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Photodynamic therapy (PDT) and photothermal therapy (PTT) are both promising therapeutic approaches for cancer. Unfortunately, the anticancer efficiency of PDT is restricted by the hypoxic tumor microenvironment and the performance of the photosensitizer (PS) while the efficiency of PTT is limited by the penetration depth of NIR light, making it difficult to further improve the efficiency of the treatment. In this paper, we strategically proposed a multifunctional nano-platform based on g-C 3 N 4 and loaded with CuS and MnO 2 nanoparticals. Interestingly, the obtained F127@CNs-CuS/MnO 2 nano-platform with high singlet oxygen quantum yield and excellent photothermal performance were used in synergistic PTT and PDT therapy to cope with the limitation of single mode cancer treatment under irradiation and has greatly improved the treatment effect. Additionally, MnO 2 nanoparticles loaded on the CNs surface could not only generate oxygen to ameliorate hypoxia in the tumor environment by reacting with H 2 O 2 in tumor cells, but also react with the over-expressed reduced glutathione (GSH) in cancer cells to further improve the synergistic therapeutic effect. In the in vitro hepatocarcinoma cell inactivation experiment, the maximum cell inactivation efficiency of the PDT, PTT and PDT/PTT synergistic treatment group reached at 65% (F127@CNs-MnO 2 ), 69.2% (CNs-MnO 2 ) and 88.6% (F127@CNs-MnO 2 ) respectively, which means that the F127@CNs-CuS/MnO 2 -mediated PTT/PDT synergy anticancer treatment was more effective than single mode therapy. In summary, the innovative multifunctional nanoplatform F127@CNs-CuS/MnO 2 used for synergistic PTT and PDT treatment has greatly improved the inactivation efficiency of cancer cells and has provided a new scheme for the treatment of hypoxic tumors., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Type 2 diabetes mellitus (T2DM) is commonly associated with hyperglycemia, dyslipidemia, oxidative stress and inflammation which are well known cardiovascular risk factors. Pomegranate peel polyphenols have a proven hypolipemic, antioxidant and anti-inflammatory activity. However, there is a lack of clinical studies that would confirm its antioxidant and anti-inflammatory effects in diabetic patients. The potential of pomegranate peel extract (PoPEx) to counteract inflammation and oxidative stress in T2DM patients was investigated. For this purpose, a randomized, double-blind placebo-controlled study involving adult T2DM patients treated with PoPEx or placebo for eight-weeks was conducted., Methods: Patients were randomly divided into two groups: the first group (n = 30) received capsules containing PoPEx 250 mg twice daily, while the placebo group (n = 30) received placebo capsules twice daily. Plasma concentration of inflammatory factors (interleukin 6 (IL-6), tumor necrosis factor α (TNF-α) and high sensitivity C reactive protein (hsCRP)), oxidative stress biomarkers (thiobarbituric acid reactive substances (TBARS), nitrites (NO2-), superoxide anion radical (O2-), hydrogen peroxide (H2O2), total antioxidant capacity (TAC)), homocysteine and lipid profile were analyzed., Results: The PoPEx treatment showed a significant reduction of inflammatory factors (IL-6, TNF-α, hsCRP), oxidative stress biomarkers (TBARS, NO2-, O2-) and homocysteine, while the TAC was increased. Moreover, a significant improvement in lipid profile was observed in the PoPEx group. Additional analysis showed a significant inverse correlation between the decrements of all measured inflammatory markers and TAC in the PoPEx group., Conclusions: The study demonstrated that eight-week-long PoPEx administration had favorable effects on inflammatory status and oxidative stress biomarkers in diabetic patients., Competing Interests: The authors declare no conflict of interest. Vladimir Jakovljević and Dragan M Djuric are serving as Guest editors of this journal. We declare that Vladimir Jakovljević and Dragan M Djuric had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Peter A. McCullough., (© 2022 The Author(s). Published by IMR Press.)

Clinical applications of nanozyme-initiated chemodynamic therapy (NCDT) have been severely limited by the poor catalytic efficiency of nanozymes, insufficient endogenous hydrogen peroxide (H 2 O 2 ) content, and its off-target consumption. Herein, the authors developed a hollow mesoporous Mn/Zr-co-doped CeO 2 tandem nanozyme (PHMZCO-AT) with regulated multi-enzymatic activities, that is, the enhancement of superoxide dismutase (SOD)-like and peroxidase (POD)-like activities and inhibition of catalase (CAT)-like activity. PHMZCO-AT as a H 2 O 2 homeostasis disruptor promotes H 2 O 2 evolution and restrains off-target elimination of H 2 O 2 to achieve intensive NCDT. PHMZCO-AT with SOD-like activity catalyzes endogenous superoxide anion (O 2 •- ) into H 2 O 2 in the tumor region. The suppression of CAT activity and depletion of glutathione by PHMZCO-AT largely weaken the off-target decomposition of H 2 O 2 to H 2 O. Elevated H 2 O 2 is then catalyzed by the downstream POD-like activity of PHMZCO-AT to generate toxic hydroxyl radicals, further inducing tumor apoptosis and death. T 1 -weighted magnetic resonance imaging and X-ray computed tomography imaging are also achieved using PHMZCO-AT due to the existence of paramagnetic Mn 2+ and the high X-ray attenuation ability of elemental Zr, permitting in vivo tracking of the therapeutic process. This work presents a typical paradigm to achieve intensive NCDT efficacy by regulating multi-enzymatic activities of nanozymes to perturb the H 2 O 2 homeostasis., (© 2022 Wiley-VCH GmbH.)

Background: Spinal cord motor neurons (MNs) from human iPS cells (iPSCs) have wide applications in disease modeling and therapeutic development for amyotrophic lateral sclerosis (ALS) and other MN-associated neurodegenerative diseases. We need highly efficient MN differentiation strategies for generating iPSC-derived disease models that closely recapitulate the genetic and phenotypic complexity of ALS. An important application of these models is to understand molecular mechanisms of action of FDA-approved ALS drugs that only show modest clinical efficacy. Novel mechanistic insights will help us design optimal therapeutic strategies together with predictive biomarkers to achieve better efficacy., Methods: We induce efficient MN differentiation from iPSCs in 4 days using synthetic mRNAs coding two transcription factors (Ngn2 and Olig2) with phosphosite modification. These MNs after extensive characterization were applied in electrophysiological and neurotoxicity assays as well as transcriptomic analysis, to study the neuroprotective effect and molecular mechanisms of edaravone, an FDA-approved drug for ALS, for improving its clinical efficacy., Results: We generate highly pure and functional mRNA-induced MNs (miMNs) from control and ALS iPSCs, as well as embryonic stem cells. Edaravone alleviates H 2 O 2 -induced neurotoxicity and electrophysiological dysfunction in miMNs, demonstrating its neuroprotective effect that was also found in the glutamate-induced miMN neurotoxicity model. Guided by the transcriptomic analysis, we show a previously unrecognized effect of edaravone to induce the GDNF receptor RET and the GDNF/RET neurotrophic signaling in vitro and in vivo, suggesting a clinically translatable strategy to activate this key neuroprotective signaling. Notably, edaravone can replace required neurotrophic factors (BDNF and GDNF) to support long-term miMN survival and maturation, further supporting the neurotrophic function of edaravone-activated signaling. Furthermore, we show that edaravone and GDNF combined treatment more effectively protects miMNs from H 2 O 2 -induced neurotoxicity than single treatment, suggesting a potential combination strategy for ALS treatment., Conclusions: This study provides methodology to facilitate iPSC differentiation and disease modeling. Our discoveries will facilitate the development of optimal edaravone-based therapies for ALS and potentially other neurodegenerative diseases., (© 2022. The Author(s).)

The outcome of sonodynamic immunotherapy is significantly limited by tumor hypoxia. To overcome this obstacle, one common solution is to catalyze the conversion of endogenous H 2 O 2 into O 2 . However, the effectiveness of this strategy is limited by the insufficient concentration of H 2 O 2 in the tumor microenvironment (TME). Herein, we developed a H 2 O 2 economizer for on-demand O 2 supply and sonosensitizer-mediated reactive oxygen species production during ultrasound activation, thereby alleviating hypoxia-associated limitations and augmenting the efficacy of sonodynamic immunotherapy. Methods: The H 2 O 2 economizer is constructed by electrostatic adsorption and π-π interactions between the Fe-doped polydiaminopyridine (Fe-PDAP) nanozyme and chlorin e6. By employing a biomimetic engineering strategy with cancer cell membranes, we addressed the premature leakage issue and increased tumor-site accumulation of nanoparticles (membrane-coated Fe-PDAP/Ce6, MFC). Results: The prepared MFC could significantly attenuate the catalytic activity of Fe-PDAP by reducing their contact with H 2 O 2 . Ultrasound irradiation promoted MFC dissociation and the exposure of Fe-PDAP for a more robust O 2 supply. Moreover, the combination of MFC-enhanced sonodynamic therapy with anti-programmed cell death protein-1 antibody (aPD-1) immune checkpoint blockade induced a strong antitumor response against both primary tumors and distant tumors. Conclusion: This as-prepared H 2 O 2 economizer significantly alleviates tumor hypoxia via reducing H 2 O 2 expenditure and that on-demand oxygen-elevated sonodynamic immunotherapy can effectively combat tumors., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

This study aimed to evaluate the effect of the bleaching gel application site on chromatic changes and postoperative sensitivity in teeth. Thirty patients were selected and allocated to three groups (n=10 per group), according to the location of the gel: GI, cervical application; GII, incisal application; and GIII, total facial. The amount and time of application of the 35% hydrogen peroxide (H2O2) gel were standardized. Color changes were analyzed by ΔE and Wid (bleaching index), using the values obtained in the readings conducted on a digital spectrophotometer in the cervical (CRs) and incisal regions (IRs) of the teeth. Spontaneous sensitivity was assessed using the questionnaire, and the stimulated sensitivity caused by the thermosensory analysis (TSA). The analysis occurred in five stages: baseline, after the first, second, and third whitening sessions (S), and 14 days after the end of the whitening, using the linear regression statistical model with mixed effects and post-test by orthogonal contrasts (p<0.05). Although the IR was momentarily favored, at the end of the treatment, the restriction of the application site provided results similar to those obtained when the gel was applied over the entire facial surface. Regarding sensitivity, only the GI showed spontaneous sensitivity. In the TSA, GIII had less influence on the threshold of the thermal sensation. It was concluded that the chromatic alteration does not depend on the gel application site. Spontaneous sensitivity is greater when the gel is concentrated in the cervical region (CR), and the teeth remain sensitized by thermal stimuli even after 14 days., (©Operative Dentistry, 2022.)

Atherosclerosis is an important pathological basis for cardiovascular disease. Thus, the treatment of atherosclerosis can effectively improve the prognosis and reduce the mortality of cardiovascular diseases. In this study, we developed simvastatin acid (SA)-loaded cross-linked dendrimer nanoparticles (SA PAM) that were adsorbed to the surface of red blood cells (RBCs) to obtain SA PAM@RBCs, a ROS and shear stress dual response drug delivery system for the treatment of atherosclerosis. SA PAM could continuously release SA in an H 2 O 2 -triggered manner, and effectively eliminate excessive H 2 O 2 in LPS-stimulated RAW 264.7 cells, achieving the target of using the special microenvironment at the plaque to release drugs. At the same time, the shear sensitive model also proved that only 12.4% of SA PAM detached from the RBCs under low shear stress (20 dynes per cm 2 ), while 61.3% SA PAM desorbed from the RBCs under a high shear stress (100 dynes per cm 2 ) stimulus, revealing that SA PAM could desorb in response to the shear stress stimulus. Both the FeCl 3 model and ApoE -/- model showed that SA PAM@RBCs had better therapeutic effects than free SA, and with excellent safety in vivo . Therefore, a biomimetic drug delivery system with dual sensitivity to ROS and shear stress would become a promising strategy for the treatment of atherosclerosis.

Objective: To evaluate the effect of combined systemic administration of paracetamol 500 mg/codeine phosphate 30 mg (PACO) and postoperative topical application of a bioactive desensitizer on in-office bleaching sensitivity and tooth color change., Materials and Methods: A randomized, triple-blind, split-mouth clinical trial was conducted. Forty volunteers ingested PACO (n = 20) or placebo (PLA) (n = 20). Their left/right hemiarches received topical application of a bioactive desensitizer [Nano-P™(NP)] and prophylactic paste (PAS), generating four treatment approaches: PACO/NP, PACO/PAS, PLA/NP, and PLA/PAS. Two bleaching sessions (35% hydrogen peroxide) were performed, and the PAS/NP were applied after the procedure. Sensitivity was obtained since the first bleaching session up to 7 days post-bleaching. The color change was evaluated using CIEDE2000 and whiteness index parameters up to 7 days post-bleaching. Data were analyzed using one- and two-way ANOVA/Tukey post hoc tests (p < 0.05)., Results: The PLA/PAS showed a sensitivity average of at least two times higher than the PACO/NP. The treatment approaches promoted statistically similar bleaching patterns (p > 0.05)., Conclusion: The combined approach of systemic administration of PACO and postoperative topical application of NP reduced the level of in-office bleaching sensitivity without jeopardizing hydrogen peroxide efficacy., Clinical Relevance: Professionals can adopt the combined approach of systemic administration of analgesic/anti-inflammatory drugs and topical application of a bioactive desensitizer for decreased bleaching sensitivity caused by 35% hydrogen peroxide in-office., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: In the present study, the authors investigated the effects of selenium on inflammation, hyaluronan production, and oxidative stress in primary cultured orbital fibroblasts of patients with Graves ophthalmopathy (GO)., Methods: Orbital adipose/connective tissue specimens were obtained during the course of orbital surgery for patients with GO (n = 7) and other noninflammatory problems (n = 5). After incubation with various concentrations of sodium selenite for 48 hours, supernatants from primary cultures were collected. Hyaluronan and cytokine levels were measured using commercially available enzyme-linked immunosorbent assay kits. To determine the effect of selenium on reactive oxygen species (ROS) production stimulated by H2O2 (100 μM) for 30 minutes, the cells were pretreated with various concentrations of sodium selenite for 60 minutes., Results: Interleukin (IL)-6 and tumor necrosis factor-alpha levels were significantly higher in orbital fibroblasts of patients with GO than in orbital fibroblasts of control patients. Hyaluronan production was suppressed by selenium in cultured orbital fibroblasts of patients with GO. Inflammatory cytokines such as IL-1α, IL-8, and tumor necrosis factor-alpha were suppressed by selenium in cultured orbital fibroblasts of patients with GO. IL-1β and IL-6 were not suppressed by selenium in cultured orbital fibroblasts of patients with GO. Selenium pretreatment reduced intracellular ROS generation stimulated by H2O2 in cultured orbital fibroblasts of patients with GO., Conclusions: In conclusion, hyaluronan production, inflammatory cytokines, and intracellular ROS generation were suppressed by selenium in cultured orbital fibroblasts of patients with GO. Several inflammatory cytokines may be suppressed by selenium in cultured orbital fibroblasts of patients with GO. This study provide the basis for use of selenium in the treatment of GO., Competing Interests: The authors have no financial or conflicts of interest to disclose., (Copyright © 2021 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Objectives: The case report describes a minimally invasive, multidisciplinary approach to a single discolored anterior tooth, with internal bleaching using traditional Japanese paper (Washi), a gingivoplasty with a three-dimensional (3D) printed surgical guide, and ultrathin feldspathic porcelain veneers., Clinical Consideration: The patient's primary concern was improving her smile. After clinical evaluation, internal tooth bleaching for the discolored tooth and gingivoplasty with restoration of the maxillary anterior six teeth and first premolars was recommended. The internal tooth whitening was accomplished with sodium perborate mixed with 30% hydrogen peroxide impregnated in Washi and sealed in the root canal with glass ionomer. Once the tooth bleaching was completed, the 3D printed surgical guide was placed in the patient's maxillary anterior region and used to guide soft tissue recontouring. After 6 months, ultrathin feldspathic porcelain veneers were placed., Conclusion: Well-planned restorative procedures combining internal tooth bleaching using Washi, gingivoplasty performed with electrosurgery using a 3D printed surgical guide, and ultrathin feldspathic porcelain veneers can achieve the desired results in the esthetic zone and remain successful for 4 years., (©Operative Dentistry, 2021.)

Objectives: A systematic review and network meta-analysis were performed to answer the following research question: Are there differences in the risk and the intensity of tooth sensitivity (TS) among eight light activation systems for in-office bleaching in adults?, Methods: Randomized controlled trials (RCTs) that compared at least two different in-office bleaching light activations were included. The risk of bias (RoB) was evaluated with the RoB tool version 1.0 from the Cochrane Collaboration tool. A random-effects Bayesian mixed treatment comparison (MTC) model was used independently for high- and low-concentration hydrogen peroxide. The certainty of the evidence was evaluated using the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) approach. A comprehensive search was performed in PubMed, Bridge Base Online (BBO), Latin American and Caribbean Health Sciences Literature database (LILACS), Cochrane Library, Scopus, Web of Science, and grey literature without date and language restrictions on April 23, 2017 (updated on September 26, 2019). Dissertations and theses, unpublished and ongoing trials registries, and IADR (International Association for Dental Research) abstracts (2001-2019) were also searched., Results: After title and abstract screening and the removal of duplicates, 32 studies remained. Six were considered to be at low RoB, three had high RoB, and the remaining had an unclear RoB. The MTC analysis showed no significant differences among the treatments in each network. In general, the certainty of the evidence was graded as low due to unclear RoB and imprecision., Conclusion: There is no evidence that the risk and intensity of TS are affected by light activation during in-office bleaching., (©Operative Dentistry, 2021.)

Although multimethod therapy has shown great promise for effective cancer treatment, it is still a great challenge to develop simple and effective strategies to construct multifunctional therapeutic reagents. According to the characteristics of the tumor microenvironment, such as a mild acidic environment and overexpression of H 2 O 2 , an intelligent therapeutic reagent with photoacoustic (PA) imaging-guided photothermal therapy, chemodynamic therapy, and in situ chemotherapy was constructed by simply loading disulfiram (DSF) in a Cu-based porous metal-organic framework (HKUST-1). The resultant material DFS@HKUST-1 shows near-infrared adsorption around 600-900 nm and effective photoacoustic imaging properties and photothermal conversion efficiency upon 808 nm irradiation. Besides, after DFS@HKUST-1 is enriched in the tumor, the acidic environment of the tumor will slowly trigger the decomposition of HKUST-1, leading to the release of Cu 2+ ions to react with DSF and endogenous H 2 O 2 to generate the Cu/DSF complex (CuET) and cytotoxic •OH for chemotherapy and chemodynamic therapy, respectively. Therefore, DFS@HKUST-1 can serve as a promising tumor microenvironment response therapeutic reagent for photoacoustic imaging-guided multimethod therapy.

This retrospective descriptive study estimates cage-level mortality distributions after six immediate delousing methods: thermal, mechanical, hydrogen peroxide, medicinal, freshwater and combination of medicinal treatments. We investigated mortality patterns associated with 4 644 delousing treatment of 1 837 cohorts of farmed Atlantic salmon (Salmo salar) stocked in sea along the Norwegian coast between 2014 and 2017. The mortality is expressed as mortality rates. We found distributions of delta mortality rate within 1, 7 and 14 days after all six delousing treatments, using mortality rate within 7 days before treatments as baseline. The results show that we can expect increased mortality rates after all six delousing methods. The median delta mortality rates after thermal and mechanical delousing are 5.4 and 6.3 times higher than medicinal treatment, respectively, for the 2017 year-class. There is a reduction in the delta median mortality for thermal and freshwater delousing from 2015 to 2019. There is a wide variability in the mortality rates, in particular for thermal delousing. Our results suggest that the variability in delta mortality for thermal delousing has been reduced from the 2014 to 2017 year-class, indicating an improvement of the technique. However, a significant increase in the number of thermal treatments from 14 in 2015 to 738 in 2018 probably contributes to the overall increased mortality in Norwegian salmon farming., (© 2021 The Authors. Journal of Fish Diseases published by John Wiley & Sons Ltd.)

Aspirin eugenol ester (AEE) is a new pharmaceutical compound esterified by aspirin and eugenol, which has anti-inflammatory, antioxidant, and other pharmacological activities. This study is aimed at identifying the protective effect of AEE against H 2 O 2 -induced apoptosis in rat adrenal pheochromocytoma PC12 cells and the possible mechanisms. The results of cell viability assay showed that AEE could increase the viability of PC12 cells stimulated by H 2 O 2 , while AEE alone had no significant effect on the viability of PC12 cells. Compared with the control group, the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were significantly decreased, and the content of malondialdehyde (MDA) was significantly increased in the H 2 O 2 group. By AEE pretreatment, the level of MDA was reduced and the levels of SOD, CAT, and GSH-Px were increased in H 2 O 2 -stimulated PC12 cells. In addition, AEE could reduce the apoptosis of PC12 cells induced by H 2 O 2 via reducing superoxide anion, intracellular ROS, and mitochondrial ROS (mtROS) and increasing the levels of mitochondrial membrane potential ( ΔΨ m). Furthermore, the results of western blotting showed that compared with the control group, the expression of p-PI3K, p-Akt, and Bcl-2 was significantly decreased, while the expression of Caspase-3 and Bax was significantly increased in the H 2 O 2 group. In the AEE group, AEE pretreatment could upregulate the expression of p-PI3K, p-Akt, and Bcl-2 and downregulate the expression of Caspase-3 and Bax in PC12 cells stimulated with H 2 O 2 . The silencing of PI3K with shRNA and its inhibitor-LY294002 could abrogate the protective effect of AEE in PC12 cells. Therefore, AEE has a protective effect on H 2 O 2 -induced PC12 cells by regulating the PI3K/Akt signal pathway to inhibit oxidative stress., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Zhen-Dong Zhang et al.)

Hydrogen peroxide (H 2 O 2 ) is used to treat sea lice infections of farmed salmonids in the Atlantic and Pacific Oceans and issues with resistance to this treatment, and others are a major threat to the sustainability of the industry. The objectives of this study were to determine how H 2 O 2 exposure affects survival and antioxidant-related gene expression in salmon lice (Lepeophtheirus salmonis) collected from the Bay of Fundy, New Brunswick. The maximum recommended dose of H 2 O 2 is 1,800 mg/L, while the EC 50 values (with 95% CI) for the population tested were 1,486 (457, 2,515) mg/L for males and 2,126 (984, 3,268) mg/L for females. Neither temperature nor pretreatment with emamectin benzoate (EMB) impacted survival after H 2 O 2 exposure. RT-qPCR was performed on pre-adult sea lice exposed to H 2 O 2 and showed that four genes classically involved in the response to oxidative stress were unchanged between treated and control groups. Seven genes were found to be significantly upregulated in males and one in females. This is the first report on the efficacy and molecular responses of Atlantic Canada sea lice to H 2 O 2 treatment., (© 2020 John Wiley & Sons Ltd.)

Background: Critical shortages of personal protective equipment, especially N95 respirators, during the coronavirus disease 2019 (COVID-19) pandemic continues to be a source of concern. Novel methods of N95 filtering face-piece respirator decontamination that can be scaled-up for in-hospital use can help address this concern and keep healthcare workers (HCWs) safe., Methods: A multidisciplinary pragmatic study was conducted to evaluate the use of an ultrasonic room high-level disinfection system (HLDS) that generates aerosolized peracetic acid (PAA) and hydrogen peroxide for decontamination of large numbers of N95 respirators. A cycle duration that consistently achieved disinfection of N95 respirators (defined as ≥6 log10 reductions in bacteriophage MS2 and Geobacillus stearothermophilus spores inoculated onto respirators) was identified. The treated masks were assessed for changes to their hydrophobicity, material structure, strap elasticity, and filtration efficiency. PAA and hydrogen peroxide off-gassing from treated masks were also assessed., Results: The PAA room HLDS was effective for disinfection of bacteriophage MS2 and G. stearothermophilus spores on respirators in a 2,447 cubic-foot (69.6 cubic-meter) room with an aerosol deployment time of 16 minutes and a dwell time of 32 minutes. The total cycle time was 1 hour and 16 minutes. After 5 treatment cycles, no adverse effects were detected on filtration efficiency, structural integrity, or strap elasticity. There was no detectable off-gassing of PAA and hydrogen peroxide from the treated masks at 20 and 60 minutes after the disinfection cycle, respectively., Conclusion: The PAA room disinfection system provides a rapidly scalable solution for in-hospital decontamination of large numbers of N95 respirators during the COVID-19 pandemic.

Cold atmospheric plasma (CAP) and plasma-treated liquids (PTLs) have recently become a promising option for cancer treatment, but the underlying mechanisms of the anti-cancer effect are still to a large extent unknown. Although hydrogen peroxide (H2O2) has been recognized as the major anti-cancer agent of PTL and may enable selectivity in a certain concentration regime, the co-existence of nitrite can create a synergistic effect. We develop a mathematical model to describe the key species and features of the cellular response toward PTL. From the numerical solutions, we define a number of dependent variables, which represent feasible measures to quantify cell susceptibility in terms of the H2O2 membrane diffusion rate constant and the intracellular catalase concentration. For each of these dependent variables, we investigate the regimes of selective versus non-selective, and of synergistic versus non-synergistic effect to evaluate their potential role as a measure of cell susceptibility. Our results suggest that the maximal intracellular H2O2 concentration, which in the selective regime is almost four times greater for the most susceptible cells compared to the most resistant cells, could be used to quantify the cell susceptibility toward exogenous H2O2. We believe our theoretical approach brings novelty to the field of plasma oncology, and more broadly, to the field of redox biology, by proposing new ways to quantify the selective and synergistic anti-cancer effect of PTL in terms of inherent cell features.

Tumors of the abdominal cavity, such as colorectal, pancreatic and ovarian cancer, frequently metastasize into the peritoneum. Large numbers of metastatic nodules hinder curative surgical resection, necessitating lavage with hyperthermic intraperitoneal chemotherapy (HIPEC). However, HIPEC not only causes severe side effects but also has limited therapeutic efficacy in various instances. At the same time, the age of immunotherapies such as biological agents, checkpoint‑ inhibitors or immune‑cell therapies, increasingly emphasizes the critical role of anticancer immunity in targeting malignancies. The present study investigated the ability of three types of long‑lived reactive species (oxidants) to inactivate cancer cells and potentially complement current HIPEC regimens, as well as to increase tumor cell expression of danger signals that stimulate innate immunity. The human abdominal cancer cell lines HT‑29, Panc‑01 and SK‑OV‑3 were exposed to different concentrations of hydrogen peroxide (H 2 O 2 ), hypochlorous acid (HOCl) and peroxynitrite (ONOO ‑ ). Metabolic activity was measured, as well as determination of cell death and danger signal expression levels via flow cytometry and detection of intracellular oxidation via high‑content microscopy. Oxidation of tumor decreased intracellular levels of the antioxidant glutathione and induced oxidation in mitochondria, accompanied by a decrease in metabolic activity and an increase in regulated cell death. At similar concentrations, HOCl showed the most potent effects. Non‑malignant HaCaT keratinocytes were less affected, suggesting the approach to be selective to some extent. Pro‑immunogenic danger molecules were investigated by assessing the expression levels of calreticulin (CRT), and heat‑shock protein (HSP)70 and HSP90. CRT expression was greatest following HOCl and ONOO ‑ treatment, whereas HOCl and H 2 O 2 resulted in the greatest increase in HSP70 and HSP90 expression levels. These results suggested that HOCl may be a promising agent to complement current HIPEC regimens targeting peritoneal carcinomatosis.

Introduction: Endoscopic necrosectomy has emerged as the preferred treatment modality for walled-off pancreatic necrosis. This study was designed to evaluate the safety and efficacy of direct endoscopic necrosectomy with and without hydrogen peroxide (H2O2) lavage., Methods: Retrospective chart reviews were performed for all patients undergoing endoscopic transmural management of walled-off pancreatic necrosis at 9 major medical centers from November 2011 to August 2018. Clinical success was defined as the resolution of the collection by imaging within 6 months, without requiring non-endoscopic procedures or surgery., Results: Of 293 patients, 204 met the inclusion criteria. Technical and clinical success rates were 100% (204/204) and 81% (166/189), respectively. For patients, 122 (59.8%) patients had at least one H2O2 necrosectomy (H2O2 group) and 82 (40.2%) patients had standard endoscopic necrosectomy. Clinical success was higher in the H2O2 group: 106/113 (93.8%) vs 60/76 (78.9%), P = 0.002. On a multivariate analysis, the use of H2O2 was associated with higher clinical success rate (odds ratio 3.30, P = 0.033) and earlier resolution (odds ratio 2.27, P < 0.001). During a mean follow-up of 274 days, 27 complications occurred. Comparing procedures performed with and without H2O2 (n = 250 vs 183), there was no difference in post-procedure bleeding (7 vs 9, P = 0.25), perforation (2 vs 3, P = 0.66), infection (1 vs 2, P = 0.58), or overall complication rate (n = 13 [5.2%] vs 14 [7.7%], P = 0.30)., Discussion: H2O2-assisted endoscopic necrosectomy had a higher clinical success rate and a shorter time to resolution with equivalent complication rates relative to standard necrosectomy.See the visual abstract at http://links.lww.com/AJG/B714.(Equation is included in full-text article.).

Early diagnosis of tumors is crucial in selecting appropriate treatment options to achieve the desired therapeutic effect, but it is difficult to accurately diagnose cancer by a single imaging modality due to technical constraints. Therefore, we synthesized a type of Fe3O4 nanoparticle with manganese dioxide grown on the surface and then prepared it by loading photosensitive drugs and traditional Chinese medicine monomers to create an integrated diagnosis/treatment multifunctional nanoplatform: Fe3O4@MnO2-celastrol (CSL)/Ce6. This nanoplatform can have full advantage of the tumor microenvironment (TME) characteristics of hypoxia (hypoxia), acidic pH (acidosis), and increased levels of reactive oxygen species (e.g., H2O2), even outside the TME. Specific imaging and drug release can also enhance tumor therapy by adjusting the hypoxic state of the TME to achieve the combined effect of chemotherapy (CT) and photodynamic therapy (PDT). Moreover, the obtained Fe3O4@MnO2-CSL/Ce6 has H2O2- and pH-sensitive biodegradation and can release the anticancer drug celastrol (CSL) and photosensitizer Ce6 in TME and simultaneously generate O2 and Mn2+. Therefore, the "dual response" synergistic strategy also confers specific drug release on nanomaterials, relieves tumor hypoxia and antioxidant capacity, and achieves significant optimization of CT and PDT. Furthermore, the resulting Mn2+ ions and Fe3O4 nanoparticles can be used for T1/T2 magnetic resonance imaging on tumor-bearing mice, and the released Ce6 can simultaneously provide fluorescence imaging functions. Therefore, Fe3O4@MnO2-CSL/Ce6 realized the synergistic treatment of PDT and CT under multimodal near-infrared fluorescence/photoacoustic (photoacoustic) imaging monitoring, showing its great potential in the accurate medical treatment of tumors.

Background: Leg ulcers are open skin wounds that occur below the knee but above the foot. The majority of leg ulcers are venous in origin, occurring as a result of venous insufficiency, where the flow of blood through the veins is impaired; they commonly arise due to blood clots and varicose veins. Compression therapy, using bandages or stockings, is the primary treatment for venous leg ulcers. Wound cleansing can be used to remove surface contaminants, bacteria, dead tissue and excess wound fluid from the wound bed and surrounding skin, however, there is uncertainty regarding the effectiveness of cleansing and the best method or solution to use., Objectives: To assess the effects of wound cleansing, wound cleansing solutions and wound cleansing techniques for treating venous leg ulcers., Search Methods: In September 2019 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting., Selection Criteria: We considered randomised controlled trials (RCTs) comparing wound cleansing with no wound cleansing, or RCTs comparing different wound cleansing solutions, or different wound cleansing techniques., Data Collection and Analysis: We screened studies for their appropriateness for inclusion, assessed their risk of bias using the Cochrane 'Risk of bias' tool, and used GRADE methodology to determine the certainty of evidence. Two review authors undertook these tasks independently, using predetermined criteria. We contacted study authors for missing data where possible., Main Results: We included four studies with a total of 254 participants. All studies included comparisons between different types of cleansing solutions, and three of these reported our primary outcomes of complete wound healing or change in ulcer size over time, or both. Two studies reported the secondary outcome, pain. One study (27 participants), which compared polyhexamethylene biguanide (PHMB) solution with saline solution for cleansing venous leg ulcers, did not report any of the review's primary or secondary outcomes. We did not identify any studies that compared cleansing with no cleansing, or that explored comparisons between different cleansing techniques. One study (61 participants) compared aqueous oxygen peroxide with sterile water. We are uncertain whether aqueous oxygen peroxide makes any difference to the number of wounds completely healed after 12 months of follow-up (risk ratio (RR) 1.88, 95% confidence interval (CI) 1.10 to 3.20). Similarly, we are uncertain whether aqueous oxygen peroxide makes any difference to change in ulcer size after eight weeks of follow-up (mean difference (MD) -1.38 cm 2 , 95% CI -4.35 to 1.59 cm 2 ). Finally, we are uncertain whether aqueous oxygen peroxide makes any difference to pain reduction, assessed after eight weeks of follow-up using a 0 to 100 pain rating, (MD 3.80, 95% CI -10.83 to 18.43). The evidence for these outcomes is of very low certainty (we downgraded for study limitations and imprecision; for the pain outcome we also downgraded for indirectness). Another study (40 participants) compared propyl betaine and polihexanide with a saline solution. The authors did not present the raw data in the study report so we were unable to conduct independent statistical analysis of the data. We are uncertain whether propyl betaine and polihexanide make any difference to the number of wounds completely healed, change in ulcer size over time, or wound pain reduction. The evidence is of very low certainty (we downgraded for study limitations and imprecision). The final study (126 participants) compared octenidine dihydrochloride/phenoxyethanol (OHP) with Ringer's solution. We are uncertain whether OHP makes any difference to the number of wounds healed (RR 0.96, 95% CI 0.53 to 1.72) or to the change in ulcer size over time (we were unable to conduct independent statistical analysis of available data). The evidence is of very low certainty (we downgraded for study limitations and imprecision). None of the studies reported patient preference, ease of use of the method of cleansing, cost or health-related quality of life. In one study comparing propyl betaine and polihexanide with saline solution the authors do not report any adverse events occurring. We are uncertain whether OHP makes any difference to the number of adverse events compared with Ringer's solution (RR 0.58, 95% CI 0.29 to 1.14). The evidence is of very low certainty (we downgraded for study limitations and imprecision)., Authors' Conclusions: There is currently a lack of RCT evidence to guide decision making about the effectiveness of wound cleansing compared with no cleansing and the optimal approaches to cleansing of venous leg ulcers. From the four studies identified, there is insufficient evidence to demonstrate whether the use of PHMB solution compared with saline solution; aqueous oxygen peroxide compared with sterile water; propyl betaine and polihexanide compared with a saline solution; or OHP compared with Ringer's solution makes any difference in the treatment of venous leg ulcers. Evidence from three of the studies is of very low certainty, due to study limitations and imprecision. One study did not present data for the primary or secondary outcomes. Further well-designed studies that address important clinical, quality of life and economic outcomes may be important, based on the clinical and patient priority of this uncertainty., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Asymptomatic and convalescent coronavirus disease 2019 (COVID-19) subjects may carry severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for months in their upper respiratory ways. Desiring to permanently clean the mucosal surfaces, we investigated the chemical agents that fit to rapidly degrade the virus. Among these, hydrogen peroxide, initially tested by two of us for tolerability, showed both good performance and acceptable side effects (burning sensation for 15-20 s). We contacted circles of family physicians and the ATS Milano (Territorial Assistance and Prevention Service), and we tested this procedure on eight persistent carriers of SARS-CoV-2, performing swabs before the procedure and after it until the reappearance of the virus or until 14 days (the incubation period), keeping the surfaces clean with a hypertonic solution. Our patients had a median time from exposure or symptom onset of 111 days, and three had relapsed after being declared "cured" (two consecutive negative swabs after quarantine). One patient had a baseline negative swab and was excluded, and two successfully ended the 14 days' course, four suppressed viral elimination for 72 h, and one for 48 h, all rebounding to weak positive (cycle thresholds above 24). Although temporarily effective, such measures may have some place in the control of viral shedding to protect the most fragile subjects., (© 2020 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Objective: This single-blind, split-mouth, randomized trial was aimed at evaluating the bleaching efficacy (BE) and tooth sensitivity (TS) of a 20% hydrogen peroxide (HP) bleaching agent used under active or passive application., Methods and Materials: Twenty-two patients with canines darker than C2 were selected. Teeth were bleached in two sessions, with a one-week interval between treatments. The bleaching agent was applied using active (HPactive) or passive (HPpassive) application. Each tooth in the HPactive-allocated hemiarch received bleaching gel with sonic activation after 10 and 30 minutes from the start of treatment, with rounded movements all over the buccal surface. The color changes were evaluated by subjective (Vita Classical and Vita Bleachedguide) and objective (VITA Easyshade Spectrophotometer) methods at baseline and 30 days after the second session. TS was recorded up to 48 hours after treatment using a 0-10 visual analog scale. Color change in shade guide units (SGUs) and ΔE was analyzed using a Wilcoxon test (α=0.05). The absolute risk and intensity of TS were evaluated using McNemar test and a Wilcoxon test, respectively (α=0.05)., Results: Significant whitening was observed in both groups after 30 days of clinical evaluation. The activation did not significantly influence BE (ΔSGU HPpassive=5.6 and HPActive=5.8; p=0.98; and ΔE HPpassive=10.6 and HPactive=10.3; p=0.83). Absolute risk of TS (HPactive=36.4% and HPpassive=31.8%; p=0.94) was similar for both groups (Fisher exact test). TS intensity (visual analogue scale) was higher during the bleaching sessions and up to 24 hours thereafter for both groups, with no differences between groups (two-way analysis of variance and Tukey)., Conclusion: The active application of a 20% HP gel did not improve BE and TS., (©Operative Dentistry, 2021.)

Oncogenic KRAS is one of the most common drivers of human cancer. Despite intense research, no effective therapy to directly inhibit oncogenic KRAS has yet been approved and KRAS mutant tumors remain associated with a poor prognosis. This short review discusses the current knowledge of the redox regulation of RAS and examines the newest findings on cysteine 118 (C118) as a potential novel target for KRAS inhibition., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: Hydrogen peroxide 40% (HP40) was approved by the US Food and Drug Administration for topical treatment of seborrheic keratosis (SK) in December 2017. This article will review phase II and III clinical trials to assess the drug's efficacy, safety, and clinical application., Data Sources: A systematic literature review was performed using the terms "Eskata AND seborrheic keratosis," and "hydrogen peroxide AND seborrheic keratosis" in the OVID MEDLINE, PubMed, Cochrane Library, EMBASE, and Web of Science databases. ClinicalTrials.gov was searched to identify ongoing or nonpublished studies., Study Selection and Data Abstraction: Articles written in English between January 2000 and mid-June 2020 discussing phase II and phase III clinical trials were evaluated., Data Synthesis: In 2 phase III clinical trials, 4% and 8% of patients treated with HP40 had a Physician Lesion Assessment score of zero for all 4 SKs, respectively, compared with 0% in both vehicle groups at the primary end point of day 106 ( P < 0.01; P < 0.0001)., Relevance to Patient Care and Clinical Practice: HP40, although less effective, has a better safety profile than other treatment options. It should be especially considered for treatment of facial SKs, where it is most efficacious and where other treatment modalities, such as cryotherapy, are more challenging., Conclusions: HP40 is a new, safe alternative treatment for SKs, although it is expensive and only modestly effective, both of which somewhat limit its overall utility. HP40 is a promising topical alternative, particularly for cosmetically sensitive locations, such as the face.

Background: There is currently no drug that slows the process of neurodegeneration or alleviates the cognitive and depressive symptoms in patients with Alzheimer's disease. Due to the increasing number of Alzheimer's patients, there is an urgent need to develop novel drugs with neuroprotective, procognitive, and antidepressant properties., Objective: The aim of this study was to design, synthesize, and evaluate novel aminoalkanamides with serotonin 5-HT 1A /5-HT ;7 receptor affinity and phosphodiesterase (PDE) inhibitory activity as a new approach to combat neurodegeneration and symptoms of Alzheimer's disease., Methods: The newly designed compounds were synthesized using classical methods of organic chemistry and tested in vitro for their receptor affinity, functional profile, enzyme inhibition, and ADME properties. The neuroprotective effect against H 2 O 2 -induced increase of reactive oxygen species level was tested in SH-SY5Y cells. The novel object recognition and forced swimming tests were used to evaluate the procognitive and antidepressant activity, respectively., Results: Synthesized aminoalkanamides were characterized as potent 5-HT 1A receptor antagonists with additional 5-HT7 receptor antagonistic properties and PDE4B inhibitory activity. Selected compound 15 showed neuroprotective, procognitive, and antidepressant properties. In addition, compound 15 revealed suitable ADME properties expressed as good membrane permeability and high metabolic stability., Conclusion: This study revealed a new class of compounds that may be useful in the search for an effective drug in the alleviation of neurodegeneration and symptoms of Alzheimer's disease., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

A review of nasal sprays and gargles with antiviral properties suggests that a number of commonly used antiseptics including povidone-iodine, Listerine ® , iota-carrageenan and chlorhexidine should be studied in clinical trials to mitigate both the progression and transmission of SARS-CoV-2. Several of these antiseptics have demonstrated the ability to cut the viral load of SARS-CoV-2 by 3-4 log 10 in 15-30 s  in vitro . In addition, hypertonic saline targets viral replication by increasing hypochlorous acid inside the cell. A number of clinical trials are in process to study these interventions both for prevention of transmission, prophylaxis after exposure, and to diminish progression by reduction of viral load in the early stages of infection.

Background: The dramatic increase in the use of cardiovascular implantable electronic devices (CIED) was associated with an increased rate of CIED infection, which has a high management cost., Aim of the Study: To test the safety and efficacy of a single-session protocol, aiming to reuse the infected pocket side and the same device and leads in patients with CIED pocket infection., Patients and Methods: We included patients with isolated pocket infection between January 2015 and November 2019. The Patient was prepared by taking a swab for culture and sensitivity before the procedure. The pocket was debrided and the capsule was removed, the pocket was rinsed with povidone-iodine and hydrogen peroxide mixture, then packed with gauze sponge soaked with povidone-iodine. The device was debrided using ultrasonic irrigation and sterilized using gas plasma. The device was reimplanted and the wound was closed in layers., Results: During the period of the study, we had 12 patients with isolated pocket infection. Nine presented with erosion, two with impending erosion, and one with a chronic sinus. Patient's age was 61.5 ± 7.64 years. The infection was diagnosed 14.2 ± 8.22 weeks post device implantation. They were admitted for 7.6 ± 1.54 days postprocedure. The follow-up duration was 26.5 ± 15 (1.7-52) months. Only one patient (8%) had a recurrence of the infection after 50 days of the procedure., Conclusion: Our protocol was successful in treating 92% of device-related pocket infection without the need to replace the device or the pocket side., (© 2020 Wiley Periodicals LLC.)

The common existence of hypoxia within the tumor microenvironment severely restricts the efficacy of photodynamic therapy (PDT), which is attributed to the fact that the PDT process is strongly oxygen (O2) dependent. Here, a multifunctional composite (named CPCG), which combines polyethylene glycol (PEG) functionalized cerium oxide nanoparticles (CeO2) with photosensitizer chlorin e6 (Ce6) and glucose oxidase (GOx), is reported for generating O2 within the tumor microenvironment by the dual-path hydrogen peroxide (H2O2)-modulated ways to ameliorate hypoxia, thereby enhancing the PDT efficiency. This process is realized based on the dual enzyme-like activity of CeO2. The first modulated way is to transform the superoxide anion (O2˙-) into H2O2 by the superoxide dismutase-like activity of CeO2. The second modulated way is to decompose glucose into H2O2 through the catalysis of GOx. Subsequently, H2O2 generated from the above dual modulated ways can further produce O2via the catalase-like activity of CeO2. Additionally, the depletion of glucose could impede the nutrient supply to obtain starvation therapy. Both in vitro and in vivo experiments indicate that the CPCG composite could enhance the efficacy of photodynamic/starvation synergistic therapy. Therefore, this strategy offers great potential to modulate the O2 level in the tumor microenvironment for better therapeutic outcomes, and can act as a promising candidate in photodynamic/starvation synergistic therapy.

Clinical Relevance: Bleaching performed at home while under the supervision of a dentist provides greater color alteration compared with whitening strips when evaluated with a spectrophotometer, although the color alteration was undetectable by unaided human eyes., Summary: Objective: A systematic review and meta-analysis were performed to answer the following research question: Does the use of whitening strips (WS) lead to an equivalent color change compared with supervised dental bleaching in patients with permanent dentition?Methods: A search was performed on August 10, 2017 (updated on March 22, 2019), in PubMed, the Brazilian Library in Dentistry, Latin American and Caribbean Health Sciences Literature database, Cochrane Library, Scopus, Web of Science, and SIGLE, without restrictions regarding date or language. Abstracts from the International Association for Dental Research, unpublished and ongoing trial registries, dissertations, and theses were also searched. Only randomized clinical trials (parallel or split mouth) in patients with permanent dentition that compared WS with dentist-supervised dental bleaching performed at home (AH) or in office (IO) were included. The risk of bias (RoB) was evaluated using the Cochrane Collaboration tool. A meta-analysis with subgroup analysis (low and high peroxide concentration) was conducted for color change ΔE* (spectrophotometer) and ΔSGU (shade guide units), risk and intensity of tooth sensitivity (TS), gingival irritation (GI), and patient satisfaction using a random effects model. Heterogeneity was assessed with the Cochrane Q test and I2 statistics. GRADE (Grading of Recommendations, Assessment, Development and Evaluation) was used to assess the quality of the evidence.Results: After the removal of duplicates, followed by title and abstract screening, 20 studies remained. Only two studies were considered to have a low RoB; 11 had a high RoB, and seven had an unclear RoB. For WS versus IO, data were not available for the meta-analysis. For WS versus AH bleaching, a significant difference in ΔE* favoring the AH group was observed (standardized mean difference [SMD] = -0.50, 95% confidence interval [CI] -0.79 to 0.21), but the risk (risk ratio = 0.78, 95% CI 0.65 to 0.93) and intensity of TS (SMD = -0.30, 95% CI -0.56 to -0.04) were lower in the WS group. Color change in ΔSGU, risk and intensity of GI, and patient satisfaction were not significantly different between groups (p>0.20). The quality of evidence for ΔE*, risk and intensity of TS, and intensity of GI were graded as moderate.Conclusion: Although the risk and intensity of TS were lower in the WS group, dentist-supervised at-home bleaching led to a better color change when measured with a spectrophotometer, although the color alteration was undetectable by unaided human eyes., (©Operative Dentistry, 2020.)

This aim of this study was to observe the effect of Yang Yan Qing E Wan (YYQEW) on senescent phenotypes and the expression of β-catenin and p16 INK4a in the hydrogen peroxide (H 2 O 2 )-induced premature senescence of normal human skin fibroblasts (NHSFs). Primary normal human skin fibroblasts were randomly divided into a normal group, a blank group, a model group, and a YYQEW group. The cells of the model group and the YYQEW group were exposed to 150 μmol/L H 2 O 2 for 2 h. The morphological changes of the cells were analyzed by microscopy and by kits used to estimate the activities of the senescence-associated β-galactosidase (SA-β-gal), reactive oxygen species (ROS), and superoxide dismutase (SOD). The outcomes revealed that dyeing rate proportion of SA-β-gal was 2.78% ± 0.22% in the normal group, 2.83% ± 0.29% in the blank group, 37.58% ± 2.56% in the model group, and 28.39% ± 0.93% in the YYQEW group. The number of SA-β-gal positive cells was thus significantly higher in the model group than in the normal or blank group. There were also fewer SA-β-gal positive cells in the YYQEW group compared with the model group. The expression of ROS and p16 INK4a in the model group increased significantly compared with that in the normal or blank groups, while the expression of ROS and p16 INK4a in the YYQEW group decreased significantly compared with that in the model group. The expression of SOD and β-catenin in the model group decreased significantly compared with that in the normal or blank group, and the expression of SOD and β-catenin in the YYQEW group increased significantly compared with that in the model group. Overall, it was found that YYQEW was able to delay the senescence of NHSFs induced by H 2 O 2 treatment by alleviating oxidative stress and regulating a number of senescence-related molecules, such as β-catenin and p16 INK4a ., (Copyright © 2020 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.)

Specifically inhibiting the proliferation of activated macrophages and clearing the high levels of reactive oxygen species (ROS) secreted by macrophages is crucial for osteoarthritis (OA) treatment. Moreover, if the clearance of these high levels of ROS can be simultaneously used to induce oxidation-responsive release of anti-inflammatory drugs, the therapeutic effect of OA may be further improved. Here, a multifunctional anti-inflammatory drug (CPHs) based on a peptide dendrimer nanogel was constructed by physically encapsulating CORM-401 and wrapping its surface with folic acid (FA)-modified hyaluronic acid (HA). CPHs is capable of efficiently entering activated macrophages via FA- and HA-mediated specific targeting effects and then rapidly release large amounts of CO by massive consumption of H 2 O 2 . The generated CO effectively suppresses the secretion of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α by inhibiting cell proliferation; inducing the activation of heme oxygenase (HO-1), and downregulating the expression of p38 MAPK, NF-kB (p50/p65) and TLR-2. In vivo experiments further confirmed that CPHs can massively deplete ROS in OA joints and effectively suppress the degradation of articular cartilage and their extracellular matrix. More importantly, CPHs is non-toxic to normal macrophages, and the high levels of CO generated in the joints do not result in notable changes in the HbCO levels in blood. Together, these results show that CPHs is an effective and safe anti-inflammatory drug and has essential application prospects in OA treatment., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Inflammation is generally accepted as a component of the host defence system and a protective response in the context of infectious diseases. However, altered inflammatory responses can contribute to disease in infected individuals. Many endogenous mediators that drive the resolution of inflammation are now known. Overall, mediators of resolution tend to decrease inflammatory responses and provide normal or greater ability of the host to deal with infection. In the lung, it seems that pro-resolution molecules, or strategies that promote their increase, tend to suppress inflammation and lung injury and facilitate control of bacterial or viral burden. Here, we argue that the demonstrated anti-inflammatory, pro-resolving, anti-thrombogenic and anti-microbial effects of such endogenous mediators of resolution may be useful in the treatment of the late stages of the disease in patients with COVID-19., (© 2020 The British Pharmacological Society.)

Background: Hydrogen peroxide (H 2 O 2 ) is one of the delousing agents used to control sea lice infestations in salmonid aquaculture. However, some Lepeophtheirus salmonis populations have developed resistance towards H 2 O 2 . An increased gene expression and activity of catalase, an enzyme that breaks down H 2 O 2 , have been detected in resistant lice, being therefore introduced as a resistance marker in the salmon industry. In the present study the aim was to validate the use of catalase expression as a marker and to identify new candidate genes as additional markers to catalase, related to H 2 O 2 resistance in L. salmonis., Methods: A sensitive and an H 2 O 2 resistant laboratory strain (P0 generation, not exposed to H 2 O 2 for several years) were batch crossed to generate a cohort with a wide range of H 2 O 2 sensitivities (F2 generation). F2 adult females were then exposed to H 2 O 2 to separate sensitive and resistant individuals. Those F2 lice, the P0 lice and field-collected resistant lice (exposed to H 2 O 2 in the field) were used in an RNA sequencing study., Results: Catalase was upregulated in resistant lice exposed to H 2 O 2 compared to sensitive lice. This was, however, not the case for unexposed resistant P0 lice. Several other genes were found differentially expressed between sensitive and resistant lice, but most of them seemed to be related to H 2 O 2 exposure. However, five genes were consistently up- or downregulated in the resistant lice independent of exposure history. The upregulated genes were: one gene in the DNA polymerase family, one gene encoding a Nesprin-like protein and an unannotated gene encoding a small protein. The downregulated genes encoded endoplasmic reticulum resident protein 29 and an aquaporin (Glp1&#95;v2)., Conclusions: Catalase expression seems to be induced by H 2 O 2 exposure, since it was not upregulated in unexposed resistant lice. This may pose a challenge for its use as a resistance marker. The five new genes associated with resistance are put forward as complementary candidate genes. The most promising was Glp1&#95;v2, an aquaglyceroporin that may serve as a passing channel for H 2 O 2 . Lower channel number can reduce the influx or distribution of H 2 O 2 in the salmon louse, being directly involved in the resistance mechanism.

Background: Hydrogen peroxide (H 2 O 2 ) is a product of respiration in mitochondria and an important oxidizing agent in biological systems. Previous investigations have shown the efficacy of H 2 O 2 in treating skin conditions such as seborrheic keratosis and actinic keratosis. In an area like the face, reconstruction of excision defects and ultimately aesthetic outcomes are of utmost importance. Hydrogen peroxide may represent a simple yet effective method at shrinking non-melanoma skin cancers (NMSC) of the head and neck before they are excised., Methods: Eleven consecutive patients presenting to our cutaneous malignancy clinic had their skin lesions evaluated by the senior author for participation in the study. Lesion length and width was measured. Hydrogen peroxide formulated at a concentration of 33% was rubbed into the lesion until blanching was observed. Lesions were re-measured at follow up. Excisional biopsy was then performed and histopathological diagnosis was obtained. Statistical analyses compared pre- and post-treatment lesion dimensions., Results: Seventeen biopsy-proven NMSC lesions were included in this investigation. Statistically significant reductions in the length (p < 0.001) and width (p < 0.001) were observed with H 2 O 2 treatment. For some lesions, H 2 O 2 was the sole treatment required, with post-treatment biopsy demonstrating no evidence of malignancy. Patients endured minimal discomfort during treatment and no long-term side effects were observed. Follow up at 6 months revealed no recurrences., Conclusions: We have demonstrated a significant reduction in the size of multiple lesions after application of 33% hydrogen peroxide, simplifying definitive excision and reconstruction. Hydrogen peroxide demonstrated an ability to successfully treat non-melanoma skin cancers as well.

The aim of this study is to analyze the efficacy of natural bleaching agents and the current technological development in this research field. Two reviewers performed a literature search up to July 2019 in 15 databases. Five laboratory studies and 25 patents were included. Data regarding natural bleaching agent used, application protocol, and the main findings of studies were analyzed. Laboratory studies that evaluated natural bleaching agents' peroxide-free or associated to peroxides and patents related to natural bleaching agents were included. The studies evaluated papain, bromelain, chlorine dioxide, sodium chloride plus vinegar and sodium bicarbonate as peroxide-free agents; and sweet potato extract, lactoperoxidase, and peroxidase associated to peroxide used were included. Twenty-five patents were included; among the most cited are the papain and the chlorine. The addition of non-peroxide agents into peroxide showed improvement in bleaching effect with the incorporation of these non-peroxide agents (p < .05). On the other hand, peroxide-free agents did not show an improvement in bleaching effect (p < .05). The evidence in literature suggested that natural bleaching agents incorporated to peroxide may improve the bleaching. Therefore, the current literature does not support the use of natural agents as dental bleaching., (© 2019 John Wiley & Sons, Ltd.)

The sample consisted of 480 hatching eggs of Japanese quails and was divided into 4 groups. Before the transfer to the incubator, the first group was not disinfected (negative control). In the second group, eggs were disinfected by means of formaldehyde fumigation (positive control). In the third and fourth group, reactive oxygen forms were used for disinfection- perhydrol (H 2 O 2 ) and ozone (O 3 ), respectively. Eggs were incubated under standard conditions. On the 14th D, eggs were candled, and proportions of fertilized eggs and died embryos were calculated. In addition, samples were collected for microbiological examination. After 17.5 D, the results of the whole hatching were evaluated. Chicks were reared for 14 D. Their survivability and body weight gain were recorded. Disinfection by means of reactive oxygen forms did not prove to be more effective in reducing the number of bacterial colonies on the shell. Reduced hatching and significantly increased mortality in the O 3 group may indicate the negative impact of this gas on developing embryos. The results of hatching from eggs disinfected with H 2 O 2 did not differ from those obtained in control groups. The biggest chicks were obtained from O 3 disinfected eggs. However, during rearing, their growth did not match the one observed for birds in the remaining groups. Chicks hatched from eggs disinfected with H 2 O 2 were characterized by the largest survivability. Disinfection with reactive oxygen forms did not significantly improve the hygiene of hatching eggs, hatching performance, and quality of hatched chicks. Hydrogen peroxide, whose application offered satisfactory hatching results, may be the recommended disinfectant. On the other hand, O 3 appears to be undesirable because of its negative impact on bird embryos., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the effect of hydrogen peroxide on anti-infection and reducing postoperative drainage in multi-segmental lumbar surgery., Methods: A clinical data of 510 patients with multi-segmental lumbar degenerative diseases who were treated with surgery between January 2017 and January 2018 was retrospectively analyzed. In study group, the incisions of 230 cases were washed with hydrogen peroxide before suture. In control group, the incisions of 280 cases were washed with normal saline before suture. There was no significant difference in gender, age, lesion type, disease duration, operative segment, and other clinical data between the two groups ( P >0.05). The operation time, intraoperative blood loss, postoperative drainage volume, and postoperative incidence of infection were recorded and compared between the two groups. The Centers for Disease Control and Prevention (CDC) standard was used to evaluate infection, which was divided into superficial infection and deep infection., Results: All operations completed successfully. There was no significant difference in operation time and intraoperative blood loss between the two groups ( P >0.05). The postoperative drainage volume in the study group was significantly less than that in the control group ( t =-2.990, P =0.005). A total of 13 patients developed infection after operation, including 10 cases of superficial infection (2 cases in the study group and 8 cases in the control group) with the infection time of (7.3±1.5) days, and 3 cases of deep infection (all in the control group) with the infection time of (16.6±3.1) days. The incidences of superficial and deep infections in the study group were lower than those in the control group, but there was no significant difference between the two groups ( χ 2 =2.595, P =0.123; P =0.256). All the superficial infections were Staphylococcus aureus infection and recovered after active dressing change. Among the patients with deep infections, 2 cases were infected by Staphylococcus aureus and 1 case was infected by Escherichia coli ; and the incisions healed after being washed and sutured thoroughly, and active dressing change., Conclusion: The incidence of postoperative infection and postoperative drainage volume can be reduced by washing the incision with hydrogen peroxide in multi-segmental lumbar surgery.

Aim: This study was designed to investigate the clinical and microbiological parameters with photochemotherapy (PCT) against conventional debridement (CD) among patients with necrotizing ulcerative gingivitis (NUG)., Materials and Methods: Patients with a diagnosis of NUG were divided into two groups: 'Group-PCT' that underwent indocyanine green-mediated PCT with adjunctive mechanical debridement, and Group-CD that underwent mechanical debridement with adjunctive 3 % hydrogen peroxide/chlorhexidine rinse. Clinical inflammatory gingival parameters including full-mouth plaque scores (FMPS), bleeding scores (FMBS), and probing depth (PD) were measured. Counts of Treponema microdentium, Fusobacterium nucleatum and Prevotella intermedia were assessed using polymerase chain reaction technique. All assessments were done at baseline, 3 weeks and 6 weeks., Results: Twenty-six participants were contacted and agreed to participate in the trial. The mean age of participants in group-PCT was 24.5 years while the mean age of patients in group-CD was 26.7 years. FMPS showed significant but equal reduction in both the groups at 3 weeks and 6 weeks (p < 0.01). The reduction in mean FMBS was higher in the group-PCT at 6 weeks follow-up (p < 0.05). All bacterial levels reduced from baseline to follow-up with both PCT and CD groups (p < 0.05). Group-PCT showed significantly reduced counts of T. microdentium and F. nucleatum at 3 weeks and 6 weeks compared with group-CD (p = 0.024). Equal reduction was shown for P. intermedia between both the groups at 3 and 6 weeks, respectively., Conclusion: Application of adjunctive photochemotherapy was both clinically and microbiologically effective in the treatment of NUG., Competing Interests: Declaration of Competing Interest The authors of the present study reports no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Hydrogen peroxide is an inexpensive and effective antimicrobial agent that can be implemented in surgical skin preparations. The purpose of this study was to evaluate the decolonization effect of Cutibacterium acnes when adding hydrogen peroxide to a standard sterile preparation for shoulder surgery., Methods: This was a single-institution, prospective, randomized controlled trial of male patients undergoing shoulder arthroscopy (April 2018 and May 2019). Patients were randomized to a standard skin preparation vs. an additional sterile preparation with 3% hydrogen peroxide. After draping, a 3-mm punch biopsy was obtained from the posterior arthroscopic portal site of all patients. Anaerobic and aerobic culture substrates were used and held for 13 days., Results: Seventy male patients were randomized into the hydrogen peroxide group and 70 male patients were in the traditional group. Twelve (17.1%) patients in the hydrogen peroxide group and 24 (34.2%) patients in the traditional group had positive cultures for C acnes (P = .033). Cultures were positive at a mean of 4.5 days (range 3-7) in the hydrogen peroxide group and 4.1 days (range 3-8) in the traditional group (P = .48). There were no cases of skin reaction to the surgical preparation in either group., Discussion: The results of this study suggest that the addition of hydrogen peroxide to preoperative surgical site preparation can reduce the C acnes culture rate. Hydrogen peroxide is inexpensive and can be added to the typical skin preparation used prior to shoulder surgery without substantial risk of skin reactions., (Copyright © 2019 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Objective: To explore the safety and efficacy of hydrogen peroxide H 2 O 2 in controlling blood loss and surgical site infection (SSI) after multisegmental lumbar spine surgery., Methods: A total of 2626 patients who had undergone multisegmental lumbar spinal surgery from January 2015 to January 2018 were included in the present study. Stratified by the use of H 2 O 2 irrigation, they were divided into 2 groups: the control group (n = 1345) and the experimental group (n = 1281). The demographic parameters, laboratory examination results, and surgery-related information (e.g., operative time, number of operated levels, intraoperative blood loss, postoperative drainage, postoperative SSI, extubation time), and perioperative complications were recorded., Results: No significant differences were seen regarding the demographic parameters, laboratory examination results, comorbidities, and surgery-related information. The extubation time and postoperative drainage collection were lower in the experimental group (3.6 ± 0.5 vs. 4.1 ± 0.6 days, P = 0.402; 251.8 ± 67.5 vs. 291.8 ± 71.3 mL, P = 0.013). In the control group, the rate of SSI was 2.4% (32 of 1345) and included 17 superficial wound infections and 15 deep wound infections. In the experimental group, the SSI rate was 1.4% (18 of 1281; 15 with a superficial wound infection and 3 with a deep wound infection). Staphylococcus aureus was the most common organism, especially in the experimental group (66.7% vs. 50%). No statistically significant difference was found between the 2 groups in the perioperative complications, including hematencephalon, deep vein thrombosis, pulmonary embolism, and myocardial infarction (P > 0.05). Pneumocephalus was not observed in either group., Conclusion: The application of H 2 O 2 in posterior lumbar interbody fusion can reduce the blood loss and incidence of SSI after surgery and was quite beneficial for controlling the increasing number of vancomycin-resistant bacteria., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Biodegradable nanoprodrugs, inheriting the antitumor effects of chemotherapy drugs and overcoming the inevitable drawback of side effects on normal tissues, hold promise as next-generation cancer therapy candidates. Biodegradable nanoprodrugs of transferrin-modified MgO 2 nanosheets are developed to selectively deliver reactive oxygen species to cancer cells for molecular dynamic therapy strategy. The nanosheets favor the acidic and low catalase activity tumor microenvironment to react with proton and release nontoxic Mg 2+ . This reaction simultaneously produces abundant H 2 O 2 to induce cell death and damage the structure of transferrin to release Fe 3+ , which will react with H 2 O 2 to produce highly toxic ·OH to kill tumor cells., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Hydrogen peroxide (H 2 O 2 ) is a commonly used treatment for a range of parasitic diseases of marine finfish, including amoebic gill disease (AGD). While this treatment is partially effective at reducing parasite load, H 2 O 2 can have detrimental effects on the host under certain conditions. Treatment temperature and dose concentration are two factors that are known to influence the toxicity of H 2 O 2 ; however, their impact on the outcome of AGD treatment remains unclear. Here, we investigated the effects of treatment temperature (8, 12 or 16°C) and dose concentration (750, 1,000, 1,250 mg/L) on the efficacy of H 2 O 2 to treat AGD. We demonstrated that a 20-min bath treatment of H 2 O 2 at all doses reduced both parasite load and gross gill score significantly. Parasite load and gross gill score were lowest in the 1,000 mg/L treatment performed at 12°C. At the high dose and temperature combinations, H 2 O 2 caused moderate gill damage and a significant increase in the plasma concentration of electrolytes (sodium, chloride and potassium). Taken together, our study demonstrates that higher H 2 O 2 treatment temperatures can adversely affect the host and do not improve the effectiveness of the treatment., (© 2019 John Wiley & Sons Ltd.)

Different light sources have been used during dental bleaching procedures. More recently, a violet LED system was introduced as a promising and viable light source, which is capable to promote dental bleaching without chemical agents, although this light source could be also associated to a bleaching agent. This case report aimed to present the association of a violet LED and a bleaching agent over a discolored non-vital tooth. After anamnesis, clinical and radiographic examinations, a dental bleaching protocol was proposed as follow: 15 applications of the violet LED during 60 s (Bright Max Whitening, MMOptics) with 30 s interval between them. Before the last 5 applications, 35% hydrogen peroxide gel (Whiteness HP Maxx, FGM) was applied inside the pulp chamber and on enamel surface of the tooth (vestibular and palatal surfaces) and then the last 5 irradiations were performed. Three sessions were performed, with 7-days interval. Color assessment using a VITA classical scale and VITA EasyShade® spectrophotometer was carried out. After dental bleaching, color changed (tooth 21) from A3.5 to B2. The protocol used in this case report showed to be satisfactory for the non-vital tooth bleaching., (Copyright © 2019. Published by Elsevier B.V.)

Hydrogen peroxide (H 2 O 2 ) is an endogenous reactive oxygen species that contributes to oxidative stress directly as a molecular oxidant and indirectly through free radical generation. Topically applied 1% to 45% H 2 O 2 can be used for a range of clinical purposes, which will be reviewed here in addition to its safety. In concentrations from 1% to 6%, H 2 O 2 has antimicrobial properties and can act as a debriding agent through its effervescence, making low-concentration H 2 O 2 useful for wound care. H 2 O 2 has also been shown to promote venous insufficiency ulcer healing, but studies in other wound types are needed. In 1% formulations, H 2 O 2 is used outside the United States to treat acne and has shown efficacy similar to or greater than benzoyl peroxide, with reduced side effects. In a concentration of 40%, H 2 O 2 is US Food and Drug Administration-approved to treat seborrheic keratoses and may cause fewer pigmentary changes than cryotherapy, although elimination often requires 2 to 4 treatments. However, H 2 O 2 should be used with caution, as exposure can cause adverse effects through its oxidant capabilities. Low H 2 O 2 concentrations cause only transient symptoms (blanching and blistering), but exposure to 9% to 45% H 2 O 2 can cause more severe skin damage, including epidermal necrosis leading to erythema and bullae. Overall, H 2 O 2 has numerous therapeutic uses, and novel indications, such as treating actinic keratoses and skin cancers, continue to be explored., (Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)