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1.
Nanotechnology ; 35(40)2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-38991514

RESUMO

The widespread use of antibiotics often increases bacterial resistance. Herein, we reported a silver peroxide-incorporated carbon dots (defined as Ag2O2-CDs) with high photothermal conversion efficiency viain situoxidation process. The prepared Ag2O2-CDs exhibited ultra-small size of 2.0 nm and hybrid phase structure. Meanwhile, the Ag2O2-CDs were of a similar optical performance comparing with traditional carbon dots (CDs). Importantly, the incorporation of Ag2O2into CDs significantly enhanced photothermal conversion efficiency from 3.8% to 28.5%. By combining silver ion toxicity and photothermal ablation, the Ag2O2-CDs were capable of destroying gram-positive and gram-negative bacterium effectively. These findings demonstrated that the Ag2O2-CDs could be served as a potential antibacterial agent for clinical applications.


Assuntos
Antibacterianos , Carbono , Pontos Quânticos , Compostos de Prata , Carbono/química , Pontos Quânticos/química , Antibacterianos/farmacologia , Antibacterianos/química , Compostos de Prata/química , Compostos de Prata/farmacologia , Óxidos/química , Óxidos/farmacologia , Peróxidos/química , Peróxidos/farmacologia , Prata/química , Prata/farmacologia , Testes de Sensibilidade Microbiana , Escherichia coli/efeitos dos fármacos
2.
Antimicrob Agents Chemother ; 68(7): e0014324, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38899927

RESUMO

In response to the spread of artemisinin (ART) resistance, ART-based hybrid drugs were developed, and their activity profile was characterized against drug-sensitive and drug-resistant Plasmodium falciparum parasites. Two hybrids were found to display parasite growth reduction, stage-specificity, speed of activity, additivity of activity in drug combinations, and stability in hepatic microsomes of similar levels to those displayed by dihydroartemisinin (DHA). Conversely, the rate of chemical homolysis of the peroxide bonds is slower in hybrids than in DHA. From a mechanistic perspective, heme plays a central role in the chemical homolysis of peroxide, inhibiting heme detoxification and disrupting parasite heme redox homeostasis. The hybrid exhibiting slow homolysis of peroxide bonds was more potent in reducing the viability of ART-resistant parasites in a ring-stage survival assay than the hybrid exhibiting fast homolysis. However, both hybrids showed limited activity against ART-induced quiescent parasites in the quiescent-stage survival assay. Our findings are consistent with previous results showing that slow homolysis of peroxide-containing drugs may retain activity against proliferating ART-resistant parasites. However, our data suggest that this property does not overcome the limited activity of peroxides in killing non-proliferating parasites in a quiescent state.


Assuntos
Antimaláricos , Artemisininas , Plasmodium falciparum , Artemisininas/farmacologia , Antimaláricos/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Resistência a Medicamentos/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , Humanos , Testes de Sensibilidade Parasitária , Animais , Peróxidos/farmacologia
3.
Trop Biomed ; 41(1): 45-51, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38852133

RESUMO

Water pollution in developing countries continues to be a major health problem due to various anthropological activities that contribute to the spread of many parasitic diseases, including those caused by helminths. The aim of this study is to explore the ability of ozone and peroxone to disinfect drinking water contaminated samples with Toxocara canis eggs. The oxidants used were ozone and ozone-hydrogen peroxide combination. The treatment of Toxocara canis eggs was carried out in a 50 ml reactor with an operating volume of 10 ml. The pH conditions (5, 7 and 10) were varied for each treatment. The treatment effect was calculated by counting eggs and examining the condition of the larvae larval condition (whole, broken and hatched larvae) using an optical microscope. The experiment was carried out by exposing the eggs for 60 and 120 minutes to ozone and peroxone. The best results were obtained for helminths treated with the ozone/hydrogen peroxide combination at pH 10, with an inactivation of 79.2%. The synergistic effect of ozone combined with hydrogen peroxide allows higher helminth egg inactivation rates, demonstrating that advanced oxidation processes are a real alternative to apply in the inactivation of Toxocara canis eggs. The results obtained in this study show that the ozone and peroxone treatment could be a useful disinfection process to destroy or inactivate Toxocara canis eggs in processes commonly applied in water treatment.


Assuntos
Desinfetantes , Desinfecção , Ozônio , Toxocara canis , Animais , Ozônio/farmacologia , Toxocara canis/efeitos dos fármacos , Desinfecção/métodos , Desinfetantes/farmacologia , Concentração de Íons de Hidrogênio , Peróxido de Hidrogênio/farmacologia , Óvulo/efeitos dos fármacos , Purificação da Água/métodos , Peróxidos/farmacologia , Larva/efeitos dos fármacos , Água Potável/parasitologia
4.
Int J Mol Sci ; 25(10)2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38791232

RESUMO

The treatment of chronic wounds involves precise requirements and complex challenges, as the healing process cannot go beyond the inflammatory phase, therefore increasing the healing time and implying a higher risk of opportunistic infection. Following a better understanding of the healing process, oxygen supply has been validated as a therapeutic approach to improve and speed up wound healing. Moreover, the local implications of antimicrobial agents (such as silver-based nano-compounds) significantly support the normal healing process, by combating bacterial contamination and colonization. In this study, silver (S) and tannylated calcium peroxide (CaO2@TA) nanoparticles were obtained by adapted microfluidic and precipitation synthesis methods, respectively. After complementary physicochemical evaluation, both types of nanoparticles were loaded in (Alg) alginate-based gels that were further evaluated as possible dressings for wound healing. The obtained composites showed a porous structure and uniform distribution of nanoparticles through the polymeric matrix (evidenced by spectrophotometric analysis and electron microscopy studies), together with a good swelling capacity. The as-proposed gel dressings exhibited a constant and suitable concentration of released oxygen, as shown for up to eight hours (UV-Vis investigation). The biofilm modulation data indicated a synergistic antimicrobial effect between silver and tannylated calcium peroxide nanoparticles, with a prominent inhibitory action against the Gram-positive bacterial biofilm after 48 h. Beneficial effects in the human keratinocytes cultured in contact with the obtained materials were demonstrated by the performed tests, such as MTT, LDH, and NO.


Assuntos
Alginatos , Peróxidos , Prata , Cicatrização , Alginatos/química , Alginatos/farmacologia , Cicatrização/efeitos dos fármacos , Humanos , Prata/química , Prata/farmacologia , Peróxidos/química , Peróxidos/farmacologia , Géis/química , Nanopartículas/química , Queratinócitos/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Nanopartículas Metálicas/química , Antibacterianos/farmacologia , Antibacterianos/química , Bandagens , Taninos/química , Taninos/farmacologia
5.
Phytomedicine ; 129: 155640, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38714091

RESUMO

BACKGROUND: The discovery of artemisinin, an endoperoxide, encouraged the scientific community to explore endoperoxides as potential anti-parasitic molecules. Although artemisinin derivatives are rapidly evolving as potent anti-malarials, their potential as anti-leishmanials is emerging gradually. The treatment of leishmaniasis, a group of neglected tropical diseases is handicapped by lack of effective vaccines, drug toxicities and drug resistance. The weak antioxidant defense mechanism of the Leishmania parasites due to lack of catalase and a selenium dependent glutathione peroxidase system makes them vulnerable to oxidative stress, and this has been successful exploited by endoperoxides. PURPOSE: The study aimed to review the available literature on the anti-leishmanial efficacy of natural endoperoxides with a view to achieve insights into their mode of actions. METHODS: We reviewed more around 110 research and review articles restricted to the English language, sourced from electronic bibliographic databases including PubMed, Google, Web of Science, Google scholar etc. RESULTS: Natural endoperoxides could potentially augment the anti-leishmanial drug library, with artemisinin and ascaridole emerging as potential anti-leishmanial agents. Due to higher reactivity of the cyclic peroxide moiety, and exploiting the compromised antioxidant defense of Leishmania, endoperoxides like artemisinin and ascaridole potentiate their leishmanicidal efficacy by creating a redox imbalance. Furthermore, these molecules minimally impair oxidative phosphorylation; instead inhibit glycolytic functions, culminating in depolarization of the mitochondrial membrane and depletion of ATP. Additionally, the carbon-centered free radicals generated from endoperoxides, participate in chain reactions that can generate even more reactive organic radicals that are toxic to macromolecules, including lipids, proteins and DNA, leading to cell cycle arrest and apoptosis of Leishmania parasites. However, the precise target(s) of the toxic free radicals remains open-ended. CONCLUSION: In this overview, the spectrum of natural endoperoxide molecules as major anti-leishmanials and their mechanism of action has been delineated. In view of the substantial evidence that natural endoperoxides (e.g., artemisinin, ascaridole) exert a noxious effect on different species of Leishmania, identification and characterization of other natural endoperoxides is a promising therapeutic option worthy of further pharmacological consideration.


Assuntos
Antiprotozoários , Artemisininas , Leishmania , Peróxidos , Leishmania/efeitos dos fármacos , Peróxidos/farmacologia , Peróxidos/química , Antiprotozoários/farmacologia , Antiprotozoários/química , Artemisininas/farmacologia , Artemisininas/química , Humanos , Leishmaniose/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/farmacologia
6.
Am J Dent ; 37(2): 78-84, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38704850

RESUMO

PURPOSE: To evaluate how fluoride- or chitosan-based toothpaste used during at-home bleaching affects enamel roughness, tooth color, and staining susceptibility. METHODS: Bovine enamel blocks were submitted to a 14-day cycling regime considering a factorial design (bleaching agent x toothpaste, 2 x 3), with n=10: (1) bleaching with 16% carbamide peroxide (CP) or 6% hydrogen peroxide (HP), and (2) daily exposure of a fluoride (1,450 ppm F-NaF) toothpaste (FT), chitosan-based toothpaste (CBT), or distilled water (control). Then, 24 hours after the last day of bleaching procedure the samples were exposed to a coffee solution. Color (ΔEab, ΔE00, L*, a*, b*) and roughness (Ra, µm) analyses were performed to compare the samples initially (baseline), after bleaching, and after coffee staining. The results were evaluated by linear models for repeated measures (L*, a*, b*, and Ra), 2-way ANOVA (ΔEab, ΔE00) and Tukey's test (α= 0.05). RESULTS: After the at-home bleaching procedure (toothpaste vs. time, P< 0.0001), the toothpaste groups presented a statistically lower Ra than the control (CBT 0.05). After coffee exposure, CBT presented lower ΔEab and ΔE00 values in the HP groups (toothpaste, P< 0.0001), and lower b* and a* values in the CP groups (toothpaste vs. time, P= 0.004). CLINICAL SIGNIFICANCE: Fluoride or chitosan delivered by toothpaste can reduce surface alterations of the enamel during at-home bleaching, without affecting bleaching efficacy.


Assuntos
Peróxido de Carbamida , Quitosana , Esmalte Dentário , Peróxido de Hidrogênio , Clareadores Dentários , Clareamento Dental , Descoloração de Dente , Cremes Dentais , Quitosana/farmacologia , Cremes Dentais/farmacologia , Animais , Bovinos , Clareamento Dental/métodos , Esmalte Dentário/efeitos dos fármacos , Clareadores Dentários/farmacologia , Peróxido de Hidrogênio/farmacologia , Peróxido de Carbamida/farmacologia , Propriedades de Superfície , Fluoretos/farmacologia , Cor , Ureia/análogos & derivados , Ureia/farmacologia , Café , Peróxidos/farmacologia
7.
Adv Healthc Mater ; 13(16): e2303314, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38558386

RESUMO

Nonhealing diabetic wounds are predominantly attributed to the inhibition of angiogenesis, re-epithelialization, and extracellular matrix (ECM) synthesis caused by hypoxia. Although oxygen therapy has demonstrated efficacy in promoting healing, its therapeutic impact remains suboptimal due to unsustainable oxygenation. Here, this work proposes an oxygen-releasing hydrogel patch embedded with polyethylene glycol-modified calcium peroxide microparticles, which sustainably releases oxygen for 7 days without requiring any supplementary conditions. The released oxygen effectively promotes cell migration and angiogenesis under hypoxic conditions as validated in vitro. The in vivo tests in diabetic mice models show that the sustainably released oxygen significantly facilitates the synthesis of ECM, induces angiogenesis, and decreases the expression of inflammatory cytokines, achieving a diabetic wound healing rate of 84.2% on day 7, outperforming the existing oxygen-releasing approaches. Moreover, the proposed hydrogel patch is designed with porous, soft, antibacterial, biodegradable, and storage stability for 15 days. The proposed hydrogel patch is expected to be promising in clinics treating diabetic wounds.


Assuntos
Diabetes Mellitus Experimental , Hidrogéis , Oxigênio , Peróxidos , Cicatrização , Cicatrização/efeitos dos fármacos , Animais , Hidrogéis/química , Hidrogéis/farmacologia , Camundongos , Oxigênio/química , Peróxidos/química , Peróxidos/farmacologia , Humanos , Polietilenoglicóis/química , Neovascularização Fisiológica/efeitos dos fármacos , Masculino , Células Endoteliais da Veia Umbilical Humana , Movimento Celular/efeitos dos fármacos
8.
ACS Appl Mater Interfaces ; 16(19): 24172-24190, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38688027

RESUMO

Of the most common, hypoxia, overexpressed glutathione (GSH), and insufficient H2O2 concentration in the tumor microenvironment (TME) are the main barriers to the advancment of reactive oxygen species (ROS) mediated Xdynamic therapies (X = photo, chemodynamic, chemo). Maximizing Fenton catalytic efficiency is crucial in chemodynamic therapy (CDT), yet endogenous H2O2 levels are not sufficient to attain better anticancer efficacy. Specifically, there is a need to amplify Fenton reactivity within tumors, leveraging the unique attributes of the TME. Herein, for the first time, we design RuxCu1-xO2-Ce6/CPT (RCpCCPT) anticancer nanoagent for TME-mediated synergistic therapy based on heterogeneous Ru-Cu peroxide nanodots (RuxCu1-xO2 NDs) and chlorine e6 (Ce6), loaded with ROS-responsive thioketal (TK) linked-camptothecin (CPT). The Ru-Cu peroxide NDs (RCp NDs, x = 0.50) possess the highest oxygen vacancy (OV) density, which grants them the potential to form massive Lewis's acid sites for peroxide adsorption, while the dispersibility and targetability of the NDs were improved via surface modification using hyaluronic acid (HA). In TME, RCpCCPT degrades, releasing H2O2, Ru2+/3+, and Cu+/2+ ions, which cooperatively facilitate hydroxyl radical (•OH) formation and deactivate antioxidant GSH enzymes through a cocatalytic loop, resulting in excellent tumor therapeutic efficacy. Furthermore, when combined with laser treatment, RCpCCPT produces singlet oxygen (1O2) for PDT, which induces cell apoptosis at tumor sites. Following ROS generation, the TK linkage is disrupted, releasing up to 92% of the CPT within 48 h. In vitro investigations showed that laser-treated RCpCCPT caused 81.5% cell death from PDT/CDT and chemotherapy (CT). RCpCCPT in cancer cells produces red-blue emission in images of cells taking them in, which allows for fluorescence image-guided Xdynamic treatment. The overall results show that RCp NDs and RCpCCPT are more biocompatible and have excellent Xdynamic therapeutic effectiveness in vitro and in vivo.


Assuntos
Cobre , Peróxido de Hidrogênio , Rutênio , Microambiente Tumoral , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/farmacologia , Microambiente Tumoral/efeitos dos fármacos , Cobre/química , Cobre/farmacologia , Animais , Camundongos , Humanos , Rutênio/química , Rutênio/farmacologia , Nanopartículas/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Peróxidos/química , Peróxidos/farmacologia , Linhagem Celular Tumoral , Fotoquimioterapia , Portadores de Fármacos/química , Espécies Reativas de Oxigênio/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/patologia
9.
Phytochemistry ; 223: 114097, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38641142

RESUMO

A chemical investigation of the dichloromethane extract from the Xisha sponge Diacarnus sp. revealed seven undescribed norterpene cyclic peroxides, named diacarperoxides T-Z, and five unreported related norterpenes, named diacarnoids E-I, and eleven previously reported compounds. The structures of these isolated compounds, including their absolute configurations, were elucidated based on extensive spectroscopic analyses, electronic circular dichroism (ECD) calculations, Snatzke's method, [Rh2(OCOCF3)4]-induced ECD spectra, and modified Mosher's method. Bioassays were performed to assess the antibacterial activity against six pathogenic bacteria, cytotoxicities toward three cancer cell lines, and antimalarial activity against Plasmodium parasites. Most of the cyclic peroxides exhibited substantial antibacterial activity (MIC 1-8 µg/mL). Diacarperoxide W and nuapapuin A showed substantial antimalarial activity with IC50 values of 0.98 and 2.83 µM. Moreover, many compounds exhibited <50% cell survival rates, and IC50 values of 0.22-6.33 µM. The apoptosis assay showed that nuapapuin A induced cancer cell apoptosis in a dose-dependent manner.


Assuntos
Antibacterianos , Antimaláricos , Peróxidos , Poríferos , Antimaláricos/farmacologia , Antimaláricos/química , Antimaláricos/isolamento & purificação , Poríferos/química , Peróxidos/farmacologia , Peróxidos/química , Peróxidos/isolamento & purificação , Humanos , Animais , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Estrutura Molecular , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Ensaios de Seleção de Medicamentos Antitumorais , Apoptose/efeitos dos fármacos , Testes de Sensibilidade Parasitária , Plasmodium falciparum/efeitos dos fármacos , Relação Estrutura-Atividade , Testes de Sensibilidade Microbiana , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Sobrevivência Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos
10.
J Colloid Interface Sci ; 668: 12-24, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38669989

RESUMO

The coexistence of antibiotic resistance genes (ARGs) and antibiotic-resistant bacteria (ARB) in the environment poses a potential threat to public health. In our study, we have developed a novel advanced oxidation process for simultaneously removing ARGs and ARB by two types of iron and nitrogen-doped biochar derived from rice straw (FeN-RBC) and sludge (FeN-SBC). All viable ARB (approximately 108 CFU mL-1) was inactivated in the FeN-RBC/ peroxymonosulfate (PMS) system within 40 min and did not regrow after 48 h even in real water samples. Flow cytometry identified 96.7 % of dead cells in the FeN-RBC/PMS system, which verified the complete inactivation of ARB. Thorough disinfection of ARB was associated with the disruption of cell membranes and intracellular enzymes related to the antioxidant system. Whereas live bacteria (approximately 200 CFU mL-1) remained after FeN-SBC/PMS treatment. Intracellular and extracellular ARGs (tetA and tetB) were efficiently degraded in the FeN-RBC/PMS system. The production of active species, primarily •OH, SO4•- and Fe (IV), as well as electron transfer, were essential to the effective disinfection of FeN-RBC/PMS. In comparison with FeN-SBC, the better catalytic performance of FeN-RBC was mainly ascribed to its higher amount of pyridine-N and Fe0, and more reactive active sites (such as CO group and Fe-N sites). Density functional theory calculations indicated the greater adsorption energy and Bader charge, more stable Fe-O bond, more easily broken OO bond in FeN-RBC/PMS, which demonstrated the stronger electron transfer capacity between FeN-RBC and PMS. To encapsulate, our study provided an efficient and dependable method for the simultaneous elimination of ARGs and ARB in water.


Assuntos
Carvão Vegetal , Ferro , Peróxidos , Piridinas , Piridinas/química , Piridinas/farmacologia , Carvão Vegetal/química , Carvão Vegetal/farmacologia , Ferro/química , Ferro/metabolismo , Peróxidos/química , Peróxidos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Nitrogênio/química , Bactérias/efeitos dos fármacos , Bactérias/genética , Propriedades de Superfície
11.
J Colloid Interface Sci ; 668: 88-97, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38669999

RESUMO

Nanotheranostic platforms, which can respond to tumor microenvironments (TME, such as low pH and hypoxia), are immensely appealing for photodynamic therapy (PDT). However, hypoxia in solid tumors harms the treatment outcome of PDT which depends on oxygen molecules to generate cytotoxic singlet oxygen (1O2). Herein, we report the design of TME-responsive smart nanotheranostic platform (DOX/ZnO2@Zr-Ce6/Pt/PEG) which can generate endogenously hydrogen peroxide (H2O2) and oxygen (O2) to alleviate hypoxia for improving photodynamic-chemo combination therapy of tumors. DOX/ZnO2@Zr-Ce6/Pt/PEG nanocomposite was prepared by the synthesis of ZnO2 nanoparticles, in-situ assembly of Zr-Ce6 as typical metal-organic framework (MOF) on ZnO2 surface, in-situ reduction of Pt nanozymes, amphiphilic lipids surface coating and then doxorubicin (DOX) loading. DOX/ZnO2@Zr-Ce6/Pt/PEG nanocomposite exhibits average sizes of ∼78 nm and possesses a good loading capacity (48.8 %) for DOX. When DOX/ZnO2@Zr-Ce6/Pt/PEG dispersions are intratumorally injected into mice, the weak acidic TEM induces the decomposition of ZnO2 core to generate endogenously H2O2, then Pt nanozymes catalyze H2O2 to produce O2 for alleviating tumor hypoxia. Upon laser (630 nm) irradiation, the Zr-Ce6 component in DOX/ZnO2@Zr-Ce6/Pt/PEG can produce cytotoxic 1O2, and 1O2 generation rate can be enhanced by 2.94 times due to the cascaded generation of endogenous H2O2/O2. Furthermore, the generated O2 can suppress the expression of hypoxia-inducible factor α, and further enable tumor cells to become more sensitive to chemotherapy, thereby leading to an increased effectiveness of chemotherapy treatment. The photodynamic-chemo combination therapy from DOX/ZnO2@Zr-Ce6/Pt/PEG nanoplatform exhibits remarkable tumor growth inhibition compared to chemotherapy or PDT. Thus, the present study is a good demonstration of a TME-responsive nanoplatform in a multimodal approach for cancer therapy.


Assuntos
Doxorrubicina , Peróxido de Hidrogênio , Oxigênio , Fotoquimioterapia , Nanomedicina Teranóstica , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/metabolismo , Animais , Camundongos , Doxorrubicina/farmacologia , Doxorrubicina/química , Doxorrubicina/administração & dosagem , Oxigênio/química , Oxigênio/metabolismo , Humanos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Tamanho da Partícula , Propriedades de Superfície , Ensaios de Seleção de Medicamentos Antitumorais , Sobrevivência Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Peróxidos/química , Peróxidos/farmacologia , Nanopartículas/química , Camundongos Endogâmicos BALB C , Zinco/química , Zinco/farmacologia , Microambiente Tumoral/efeitos dos fármacos , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/administração & dosagem
12.
Phytochemistry ; 222: 114070, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38574957

RESUMO

Ten ergostane-type steroids, including seven undescribed ones named spectasteroids A-G, were obtained from Aspergillus spectabilis. Their structures and absolute configurations were determined based on HRESIMS, NMR, ECD calculations, and single-crystal X-ray diffraction analyses. Structurally, spectasteroid A was a unique example of aromatic ergostane-type steroid that featured a rare peroxide ring moiety; spectasteroid B contained a rare oxetane ring system formed between C-9 and C-14; and spectasteroid C was an unusual 3,4-seco-ergostane steroid with an extra lactone ring between C-3 and C-9. Spectasteroids F and G specifically showed inhibitory effects against concanavalin A-induced T lymphocyte proliferation and lipopolysaccharide-induced B lymphocyte proliferation, with IC50 values ranging from 2.33 to 4.22 µM. Spectasteroid F also showed excellent antimultidrug resistance activity, which remarkable enhanced the inhibitory activity of PTX on the colony formation of SW620/Ad300 cells.


Assuntos
Aspergillus , Imunossupressores , Peróxidos , Aspergillus/química , Imunossupressores/farmacologia , Imunossupressores/química , Imunossupressores/isolamento & purificação , Peróxidos/química , Peróxidos/farmacologia , Peróxidos/isolamento & purificação , Estrutura Molecular , Humanos , Lactonas/química , Lactonas/farmacologia , Lactonas/isolamento & purificação , Ergosterol/química , Ergosterol/farmacologia , Ergosterol/isolamento & purificação , Ergosterol/análogos & derivados , Proliferação de Células/efeitos dos fármacos , Éteres Cíclicos/química , Éteres Cíclicos/farmacologia , Éteres Cíclicos/isolamento & purificação , Relação Estrutura-Atividade , Relação Dose-Resposta a Droga , Camundongos , Linfócitos T/efeitos dos fármacos
13.
Clin Oral Investig ; 28(4): 224, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38509406

RESUMO

OBJECTIVES: To evaluate the bleaching efficacy and permeability of hydrogen peroxide (HP) in the pulp chamber of human teeth bleached with lower concentrations of carbamide peroxide gel (4%, 5% and 7% CP). MATERIALS AND METHODS: Bleaching gels with lower concentrations were formulated and a commercial standard gel, 10% CP, was used as a reference. Fifty-six human premolars were randomly divided into four groups. Applications of the bleaching gel were made for 3 h for 21 days. The bleaching efficacy was evaluated by digital spectrophotometry on 1, 7, 14 and 21 days, with analysis in the ∆Eab, ∆E00 and WID color spaces. The concentration of HP in the pulp chamber was measured in the same periods by UV-Vis spectrophotometry (µg/mL). Two-way repeated analysis of variance (ANOVA) examined bleaching efficacy and HP permeability, followed by Tukey's post-hoc test (α = 0.05). RESULTS: All groups showed significant color changes, with no statistical differences after the second and third week of bleaching (p > 0.05). The 'time' factor was statistically different (p < 0.05), increasing the bleaching efficacy throughout the treatment. The 4% CP group had lower HP levels in the pulp chamber (p < 0.05). CONCLUSIONS: The results seem promising, revealing that low concentration gels are as effective as 10% CP with the benefit of reducing the amount of HP in the pulp chamber. CLINICAL RELEVANCE: Low concentration 4% PC and 5% PC maintains bleaching efficacy, reduces the penetration of HP peroxide into the pulp chamber, and may reduce tooth sensitivity.


Assuntos
Clareadores Dentários , Clareamento Dental , Humanos , Peróxido de Carbamida , Cavidade Pulpar , Clareadores Dentários/farmacologia , Peróxido de Hidrogênio , Clareamento Dental/métodos , Ácido Hipocloroso , Géis , Ureia/farmacologia , Peróxidos/farmacologia
14.
Spectrochim Acta A Mol Biomol Spectrosc ; 313: 124142, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38493515

RESUMO

In this work, we investigated the oxidative stress-related biochemical alterations in red blood cells (RBCs) and their membranes with the use of spectroscopic techniques. We aimed to show their great advantage for the in situ detection of lipid classes and secondary structures of proteins without the need for their extraction in the cellular environment. The exposition of the cells to peroxides, t-butyl hydroperoxide (tBOOH) or hydrogen peroxide (H2O2) led to different degradation processes encompassing the changes in the composition of membranes and structural modifications of hemoglobin (Hb). Our results indicated that tBOOH is generally a stronger oxidizing agent than H2O2 and this observation was congruent with the activity of superoxide and glutathione peroxidase. ATR-FTIR and Raman spectroscopies of membranes revealed that tBOOH caused primarily the partial loss and peroxidation of the lipids resulting in loss of the integrity of membranes. In turn, both peroxides induced several kinds of damage in the protein layer, including the partial decrease of their content and irreversible aggregation of spectrin, ankyrin, and membrane-bound globin. These changes were especially pronounced on the membrane surface where stress conditions induced the formation of ß-sheets and intramolecular aggregates, particularly for tBOOH. Interestingly, nano-FTIR spectroscopy revealed the lipid peroxidative damage on the membrane surface in both cases. As far as hemoglobin was concerned, tBOOH and H2O2 caused the increase of the oxyhemoglobin species and conformational alterations of its polypeptide chain into ß-sheets. Our findings confirm that applied spectroscopies effectively track the oxidative changes occurring in the structural components of red blood cells and the simplicity of conducting measurements and sample preparation can be readily applied to pharmacological and clinical studies.


Assuntos
Eritrócitos , Peróxido de Hidrogênio , Humanos , Peróxido de Hidrogênio/farmacologia , Peróxido de Hidrogênio/metabolismo , Eritrócitos/metabolismo , Hemoglobinas/metabolismo , Peróxidos/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Lipídeos , Estresse Oxidativo
15.
J Dent ; 143: 104902, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38432352

RESUMO

OBJECTIVE: To investigate the effect of tooth whitening on biomechanical properties of vacuum-formed retainers (VFRs). METHODS: Using a split-mouth, randomised controlled trial design, thirty participants were randomly allocated to receive whitening on either the upper or the lower arch, using 10 % carbamide peroxide for two weeks. Biomechanical properties such as hardness, tensile strength, and surface roughness were assessed two weeks after whitening was completed. RESULTS: Tensile strength of the whitening arch (mean ± SD: 40.93 ± 3.96 MPa) was significantly lower than that of the control (47.40 ± 5.03 MPa) (difference 6.47 MPa, 95 % CI 4.51 - 8.42, p < 0.001). Hardness and internal roughness of the whitening arch (VHN = 14.63 ± 2.29 N/mm2 and Ra = 1.33 ± 0.35 µm, respectively) were significantly greater than those of the control (12.22 ± 1.86 N/mm2 and 0.96 ± 0.29 µm, respectively) (differences 2.41 N/mm2, 95 % CI 1.56 - 3.25, p < 0.001 and 0.37 µm, 95 % CI 0.23 - 0.51, p < 0.001, respectively). The whitening arch showed greater tooth colour change (ΔE = 6.00 ± 3.32) than the control (ΔE = 2.50 ± 1.70) (difference = 3.50, 95 % CI 2.43 - 4.56, p < 0.001). CONCLUSIONS: Based on this short-term study, marked tooth colour change was achieved by whitening with VFRs as the whitening trays, but this changed the VFRs' biomechanical properties, including a decrease in tensile strength and an increase in hardness and internal roughness. CLINICAL SIGNIFICANCE: The application of carbamide peroxide in VFRs may compromise their mechanical properties.


Assuntos
Clareadores Dentários , Clareamento Dental , Dente , Humanos , Peróxido de Carbamida , Vácuo , Clareadores Dentários/farmacologia , Ureia , Peróxidos/farmacologia , Peróxido de Hidrogênio/farmacologia , Combinação de Medicamentos
16.
J Nat Prod ; 87(2): 358-364, 2024 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-38320400

RESUMO

Bioassay-guided isolation of the extract from the marine sponge Diacarnus spinipoculum showing inhibitory activity against human transient receptor potential ankyrin 1 (hTRPA1) resulted in the isolation of 12 norditerpene cyclic peroxides (1-12) and eight norsesterterpene cyclic peroxides (13-20). Among these, 10 (5-7, 11, 12, 16-20) are unprecedented analogs. Compounds with either a hydroxy (5, 11) or a methoxy (6, 12) group attached to the cyclohexanone moiety were obtained as epimeric mixtures at C-11, while compounds 4, 6, 10, and 12 are likely the artifacts of isolation. The absolute configurations of the new compounds were established based on an NMR-based empirical method and comparison of specific rotation values. Mosher ester analysis revealed the absolute configurations of compounds 17-20. The inhibitory activity of the isolated compounds against hTRPA1 varied significantly depending on their structures, with the norsesterterpenoid 19 displaying the most potent activity (IC50 2.0 µM).


Assuntos
Diterpenos , Poríferos , Animais , Humanos , Anquirinas/antagonistas & inibidores , Estrutura Molecular , Peróxidos/farmacologia , Peróxidos/química , Poríferos/química , Terpenos/farmacologia , Terpenos/química
17.
Adv Healthc Mater ; 13(15): e2304212, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38259234

RESUMO

The emergence of nanomotor provides an innovative concept for tumor treatment strategies. Conventional chemotherapeutic agents for tumors exit various therapeutic constraints due to the unique microenvironment of the tumor itself. Calcium overload, the aberrant accumulation of free calcium ions in the cytoplasm, is a well-recognized contributor to damage and even cell death in numerous cell types. Such undesired destructive processes can be a novel means applicable to cancer ion interference therapy. Herein, the chemotherapeutic drug doxorubicin (DOX) and calcium peroxide as the driving force into nanomotors through a facile and understandable experimental scheme are successfully assembled. The modification of nucleic acid aptamer and NIR-II fluorescent molecules on its surface simultaneously strengthens both the active targeting and imaging capability of tumor loci. Therefore, by a comprehensive assessment of nanomotors both in vitro and in vivo experiments, CaO2/DOX@HPS-IR-1061-AS1411 demonstrates superior killing effects on tumor cells, and the intracellular reactive oxygen species produced by nanomotors is verified by molecular biology experiments to induce apoptosis of tumor cells and further achieve tumor therapeutic effects.


Assuntos
Doxorrubicina , Neoplasias , Doxorrubicina/farmacologia , Doxorrubicina/química , Doxorrubicina/uso terapêutico , Humanos , Animais , Linhagem Celular Tumoral , Camundongos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Espécies Reativas de Oxigênio/metabolismo , Peróxidos/química , Peróxidos/farmacologia , Apoptose/efeitos dos fármacos , Aptâmeros de Nucleotídeos/química , Aptâmeros de Nucleotídeos/farmacologia , Nanopartículas/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Camundongos Nus , Camundongos Endogâmicos BALB C
18.
Eur J Oral Sci ; 132(1): e12958, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37853653

RESUMO

This clinical trial investigated the effects of pre-application enamel moistening on the impact of a 37% carbamide peroxide whitener on tooth color changes and the influence of repositioning guide colors. Forty participants were randomly assigned to in-office tooth bleaching with either moistened enamel (experimental) or dry enamel (control). The whitener was applied for 45 min over two sessions. Tooth color was visually measured or assessed using a spectrophotometer with purple or green silicone guides. Tooth bleaching was assessed using CIE76 (ΔEab ) and CIEDE2000 (ΔE00 ) formulas and by whitening and bleaching index score changes. Moistening the enamel did not significantly affect tooth color. However, the guide color choice only impacted tooth color when measured instrumentally. At baseline, the green guide resulted in statistically significantly whiter teeth than the purple guide. Less pronounced differences in the b* coordinate between baseline and final measurements were found using the green guide. The green guide also produced lower ΔEab values and less change in indexes. In conclusion, moistening the enamel did not significantly impact tooth color changes. However, the repositioning guide color influenced the tooth bleaching measured instrumentally, except for ΔE00 .


Assuntos
Clareadores Dentários , Clareamento Dental , Descoloração de Dente , Humanos , Clareamento Dental/métodos , Peróxidos/farmacologia , Clareadores Dentários/farmacologia , Ureia , Esmalte Dentário , Cor , Peróxido de Hidrogênio
19.
Neurotox Res ; 42(1): 2, 2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-38095761

RESUMO

A feature in neurodegenerative disorders is the loss of neurons, caused by several factors including oxidative stress induced by reactive oxygen species (ROS). In this work, static magnetic field (SMF) was applied in vitro to evaluate its effect on the viability, proliferation, and migration of human neuroblastoma SH-SY5Y cells, and on the toxicity induced by hydrogen peroxide (H2O2), tert-butyl hydroperoxide (tBHP), H2O2/sodium azide (NaN3) and photosensitized oxidations by photodynamic therapy (PDT) photosensitizers. The SMF increased almost twofold the cell expression of the proliferation biomarker Ki-67 compared to control cells after 7 days of exposure. Exposure to SMF accelerated the wound healing of scratched cell monolayers and significantly reduced the H2O2-induced and the tBHP-induced cell deaths. Interestingly, SMF was able to revert the effects of NaN3 (a catalase inhibitor), suggesting an increased activity of catalase under the influence of the magnetic field. In agreement with this hypothesis, SMF significantly reduced the oxidation of DCF-H2, indicating a lower level of intracellular ROS. When the redox imbalance was triggered through photosensitized oxidation, no protection was observed. This observation aligns with the proposed role of catalase in cellular proctetion under SMF.  Exposition to SMF should be further validated in vitro and in vivo as a potential therapeutic approach for neurodegenerative disorders.


Assuntos
Neuroblastoma , Doenças Neurodegenerativas , Humanos , Espécies Reativas de Oxigênio/metabolismo , Peróxidos/farmacologia , Peróxido de Hidrogênio/toxicidade , Linhagem Celular Tumoral , Catalase/metabolismo , Neuroblastoma/metabolismo , Estresse Oxidativo , Campos Magnéticos
20.
J Mater Chem B ; 11(40): 9685-9696, 2023 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-37789698

RESUMO

Ferroptosis has appealing antitumor potential that is mainly based on the accumulation of lipid peroxide to a lethal level. The cytotoxic singlet oxygen (1O2) generated from nanoscale X-ray-induced photodynamic therapy (X-PDT) may facilitate glutathione (GSH) depletion and further activate ferroptosis. To realize combined X-PDT and ferroptosis, a nanocarrier (D-NPVR) was engineered with a hyperbranched copolymer with 1O2-sensitive linkers, where both the photosensitizer (verteporfin) and ferroptosis inducer RAS-selective lethal small molecule 3 (RSL3) were encapsulated. Upon X-ray radiation, D-NPVR could produce a large amount of 1O2 for apoptosis. Subsequently, 1O2 triggered D-NP dissociation by cleavage of 1,2-bis(2-hydroxyethylthio)ethylene bonds to boost payload release and decrease levels of intracellular GSH via thiol oxidation. Liberated RSL3 is a covalent inhibitor for glutathione peroxide 4 (GPX4), which is responsible for detoxifying lipid peroxides to lipid alcohols with GSH assistance, and both 1O2-induced GSH depletion and GPX4 inactivation thereby produced ferroptotic cell death. Tumor growth inhibition in murine 4T1 tumor-bearing mice demonstrated that D-NPVR produced pronounced therapeutic efficiency where ferroptosis induction was supported by the GPX4 content and expression. This study highlights the contribution of 1O2-sensitive nanocarriers for promoting the potency of combined X-PDT and ferroptosis.


Assuntos
Ferroptose , Neoplasias , Fotoquimioterapia , Animais , Camundongos , Oxigênio Singlete , Raios X , Linhagem Celular Tumoral , Peróxidos/farmacologia , Peróxidos Lipídicos/farmacologia , Glutationa/metabolismo
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