Effectiveness of Three Bleaching Techniques for Endodontically Treated Teeth: A Randomized Clinical Trial.

BACKGROUND: Various techniques, products, and protocols are used for the bleaching of non-vital teeth. The walking bleach technique involves sealing the bleaching agent in the pulp chamber. In the inside/outside technique, a low-concentration bleaching agent is applied at home using a custom tray. In the in-office technique, a high-concentration bleaching agent is applied by a dental professional. Limited research has compared the effectiveness of these techniques. OBJECTIVE: This clinical trial aimed to evaluate the effectiveness of the walking bleach, the inside/outside, and the in-office bleaching techniques. METHODS AND MATERIALS: Fifty-four discolored teeth were selected according to eligibility criteria, randomized, and assigned to three treatment groups (n=18): walking bleach (sodium perborate - SP), inside/outside bleaching (7.5% hydrogen peroxide -HP7.5), and in-office bleaching (35% hydrogen peroxide - HP35). A cervical seal was placed in all the teeth, and nonvital bleaching was performed according to each technique. The CIELab color coordinates were measured using a clinical spectrophotometer at baseline, weekly, and at the 1-week follow-up. ΔE00 and ΔWID were calculated between the baseline and each evaluation time point. The ANOVA, Fisher exact, and Kruskal-Wallis tests were used to compare the quantitative variables, and the Fisher exact test, to determine the association among categorical variables. Bleaching effectiveness was interpreted by 50:50% perceptibility and acceptability thresholds. RESULTS: As the treatment progressed, all techniques presented a significant increase in L* and WID (p<0.001), and a significant decrease in a* and b* (p<0.001). HP7.5 and HP35 presented greater increases in WID mean values, in comparison with SP (p=0.006). No significant differences were observed among the techniques for ΔE00 after treatment completion (p=0.383). There were no statistical differences in bleaching effectiveness among the techniques after treatment completion (p=0.098). CONCLUSION: All techniques presented excellent effectiveness after treatment completion. However, HP7.5 and HP35 techniques provided a more rapid whitening response.

Enhanced tooth bleaching with a hydrogen peroxide/titanium dioxide gel.

BACKGROUND: This study aimed to explore the effects of the titanium dioxide (TiO2) concentration and particle size in hydrogen peroxide (HP) on tooth bleaching effectiveness and enamel surface properties. METHODS: TiO2 at different concentrations and particle sizes was incorporated into 40% HP gel to form an HP/TiO2 gel. The specimens were randomly divided into 8 groups: C1P20: HP + 1% TiO2 (20 nm); C3P20: HP + 3% TiO2 (20 nm); C5P20: HP + 5% TiO2 (20 nm); C1P100: HP + 1% TiO2 (100 nm); C3P100: HP + 3% TiO2 (100 nm); C5P100: HP + 5% TiO2 (100 nm); C0: HP with LED; and C0-woL: HP without LED. Bleaching was conducted over 2 sessions, each lasting 40 min with a 7-day interval. The color differences (ΔE00), whiteness index for dentistry (WID), surface microhardness, roughness, microstructure, and composition were assessed. RESULTS: The concentration and particle size of TiO2 significantly affected ΔE00 and ΔWID values, with the C1P100 group showing the greatest ΔE00 values and C1P100, C3P100, and C5P100 groups showing the greatest ΔWID values (p < 0.05). No significant changes were observed in surface microhardness, roughness, microstructure or composition (p > 0.05). CONCLUSIONS: Incorporating 1% TiO2 with a particle size of 100 nm into HP constitutes an effective bleaching strategy to achieve desirable outcomes.

Satisfaction with government recommended pre-procedural mouth rinses in the mitigation of Covid-19 in Hong Kong SAR: A triple blind randomized controlled clinical trial.

OBJECTIVE: To evaluate satisfaction and acceptability with three pre-procedural mouthrinses recommended by the Government of Hong Kong Special Administrative Region (HKSAR) during the COVID-19 pandemic. MATERIAL AND METHODS: A triple-blind parallel-arm randomised controlled clinical trial was conducted. Following eligibility assessment, participants were block-randomised to the three intervention pre-procedural mouthrinses groups: Povidone-iodine, Hydrogen Peroxide and Chlorhexidine Digluconate. Participants rinsed with one of the mouthrinses assigned prior to any dental treatment. Participants, operators and assessors were blind to the assigned mouthrinses (triple blind). Satisfaction ratings were assessed on a 10 cm visual analogue scale (VAS) and acceptability of the mouthrinses were determined. RESULTS: Following clinical screening, 228 participants were involved in the trial. The mean overall VAS satisfaction was 7.35 (SD 1.68). There was no significant difference in VAS satisfaction ratings among the three groups (p>0.05) nor in between groups. Acceptability of the mouthrinses was high with the vast majority (89.5 %, 204) willing to use the mouthrinses again if pre-procedural mouthrinsing is required. There was no significant difference in acceptability ratings (p>0.05). There were some aspects such as taste and smell that participants commented on (on average, 24.6 %, 56), although no significant difference in prevalence of reports among groups (p>0.05). CONCLUSIONS: There were high rates of satisfaction and acceptability of the HKSAR Government recommended pre-procedural mouthrinses for the mitigation of COVID-19 transmission in the dental setting. There was no significant difference in satisfaction and acceptability rates among the three recommended pre-procedural mouthrinses. CLINICAL RELEVANCE: The high satisfaction and acceptability rates of the HKSAR Government recommended pre-procedural mouthrinses in the mitigation of COVID-19 in this clinical trial lends support for the HKSAR's policy on pre-procedural mouthrinses in the dental setting and this has implications for practice and policy during pandemics.

Comparative evaluation of hydrogen peroxide and chlorhexidine mouthwash on salivary interleukin-1ß levels in patients with type 2 diabetes mellitus and chronic periodontitis: a randomized controlled clinical trial / Evaluación comparativa de enjuague bucal con peróxido de hidrógeno y clorhexidina sobre los niveles de interleucina-1ß salival en pacientes con diabetes mellitus tipo 2 y periodontitis crónica: ensayo clínico controlado aleatorio

Introduction: Periodontal inflammation causes dysbiosis and change in the microbiota. Nonsurgical periodontal therapy (NSPT) helps in removal of plaque and restoring periodontal health. Various adjunctive therapy like use of mouthwash helps in maintenance of periodontal health and reducing inflammatory load. Materials and Methods: A total of 108 subjects diagnosed with type 2 diabetes mellitus and periodontitis were divided into three groups: Group 1 received NSPT and rinsing with 0.2% chlorhexidine mouthwash for 3 months, Group 2 received NSPT and rinsing with 1.5% hydrogen peroxide mouthwash for 3 months, Group 3- received NSPT only (control group). The clinical parameters measured included Plaque Index (PI), Gingival Index (GI), Bleeding on probing (BOP) and probing (PD) at baseline, 1, 2, 3 months follow up. Salivary interleukin 1ßlevels were measured at baseline and 3 months interval. Results: Group 1, 2 and 3 showed significant reduction in PI, GI, BOP and PD at 1 and 3 months follow up (p<0.05). However, Intergroup comparison of clinical parameters showed significant reduction in group 1 and 2 when compared with group 3 (p<0.05). Salivary interleukin 1-ß levels showed significant reduction from baseline to 3 months in all the three groups and intergroup comparison didn't show any significant changes, (p>0.05). Conclusions: Hydrogen peroxide mouthwash as an adjunct to NSPT can be considered as a safe and effective measure to reduce periodontal inflammation in type 2 diabetes mellitus patients with chronic periodontitis.

Introducción: La inflamación periodontal causa disbiosis y cambios en la microbiota. La terapia periodontal no quirúrgica (NSPT) ayuda a eliminar la placa y restaurar la salud periodontal. Diversas terapias complementarias, como el uso de enjuague bucal, ayudan a mantener la salud periodontal y reducir la carga inflamatoria. Materiales y Métodos: Un total de 108 sujetos diagnosticados con diabetes mellitus tipo 2 y periodontitis se dividieron en tres grupos: el grupo 1 recibió NSPT y enjuague con enjuague bucal de clorhexidina al 0,2% durante 3 meses, el grupo 2 recibió NSPT y enjuague con enjuague bucal de peróxido de hidrógeno al 1,5% durante 3 meses, y el Grupo 3 recibió NSPT únicamente (grupo de control). Los parámetros clínicos medidos fueron el índice de placa (PI), el índice gingival (GI), el sangrado al sondaje (BOP) y al sondaje (PD) al inicio del estudio, 1, 2, y 3 meses de seguimiento. Los niveles de interleucina 1ß en saliva se midieron al inicio y a los 3 meses. Resultado: Los grupos 1, 2 y 3 mostraron una reducción significativa en IP, GI, BOP y PD al mes y 3 meses de seguimiento (p<0,05). Sin embargo, la comparación intergrupal de los parámetros clínicos mostró una reducción significativa en los grupos 1 y 2 en comparación con grupo 3 (p<0,05). Los niveles de interleucina 1-ß salival mostraron una reducción significativa desde el inicio hasta los 3 meses en los tres grupos y la comparación entre grupos no mostró ningún cambio significativo (p>0,05). Conclusión: El enjuague bucal con peróxido de hidrógeno como complemento de la NSPT puede considerarse una medida segura y eficaz para reducir la inflamación periodontal en pacientes con diabetes mellitus tipo 2 y periodontitis crónica.

Hydrogen Peroxide May Reduce the Risk for Revision Surgery and Infection in Primary Shoulder Arthroplasty: Two-year Follow-up From a Prospective, Blinded, Controlled Trial.

BACKGROUND: The purpose of this study was to determine whether the addition of hydrogen peroxide to the preoperative skin preparation for primary total shoulder arthroplasty is associated with a difference in patient-reported outcomes, risk for postoperative infection, and risk for revision surgery at a minimum of 2-year follow-up. METHODS: This was a prospective, blinded, and controlled trial, which included a consecutive series of patients undergoing primary shoulder arthroplasty. The control group underwent standard sterile skin preparation using ethyl alcohol and ChloraPrep applicators, and the peroxide group had the same preparation with the addition of hydrogen peroxide between the alcohol and ChloraPrep applications. We then compared patient-reported outcome scores (American Shoulder and Elbow Surgeons Shoulder Score [ASES], simple shoulder test [SST], visual analog scale [VAS]), infections, and revision surgeries between the two groups at 2-year follow-up. RESULTS: Of the 61 patients included in the original study, 52 of 58 (85%) living patients agreed to participate in this study. No preoperative differences were observed between groups. No difference was observed in ASES, SST, or VAS scores at 2 years. More revision surgeries were done in the control group (7 versus 2, P = 0.268) and Cutibacterium acnes infections (2 versus 0, P = 0.168). CONCLUSION: The addition of hydrogen peroxide to the preoperative skin preparation before primary shoulder arthroplasty is safe, and additional research is warranted to investigate whether it may decrease the risk for revision surgery and postoperative C acnes infection. LEVEL OF EVIDENCE: III.

Recombinant hirudin attenuates pulmonary hypertension and thrombosis in acute pulmonary embolism rat model.

Background: Acute pulmonary embolism (APE) is classified as a subset of diseases that are characterized by lung obstruction due to various types of emboli. Current clinical APE treatment using anticoagulants is frequently accompanied by high risk of bleeding complications. Recombinant hirudin (R-hirudin) has been found to have antithrombotic properties. However, the specific impact of R-hirudin on APE remains unknown. Methods: Sprague-Dawley (SD) rats were randomly assigned to five groups, with thrombi injections to establish APE models. Control and APE group rats were subcutaneously injected with equal amounts of dimethyl sulfoxide (DMSO). The APE+R-hirudin low-dose, middle-dose, and high-dose groups received subcutaneous injections of hirudin at doses of 0.25 mg/kg, 0.5 mg/kg, and 1.0 mg/kg, respectively. Each group was subdivided into time points of 2 h, 6 h, 1 d, and 4 d, with five animals per point. Subsequently, all rats were euthanized, and serum and lung tissues were collected. Following the assessment of right ventricular pressure (RVP) and mean pulmonary artery pressure (mPAP), blood gas analysis, enzyme-linked immunosorbnent assay (ELISA), pulmonary artery vascular testing, hematoxylin-eosin (HE) staining, Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining, immunohistochemistry, and Western blot experiments were conducted. Results: R-hirudin treatment caused a significant reduction of mPAP, RVP, and Malondialdehyde (MDA) content, as well as H2O2 and myeloperoxidase (MPO) activity, while increasing pressure of oxygen (PaO2) and Superoxide Dismutase (SOD) activity. R-hirudin also decreased wall area ratio and wall thickness to diameter ratio in APE rat pulmonary arteries. Serum levels of endothelin-1 (ET-1) and thromboxaneB2 (TXB2) decreased, while prostaglandin (6-K-PGF1α) and NO levels increased. Moreover, R-hirudin ameliorated histopathological injuries and reduced apoptotic cells and Matrix metalloproteinase-9 (MMP9), vascular cell adhesion molecule-1 (VCAM-1), p-Extracellular signal-regulated kinase (ERK)1/2/ERK1/2, and p-P65/P65 expression in lung tissues. Conclusion: R-hirudin attenuated pulmonary hypertension and thrombosis in APE rats, suggesting its potential as a novel treatment strategy for APE.

Over-the-counter products in tooth bleaching: A scoping review.

OBJECTIVE: To map and summarize the current scientific evidence concerning the active ingredients, effectiveness, and adverse effects of over-the-counter (OTC) bleaching products. DATA AND SOURCE: This study was conducted according to the PRISMA-ScR guidelines for scoping reviews and registered on the Open Science Framework platform. STUDY SELECTION: Database searches were conducted in PubMed/MEDLINE, Embase, and Scopus up to January 2024. All in vitro, in situ, and clinical studies evaluating the effectiveness and adverse effects of OTC bleaching products were included. A descriptive analysis of the included studies was performed. RESULTS: A total of 88 studies were included. Most of them were in vitro studies (n = 49), followed by randomized clinical trials (n = 28). The main OTC bleaching products identified were whitening or stain-removing toothpastes (n = 42), followed by whitening strips (n = 39). Most clinical studies indicate that whitening strips are effective in improving tooth color and providing whitening benefits. In contrast, the bleaching effectiveness of toothpastes, mouth rinses and whitening trays was mainly supported by in vitro studies. The main adverse effects associated with OTC bleaching agents were tooth sensitivity and gingival irritation. CONCLUSION: A wide variety of OTC bleaching products is available for consumer self-administered use. Clinical studies have mainly confirmed the bleaching effectiveness of whitening strips, while the validation for toothpastes, mouth rinses and whitening trays has mainly relied on in vitro studies. Nevertheless, the use of OTC bleaching products may result in adverse effects, including tooth sensitivity, gingival irritation, and enamel surface changes. CLINICAL SIGNIFICANCE: Some over-the-counter bleaching products may have whitening properties supported by clinical studies, particularly those containing hydrogen or carbamide peroxide. Nonetheless, clinicians must be aware of the potential risks associated with excessive self-administration of these products, which may result in adverse effects.

Evaluation of Stain Removal Efficacy and Color Stability of Three Different Dentifrices on Artificially Stained Enamel Surface-An In Vitro Study.

AIM: The aim of the present study was to assess the stain removal ability and color stability of three distinct dentifrices on artificially stained enamel surface. MATERIALS AND METHODS: This study included 75 intact, healthy premolars free of dental caries that were extracted during orthodontic therapy. The samples were allowed to dry for 6 hours after being submerged in the prepared tea solution for roughly 18 hours every day. Then this procedure was repeated for seven successive days. All samples were randomly divided into three experimental groups with 25 samples in each group. Group I: control dentifrice, group II: dentifrice containing hydrogen peroxide, group III: dentifrice containing papain and bromelain. A specially designed toothbrushing simulator was used to brush every sample in the relevant group. Using a spectrophotometer and a measurement program, color measurement was evaluated after staining process after 4 weeks and 8 weeks of teeth cleaning. Using a profilometer, the surface roughness values (Ra) were assessed. RESULTS: After 8 weeks of brushing of stained samples, the color stability was better in dentifrice containing hydrogen peroxide (1.14 ± 0.11) followed by dentifrice containing papain and bromelain (1.22 ± 0.08) and control group (1.30 ± 0.09). And after 8 weeks of brushing of stained samples, the surface roughness was more in dentifrice containing hydrogen peroxide (0.237 ± 0.02) followed by dentifrice containing papain and bromelain (0.229 ± 0.13) and control group (0.207 ± 0.05). CONCLUSION: The present study concluded that the dentifrice containing hydrogen peroxide showed a superior whitening effect on the stained enamel surface than dentifrice containing papain and bromelain and control dentifrice. CLINICAL SIGNIFICANCE: The development of various dentifrice products has been greatly aided by the increased demand for an improved esthetic appearance. Teeth's natural color and any external stains that could accumulate on the tooth surface combine to determine a tooth's color. Additionally, the use of whitening dental pastes to remove external stains has grown in favor. With the development of these whitening toothpastes, dentifrices' ability to lessen or eliminate extrinsic dental stains has increased. How to cite this article: Mishra D, Kamath DG, Alagla M, et al. Evaluation of Stain Removal Efficacy and Color Stability of Three Different Dentifrices on Artificially Stained Enamel Surface-An In Vitro Study. J Contemp Dent Pract 2024;25(1):68-71.

A copper-loaded self-assembled nanoparticle for disturbing the tumor redox balance and triple anti-tumor therapy.

Both chemodynamic therapy and photodynamic therapy, based on the production of reactive oxygen (ROS), have excellent potential in cancer therapy. However, the abnormal redox homeostasis in tumor cells, especially the overexpressed glutathione (GSH) could scavenge ROS and reduce the anti-tumor efficiency. Therefore, it is essential to develop a simple and effective tumor-specific drug delivery system for modulating the tumor microenvironment (TME) and achieving synergistic therapy at the tumor site. In this study, self-assembled nanoparticles (named CDZP NPs) were developed using copper ion (Cu2+), doxorubicin (Dox), zinc phthalocyanine (ZnPc) and a trace amount of poly(2-(di-methylamino)ethylmethacrylate)-poly[(R)-3-hydroxybutyrate]-poly(2-(dimethylamino)ethylmethacrylate) (PDMAEMA-PHB-PDMAEMA) through chelation, π-π stacking and hydrophobic interaction. These triple factor-responsive (pH, laser and GSH) nanoparticles demonstrated unique advantages through the synergistic effect. Highly controllable drug release ensured its effectiveness at the tumor site, Dox-induced chemotherapy and ZnPc-mediated fluorescence (FL) imaging exhibited the distribution of nanoparticles. Meanwhile, Cu2+-mediated GSH-consumption not only reduced the intracellular ROS elimination but also produced Cu+ to catalyze hydrogen peroxide (H2O2) and generated hydroxyl radicals (˙OH), thereby enhancing the chemodynamic and photodynamic therapy. Herein, this study provides a green and relatively simple method for preparing multifunctional nanoparticles that can effectively modulate the TME and improve synergetic cancer therapy.

Oxygen self-supplying small size magnetic nanoenzymes for synergistic photodynamic and catalytic therapy of breast cancer.

In recent years, tumor catalytic therapy based on nanozymes has attracted widespread attention. However, its application is limited by the tumor hypoxic microenvironment (TME). In this study, we developed oxygen-supplying magnetic bead nanozymes that integrate hemoglobin and encapsulate the photosensitizer curcumin, demonstrating reactive oxygen species (ROS)-induced synergistic breast cancer therapy. Fe3O4 magnetic bead-mediated catalytic dynamic therapy (CDT) generates hydroxyl radicals (˙OH) through the Fenton reaction in the tumor microenvironment. The Hb-encapsulated Fe3O4 magnetic beads can be co-loaded with the photosensitizer/chemotherapeutic agent curcumin (cur), resulting in Fe3O4-Hb@cur. Under hypoxic conditions, oxygen molecules are released from Fe3O4-Hb@cur to overcome the TME hypoxia, resulting in comprehensive effects favoring anti-tumor responses. Upon near-infrared (NIR) irradiation, Fe3O4-Hb@cur activates the surrounding molecular oxygen to generate a certain amount of singlet oxygen (1O2), which is utilized for photodynamic therapy (PDT) in cancer treatment. Meanwhile, we validated that the O2 carried by Hb significantly enhances the intracellular ROS level, intensifying the catalytic therapy mediated by Fe3O4 magnetic beads and inflicting lethal damage to cancer cells, effectively inhibiting tumor growth. Therefore, significant in vivo synergistic therapeutic effects can be achieved through catalytic-photodynamic combination therapy.

At-home bleaching versus whitening toothpastes for treatment of tooth discoloration: a cost-effectiveness analysis.

OBJECTIVES: This study aimed to analyze the cost-effectiveness of whitening toothpastes and at-home bleaching for the treatment of tooth discoloration. METHODOLOGY: A cost-effectiveness economic analysis was conducted, and eight randomized clinical trials were selected based on the whitening agent product used: blue covarine dentifrices (BCD), hydrogen peroxide dentifrices (HPD), dentifrices without bleaching agents (CD, negative control), and 10% carbamide peroxide (CP10, positive control) for at-home bleaching. The consumer/patient perspective was adopted, macro-costing techniques were used and a decision tree model was performed considering the costs in the American and Brazilian markets. The color change evaluation (ΔE*ab) was used to calculate the effectiveness of tooth bleaching. A probabilistic analysis was performed using a Monte Carlo simulation and incremental cost-effectiveness ratios were obtained. RESULTS: CP10 resulted in the highest cost-effectiveness compared to the use of dentifrices in both markets. In Brazil, HPD was more cost-effective than BCD and CD. In the US, the increased costs of HPD and BCD did not generate any whitening benefit compared to CD. CONCLUSIONS: CP10 was more cost-effective than BCD and HPD for tooth bleaching from the perspectives of the Brazilian and American markets. Decision-making should consider the use of CP10 for treating tooth discoloration.

Whitening efficacy of activated charcoal-based products: A single-blind randomized controlled clinical trial.

OBJECTIVE: This randomized controlled clinical trial evaluated the whitening efficacy, tooth sensitivity (TS), and volunteers' satisfaction following the use of activated charcoal powder and toothpaste. METHODS: Fifty-six volunteers were randomly allocated into 4 groups (n = 14) according to a 14-day toothbrushing or whitening treatment with activated charcoal powder (ACPW), activated charcoal toothpaste (ACT), regular fluoridated toothpaste (RT), and 10 % carbamide peroxide (CP). Objective (ΔE00) and subjective (ΔSGU) color and whiteness index (ΔWID) changes were calculated. Patients self-reported the risk and intensity of TS using a visual analogue scale and the volunteer's satisfaction was determined by a questionnaire. Color assessments were analyzed by Kruskal-Wallis followed by Dwas-Steel-Crithlow-Fligner, and absolute TS risk and volunteer's satisfaction by Fisher exact test (p < 0.05). RESULTS: ACPW and ACT promoted similar effects in ΔE00, ΔSGU, and ΔWID to that observed for RT. No significant difference was found in terms of TS risk intensity. TS risk became high after 7 and 14 days, with higher TS prevalence in CP. Volunteers reported that ACPW exhibited the lowest ease-of-use, comfort, and whitening satisfaction among groups (p < 0.05). CONCLUSION: Activated charcoal-based products presented a minor and unsatisfactory whitening effect while CP resulted in optimal tooth whitening and the highest level of satisfaction among volunteers. Risk was higher from 7 days onwards and was more pronounced in the CP. CLINICAL RELEVANCE: Based on the whitening effect and patient satisfaction, this controlled-randomized clinical evidence supports that the use of activated charcoal-based products should be discouraged.

Multifunctional siRNA/ferrocene/cyclodextrin nanoparticles for enhanced chemodynamic cancer therapy.

The therapeutic outcome of chemodynamic therapy (CDT) is greatly hindered by the presence of oxidative damage repair proteins (MTH1) inside cancer cells. These oxidative damage repair proteins detoxify the action of radicals generated by Fenton or Fenton-like reactions. Hence, it is extremely important to develop a simple strategy for the downregulation of MTH1 protein inside cancer cells along with the delivery of metal ions into cancer cells. A one-pot host-guest supramolecular approach for the codelivery of MTH1 siRNA and metal ions into a cancer cell is reported. Our approach involves the fabrication of an inclusion complex between cationic ß-cyclodextrin and a ferrocene prodrug, which spontaneously undergoes amphiphilicity-driven self-assembly to form spherical nanoparticles (NPs) having a positively charged surface. The cationic surface of the NPs was then explored for the loading of MTH1 siRNA through electrostatic interactions. Using HeLa cells as a representative example, efficient uptake of the NPs, delivery of MTH1 siRNA and the enhanced CDT of the nanoformulation are demonstrated. This work highlights the potential of the supramolecular approach as a simple yet efficient method for the delivery of siRNA across the cell membrane for enhanced chemodynamic therapy.

Dual-modality probe nanodrug delivery systems with ROS-sensitivity for atherosclerosis diagnosis and therapy.

Most acute cardiovascular and cerebrovascular diseases are caused by atherosclerotic plaque rupture leading to blocked arteries. Targeted nanodelivery systems deliver imaging agents or drugs to target sites for diagnostic imaging or the treatment of various diseases, providing new insights for the detection and treatment of atherosclerosis. Based on the pathological characteristics of atherosclerosis, a hydrogen peroxide-sensitive bimodal probe PPIS@FC with integrated diagnosis and treatment function was designed. Bimodal probes Fe3O4@SiO2-CDs (FC) were prepared by coupling superparamagnetic iron oxide and carbon quantum dots synthesized with citric acid, and self-assembled with hydrogen peroxide stimulus-responsive amphiphilic block polymer PGMA-PEG modified with simvastatin (Sim) and target molecule ISO-1 to obtain drug-loaded micelles PGMA-PEG-ISO-1-Sim@FC (PPIS@FC). PPIS@FC could release Sim and FC in an H2O2-triggered manner, achieving the goal of releasing drugs using the special microenvironment at the plaque. At the same time, in vivo magnetic resonance and fluorescence imaging results proved that PPIS@FC possessed targeting ability, magnetic resonance imaging and fluorescence imaging effects. The results of the FeCl3 and ApoE-/- model showed that PPIS@FC had an excellent therapeutic effect and in vivo safety. Therefore, dual-modality imaging drug delivery systems with ROS response will become a promising strategy for the diagnosis and treatment of atherosclerosis.

Norepinephrine protects against cochlear outer hair cell damage and noise-induced hearing loss via α2A-adrenergic receptor.

BACKGROUND: The cochlear sympathetic system plays a key role in auditory function and susceptibility to noise-induced hearing loss (NIHL). The formation of reactive oxygen species (ROS) is a well-documented process in NIHL. In this study, we aimed at investigating the effects of a superior cervical ganglionectomy (SCGx) on NIHL in Sprague-Dawley rats. METHODS: We explored the effects of unilateral and bilateral Superior Cervical Ganglion (SCG) ablation in the eight-ten weeks old Sprague-Dawley rats of both sexes on NIHL. Auditory function was evaluated by auditory brainstem response (ABR) testing and Distortion product otoacoustic emissions (DPOAEs). Outer hair cells (OHCs) counts and the expression of α2A-adrenergic receptor (AR) in the rat cochlea using immunofluorescence analysis. Cells culture and treatment, CCK-8 assay, Flow cytometry staining and analysis, and western blotting were to explore the mechanisms of SCG fibers may have a protective role in NIHL. RESULTS: We found that neither bilateral nor unilateral SCGx protected the cochlea against noise exposure. In HEI-OC1 cells, H2O2-induced oxidative damage and cell death were inhibited by the application of norepinephrine (NE). NE may prevent ROS-induced oxidative stress in OHCs and NIHL through the α2A-AR. CONCLUSION: These results demonstrated that sympathetic innervation mildly affected cochlear susceptibility to acoustic trauma by reducing oxidative damage in OHCs through the α2A-AR. NE may be a potential therapeutic strategy for NIHL prevention.

The Effect of S-Allyl L-Cysteine on Retinal Ischemia: The Contributions of MCP-1 and PKM2 in the Underlying Medicinal Properties.

Retinal ischemia plays a vital role in vision-threatening retinal ischemic disorders, such as diabetic retinopathy, age-related macular degeneration, glaucoma, etc. The aim of this study was to investigate the effects of S-allyl L-cysteine (SAC) and its associated therapeutic mechanism. Oxidative stress was induced by administration of 500 µM H2O2 for 24 h; SAC demonstrated a dose-dependent neuroprotective effect with significant cell viability effects at 100 µM, and it concurrently downregulated angiogenesis factor PKM2 and inflammatory biomarker MCP-1. In a Wistar rat model of high intraocular pressure (HIOP)-induced retinal ischemia and reperfusion (I/R), post-administration of 100 µM SAC counteracted the ischemic-associated reduction of ERG b-wave amplitude and fluorogold-labeled RGC reduction. This study supports that SAC could protect against retinal ischemia through its anti-oxidative, anti-angiogenic, anti-inflammatory, and neuroprotective properties.

ICAM-1 targeted and ROS-responsive nanoparticles for the treatment of acute lung injury.

Acute lung injury (ALI) is an inflammatory disease caused by multiple factors such as infection, trauma, and chemicals. Without effective intervention during the early stages, it usually quickly progresses to acute respiratory distress syndrome (ARDS). Since ordinary pharmaceutical preparations cannot precisely target the lungs, their clinical application is limited. In response, we constructed a γ3 peptide-decorated and ROS-responsive nanoparticle system encapsulating therapeutic dexamethasone (Dex/PSB-γ3 NPs). In vitro, Dex/PSB-γ3 NPs had rapid H2O2 responsiveness, low cytotoxicity, and strong intracellular ROS removal capacity. In a mouse model of ALI, Dex/PSB-γ3 NPs accumulated at the injured lung rapidly, alleviating pulmonary edema and cytokine levels significantly. The modification of NPs by γ3 peptide achieved highly specific positioning of NPs in the inflammatory area. The ROS-responsive release mechanism ensured the rapid release of therapeutic dexamethasone at the inflammatory site. This combined approach improves treatment accuracy, and drug bioavailability, and effectively inhibits inflammation progression. Our study could effectively reduce the risk of ALI progressing to ARDS and hold potential for the early treatment of ALI.

Antioxidative effects of ghrelin on human trabecular meshwork cells.

Glaucoma is a group of neurodegenerative diseases characterized by loss of retinal ganglion cells and visual field defects and is one of the major causes of irreversible blindness worldwide. Primary open-angle glaucoma (POAG) is one of the classifications of glaucoma. Oxidative stress in trabecular reticulated cells is one of the possible mechanisms of the development of glaucoma. At present, there is still a lack of effective methods to treat glaucoma. Ghrelin is characterized by its wide distribution and high potency and has anti-inflammatory, antioxidant, and anti-apoptotic effects, which may be beneficial in the treatment of glaucoma. In this study, we investigated whether ghrelin can protect human trabecular meshwork cells (HTMCs) from oxidative damage induced by hydrogen peroxide (H2O2), as well as the possible mechanism of action. CCK8 and flow cytometry results revealed that treatment of HTMCs with ghrelin showed a dose-dependent protective effect against H2O2-induced damage. Ghrelin significantly decreased the rate of apoptosis and levels of reactive oxygen species (ROS) and malondialdehyde (MDA) and increased the level of superoxide dismutase (SOD) and catalase (CAT) in HTMCs. The difference was statistically significant compared with the H2O2 group. Ghrelin activated Nrf2/HO-1/NQO-1 signaling pathways and decreased HIF-1α level in H2O2-injured HTMCs as shown on qPCR and Western blot. In conclusion, ghrelin can protect HTMCs from oxidative damage induced by H2O2 and reduce apoptosis in HTMCs, which can be a new approach to treating POAG. The underlying therapeutic mechanism may be related to Nrf2/HO-1/NQO-1 signaling pathways and HIF-1α.

Improved Glycaemic Control and Nephroprotective Effects of Empagliflozin and Paricalcitol Co-Therapy in Mice with Type 2 Diabetes Mellitus.

Herein, we measured the antidiabetic and nephroprotective effects of the sodium-glucose cotransporter-2 inhibitor (empagliflozin; SGLT2i) and synthetic active vitamin D (paricalcitol; Pcal) mono- and co-therapy against diabetic nephropathy (DN). Fifty mice were assigned into negative (NC) and positive (PC) control, SGLT2i, Pcal, and SGLT2i+Pcal groups. Following establishment of DN, SGLT2i (5.1 mg/kg/day) and/or Pcal (0.5 µg/kg/day) were used in the designated groups (5 times/week/day). DN was affirmed in the PC group by hyperglycaemia, dyslipidaemia, polyuria, proteinuria, elevated urine protein/creatinine ratio, and abnormal renal biochemical parameters. Renal SREBP-1 lipogenic molecule, adipokines (leptin/resistin), pro-oxidant (MDA/H2O2), pro-inflammatory (IL1ß/IL6/TNF-α), tissue damage (iNOS/TGF-ß1/NGAL/KIM-1), and apoptosis (TUNEL/Caspase-3) markers also increased in the PC group. In contrast, renal lipolytic (PPARα/PPARγ), adiponectin, antioxidant (GSH/GPx1/SOD1/CAT), and anti-inflammatory (IL10) molecules decreased in the PC group. Both monotherapies increased insulin levels and mitigated hyperglycaemia, dyslipidaemia, renal and urine biochemical profiles alongside renal lipid regulatory molecules, inflammation, and oxidative stress. While SGLT2i monotherapy showed superior effects to Pcal, their combination demonstrated enhanced remedial actions related to metabolic control alongside renal oxidative stress, inflammation, and apoptosis. In conclusion, SGLT2i was better than Pcal monotherapy against DN, and their combination revealed better nephroprotection, plausibly by enhanced glycaemic control with boosted renal antioxidative and anti-inflammatory mechanisms.

Decontamination and Repair Protocol Promotes Positive Outcomes in Implants Affected by Peri-implantitis: A Human Case Series.

This study assessed the effectiveness and predictability of a readily available protocol to treat peri-implantitis utilizing mechanical debridement, chemical antiseptic surface detoxification, and osseous grafting. Nine patients (7 women, 2 men; mean age: 56.5 years) with 15 implants with peri-implantitis were included. Pocket probing depth (PPD), bleeding on probing (BOP), and standardized digital periapical radiographic measurements were taken. Surgical flaps were elevated, and the implant threads were cleaned with a plastic curette. Chemical decontamination was performed by scrubbing solutions of 0.25% sodium hypochlorite (NaClO) and 1.5% hydrogen peroxide (H2O2) around the exposed implant using cotton pellets. Bony defects were filled with a 50/50 mixture of bovine hydroxyapatite and nanocrystalline calcium sulfate (CaSO4). A porcine collagen membrane was placed over the grafted bony defect. Follow-up appointments were scheduled 1 week, 2 weeks, 3 months, 6 months, 9 months, and 1 year posttreatment. Clinical and radiographic parameters were assessed and compared. At baseline, PPD ranged from 5 to 7.5 mm (mean: 6 ± 0.7 mm). At 12 months, PPD ranged from 1.5 to 4.2 mm (mean: 2.5 ± 0.8 mm). The mean PPD reduction of 3.6 mm (59.2%) was statistically significant (P < .001). The number of bleeding sites around each test implant decreased significantly from 4 to 0.4 sites between baseline and 12 months (P < .001). Mean radiographic bone loss decreased from 4.8 ± 1.3 mm to 2.7 ± 1.2 mm (P < .001). The proposed method of mechanical decontamination, chemical detoxification, and bone regeneration is clinically effective and reproducible. Clinical peri-implant parameters and radiographic bone levels were improved and maintained their stability for 1 year using this peri-implantitis treatment protocol.