Intravital Microscopy Evidence That Methylene Blue Should Be a Vasopressor-Sparing Agent in Sepsis Vasoplegia.

Microvasculature failure is expected in sepsis and at higher amine concentrations. Therefore, special attention focused individually on microcirculation is needed. Here, we present that methylene blue can prevent leukocytes from adhering to the endothelium in a rat model of lipopolysaccharide-induced endotoxemia. As hypothesis evidence, an intravital microscopy image is presented.

Polydopamine-Coated Liposomes for Methylene Blue Delivery in Anticancer Photodynamic Therapy: Effects in 2D and 3D Cellular Models.

Photodynamic therapy (PDT) is a therapeutic option for cancer, in which photosensitizer (PS) drugs, light, and molecular oxygen generate reactive oxygen species (ROS) and induce cell death. First- and second-generation PSs presented with problems that hindered their efficacy, including low solubility. Thus, second-generation PSs loaded into nanocarriers were produced to enhance their cellular uptake and therapeutic efficacy. Among other compounds investigated, the dye methylene blue (MB) showed potential as a PS, and its photodynamic activity in tumor cells was reported even in its nanocarrier-delivered form, including liposomes. Here, we prepared polydopamine (PDA)-coated liposomes and efficiently adsorbed MB onto their surface. lipoPDA@MB vesicles were first physico-chemically characterized and studies on their light stability and on the in vitro release of MB were performed. Photodynamic effects were then assessed on a panel of 2D- and 3D-cultured cancer cell lines, comparing the results with those obtained using free MB. lipoPDA@MB uptake, type of cell death induced, and ability to generate ROS were also investigated. Our results show that lipoPDA@MB possesses higher photodynamic potency compared to MB in both 2D and 3D cell models, probably thanks to its higher uptake, ROS production, and apoptotic cell death induction. Therefore, lipoPDA@MB appears as an efficient drug delivery system for MB-based PDT.

Targeting mitochondrial dysfunction using methylene blue or mitoquinone to improve skeletal aging.

Methylene blue (MB) is a well-established antioxidant that has been shown to improve mitochondrial function in both in vitro and in vivo settings. Mitoquinone (MitoQ) is a selective antioxidant that specifically targets mitochondria and effectively reduces the accumulation of reactive oxygen species. To investigate the effect of long-term administration of MB on skeletal morphology, we administered MB to aged (18 months old) female C57BL/J6 mice, as well as to adult male and female mice with a genetically diverse background (UM-HET3). Additionally, we used MitoQ as an alternative approach to target mitochondrial oxidative stress during aging in adult female and male UM-HET3 mice. Although we observed some beneficial effects of MB and MitoQ in vitro, the administration of these compounds in vivo did not alter the progression of age-induced bone loss. Specifically, treating 18-month-old female mice with MB for 6 or 12 months did not have an effect on age-related bone loss. Similarly, long-term treatment with MB from 7 to 22 months or with MitoQ from 4 to 22 months of age did not affect the morphology of cortical bone at the mid-diaphysis of the femur, trabecular bone at the distal-metaphysis of the femur, or trabecular bone at the lumbar vertebra-5 in UM-HET3 mice. Based on our findings, it appears that long-term treatment with MB or MitoQ alone, as a means to reduce skeletal oxidative stress, is insufficient to inhibit age-associated bone loss. This supports the notion that interventions solely with antioxidants may not provide adequate protection against skeletal aging.

The impact of methylene blue photosensitizer, aPDT and a calcium hydroxide-based paste on the physicochemical and mechanical characteristics of root canal dentin and the bonding interface of fiberglass posts.

PURPOSE: To investigate the influence of methylene blue (MB)-mediated antimicrobial photodynamic therapy (aPDT) and calcium hydroxide (CH) medication on the mechanical characteristics, degree of conversion (DC), quantification, and volume of gaps at the adhesive interface of glass fiber posts (GFPs) luted to distinct thirds of root canal dentin. Additionally, the microhardness (MH), elastic modulus (Eit), morphology, and chemical structure of the intraradicular dentin were assessed. MATERIALS AND METHODS: 6 experimental groups were formed by sorting 102 bovine incisors. Canals receiving deionized water irrigation as a negative control; canals receiving deionized water irrigation and filled with CH as a positive control; groups treated with CH + MB at 50 and 100 mg/L without irradiation; and groups treated with CH + MB at 50 and 100 mg/L irradiated by red laser for 60 s (660 nm; 100 mW; 6.5 J; 72 J/cm2). MH, Eit, and DC properties were evaluated for both the resin cement layer and root dentin substrate (n = 8). Volume and quantification of gaps at the bonding interface (n = 6), and dentin morphology and chemical content were investigated (n = 3). Data were analyzed using a repeated-measures 2-way ANOVA followed by Tukey post hoc analysis (α = 0.05). RESULTS: The distinct intraradicular thirds and treatment with MB-mediated aPDT, whether activated or not, in combination with CH, had a significant impact on the mechanical characteristics of the root dentin. This effect was also observed in the MH, Eit, DC, quantification, and volume of gaps at the luting interface (P < .05). In general, a higher concentration of MB, whether activated by a red laser or not, led to lower values in the mechanical properties of the root dentin, as well as in MH, Eit, and DC at the adhesive interface (P < .05). Additionally, these groups exhibited higher values for quantification and volume of gaps at the luting substrate (P < .05). Scanning electron micrographs and energy dispersive X-ray spectra showed qualitative similarity among all groups, except for the negative experimental control group. CONCLUSIONS: MB-mediated aPDT at 50 mg/L, in combination with CH, demonstrated favorable physico-chemical and mechanical characteristics in intraradicular dentin, along with satisfactory mechanical features and the adhesive interface integrity for GFPs at all intraradicular depths. CLINICAL SIGNIFICANCE: MB-mediated aPDT at a concentration of 50 mg/L combined to CH medication represents a suitable choice for photosensitization in the context of intracanal disinfection following the biomechanical procedure and prior to luting of intraradicular restorations.

First in human measurements of abscess cavity optical properties and methylene blue uptake prior to photodynamic therapy by in vivo diffuse reflectance spectroscopy.

Significance: Efficacious photodynamic therapy (PDT) of abscess cavities requires personalized treatment planning. This relies on knowledge of abscess wall optical properties, which we report for the first time in human subjects. Aim: The objective was to extract optical properties and photosensitizer concentration from spatially resolved diffuse reflectance measurements of abscess cavities prior to methylene blue (MB) PDT, as part of a phase 1 clinical trial. Approach: Diffuse reflectance spectra were collected at the abscess wall of 13 human subjects using a custom fiber-optic probe and optical spectroscopy system, before and after MB administration. A Monte Carlo lookup table was used to extract optical properties. Results: Pre-MB abscess wall absorption coefficients at 665 nm were 0.15±0.1 cm-1 (0.03 to 0.36 cm-1) and 10.74±15.81 cm-1 (0.08 to 49.3 cm-1) post-MB. Reduced scattering coefficients at 665 nm were 8.45±2.37 cm-1 (4.8 to 13.2 cm-1) and 5.6±2.26 cm-1 (1.6 to 9.9 cm-1) for pre-MB and post-MB, respectively. Oxygen saturations were found to be 58.83%±35.78% (5.6% to 100%) pre-MB and 36.29%±25.1% (0.0001% to 76.4%) post-MB. Determined MB concentrations were 71.83±108.22 µM (0 to 311 µM). Conclusions: We observed substantial inter-subject variation in both native wall optical properties and MB uptake. This underscores the importance of making these measurements for patient-specific treatment planning.

In vitro photoinactivation effectiveness of a portable LED device aimed for intranasal photodisinfection and a photosensitizer formulation comprising methylene blue and potassium iodide against bacterial, fungal, and viral respiratory pathogens.

Antimicrobial photodynamic therapy (aPDT) can be a viable option for management of intranasal infections. However, there are light delivery, fluence, and photosensitizer-related challenges. We report in vitro effectiveness of an easily fabricated, low-cost, portable, LED device and a formulation comprising methylene blue (MB) and potassium iodide (KI) for photoinactivation of pathogens of the nasal cavity, namely, methicillin-resistant Staphylococcus aureus, antibiotic-resistant Klebsiella pneumoniae, multi-antibiotic-resistant Pseudomonas aeruginosa, Candida spp., and SARS-CoV-2.In a 96-well plate, microbial suspensions incubated with 0.005% MB alone or MB and KI formulation were exposed to different red light (~ 660 ± 25 nm) fluence using the LED device fitted to each well. Survival loss in bacteria and fungi was quantified using colony-forming unit assay, and SARS-CoV-2 photodamage was assessed by RT-PCR.The results suggest that KI addition to MB leads to KI concentration-dependent potentiation (up to ~ 5 log10) of photoinactivation in bacteria and fungi. aPDT in the presence of 25 or 50 mM KI shows the following photoinactivation trend; Gm + ve bacteria > Gm - ve bacteria > fungi > virus. aPDT in the presence of 100 mM KI, using 3- or 5-min red light exposure, results in complete eradication of bacteria or fungi, respectively. For SARS-CoV-2, aPDT using MB-KI leads to a ~ 6.5 increase in cycle threshold value.The results demonstrate the photoinactivation effectiveness of the device and MB-KI formulation, which may be helpful in designing of an optimized protocol for future intranasal photoinactivation studies in clinical settings.

Adjuvant effect of antimicrobial photodynamic therapy (aPDT) in the treatment of diabetic foot ulcers: A case series.

This study aimed to evaluate the clinical evolution of patients with diabetic foot ulcer treated with antimicrobial photodynamic therapy (aPDT) using the Bates-Jensen (BJ) scale. A total of 21 patients were monitored, with an average age of 58 years. Patients underwent the standard treatment protocol of the institution, supplemented with aPDT utilizing 0.01% methylene blue (MB) and laser irradiation (660 nm, 100 mW, 6 J per point). Following aPDT, the lesions were protected with hydrofiber dressings containing silver. The Bates-Jensen Scale was employed at pre-treatment and post-aPDT sessions to assess lesion progression. The results demonstrated a significant difference between pre- and post-treatment values in the overall BJ score. The use of MB in aPDT proved to be an effective, safe, well-tolerated treatment with high patient adherence and the potential for implementation in the care of diabetic foot conditions.

In vitro study: methylene blue-based antibacterial photodynamic inactivation of Pseudomonas aeruginosa.

Pseudomonas aeruginosa is one of the most antibiotic-resistant and opportunistic pathogens in immunocompromised and debilitated patients. It is considered the cause of most severe skin infections and is frequently found in hospital burn units. Due to its high antibiotic resistance, eliminating P. aeruginosa from skin infections is quite challenging. Therefore, this study aims to assess the novel in vitro antibacterial activity of methylene blue using a 635-nm diode laser to determine the effective power and energy densities for inhibition of P. aeruginosa. The strain was treated with various concentrations of methylene blue and 635-nm diode laser at powers of 300 mW/cm2 and 250 mW/cm2. The diode laser's potency in the photo-destruction of methylene blue and its degradation through P. aeruginosa were also evaluated. Colony-forming unit (CFU)/ml, fluorescence spectroscopy, optical density, and confocal microscopy were used to measure the bacterial killing effect. As a result, the significant decrease of P. aeruginosa was 2.15-log10, 2.71-log10, and 3.48-log10 at 60, 75, and 90 J/cm2 after excitation of MB for 240, 300, and 360 s at a power of 250 mW/cm2, respectively. However, a maximum decrease in CFU was observed by 2.54-log10 at 72 J/cm2 and 4.32-log10 at 90 and 108 J/cm2 after 300 mW/cm2 of irradiation. Fluorescence images confirmed the elimination of bacteria and showed a high degree of photo-destruction compared to treatment with methylene blue and light alone. In conclusion, MB-induced aPDT demonstrated high efficacy, which could be a potential approach against drug-resistant pathogenic bacteria. KEY POINTS: • Combination of methylene blue with 635-nm diode laser for antibacterial activity. • Methylene blue photosensitizer is employed as an alternative to antibiotics. • aPDT showed promising antibacterial activity against Pseudomonas aeruginosa.

Spectrophotometric analysis of the effectiveness of different dentin tubule occlusion techniques in preventing discoloration caused by photosensitizers used in photodynamic therapy.

AIM: The efficacy of Copal Varnish (CV), dentin bonding agent (DBA), Nd:YAG laser and Er:YAG laser, which occludes dentin tubules by different mechanisms, was investigated in order to prevent unwanted coloration caused by methylene blue (MB) and phthalocyanine used in photodynamic therapy (PDT). MATERIALS AND METHODS: 165 upper incisors included in the study. Root canals were prepared up to 30/0.6 size for all teeth using Protaper Next rotary files. Then the teeth were randomly divided into 2 main groups (n = 60); MB and phthalocyanine. Each main group was randomly divided into 5 subgroups (n = 15); Positive control, DBA, CV, Er:YAG and Nd:YAG. Root canals were filled with photosensitizers (PS) and activated after the dentin tubule occlusion method was applied to all teeth. Then, the residual PSs were removed by irrigation. Color measurements of the samples were carried out 5 different time periods. RESULTS: Clinically detectable color change was observed in all groups except for the negative control (ΔE≥3.3). It was determined that the positive control using MB caused more unwanted coloration in the CV on the 30th and 90th days compared to the phthalocyanine used in the 90th day (p < 0.05). While none of the dentin tubule occlusion methods were superior to each other in preventing undesirable coloration caused by phthalocyanine, Er:YAG caused less unwanetd coloration than CV only on the 90th day in preventing unwanted coloration caused by MB (p < 0.05). CONCLUSIONS: All dentin tubule occlusion methods used in the present study were effective in preventing some degree of unwanted discoloration. However, it was found that no technique could completely prevent unwanted coloration.

Association of Papacarie Duo® and low-level laser in antimicrobial photodynamic therapy (aPDT).

Dental caries is a multifactorial, non-communicable disease. Effective treatment options for minimally invasive removal of carious tissue include Papacarie Duo® gel and antimicrobial photodynamic therapy (aPDT). aPDT involves a combination of a light source and photosensitizer. Given that Papacarie Duo® contains a percentage of blue dye, this study aims to explore the antimicrobial potential of Papacarie Duo® when associated with a light source against Streptococcus mutans strains. The chosen light source was a low-power diode laser (λ = 660 nm, E = 3 J, P = 100 mW, t = 30 s). To assess antimicrobial capacity, planktonic suspensions of Streptococcus mutans were plated on Brain Heart Infusion Agar (BHI) to observe the formation of inhibition halos. The studied groups included methylene blue (0.005%), Papacarie Duo®, distilled water (negative control), 2% chlorhexidine (positive control), Papacarie Duo® + laser, and methylene blue (0.005%) + laser. Following distribution onto plates, each group was incubated at 37 °C for 48 h under microaerophilic conditions. Inhibition halos were subsequently measured using a digital caliper. The results showed that chlorhexidine had the greatest antimicrobial effect followed by the group of irradiated methylene blue and irradiated Papacarie Duo®. All experimental groups demonstrated antimicrobial potential, excluding the negative control group. The study concludes that Papacarie Duo® exhibits antimicrobial properties when associated with a low-power diode laser.

Iontophoresis use for increasing drug penetration into root canals and dentinal tubules: A proof-of-concept study.

INTRODUCTION: The success of endodontic treatment depends on the significant disinfection of the root canal system, its irregularities, and dentinal tubules. However, achieving complete disinfection remains challenging, with frequent failures and occurrence of secondary infections. Here, we propose using iontophoresis to increase the penetration and distribution of disinfecting agents into root canals, using methylene blue for proof-of-concept. METHODS: The marker was applied in bovine root canals, and the radial distribution of the dye in the dentinal tubules was evaluated by optical microscopy. Iontophoresis was applied at 0.5 and 1.5 mA for 5 and 15 min. RESULTS: A significant statistical difference (p < 0.05) was observed in the marker penetration between passive and iontophoretic applications. Both current density and application time had an important effect on methylene blue distribution, with a greater efficacy delivery to the apical region achieved after 1.5 mA for 5 min or 0.5 mA for 15 min, showing longer application time can compensate for lower application current. CONCLUSION: Iontophoresis increases the penetration and distribution of methylene blue into bovine root canals and dentinal tubules, including its innermost portions. CLINICAL SIGNIFICANCE: Iontophoresis has shown to be a promising technique for root canal and dentinal tubule disinfection.

Larvicidal activity of the photosensitive insecticides, methylene blue and rose bengal, in Aedes aegypti and Anopheles gambiae mosquitoes.

BACKGROUND: Insecticides are critical for controlling mosquito populations and mitigating the spread of vector-borne disease, but their overuse has selected for resistant populations. A promising alternative to classical chemical insecticides is photosensitive molecules - here called photosensitive insecticides or PSIs - that when ingested and activated by light, generate broadly toxic reactive oxygen species. This mechanism of indiscriminate oxidative damage decreases the likelihood that target site modification-based resistance evolves. Here, we tested whether the PSIs, methylene blue (MB) and rose bengal (RB), are viable insecticides across the mosquito lineage. RESULTS: MB and RB are phototoxic to both Aedes aegypti and Anopheles gambiae at micromolar concentrations, with greatest toxicity when larvae are incubated in the dark with the PSIs for 2 h prior to photoactivation. MB is ten times more toxic than RB, and microscopy-based imaging suggests that this is because ingested MB escapes the larval gut and disperses throughout the hemocoel whereas RB remains confined to the gut. Adding food to the PSI-containing water has a bidirectional, concentration-dependent effect on PSI toxicity; toxicity increases at high concentrations but decreases at low concentrations. Finally, adding sand to the water increases the phototoxicity of RB to Ae. aegypti. CONCLUSION: MB and RB are larvicidal via a light activated mechanism, and therefore, should be further investigated as an option for mosquito control. © 2023 Society of Chemical Industry.

Evaluation of cytotoxicity impacts of combined methylene blue-mediated photodynamic therapy and intracanal antibiotic medicaments on dental stem cells.

Root canal therapy is a predominant method for treatment of dental pulp and periapical diseases. Conventional methods such as mechanical instrumentations, chemical irrigation and intracanal medicaments pose a huge limitation to root canal disinfection as they kill bacteria and dental stem cells simultaneously. Therefore, much attention has been focused on finding more efficacious antibacterial methods that has no or negligible cytotoxicity for dental stem cells. Herein, we hypothesized that combining antibacterial medicaments with Antimicrobial photodynamic therapy (aPDT) and methylene blue (MB) as a photosensitizer would be effective in reducing death of dental pulp stem cells (DPSCs). To examine this, DPSCs were isolated from third molar teeth through enzymatic digestion. Isolated cells were cultured in αMEM and when reached adequate confluency, were used for further analysis. Cytotoxicity effect of different groups of MB, DAP, MB, LED and their combination on DPSCs was analyzed using MTT assay. DPSCs membrane integrity as a marker of live cells was assessed through measuring lipid peroxidation and lactate dehydrogenase (LDH) release into extracellular space. Results showed that the combination of LED, MB and TAP or aPDT, MB and DAP was more effective in reducing DPSCs death rate compared to TAP and DAP administration alone. Moreover, Malondialdehyde (MDA) and LDH levels were found to be decreased in cells exposed to combination treatment in comparison with single TAP or DAP therapy. Our study shows the promising perspectives of employing combined aPDT, MB and antibiotic medicaments for reduction of dental stem cell death.

Interaction of Methylene Blue with Severe Acute Respiratory Syndrome Coronavirus 2 Envelope Revealed by Molecular Modeling.

Methylene blue has multiple antiviral properties against Severe Acute Respiratory Syndrome-related Coronavirus 2 (SARS-CoV-2). The ability of methylene blue to inhibit different stages of the virus life cycle, both in light-independent and photodynamic processes, is used in clinical practice. At the same time, the molecular aspects of the interactions of methylene blue with molecular components of coronaviruses are not fully understood. Here, we use Brownian dynamics to identify methylene blue binding sites on the SARS-CoV-2 envelope. The local lipid and protein composition of the coronavirus envelope plays a crucial role in the binding of this cationic dye. Viral structures targeted by methylene blue include the S and E proteins and negatively charged lipids. We compare the obtained results with known experimental data on the antiviral effects of methylene blue to elucidate the molecular basis of its activity against coronaviruses.

Anticholinergic Toxidrome as a Possible Explanation for Methylene Blue Toxicity.

BACKGROUND Methylene blue has multiple uses in medicine. It is generally used to treat refractory vasoplegia and methemoglobin toxicity, and can be used as a dye to localize the parathyroid glands intra-operatively. In refractory vasoplegia, methylene blue inhibits endothelial nitric oxide and guanylate cyclase, causing vasoconstriction and potentially stabilizing blood pressure. Multiple complications have been associated with the use of methylene blue. These are related to either the sole effect of methylene blue or the combined effect of methylene blue and certain antidepressants, such as selective serotonin reuptake inhibitors (SSRIs). To the best of our knowledge, in the setting of post-cardiac surgery vasoplegia, there have been no reports of the neurological toxicity of methylene blue in the absence of SSRI use. In this case report, we describe the anticholinergic manifestations associated with the use of methylene blue in post-cardiac surgery vasoplegia. CASE REPORT A male patient in his mid-sixties with severe mitral regurgitation underwent elective mitral valve replacement. Postoperatively, he was hypotensive and required a high dose of vasopressors. Methylene blue was administered to treat refractory vasoplegia. The patient became anuric and febrile, with bilateral mydriasis. Internal cooling and continuous renal replacement therapy were initiated, and symptoms rapidly resolved. The patient was discharged after prolonged hospitalization with a permanent catheter for hemodialysis. CONCLUSIONS Anticholinergic toxidrome may explain the neurological adverse effects associated with high doses of methylene blue. Physicians should be cautious when using methylene blue in combination with other anticholinergic drugs and in conditions of renal failure. The development of methylene blue toxicity warrants the urgent discontinuation of the agent and early drug elimination.

Phenylalanine-Arginine-ß-Naphthylamide Enhances the Photobactericidal Effect of Methylene Blue on Pseudomonas aeruginosa.

Objective: To investigate the effectiveness, dosing sequence, concentration, and mechanism of antimicrobial photodynamic inactivation (aPDI) using methylene blue (MB) plus phenylalanine-arginine-ß-naphthylamide (PAßN) against Pseudomonas aeruginosa. Methods: P. aeruginosa bacterial suspension was incubated with MB for different times (5-240 min), and then, 10 J/cm2 red light was irradiated. The efflux pump inhibitor (EPI) PAßN (10-100 µg/mL) was combined with MB (1-20 µM) in different sequences (PAßN-first, PAßN+MB, PAßN-after). Colony-forming units were then determined by serial dilution. Results: Using MB 10 µM plus 10 J/cm2, the killing effect of MB-aPDI on P. aeruginosa increased first and then decreased with longer incubation time. The killing effect of MB+PAßN-aPDI on P. aeruginosa was better than that of MB-aPDI (p < 0.05) by up to 2 logs. PAßN-first had the best killing effect, whereas PAßN-after had the worst killing effect. The killing effect increased with PAßN concentration and at 100 µg/mL reached 5.1 logs. Conclusions: The EPI PAßN enhanced the bactericidal effect of MB-aPDI on P. aeruginosa, especially when added before MB. It is proposed that MB is a substrate of the resistance-nodulation-division family efflux pump.

Photodynamic reactions using high-intensity red LED promotes gingival wound healing by ROS induction.

Photodynamic therapy is a treatment that combines a light source with a photosensitizer. LEDs have attracted considerable attention in clinical dentistry because they are inexpensive and safe to use. Although the interaction between photosensitizers and LEDs in dental practice is effective for treating periodontal disease by killing periodontopathic bacteria, little is known about the effects of LEDs on human gingival fibroblasts (HGnFs), which play an important role in gingival wound healing. In this study, we investigated the effects of high-intensity red LED irradiation on HGnFs after the addition of methylene blue (MB), one of the least harmful photosensitizers, on wound healing and reactive oxygen species (ROS) production induced by photodynamic reactions. We found that irradiation of MB with high-intensity red LED at controlled energy levels promoted cell proliferation, migration, and production of wound healing factors. Furthermore, ROS production by a photodynamic reaction enabled the translocation of phosphorylated Grb2-associated binder-1, activating Extracellular signal-regulated kinase 1/2 and c-Jun N-terminal kinase signals. Our findings suggest that proper control of ROS production has a beneficial effect on gingival fibroblasts, which constitute periodontal tissue, from the perspective of gingival wound healing.

Methylene blue accelerates liquid-to-gel transition of tau condensates impacting tau function and pathology.

Preventing tau aggregation is a potential therapeutic strategy in Alzheimer's disease and other tauopathies. Recently, liquid-liquid phase separation has been found to facilitate the formation of pathogenic tau conformations and fibrillar aggregates, although many aspects of the conformational transitions of tau during the phase transition process remain unknown. Here, we demonstrate that the tau aggregation inhibitor methylene blue promotes tau liquid-liquid phase separation and accelerates the liquid-to-gel transition of tau droplets independent of the redox activity of methylene blue. We further show that methylene blue inhibits the conversion of tau droplets into fibrils and reduces the cytotoxicity of tau aggregates. Although gelation slows down the mobility of tau and tubulin, it does not impair microtubule assembly within tau droplets. These findings suggest that methylene blue inhibits tau amyloid fibrillization and accelerates tau droplet gelation via distinct mechanisms, thus providing insights into the activity of tau aggregation inhibitors in the context of phase transition.

In Situ Polymerization of Methylene Blue on Bacterial Cellulose for Photodynamic/Photoelectricity Synergistic Inhibition of Bacterial Biofilm Formation.

In the context of long-term antimicrobial treatment, the emergence of bacterial resistance poses a significant challenge. Therefore, there is a pressing need to develop novel antimicrobial materials and methods that can effectively and safely combat microbial infections. This study focuses on the synthesis of bacterial cellulose-polymethylene blue (BC-PMB) with integrated photodynamic and photoelectric antimicrobial properties. The polymerization of methyl blue (MB) onto bacterial celluloses (BC) was achieved, and through comprehensive computational analyses using density functional theory (DFT) and molecular dynamics simulations, it was confirmed that this polymerization greatly enhanced the binding efficiency between methylene blue and BC. Additionally, polymethylene blue (PMB) exhibited superior photoexcitation efficiency and conductivity compared to its precursor. When BC-PMB was exposed to a 30 mW 660 nm light source for 30 min, the material demonstrated a remarkable antimicrobial efficacy of 93.99% against Escherichia coli and 98.58% against Staphylococcus aureus. Furthermore, the synergistic effect of photodynamic and photoelectric antimicrobial mechanisms exhibited long-term inhibitory capabilities against bacterial biofilms.