacterial material.

Curcumin-loaded multifunctional chitosan gold nanoparticles: An enhanced PDT/PTT dual-modal phototherapeutic and pH-responsive antimicrobial agent.

Overuse of antibiotics has led to the emergence of multidrug resistant (MDR) bacteria.. Photothermal (PTT) and photodynamic therapy (PDT) have may be effective alternatives for antibiotics in the treatment of bacterial infections. In this study, based on chitosan (CS)-coated gold nanoparticles, a pH stimulus-responsive drug delivery system was developed, which can anchor to the cell membrane for photodynamic therapy and photothermal therapy, and enhance the therapeutic potential of curcumin (Cur). Release experiments showed that AuNPs/CS-Cur nanocomposites released curcumin in a pH-dependent manner, which may facilitate the drug to be delivered to the acidic bacterial infection environment. CS as the outer layer covered on gold nanoparticles could improve the dispersibility of Cur in aqueous solution, gold nanoparticles prevent rapid photobleaching of curcumin, thus ensuring the yield of singlet oxygen under irradiation, and enhance the electrostatic binding with bacteria cell membrane. Under light conditions, AuNPs/CS-Cur can produce a large amount of reactive oxygen species and heat to kill S. aureus and E. coli. Compared with free Cur-mediated PDT, the complex significantly improved the synergistic PTT/PDT photoinactivation ability against S. aureus and E. coli. In addition, AuNPs/CS-Cur had good biocompatibility. Therefore, AuNPs/CS-Cur possessed the characteristics of electrostatic targeting, photodynamic and photothermal antibacterial therapy, which would become an efficient and safe antibacterial nano-platform and provide new ideas for the treatment of bacterial infection.

Orange-red to NIR emissive carbon dots for antimicrobial, bioimaging and bacteria diagnosis.

Antimicrobial photodynamic therapy (aPDT) has become a popular technology for the treatment of bacterial infections. The development of antimicrobial agents combining diagnosis and treatment remains a major challenge. Herein, curcumin carbon quantum dots (Cur-NRCQDs) with antibacterial and imaging effects were synthesized using a hydrothermal method. The fluorescence absorption range of the Cur-NRCQDs in aqueous solution was 555 to 850 nm, showing orange-red to near infrared (NIR) fluorescence, and its maximum emission wavelength was 635 nm. At the same time, Cur-NRCQDs improved the efficiency of Cur as the photosensitizer (PS), showed good storage and light stability, and enhanced the efficiency of reactive oxygen (ROS) generation and antibacterial activity. Under the irradiation of a xenon lamp, Cur-NRCQDs inactivated 100% Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) at concentrations of 10 and 15 µM, respectively. The possible reason for this was that under PDT, the ROS produced by the Cur-NRCQDs destroyed the integrity of the cell membrane, resulting in leakage of the contents. In addition, the Cur-NRCQDs showed good cell compatibility, as they can also enter bacteria and cells for imaging, so they can be employed for the detection of bacteria and cell tissues. Therefore, Cur-NRCQDs are an ideal candidate material for aPDT treatment and fluorescent bioimaging.

Photo-enhanced antibacterial activity of polydopamine-curcumin nanocomposites with excellent photodynamic and photothermal abilities.

Background and objective Photodynamic therapy (PDT) and photothermal therapy (PTT) have gradually become options for select anti-tumor and antibacterial treatment . The combination of PDT and PTT show great research value, which may greatly improve the curative effect. The aim of the present study was to prepare a compound system of polydopamine and curcumin (PDA-Cur nanocomposites) with excellent antibacterial effect towards Gram-positive and Gram-negative bacteria. Methods Dopamine hydrochloride was oxidized and self polymerized in alkaline condition to form PDA-Cur nanocomposites. The structure and morphology of PDA-Cur were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), laser scattering microscopy (LSM), ultraviolet spectrophotometer (UV-vis), infrared spectroscopy (IR) and fluorescence emission spectrometer. Using 1,1-diphenyl-2-picrylhydrazyl radical (DPPH), 1,3-diphenylbenzofuran (DPBF) and 2',7'-Dichlorodihydrofluorescein diacetate (DCFH-DA) were used to detect the production of reactive oxygen species (ROS). The thermal stability of PDA-Cur nanocomposites was investigated by temperature rising test. The antibacterial effect of PDA-Cur was determined by plate counting technique using Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) as models. In addition, the stability and antibacterial mechanism of PDA-Cur were investigated. Finally, the biocompatibility was evaluated by cytotoxicity and hemolysis tests. Results The compound system of polydopamine and curcumin was successfully prepared, which showed improved stability compared with Cur. The consumption of DPBF by the singlet oxygen produced by PDA-Cur was as high as 80%. In the heating test, the highest temperature increased to 59 °C, which contributed to the photodynamic and photothermal inactivation of bacteria. PDA-Cur nanocomposites showed good antibacterial activity against S. aureus and E. coli. Under 405 nm light, the bactericidal rate of PDA-Cur against S. aureus can reach 100% at a low concentration of 10-4 nM, and that against E. coli was 100% at 1 nM. Under 405 + 808 nm light, the bactericidal rate of PDA-Cur against E. coli enhanced to 100% at 0.1 nM. In addition, PDA-Cur had low cytotoxicity and negligible hemolytic activity, showing good biocompatibility. Conclusion PDA-Cur nanocomposites had good photodynamic effect, photo thermal conversion ability and biocompatibility. Compared with free Cur, the antibacterial activity of PDA-Cur was significantly improved, and the antibacterial effect with combined light was stronger than that of free Cur. Therefore, the construction of PDA-Cur nanocomposites have confirmed that the combination of PDT and PTT can greatly improve the antibacterial effect and reach bactericidal effect at low concentration, which provides a strategy for the design of next generation antimicrobial agents.

Fluorescent Carbon Dot-Curcumin Nanocomposites for Remarkable Antibacterial Activity with Synergistic Photodynamic and Photothermal Abilities.

Photosensitizer (PS)-mediated photodynamic therapy (PDT) has attracted more and more attention as an alternative to traditional antibiotic therapy. Nevertheless, the limitations of traditional photosensitizers seriously hinder their practical application, as a result, the methods to improve the antibacterial properties of traditional photosensitizers have become a hot topic in the field of photomedicine. Herein, a compound nano-PS system has been constructed with synergistic photodynamic and photothermal (PTT) antibacterial effects, triggered by a dual-wavelength illumination. Fluorescent carbon dots (CDs) were synthesized and employed as carriers for the delivery of curcumin (Cur) to obtain CDs/Cur. Upon combined near-infrared and 405 nm visible dual-wavelength irradiation, CDs/Cur could simultaneously generate ROS and a moderate temperature increase, triggering synergistic antibacterial effects against both Gram-positive and Gram-negative bacteria. The results of scanning electron microscopy and fluorescence confocal imaging showed that the combined effect of CDs/Cur with PDT and PTT caused more serious damage to the cell membrane. In addition, CDs/Cur exhibited low cytotoxicity and negligible hemolytic activity, showing great biocompatibility. Therefore, the construction of CDs/Cur by employing CDs as photosensitizer delivery carriers provides a strategy for the improvement of the antibacterial effect of the photosensitizer and the design of next-generation antibacterial agents in photomedicine.