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1.
PeerJ ; 12: e17039, 2024.
Article in English | MEDLINE | ID: mdl-38590700

ABSTRACT

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


Subject(s)
Hominidae , Hypertension, Pulmonary , Pulmonary Embolism , Thrombosis , Rats , Animals , Hypertension, Pulmonary/drug therapy , Rats, Sprague-Dawley , Hirudins/pharmacology , Hydrogen Peroxide/therapeutic use , Pulmonary Embolism/complications , Thrombosis/drug therapy
2.
J Mater Chem B ; 12(14): 3509-3520, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38516824

ABSTRACT

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


Subject(s)
Methacrylates , Methylmethacrylates , Nanoparticles , Neoplasms , Nylons , Humans , Copper/therapeutic use , Reactive Oxygen Species , Hydrogen Peroxide/therapeutic use , Nanoparticles/chemistry , Doxorubicin/pharmacology , Doxorubicin/therapeutic use , Neoplasms/drug therapy , Glutathione/chemistry , Oxidation-Reduction , Tumor Microenvironment
3.
J Contemp Dent Pract ; 25(1): 68-71, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-38514434

ABSTRACT

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.


Subject(s)
Dental Caries , Dentifrices , Tooth Bleaching , Tooth Discoloration , Humans , Dentifrices/therapeutic use , Bromelains/therapeutic use , Hydrogen Peroxide/therapeutic use , Coloring Agents , Tooth Discoloration/drug therapy , Papain/therapeutic use , Dental Caries/drug therapy , Toothbrushing , Dental Enamel
4.
J Dent ; 143: 104877, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38316199

ABSTRACT

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


Subject(s)
Dentin Sensitivity , Tooth Bleaching , Humans , Hydrogen Peroxide/therapeutic use , Charcoal/therapeutic use , Toothpastes/therapeutic use , Powders , Single-Blind Method , Tooth Bleaching/methods , Carbamide Peroxide , Dentin Sensitivity/drug therapy
5.
Nanoscale ; 16(7): 3755-3763, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38299362

ABSTRACT

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


Subject(s)
Cyclodextrins , Ferrous Compounds , Nanoparticles , Neoplasms , Humans , RNA, Small Interfering , HeLa Cells , Metallocenes/pharmacology , Nanoparticles/therapeutic use , Cations , Cell Line, Tumor , Neoplasms/drug therapy , Neoplasms/metabolism , Hydrogen Peroxide/therapeutic use
6.
J Appl Oral Sci ; 32: e20230336, 2024.
Article in English | MEDLINE | ID: mdl-38324805

ABSTRACT

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.


Subject(s)
Tooth Bleaching Agents , Tooth Bleaching , Tooth Discoloration , Humans , Color , Cost-Effectiveness Analysis , Dentifrices/therapeutic use , Hydrogen Peroxide/therapeutic use , Tooth Bleaching/methods , Tooth Bleaching Agents/therapeutic use , Tooth Discoloration/drug therapy , Toothpastes/therapeutic use , Urea , Randomized Controlled Trials as Topic
7.
Nanoscale ; 16(8): 4095-4104, 2024 Feb 22.
Article in English | MEDLINE | ID: mdl-38333905

ABSTRACT

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


Subject(s)
Breast Neoplasms , Curcumin , Neoplasms , Photochemotherapy , Humans , Female , Breast Neoplasms/drug therapy , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Oxygen , Reactive Oxygen Species/pharmacology , Curcumin/pharmacology , Curcumin/therapeutic use , Cell Line, Tumor , Photochemotherapy/methods , Neoplasms/drug therapy , Hypoxia , Magnetic Phenomena , Tumor Microenvironment , Hydrogen Peroxide/therapeutic use
8.
BMC Neurosci ; 25(1): 5, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38291397

ABSTRACT

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


Subject(s)
Hearing Loss, Noise-Induced , Rats , Male , Female , Animals , Hearing Loss, Noise-Induced/drug therapy , Hair Cells, Auditory, Outer , Reactive Oxygen Species , Rats, Sprague-Dawley , Norepinephrine , Hydrogen Peroxide/pharmacology , Hydrogen Peroxide/therapeutic use , Cochlea , Evoked Potentials, Auditory, Brain Stem , Receptors, Adrenergic/therapeutic use
9.
Nanoscale ; 16(4): 1983-1998, 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38189459

ABSTRACT

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


Subject(s)
Acute Lung Injury , Nanoparticles , Respiratory Distress Syndrome , Mice , Animals , Reactive Oxygen Species/pharmacology , Intercellular Adhesion Molecule-1 , Hydrogen Peroxide/therapeutic use , Acute Lung Injury/drug therapy , Lung , Respiratory Distress Syndrome/drug therapy , Nanoparticles/therapeutic use , Peptides/pharmacology , Peptides/therapeutic use , Dexamethasone/pharmacology , Dexamethasone/therapeutic use
10.
J Mater Chem B ; 12(5): 1344-1354, 2024 Jan 31.
Article in English | MEDLINE | ID: mdl-38230621

ABSTRACT

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


Subject(s)
Atherosclerosis , Nanoparticles , Plaque, Atherosclerotic , Humans , Reactive Oxygen Species , Hydrogen Peroxide/therapeutic use , Proton Pump Inhibitors/therapeutic use , Silicon Dioxide/therapeutic use , Atherosclerosis/diagnostic imaging , Atherosclerosis/drug therapy , Plaque, Atherosclerotic/diagnostic imaging , Plaque, Atherosclerotic/drug therapy
11.
Int J Mol Sci ; 25(2)2024 Jan 22.
Article in English | MEDLINE | ID: mdl-38279349

ABSTRACT

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


Subject(s)
Glaucoma , Neuroprotective Agents , Reperfusion Injury , Retinal Diseases , Rats , Animals , Rats, Wistar , Cysteine/pharmacology , Cysteine/therapeutic use , Hydrogen Peroxide/therapeutic use , Reperfusion Injury/drug therapy , Retinal Diseases/drug therapy , Ischemia/drug therapy , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Glaucoma/drug therapy
12.
J Fr Ophtalmol ; 47(1): 103746, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37806937

ABSTRACT

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


Subject(s)
Glaucoma, Open-Angle , Glaucoma , Humans , Antioxidants/pharmacology , Antioxidants/metabolism , Trabecular Meshwork , Glaucoma, Open-Angle/drug therapy , Hydrogen Peroxide/pharmacology , Hydrogen Peroxide/metabolism , Hydrogen Peroxide/therapeutic use , Ghrelin/pharmacology , Ghrelin/metabolism , Ghrelin/therapeutic use , NF-E2-Related Factor 2/metabolism , NF-E2-Related Factor 2/pharmacology , NF-E2-Related Factor 2/therapeutic use
13.
Int J Mol Sci ; 24(24)2023 Dec 12.
Article in English | MEDLINE | ID: mdl-38139208

ABSTRACT

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


Subject(s)
Diabetes Mellitus, Type 2 , Diabetic Nephropathies , Dyslipidemias , Hyperglycemia , Sodium-Glucose Transporter 2 Inhibitors , Mice , Animals , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Sodium-Glucose Transporter 2 Inhibitors/pharmacology , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Glycemic Control , Hydrogen Peroxide/therapeutic use , Diabetic Nephropathies/metabolism , Inflammation , Antioxidants/pharmacology , Antioxidants/therapeutic use , Anti-Inflammatory Agents/therapeutic use
14.
Aust Dent J ; 68 Suppl 1: S141-S152, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37975331

ABSTRACT

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.


Subject(s)
Bleaching Agents , Tooth Bleaching , Humans , Tooth Bleaching/methods , Borates , Australia , Hydrogen Peroxide/therapeutic use
15.
J Clin Invest ; 134(3)2023 Nov 16.
Article in English | MEDLINE | ID: mdl-37971886

ABSTRACT

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.


Subject(s)
Glioblastoma , Humans , Glioblastoma/pathology , Cystathionine/therapeutic use , Cysteine/metabolism , Reactive Oxygen Species/metabolism , Hydrogen Peroxide/therapeutic use , Multiomics , Hydrogels
16.
Int J Periodontics Restorative Dent ; 43(6): 699-705, 2023 Nov 03.
Article in English | MEDLINE | ID: mdl-37921607

ABSTRACT

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.


Subject(s)
Dental Implants , Peri-Implantitis , Male , Swine , Humans , Female , Animals , Cattle , Middle Aged , Peri-Implantitis/diagnostic imaging , Peri-Implantitis/surgery , Hydrogen Peroxide/therapeutic use , Decontamination , Treatment Outcome
17.
Int J Periodontics Restorative Dent ; (7): s18-s25, 2023 10 24.
Article in English | MEDLINE | ID: mdl-37879050

ABSTRACT

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.


Subject(s)
Tooth Bleaching Agents , Tooth Bleaching , Animals , Cattle , Dental Enamel/chemistry , Hydrogen Peroxide/pharmacology , Hydrogen Peroxide/therapeutic use , Hydrogen Peroxide/analysis , Minerals , Tooth Bleaching/methods , Tooth Bleaching Agents/pharmacology , Tooth Bleaching Agents/therapeutic use , Tooth Bleaching Agents/analysis
18.
J Dent ; 139: 104744, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37852572

ABSTRACT

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.


Subject(s)
Bleaching Agents , Tooth Bleaching Agents , Tooth Bleaching , Humans , Tooth Bleaching/methods , Carbamide Peroxide , Charcoal/therapeutic use , Tooth Bleaching Agents/therapeutic use , Esthetics, Dental , Quality of Life/psychology , Powders , Toothpastes , Perception , Hydrogen Peroxide/therapeutic use , Urea/therapeutic use , Peroxides/therapeutic use
19.
J Mater Chem B ; 11(42): 10108-10120, 2023 11 01.
Article in English | MEDLINE | ID: mdl-37853796

ABSTRACT

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 Ca2+-crosslinked sodium alginate incorporated with photosensitizer-loaded MnO2 nanosheets and CaO2 nanoparticles for O2 self-sufficient PDT to eradicate biofilm infection. In our design, CaO2 reacts with water to produce locally concentrated H2O2, which could be catalyzed by MnO2 nanosheets (catalase-mimic nanozymes) to generate O2 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.


Subject(s)
Photochemotherapy , Staphylococcal Infections , Mice , Animals , Humans , Hydrogels/pharmacology , Hydrogels/therapeutic use , Manganese Compounds/therapeutic use , Hydrogen Peroxide/therapeutic use , Oxides/therapeutic use , Staphylococcal Infections/drug therapy , Biofilms
20.
Oper Dent ; 48(6): 627-637, 2023 Nov 01.
Article in English | MEDLINE | ID: mdl-37881142

ABSTRACT

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.


Subject(s)
Dentin Sensitivity , Tooth Bleaching Agents , Tooth Bleaching , Humans , Dentin Sensitivity/etiology , Hydrogen Peroxide/therapeutic use , Toothpastes/therapeutic use , Tooth Bleaching Agents/therapeutic use , Tooth Bleaching/adverse effects , Tooth Bleaching/methods , Treatment Outcome
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