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Objective: To compare the risk and intensity of tooth sensitivity (TS) and gingival irritation (GI), as well as bleaching efficacy (BE) in the maxillary and mandibular arches after in-office dental bleaching., Materials and Methods: 90 participants were randomly into two groups according to the arch (maxillary or mandibular) in which the patient will first receive a 35 % hydrogen peroxide gel (2 sessions; 1 × 30 min; 1 week apart). TS and GI were recorded immediately after, up to 1 h, 24 h and 48 h after bleaching, using the 0-10 Visual Analogue Scale (VAS). BE was assessed before bleaching and 30 days after the end of the treatment (shade guide units [ΔSGU], CIELab [ΔE ab ], CIEDE2000 [ΔE 00 ] , and Whiteness Index for Dentistry [WI D ]). TS and GI were compared using McNemar's and paired t-test. BE were compared with Wilcoxon Signed Rank Test (ΔSGU) and paired t-test (ΔE ab , ΔE 00, and WI D ) (α = 0.05)., Results: The risk and the intensity of TS was statistically higher for the mandibular arch (p < 0.003). The risk and intensity of GI did not differ between arches (p > 0.38). Both arches demonstrated significant BE (ΔSGU, ΔE ab , ΔE 00 and WI D ), without differences between them (p > 0.08)., Conclusions: In-office dental bleaching induces higher risk and the intensity of TS in the mandibular arch when compared to maxillary arch, without significant differences in gingival irritation, or bleaching efficacy., Clinical Relevance: Most patients experience tooth sensitivity regardless of the dental arch involved. However, when performing in-office dental bleaching, clinicians should consider that the mandibular arch is more likely to experience greater sensitivity compared to the maxillary arch., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Decontamination of the clinical working environment and reprocessing of reusable dental instruments and devices are key components of modern infection control. This narrative review, which is part of a special issue devoted to contemporary infection control practices, highlights the latest evidence and the potential role of emerging technologies. The underpinning concepts of environmental decontamination and reprocessing have remained unchanged for many years, and key principles such as cleaning before disinfection or sterilisation remain true to the present day. What has changed in recent years are the range of options available, most notably for no-touch decontamination as an adjunct to regular environmental cleaning methods, including vapourised hydrogen peroxide, hydroxyl radicals, and ultraviolet C irradiation. In the realm of sterilisation, newer approaches include solar autoclaves and hydrogen peroxide gas plasma sterilisation. With all new and emerging technologies, greater attention is now being paid to safety as well as effectiveness, with stronger consideration of environmental impacts. This is especially relevant to the use of fully disposable surgical instruments vs reusable instruments. Because dental clinics have many configurations and sizes, each clinic needs to undertake local risk assessments to inform their decisions regarding suitable decontamination and reprocessing methods., Competing Interests: Conflict of interest None disclosed., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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., (©Operative Dentistry, 2024.)

Background: This study aimed to explore the effects of the titanium dioxide (TiO 2 ) concentration and particle size in hydrogen peroxide (HP) on tooth bleaching effectiveness and enamel surface properties., Methods: TiO 2 at different concentrations and particle sizes was incorporated into 40% HP gel to form an HP/TiO 2 gel. The specimens were randomly divided into 8 groups: C1P20: HP + 1% TiO 2 (20 nm); C3P20: HP + 3% TiO 2 (20 nm); C5P20: HP + 5% TiO 2 (20 nm); C1P100: HP + 1% TiO 2 (100 nm); C3P100: HP + 3% TiO 2 (100 nm); C5P100: HP + 5% TiO 2 (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 (ΔE 00 ), whiteness index for dentistry (WI D ), surface microhardness, roughness, microstructure, and composition were assessed., Results: The concentration and particle size of TiO 2 significantly affected ΔE 00 and ΔWI D values, with the C1P100 group showing the greatest ΔE 00 values and C1P100, C3P100, and C5P100 groups showing the greatest ΔWI D values (p < 0.05). No significant changes were observed in surface microhardness, roughness, microstructure or composition (p > 0.05)., Conclusions: Incorporating 1% TiO 2 with a particle size of 100 nm into HP constitutes an effective bleaching strategy to achieve desirable outcomes., (© 2024. The Author(s).)

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., (Copyright © 2024 by the American Academy of Orthopaedic Surgeons.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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 H 2 O 2 and myeloperoxidase (MPO) activity, while increasing pressure of oxygen (PaO 2 ) 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-PGF1 α ) 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., Competing Interests: The authors declare there are no competing interests., (©2024 Wei et al.)

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 (Cu 2+ ), 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, Cu 2+ -mediated GSH-consumption not only reduced the intracellular ROS elimination but also produced Cu + to catalyze hydrogen peroxide (H 2 O 2 ) 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.

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 (ΔE 00 ) and subjective (ΔSGU) color and whiteness index (ΔWI D ) 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 ΔE 00 , ΔSGU, and ΔWI D 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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. Fe 3 O 4 magnetic bead-mediated catalytic dynamic therapy (CDT) generates hydroxyl radicals (˙OH) through the Fenton reaction in the tumor microenvironment. The Hb-encapsulated Fe 3 O 4 magnetic beads can be co-loaded with the photosensitizer/chemotherapeutic agent curcumin (cur), resulting in Fe 3 O 4 -Hb@cur. Under hypoxic conditions, oxygen molecules are released from Fe 3 O 4 -Hb@cur to overcome the TME hypoxia, resulting in comprehensive effects favoring anti-tumor responses. Upon near-infrared (NIR) irradiation, Fe 3 O 4 -Hb@cur activates the surrounding molecular oxygen to generate a certain amount of singlet oxygen (1 O 2 ), which is utilized for photodynamic therapy (PDT) in cancer treatment. Meanwhile, we validated that the O 2 carried by Hb significantly enhances the intracellular ROS level, intensifying the catalytic therapy mediated by Fe 3 O 4 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.

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 β-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.

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.

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 Fe 3 O 4 @SiO 2 -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 H 2 O 2 -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 FeCl 3 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.

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 α 2A -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, H 2 O 2 -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 α 2A -AR., Conclusion: These results demonstrated that sympathetic innervation mildly affected cochlear susceptibility to acoustic trauma by reducing oxidative damage in OHCs through the α 2A -AR. NE may be a potential therapeutic strategy for NIHL prevention., (© 2024. The Author(s).)

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 H 2 O 2 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.

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 H 2 O 2 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.

Background: Acute respiratory distress syndrome in the elderly with COVID-19 complicated by airway obstruction with sputum and mucus, and cases of asphyxia with blood, serous fluid, pus, or meconium in newborns and people of different ages can sometimes cause hypoxemia and death from hypoxic damage to brain cells, because the medical standard does not include intrapulmonary injections of oxygen-producing solutions. The physical-chemical repurposing of hydrogen peroxide from an antiseptic to an oxygen-producing antihypoxant offers hope for the development of new drugs., Methods: This manuscript is a meta-analysis performed according to PRISMA guidelines., Results: It is shown that replacement of the traditional acidic activity of hydrogen peroxide solutions by alkaline activity with pH 8.4 and heating the solutions to the temperature of +37 - +42 °C allows to repurpose hydrogen peroxide from antiseptics into inhalation and intrapulmonary mucolytics, pyolytics and antihypoxants releasing oxygen. The fact is that warm alkaline hydrogen peroxide solution (WAHPS) in local interaction with sputum, mucus, pus, blood and meconium provides optimal conditions for the metabolism of hydrogen peroxide to oxygen gas under the action of the enzyme catalase, always present in these tissues. It was established that WAHPS liquefies these biological masses due to alkaline saponification of lipid and protein-lipid complexes and simultaneously transforms dense masses into soft oxygen foam due to active enzymatic metabolism of hydrogen peroxide to oxygen gas, the rapidly appearing bubbles of which are formed by the type of "cold boiling" and literally explode these masses. The results of the first experiments showed that inhalation and intrapulmonary injections of WAHPS can significantly optimize the treatment of suffocation and hypoxemia., Discussion: The results showed that catalase, which is found in sputum, mucus, pus, and blood, may be a target for localized WAHPS because this enzyme provides an intensive metabolism of hydrogen peroxide to oxygen gas up to the formation of the cold boiling process., Conclusion: These data provide a new perspective way for intrapulmonary drugs and new technologies for the emergency increase of blood oxygenation through the lungs in asphyxia with thick sputum, mucus, pus, meconium and blood., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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 (H 2 O 2 ), 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 H 2 O 2 -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 H 2 O 2 group. Ghrelin activated Nrf2/HO-1/NQO-1 signaling pathways and decreased HIF-1α level in H 2 O 2 -injured HTMCs as shown on qPCR and Western blot. In conclusion, ghrelin can protect HTMCs from oxidative damage induced by H 2 O 2 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., (Copyright © 2023. Published by Elsevier Masson SAS.)

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.

Background: Sesquiterpene lactones are secondary plant metabolites with a wide variety of biological activities. The process of lactone conjugation to other pharmacophores can increase the efficacy and specificity of the conjugated agent effect on molecular targets in various diseases, including brain pathologies. Derivatives of biogenic indoles, including neurotransmitter serotonin, are of considerable interest as potential pharmacophores. Most of these compounds have neurotropic activity and, therefore, can be used in the synthesis of new drugs with neuroprotective properties., Aim: The aim of this experimental synthesis was to generate potential treatment agents for Alzheimer's disease using serotonin conjugated with natural sesquiterpene lactones., Methods: Three novel compounds were obtained via the Michael reaction and used for biological testing. The obtained conjugates demonstrated complex neuroprotective activities. Serotonin conjugated to isoalantolactone exhibited strong antioxidant and mitoprotective activities., Results: The agent was also found to inhibit β-site amyloid precursor protein cleaving enzyme 1 (BACE-1), prevent the aggregation of β-amyloid peptide 1-42, and protect SH-SY5Y neuroblastoma cells from neurotoxins such as glutamate and H 2 O 2 . In a transgenic animal model of Alzheimer's disease (5xFAD line), the conjugated agent restored declined cognitive functions and improved learning and memory., Conclusion: In conclusion, the obtained results indicate that serotonin conjugates to sesquiterpene lactones are promising agents for the treatment of symptoms associated with Alzheimer's disease., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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/H 2 O 2 ), pro-inflammatory (IL1β/IL6/TNF-α), tissue damage (iNOS/TGF-β1/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.

Objective: To evaluate the effects of activated charcoal-based products used in two presentation forms (powder or toothpaste), compared to 10 % carbamide peroxide and conventional toothpaste on aesthetic perception and psychosocial impact before and after treatment., Methods: Fifty-six participants were divided into 4 experimental groups (n = 14). Activated charcoal-based powder (PW); Activated charcoal-based dentifrice (AC); Conventional fluoride toothpaste (CD) and 10 % carbamide peroxide (CP). All products were used for 14 days. Psychosocial impact on dental esthetics (PIDAQ), oral health impact profile (OHIP- Esthetics) and orofacial esthetics scale (OES) questionnaires were applied before and after treatment. Descriptive and exploratory data analyses were performed and analyzed using linear mixed models for repeated measures over time considering significance level of α = 0.05., Results: For PIDAQ, the CP group showed significant decrease in psychological impact, aesthetic perception domains and overall score, while in the PW group, there was only a significant decrease in the psychological impact domain. Decrease in OHIP was observed for the functional limitation domain scores for treatments with CP and PW, in the psychological discomfort domain, decrease was observed for all groups, while for the OES questionnaire, significant increase in the color domain was observed for the CP group., Conclusion: Activated charcoal-based products showed lower scores in all questionnaires when compared with carbamide peroxide; thus, charcoal-based products promoted lower impact on quality of life and aesthetic perception., Clinical Relevance: In this randomized clinical trial, charcoal-based OTC products had inferior quality of life and aesthetic perception results compared to conventional carbamide peroxide bleaching., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Seborrheic keratoses (SKs) are benign epidermal neoplasms presenting as waxy, brown to black papules and plaques. Patients often seek removal for cosmetic reasons or irritation. The objective of this systematic review is to assess the efficacy and safety of topical treatments for SKs. Studies involving any topical medication indicated for SK removal were retrieved from Embase, Scopus, PubMed, and Cochrane. The final search was conducted on November 9, 2021, and 26 reports met inclusion criteria. A quality rating scheme was utilized to assess evidence quality. Heterogeneity of treatments and outcome measures precluded meta-analysis. Topical treatments that yielded a good-to-excellent response include hydrogen peroxide, Maxacalcitol 25 µg/g, BID Tazarotene 0.1% cream, 5% potassium dobesilate cream, 1% diclofenac sodium solution, urea-based solution, and 65% and 80% trichloroacetic acid. Local skin reactions were often mild and transient. Topical hydrogen peroxide showed the greatest evidence for clinical clearance of SKs, although there are no studies to our knowledge that directly compared hydrogen peroxide to current first-line treatments (e.g. cryotherapy or shave excision). The results of this review suggest viable and safe treatment of SK with topical therapies; however, there remains demand for topical treatments that reliably equate or exceed the efficacy of current first-line therapies.Key Points Question: Are safe and efficacious topical treatments for seborrheic keratoses available? Findings: Topical treatments for seborrheic keratoses yield different responses and may be associated with local skin reactions. Topical hydrogen peroxide shows the greatest evidence for clinical clearance of seborrheic keratoses and may be a viable option for patients requesting noninvasive removal. No studies to our knowledge directly compare hydrogen peroxide to current first-line treatments. Meaning: There remains demand for topical treatments that reliably equate or exceed the efficacy of current first-line therapies.

While the poor prognosis of glioblastoma arises from the invasion of a subset of tumor cells, little is known of the metabolic alterations within these cells that fuel invasion. We integrated spatially addressable hydrogel biomaterial platforms, patient site-directed biopsies, and multiomics analyses to define metabolic drivers of invasive glioblastoma cells. Metabolomics and lipidomics revealed elevations in the redox buffers cystathionine, hexosylceramides, and glucosyl ceramides in the invasive front of both hydrogel-cultured tumors and patient site-directed biopsies, with immunofluorescence indicating elevated reactive oxygen species (ROS) markers in invasive cells. Transcriptomics confirmed upregulation of ROS-producing and response genes at the invasive front in both hydrogel models and patient tumors. Among oncologic ROS, H2O2 specifically promoted glioblastoma invasion in 3D hydrogel spheroid cultures. A CRISPR metabolic gene screen revealed cystathionine γ-lyase (CTH), which converts cystathionine to the nonessential amino acid cysteine in the transsulfuration pathway, to be essential for glioblastoma invasion. Correspondingly, supplementing CTH knockdown cells with exogenous cysteine rescued invasion. Pharmacologic CTH inhibition suppressed glioblastoma invasion, while CTH knockdown slowed glioblastoma invasion in vivo. Our studies highlight the importance of ROS metabolism in invasive glioblastoma cells and support further exploration of the transsulfuration pathway as a mechanistic and therapeutic target.

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.

Pharmacological ascorbate (P-AscH-, high dose, intravenous vitamin C) preferentially sensitizes human pancreas ductal adenocarcinoma (PDAC) cells to radiation-induced toxicity compared to non-tumorigenic epithelial cells. Radiation-induced G2-checkpoint activation contributes to the resistance of cancer cells to DNA damage induced toxicity. We hypothesized that P-AscH- induced radio-sensitization of PDAC cells is mediated by perturbations in the radiation induced activation of the G2-checkpoint pathway. Both non-tumorigenic pancreatic ductal epithelial and PDAC cells display decreased clonogenic survival and increased doubling times after radiation treatment. In contrast, the addition of P-AscH- to radiation increases clonogenic survival and decreases the doubling time of non-tumorigenic epithelial cells but decreasing clonogenic survival and increasing the doubling time of PDAC cells. Results from the mitotic index and propidium iodide assays showed that while the P-AscH- treatments did not affect radiation-induced G2-checkpoint activation, it enhanced G2-accumulation. The addition of catalase reverses the increases in G2-accumulation, indicating a peroxide-mediated mechanism. In addition, P-AscH- treatment of PDAC cells suppresses radiation-induced accumulation of cyclin B1 protein levels. Both translational and post-translational pathways appear to regulate cyclin B1 protein levels after the combination treatment of PDAC cells with P-AscH- and radiation. The protein changes seen are reversed by the addition of catalase suggesting that hydrogen peroxide mediates P-AscH- induced radiation sensitization of PDAC cells by enhancing G2-accumulation and reducing cyclin B1 protein levels., (©2023 by Radiation Research Society. All rights of reproduction in any form reserved.)

Diffuse intrinsic pontine gliomas (DIPG) are an aggressive type of pediatric brain tumor with a very high mortality rate. Surgery has a limited role given the tumor's location. Palliative radiation therapy alleviates symptoms and prolongs survival, but median survival remains less than 1 year. There is no clear role for chemotherapy in DIPGs as trials adding chemotherapy to palliative radiation therapy have failed to improve survival compared to radiation alone. Thus, there is a critical need to identify tissue-specific radiosensitizers to improve clinical outcomes for patients with DIPGs. Pharmacologic (high dose) ascorbate (P-AscH-) is a promising anticancer therapy that sensitizes human tumors, including adult high-grade gliomas, to radiation by acting selectively as a generator of hydrogen peroxide (H2O2) in cancer cells. In this study we demonstrate that in contrast to adult glioma models, P-AscH- does not radiosensitize DIPG. DIPG cells were sensitive to bolus of H2O2 but have faster H2O2 removal rates than GBM models which are radiosensitized by P-AscH-. These data support the hypothesis that P-AscH- does not enhance DIPG radiosensitivity, likely due to a robust capacity to detoxify and remove hydroperoxides., (©2023 by Radiation Research Society. All rights of reproduction in any form reserved.)

Bacterial biofilm-associated infectious diseases remain serious menaces to human health. Recently, photodynamic therapy (PDT) has become a prospective strategy for combating biofilm infection. However, anaerobic conditions in a biofilm greatly inhibit its therapeutic efficacy. Here, a nanozyme-reinforced injectable hydrogel is prepared using Ca 2+ -crosslinked sodium alginate incorporated with photosensitizer-loaded MnO 2 nanosheets and CaO 2 nanoparticles for O 2 self-sufficient PDT to eradicate biofilm infection. In our design, CaO 2 reacts with water to produce locally concentrated H 2 O 2 , which could be catalyzed by MnO 2 nanosheets (catalase-mimic nanozymes) to generate O 2 and greatly relieve the hypoxic conditions in the biofilm, thus significantly strengthening PDT efficacy. In vitro assays confirmed that the hybrid hydrogel not only exhibits high-performance bactericidal activity in combating both Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli but also shows great efficacy in eliminating biofilm infection. Moreover, benefiting from its good syringeability, the hybrid hydrogel is prone to fit irregular wounds and exhibits high efficiency in promoting wound healing in a biofilm-infected mice model. Besides, no obvious toxicity is detected in the hybrid hydrogel. Overall, we envision that our designed hydrogel could provide a prospective solution for combating biofilm-associated infections.

Objectives: The present study aimed to evaluate the desensitizing effect of toothpaste for sensitive teeth on patient tooth sensitivity and on bleaching efficacy of the 38% hydrogen peroxide bleaching agent used for in-office bleaching compared to a regular toothpaste in a randomized clinical trial., Methods and Materials: Forty-eight patients having maxillary right central incisors with darkness greater than A1 were selected for the present double-blind randomized clinical trial. Patients were randomly allocated into two groups: the placebo group, which used regular toothpaste, and the experimental group, which used sensitivity toothpaste. The intervention consisted of applying toothpaste with the aid of an individual tray for a period of 4 minutes daily, starting one week before the first bleaching session and interrupting use immediately after the second session. After allocation to one of the groups, individuals received in-office dental bleaching with a 40-minute application of 38% hydrogen peroxide for two sessions with an interval of one week. The incidence and intensity of sensitivity were assessed using a visual analogue scale and a numeric analogue scale. Sensitivity was measured immediately before each session, 1 hour, 24 hours, and 48 hours after each bleaching session and four weeks after the second bleaching session. Tooth shade was evaluated using a spectrophotometer and by comparison with the VITA Classical Shade Guide (Vita Zahnfabrik, Bad Säckingen, Germany). Tooth shade was evaluated before the first bleaching session, one week after the first bleaching session, one week after the second bleaching session and four weeks after the second bleaching session. Participants and professionals who performed the bleaching, shade, and sensitivity assessments were blinded to the group of patients they were treating or assessing. For the incidence of hypersensitivity, the results were evaluated by comparing the groups at different evaluation times with the Mann-Whitney test for comparison between groups, the Friedman test for repeated measures, and the Tukey test for comparison of times. Shade change on the guide was analyzed using the Mann-Whitney test for comparison between groups and the Wilcoxon test for comparison between times. Shade change by the spectrophotometer was analyzed using the t-test for comparison between groups and the paired t-test for comparison between times. All analyses were performed with a significance level of 5%., Results: There was no difference in the pattern of dental hypersensitivity between groups. For all shade measures, there was no difference between the bleaching results, and no statistically significant difference was observed between the study groups., Conclusion: The use of arginine-based desensitizing toothpaste did not interfere with the bleaching ability of hydrogen peroxide and was not effective in reducing the sensitivity caused by in-office tooth bleaching., (©Operative Dentistry, 2023.)

Enzymatic reactions can consume endogenous nutrients of tumors and produce cytotoxic species and are therefore promising tools for treating malignant tumors. Inspired by nature where enzymes are compartmentalized in membranes to achieve high reaction efficiency and separate biological processes with the environment, we develop liposomal nanoreactors that can perform enzymatic cascade reactions in the aqueous nanoconfinement of liposomes. The nanoreactors effectively inhibited tumor growth in vivo by consuming tumor nutrients (glucose and oxygen) and producing highly cytotoxic hydroxyl radicals (⋅OH). Co-compartmentalization of glucose oxidase (GOx) and horseradish peroxidase (HRP) in liposomes could increase local concentration of the intermediate product hydrogen peroxide (H 2 O 2 ) as well as the acidity due to the generation of gluconic acid by GOx. Both H 2 O 2 and acidity accelerate the second-step reaction by HRP, hence improving the overall efficiency of the cascade reaction. The biomimetic compartmentalization of enzymatic tandem reactions in biocompatible liposomes provides a promising direction for developing catalytic nanomedicines in antitumor therapy., (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Nanomaterial-based cancer therapy faces significant limitations due to the complex nature of the tumor microenvironment (TME). Starvation therapy is an emerging therapeutic approach that targets tumor cell metabolism using glucose oxidase (GOx). Importantly, it can provide a material or environmental foundation for other diverse therapeutic methods by manipulating the properties of the TME, such as acidity, hydrogen peroxide (H 2 O 2 ) levels, and hypoxia degree. In recent years, this cascade strategy has been extensively applied in nanoplatforms for ongoing synergetic therapy and still holds undeniable potential. However, only a few review articles comprehensively elucidate the rational designs of nanoplatforms for synergetic therapeutic regimens revolving around the conception of the cascade strategy. Therefore, this review focuses on innovative cascade strategies for GOx-based synergetic therapy from representative paradigms to state-of-the-art reports to provide an instructive, comprehensive, and insightful reference for readers. Thereafter, we discuss the remaining challenges and offer a critical perspective on the further advancement of GOx-facilitated cancer treatment toward clinical translation.

Purpose: To evaluate the effects of desensitizing MI Varnish (GC America) applied before or after bleaching on the mineral component of enamel and surface topography., Materials and Methods: The coronal portions of 10 freshly extracted bovine teeth were segmented for a total of 40 specimens. Enamel specimens obtained from each tooth were randomly divided into four groups (n = 10): Group A = no bleaching; Group B = bleaching with 40% hydrogen peroxide (HP); Group C = MI Varnish applied before bleaching; and Group D = MI Varnish applied after bleaching. The calcium (Ca) and phosphorus (P) levels of the specimens in each group were determined by energy dispersive spectroscopy (EDS). Morphologic changes were observed using scanning electron microscopy (SEM). One-way ANOVA and Tukey HSD tests were used for statistical analyses (α = .05)., Results: The mean Ca content of Group B was significantly lower than those of Groups A, C, and D (P < .05). The mean Ca content of Group C was significantly lower than that of Group A (P < .05). There was no significant difference in Ca content between the other groups (P > .05). The mean P content of Group A was significantly higher than those of Groups B to D (P < .05). There was no significant difference in P content between Groups B to D (P > .05)., Conclusions: Application of MI Varnish before or after in-office bleaching was effective in reducing mineral loss. However, applying MI Varnish after bleaching was more effective.

Objectives: This in vitro study aimed to evaluate the bleaching efficacy (BE), hydrogen peroxide penetration into the pulp chamber (HPP), and physical-chemical properties (concentration, pH, and viscosity) of in-office bleaching gels immediately and after 1 week of mixing., Methods and Materials: We randomly divided 49 premolars into seven groups: control (no bleaching) and the following in-office bleaching (Opalescence Boost 40%, Total Blanc One Step 35%, and Whiteness HP Blue 35%) applied at two storage times: immediately and after 1 week. We evaluated the BE using a digital spectrophotometer and the HPP through UV-Vis spectroscopy. We measured the initial concentration, pH, and viscosity using titration, a Digital pH meter and Rheometer, respectively. For statistical analysis, we used a twoway analysis of variance and Tukey and Dunnet tests (α=0.05)., Results: We observed higher BE and HPP for Opalescence Boost and Total Blanc One Step after 1 week of mixing than for Whiteness HP Blue (p<0.001). We observed a significantly lower initial concentration for Whiteness HP Blue 1 week after mixing compared to immediately (p=0.00001). All bleaching gels showed a decrease in pH after 1 week of mixing (p=0.00003). However, Total Blanc One Step had a lower pH at both evaluation times (p<0.001). Only Opalescence Boost maintained viscosity 1 week after mixing., Conclusions: Opalescence Boost was the only bleaching gel able to keep bleaching efficacy, with the same characteristics of permeability and physical- chemical properties after 1 week of mixing., (©Operative Dentistry, 2023.)

With the recent interest in the role of oxidative species/radicals in diseases, inorganic nanomaterials with redox activities have been extensively investigated for their potential use in nanomedicine. While many studies focusing on relieving oxidative stress to prevent pathogenesis and to suppress the progression of diseases have shown considerable success, another approach for increasing oxidative stress using nanomaterials to kill malignant cells has suffered from low efficiency despite its wide applicability to various targets. Chemodynamic therapy (CDT) is an emerging technique that can resolve such a problem by exploiting the characteristic tumour microenvironment to achieve high selectivity. In this review, we summarize the recent strategies and underlying mechanisms that have been used to improve the CDT performance using inorganic nanoparticles. In addition to the design of CDT agents, the effects of contributing factors, such as the acidity and the levels of hydrogen peroxide and antioxidants in the tumour microenvironment, together with their modulation and application in combination therapy, are presented. The challenges lying ahead of future clinical translation of this rapidly advancing technology are also discussed.

Great effort has been devoted to the synthesis of novel multi-target directed tacrine derivatives in the search of new treatments for Alzheimer's disease (AD). Herein we describe the proof of concept of MBA121, a compound designed as a tacrine-ferulic acid hybrid, and its potential use in the therapy of AD. MBA121 shows good β -amyloid (A β ) anti-aggregation properties, selective inhibition of human butyrylcholinesterase, good neuroprotection against toxic insults, such as A β 1-40 , A β 1-42 , and H 2 O 2 , and promising ADMET properties that support translational developments. A passive avoidance task in mice with experimentally induced amnesia was carried out, MBA121 being able to significantly decrease scopolamine-induced learning deficits. In addition, MBA121 reduced the A β plaque burden in the cerebral cortex and hippocampus in APP swe /PS1 ΔE9 transgenic male mice. Our in vivo results relate its bioavailability with the therapeutic response, demonstrating that MBA121 is a promising agent to treat the cognitive decline and neurodegeneration underlying AD.

Objectives: The aim of this systematic review was to evaluate the prognosis of at-home dental bleaching using low concentration bleaching products., Materials and Methods: This review was conducted was performed following the recommendations of the 2020 PRISMA statement and was registered in the International Prospective Register of Systematic Reviews (PROSPERO-CRD42022360530). The PICO question was "What is the prognosis of home teeth whitening treatment?". An advanced electronic search was made in three databases: PubMed, Web of Science, and Embase., Results: The database search led to the retrieval of 225 articles. After elimination of duplicate references, the titles and abstracts of the articles were analyzed with respect to the eligibility criteria, and 24 studies were included for the development of the systematic review., Conclusions: Most authors state that the color remains stable between 1 and 2.5 years regardless of the type of bleaching agent or the forms of administration, and color stability in cases of severe discolorations presents a higher degree of recurrence., Clinical Relevance: Given the growing demand for dental cosmetic treatments, the following systematic review may aid the clinician's continuing education and evidence-based practice by providing knowledge on the field of at-home dental bleaching agents and their long-term effects., (© 2023. The Author(s).)

The typical hypoxia of tumor microenvironments seriously affects the efficacy of starvation therapy (ST) and photodynamic therapy (PDT). Therefore, it is of great significance to prepare a multimodal combined therapy nanocomposite with the ability to relieve tumor hypoxia. It is an effective method to release oxygen into the tumor microenvironment using a nanoenzyme. In this work, two-dimensional black phosphorus nanosheets (BPNSs) were used as photothermal reagents and photosensitized agents due to the unique physical properties and also used as nano-carriers for the in situ reduction deposition of Au nanoparticles and fragmented MnO 2 coatings. Finally, polyethylene glycol was introduced to obtain the nanocomposite BP@Au@MnO 2 -PEG ( i.e. , AMGP). In the tumor microenvironment, MnO 2 can catalyze endogenous H 2 O 2 to produce oxygen, improving the effect of ST and PDT. H 2 O 2 generated via the catalytic oxidation of glucose by Au nanoparticles can continue to be used as the substrate catalyzed by MnO 2 . Meanwhile, black phosphorus nanosheets have excellent photothermal properties for photothermal treatment. The results of in vitro and in vivo experiments indicated that AMGP nanocomposites have good combined antitumor efficacies and biosafety.

Background and Objectives : Tooth whitening is a relatively conservative and effective option to treat discolored teeth. However, questions remain whether in-office or at-home tooth whitening products with short treatment durations are as effective and stable as products with longer treatment durations. Materials and Methods : Forty human third molars with intact enamel surfaces were divided into four groups of ten each, subjected to discoloration challenges with coffee for 60 h, and they were treated with four professional tooth whitening systems: two for take-home use-6% hydrogen peroxide for 30 min/d for a total of 7 h in 14 days (HP6), 10% carbamide peroxide for 10 h/d for 140 h in 14 days (CP10), as well as two for in-office use-35% HP for 10 min × 3 (HP35) for a total of 30 min and 40% HP for 20 min × 3 (HP40) for a total of 60 min. Teeth colors were assessed in the CIE L*a*b* color space with a spectrophotometer immediately and six months after whitening treatments. Surface roughness (Sa) for the treated and untreated enamel surfaces of the teeth in all groups were evaluated with a three-dimensional laser scanning microscope after six months. Results : No significant differences were found between HP6 and CP10 groups immediately after whitening (∆ E 10.6 ± 1.6 vs. 11.4 ± 1.7, p > 0.05) and at six months after treatments (∆ E 9.0 ± 1.9 vs. 9.2 ± 2.5, p > 0.05), or between HP35 and HP40 groups immediately after whitening (∆ E 5.9 ± 1.2 vs. 5.3 ± 1.7, p > 0.05) and at six months after treatments (∆ E 7.2 ± 1.6 vs. 7.7 ± 1.3, p > 0.05). The two at-home whitening systems achieved significantly better whitening outcomes than the two in-office products immediately after whitening ( p < 0.05). However, at six months after treatments, the differences between at-home and in-office treatments had narrowed significantly ( p > 0.05). There were no statistically significant differences with respect to the Sa values between the treated and untreated surfaces ( p > 0.05). Conclusions : Tooth whitening products in the same product category have similar whitening efficacies, despite significant differences in treatment durations (7 vs. 140 h, and 30 min vs. 60 min, respectively). Take-home products achieved better whitening outcomes than in-office products, but they needed 14 to 280 times longer treatment durations.

Carbon monoxide (CO) is an endogenous signaling molecule with broad therapeutic effects. Here, a multifunctional X-ray-triggered carbon monoxide (CO) and manganese dioxide (MnO 2 ) generation nanoplatform based on metal carbonyl and scintillating nanoparticles (SCNPs) is reported. Attributed to the radioluminescent characteristic of SCNPs, UV-responsive Mn 2 (CO) 10 is not only indirectly activated to release CO by X-ray but can also be degraded into MnO 2 . A high dose of CO can be used as a glycolytic inhibitor for tumor suppression; it will also sensitize tumor cells to radiotherapy. Meanwhile MnO 2 , as the photolytic byproduct of Mn 2 (CO) 10 , has both glutathione (GSH) depletion and Fenton-like Mn 2+ delivery properties to produce highly toxic hydroxyl radical (⋅OH) in tumors. Thus, this strategy can realize X-ray-activated CO release, GSH depletion, and ⋅OH generation for cascade cancer radiosensitization. Furthermore, X-ray-activated Mn 2+ in vivo demonstrates an MRI contrast effect, making it a potential theranostic nanoplatform., (© 2023 Wiley-VCH GmbH.)

Tissue plasminogen activator, aiming to restore cerebral blood flow (CBF), has been used for acute ischemic strokes in clinics; however, its narrow therapeutic time window remains a serious concern. To develop novel prophylactic drugs to alleviate cerebral ischemia/reperfusion injuries, ferulic acid derivative 012 (FAD012) was synthesized and showed comparable antioxidant properties to ferulic acid (FA) and probably possesses the potent ability to cross the blood-brain barrier. A more potent cytoprotective effect of FAD012 against H 2 O 2 -induced cytotoxicity in PC12 cells was also observed. In vivo toxicity was not observed in rats given a long-term oral administration of FAD012, indicating its good tolerability. A one-week-course oral administration of FAD012 significantly alleviated middle cerebral artery occlusion (MCAO)-induced cerebral ischemia/reperfusion injuries in rats, accompanied by the restoration of CBF and endothelial nitrogen oxide synthetase (eNOS) expression. Treatment with FAD012 significantly restored the cell viability and eNOS expression damaged by H 2 O 2 , used to mimic MCAO-triggered oxidative stress, in rat brain microvascular endothelial cells. Our findings suggested that FAD012 protected the viability of vascular endothelium and maintained eNOS expression, ultimately contributing to the restoration of CBF, and may provide a rationale for the development of FAD012 into an effective prophylactic drug for patients at high risk of stroke.

Covalent organic frameworks (COFs) have emerged as a promising platform for nanomedicine, while developing multifunctional COF nanoplatforms remains challenging due to the lack of efficient strategies for COF modification. Herein, we propose a nanozyme bridging (NZB) strategy for COF functionalization. Platinum nanoparticles (Pt NPs) as catalase mimics were in situ grown on the surface of COF NPs without reducing their drug loading capacity (CP), and thiol-terminated aptamer was further densely decorated onto CP NPs via a stable Pt-S bond (CPA). Pt nanozyme engineering and aptamer functionalization rendered the nanoplatform with excellent photothermal conversion, tumor targeting, and catalase-like catalytic performances. Using clinical-approved photosensitizer indocyanine green (ICG) as a model drug, we fabricated a nanosystem (ICPA) for tumor-targeted self-strengthening therapy. ICPA can effectively accumulate into tumor tissue and relieve the hypoxia microenvironment by decomposing the overexpressed H 2 O 2 and generating O 2 . Under monowavelength NIR light irradiation, the catalase-like catalytic and singlet oxygen generation activities of ICPA can be significantly strengthened, leading to admirable photocatalytic treatment effects against malignant cells as well as tumor-bearing mice in a self-strengthening manner., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Intracoronal bleaching is a minimally invasive procedure that was introduced into dentistry in the 19th century. The role of that procedure in enhancing the colour of teeth subjected to internal discolouration while being conservative made it extremely popular amongst dental professionals. Different materials and techniques have been utilized over the years attempting to obtain predictable long-term results while minimizing any associated risks. Contemporarily, bleaching agents are mainly based on peroxide-releasing compounds in different formulations and delivery systems. Different theories have been formulated on the bleaching mechanism of such agents, but the exact mechanism is yet to be proven. The effect of hydrogen peroxide-based bleaching agents on the organic structure of enamel and dentine has been extensively investigated to address the effects of bonding of resin-based restorative materials to hard tooth structure. Multiple case reports raised a concern about the contribution of intracoronal bleaching in developing invasive root resorption. Modification of intracoronal bleaching techniques was thus necessary to address such concerns. This review will provide a summary of the important aspects of intracoronal bleaching, focusing on how it applies to the contemporary clinical setting. © 2023 Australian Dental Association., (© 2023 The Authors. Australian Dental Journal published by John Wiley & Sons Australia, Ltd on behalf of Australian Dental Association.)

It remains an extreme challenge to develop multifunctional drug delivery systems with tumor specificity and a tumor microenvironment (TME) remodeling ability for achieving improved chemotherapy against malignant tumors. Herein, we report the design of diselenide-crosslinked poly( N -vinylcaprolactam) (PVCL) nanogels (NGs) co-loaded with gold (Au) nanoparticles (NPs) and methotrexate (MTX) as a multifunctional nanoplatform (for short, MTX/Au@PVCL NGs) for improved chemotherapy and computed tomography (CT) imaging of tumors. The designed MTX/Au@PVCL NGs show excellent colloidal stability under physiological conditions, while dissociating rapidly to release the incorporated Au NPs and MTX in the H 2 O 2 -abundant and slightly acidic TME. The responsive release of Au NPs and MTX effectively induces the apoptosis of cancer cells and prevents DNA replication, together contributing to the repolarization of macrophages from protumor M2-like to antitumor M1-like phenotype in vitro . The MTX/Au@PVCL NGs also enable the remodeling of tumor-associated macrophages to the M1-like phenotype in vivo in a subcutaneous mouse melanoma model, which increases the recruitment of effector T lymphocytes and reduces the content of immunosuppressive regulatory T cells to achieve synergistically enhanced antitumor efficacy when combined with MTX-mediated chemotherapy. Moreover, the MTX/Au@PVCL NGs can be used for Au-mediated CT imaging of tumors. The thus developed NG platform shows great promise as an updated nanomedicine formulation for immune modulation-enhanced tumor chemotherapy under the guidance of CT imaging.

Chemodynamic therapy (CDT), a novel therapeutic approach based on Fenton (Fenton-like) reaction, has been widely employed for tumor therapy. This approach utilizes Fe, Cu, or other metal ions (Mn, Zn, Co, or Mo) to react with the excess hydrogen peroxide (H 2 O 2 ) in tumor microenvironments (TME), and form highly cytotoxic hydroxyl radical (˙OH) to kill cancer cells. Recently, nanoscale metal-organic frameworks (nMOFs) have attracted considerable attention as promising CDT agents with the rapid development of cancer CDT. This review focuses on summarizing the latest advances (2020-2022) on the design of nMOFs as nanomedicine for CDT or combination therapy of CDT and other therapies. The future development and challenges of CDT are also proposed based on recent progress. Our group hopes that this review will enlighten the research and development of nMOFs for CDT.

Objectives: To compare the bleaching efficacy and tooth sensitivity (TS) of 4% hydrogen peroxide (HP) in adults using a continuous or fractioned protocol., Methods and Materials: A single-blind randomized controlled trial with a parallel design was conducted. Eighty-six patients with upper canines A2 or darker were submitted to bleaching with 4% HP gel for three weeks after random allocation into the fractioned protocol (two 30-minute daily applications) or continuous protocol (single one-hour application). We evaluated the color change at baseline, weekly, and 30 days after the bleaching using Vita Classical and Vita Bleachedguide using the units of shade guides (SGU) and by spectrophotometer using CIELab 1976 (ΔEab) and CIEDE 2000 formulas (ΔE00), as well as Whiteness Index (ΔWID). We assessed the absolute risk of TS with a visual analog scale (VAS) and numeric rating scale (NRS). Color changes in each recall were compared with the Student t-test. The risk of TS was evaluated by the Chi-square test, and the intensity by Mann-Whitney test (NRS) and Student t-test (VAS)., Results: The mean difference for the ΔSGU Vita Classical (0.5; 95% CI: -0.5 to 1.5), ΔSGU Vita Bleachedguide (-0.4; 95% CI: -1.5 to 0.7), ΔEab (1.4; 95% CI: -0.1 to 2.9), ΔE00 (0.6; 95% CI: -0.4 to 1.6), and ΔWID (-3.2; 95% CI: -7.3 to 0.9) after three weeks of bleaching was not clinically or statistically significant (p>0.10). The absolute risk of TS was 44% (95% CI: 30-58%) and 46% (95% CI: 32-61%) in the fractioned and continuous protocols, respectively (RR=1.0; 95% CI: 0.6 to 1.5; p>0.91)., Conclusion: A fractioned bleaching protocol with 4% HP (30 minutes twice daily) did not increase the whitening degree nor affect the risk and intensity of TS when compared with the one-hour continuous protocol., (©Operative Dentistry, 2023.)

Objective: The aim of this study was to compare the clinical efficacy of at-home, in-office, and combined bleaching regimens., Methods: Forty-eight participants were recruited and randomly divided into four groups based on the bleaching regimen (n=12) as follows: 1) at-home bleaching using 10% carbamide peroxide (Opalescence PF 10%, Ultradent) for 14 days (HB); 2) two sessions of in-office bleaching using 40% hydrogen peroxide (Opalescence BOOST PF 40%, Ultradent) with a one-week interval (OB); 3) one session of in-office bleaching followed by at-home bleaching for seven days (OHB); and 4) at-home bleaching for seven days followed by one session of in-office bleaching (HOB). Tooth color was measured using a spectrophotometer (Easyshade, Vita ZahnFabrik) at baseline (T0), day 8 (T1), day 15 (T2), and day 43 (T3, four weeks after the end of the bleaching treatment). The color data were calculated using the CIEDE2000 (ΔE00) and whiteness index for dentistry (WID) formulas. Tooth sensitivity (TS) was recorded using a visual analogue scale (VAS) for 16 days. Data were analyzed by one-way analysis of variance (ANOVA) and the Wilcoxon signed-rank test (α=0.05)., Results: All bleaching regimens resulted in a significant increase in WID values (all p<0.05), while no significant differences in WID and ΔWID values were found among the different groups at each time point (all p>0.05). Significant differences in ΔE00 values were observed between T1 and T3 for all groups (all p<0.05), while no significant differences in ΔE00 values were found among the different groups at any time point (all p>0.05). Significantly lower TS values were observed in the HB group than in the OB and HOB groups (p=0.006 and p=0.001, respectively)., Conclusions: All bleaching regimens resulted in great color improvement, and different regimens led to similar color changes at any of the evaluation time points. The sequence of treatments applying in-office bleaching or at-home bleaching did not affect the bleaching efficacy. The in-office bleaching and combined bleaching regimens yielded a higher intensity of TS than did at-home bleaching., (©Operative Dentistry, 2023.)

Background: Reactive oxygen species (ROS) are powerful weapons for various anticancer therapies. However, high glutathione (GSH) levels in cancer cells can significantly reduce the efficacy of such therapies. Methods: In this study, pH-responsive fluorescein-encapsulated zeolitic imidazolate framework-8 nanoparticles were synthesized for ROS-mediated combination therapy. Results: Upon blue light activation, fluorescein displayed a high singlet oxygen photogeneration ability for photodynamic therapy. Concurrently, accumulated Zn 2+ from degraded zeolitic imidazolate framework-8 stimulated simultaneous ROS generation and GSH depletion, thereby successfully inducing chemodynamic therapy. This triggered a cascade of photo-physical and chemical processes culminating in the localized generation of ROS, ultimately breaking the intracellular redox equilibrium. Conclusion: This nanoformulation can potentially be used for light-activated ROS-mediated therapy for the management of superficial tumors.

Objectives: This study aimed to observe the color rebound and rebound rates of non-pulp discolored teeth within 1 year after routine internal bleaching to guide clinical practice and prompt prognosis., Methods: In this work, the efficacy of bleaching was observed in 20 patients. The color of discolored teeth was measured by using a computerized colorimeter before bleaching; immediately after bleaching; and at the 1st, 3rd, 6th, 9th, and 12th months after bleaching. The L*, a*, and b* values of the color of cervical, mesial, and incisal parts of the teeth were obtained, and the color change amounts ΔE*, ΔL*, Δa*, and Δb* were calculated. The overall rebound rate (P*) and the color rebound velocity (V*) were also analyzed over time., Results: In 20 patients following treatment, the average ΔE* of tooth color change was 14.99. After bleaching, the neck and middle of the teeth ΔE* and ΔL* decreased in the 1st, 3rd, 6th, 9th, and 12th months, and the differences were statistically significant. Meanwhile, from the 9th month after bleaching, the rebound speed was lower than that in the 1st month, and the difference was statistically significant. The incisal end of the tooth ΔE* and ΔL* decreased in the 6th, 9th, and 12th months after bleaching, and the differences were statistically significant. No significant difference was found in the rebound speed between time points. However, this rate settled after the 9th month, with an average color rebound rate of 30.11% in 20 patients., Conclusions: The results indicated that internal bleaching could cause a noticeable color change on pulpless teeth. The color rebound after bleaching was mainly caused by lightness (L*), which gradually decreased with time, and it was slightly related to a* and b*. The color of the teeth after internal bleaching rebounded to a certain extent with time, but the color rebound speed became stable from the 9th month. Clinically, secondary internal bleaching can be considered at this time according to whether the colors of the affected tooth and the adjacent tooth are coordinated and depending on the patient's needs.