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1.
Biol Res ; 54(1): 27, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488902

RESUMO

BACKGROUND: Demethylzeylasteral (T-96) is a pharmacologically active triterpenoid monomer extracted from Tripterygium wilfordii Hook F (TWHF) that has been reported to exhibit anti-neoplastic effects against several types of cancer cells. However, the potential anti-tumour effects of T-96 against human Prostate cancer (CaP) cells and the possible underlying mechanisms have not been well studied. RESULTS: In the current study, T-96 exerted significant cytotoxicity to CaP cells in vitro and induced cell cycle arrest at S-phase in a dose-dependent manner. Mechanistically, T-96 promoted the initiation of autophagy but inhibited autophagic flux by inducing ROS-mediated endoplasmic reticulum (ER) stress which subsequently activated the extrinsic apoptosis pathway in CaP cells. These findings implied that T-96-induced ER stress activated the caspase-dependent apoptosis pathway to inhibit proliferation of CaP cells. Moreover, we observed that T-96 enhances the sensitivity of CaP cells to the chemotherapeutic drug, cisplatin. CONCLUSIONS: Taken together, our data demonstrated that T-96 is a novel modulator of ER stress and autophagy, and has potential therapeutic applications against CaP in the clinic.


Assuntos
Autofagia , Neoplasias da Próstata , Apoptose , Linhagem Celular Tumoral , Humanos , Masculino , Neoplasias da Próstata/tratamento farmacológico , Espécies Reativas de Oxigênio , Triterpenos
2.
Appl Microbiol Biotechnol ; 105(18): 6707-6718, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34476516

RESUMO

Pneumocandin B0, the precursor of the antifungal drug caspofungin, is a lipohexapeptide produced by the fungus Glarea lozoyensis. Oxidative stress and the resulting production of reactive oxygen species (ROS) are known to be involved in the regulation of pneumocandin B0 biosynthesis. In this study, the Glyap1 gene of Glarea lozoyensis, a homologue of the yeast redox regulator YAP1, was knocked out. The intracellular ROS levels of the resulting ΔGlyap1 strain were higher than in the wild-type strain, which was caused by the downregulated expression of superoxide dismutase (SOD) and catalase (CAT). Compared with the wild-type strain, ΔGlyap1 exhibited an oxidative phenotype throughout its life cycle, which resulted in significantly higher pneumocandin B0 production per unit biomass. In addition, ΔGlyap1 showed growth inhibition and decreased pneumocandin B0 production in the presence of CCl4, which leads to strong oxidative stress. To overcome the strain's sensitivity, a three-stage antioxidant addition strategy was developed. This approach significantly improved the growth of ΔGlyap1 while maintaining a high pneumocandin B0 production per unit biomass, which reached 38.78 mg/g DCW. Notably, this result represents a 50% increase over the wild-type strain. These findings provide new insights into the regulatory mechanisms that control pneumocandin B0 production under oxidative stress, which may be applied to improve the production of other secondary metabolites. KEY POINTS: • Glyap1 is involved in expression of redox and pneumocandin B0 synthesis-related genes. • Addition of a three-stage antioxidant alleviated the sensitivity of ΔGlyap1 strain. • The yield of pneumocandin B0 per unit biomass of ΔGlyap1 strain was 38.78 mg/g DCW.


Assuntos
Ascomicetos , Equinocandinas , Ascomicetos/genética , Ascomicetos/metabolismo , Equinocandinas/metabolismo , Oxirredução , Estresse Oxidativo , Espécies Reativas de Oxigênio
3.
Cancer Genomics Proteomics ; 18(5): 661-673, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34479918

RESUMO

BACKGROUND/AIM: Coronavirus disease 2019 (COVID-19) poses a great challenge for the treatment of cancer patients. It presents as a severe respiratory infection in aged individuals, including some lung cancer patients. COVID-19 may be linked to the progression of aggressive lung cancer. In addition, the side effects of chemotherapy, such as chemotherapy resistance and the acceleration of cellular senescence, can worsen COVID-19. Given this situation, we investigated the role of paclitaxel (a chemotherapy drug) in the cell proliferation, apoptosis, and cellular senescence of gefitinib-resistant non-small-cell lung cancer (NSCLC) cells (PC9-MET) to clarify the underlying mechanisms. MATERIALS AND METHODS: PC9-MET cells were treated with paclitaxel for 72 h and then evaluated by a cell viability assay, DAPI staining, Giemsa staining, apoptosis assay, a reactive oxygen species (ROS) assay, SA-ß-Gal staining, a terminal deoxynucleotidyl transferase dUTP nick-end labeling assay and Western blotting. RESULTS: Paclitaxel significantly reduced the viability of PC9-MET cells and induced morphological signs of apoptosis. The apoptotic effects of paclitaxel were observed by increased levels of cleaved caspase-3 (Asp 175), cleaved caspase-9 (Asp 330) and cleaved PARP (Asp 214). In addition, paclitaxel increased ROS production, leading to DNA damage. Inhibition of ROS production by N-acetylcysteine attenuates paclitaxel-induced DNA damage. Importantly, paclitaxel eliminated cellular senescence, as observed by SA-ß-Gal staining. Cellular senescence elimination was associated with p53/p21 and p16/pRb signaling inactivation. CONCLUSION: Paclitaxel may be a promising anticancer drug and offer a new therapeutic strategy for managing gefitinib-resistant NSCLC during the COVID-19 pandemic.


Assuntos
Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Gefitinibe/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Paclitaxel/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
4.
J Agric Food Chem ; 69(36): 10606-10616, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34482683

RESUMO

We previously identified peptides derived from round scad as potential Nrf2 activators. However, the neuroprotection of these peptides is still unclear. In this study, we aimed to investigate the neuroprotective effect of WCPFSRSF against glutamate-induced neurotoxicity, and the memory-improving effects of WCPFSRSF in mice were also explored. Results showed that WCPFSRSF ameliorated oxidative stress by improving the activities of antioxidant enzymes and promoting the Nrf2-mediated endogenous defense system. Moreover, there is an interaction between the up-regulation of Nrf2 and the down-regulation of NFκB induced by the peptide, which was related to the generation of reactive oxygen species (ROS) and could be abolished by the Akt inhibitor LY294002. Further analysis demonstrated that WCPFSRSF may act as a radical scavenger and Nrf2 activator. The antioxidant and anti-inflammatory effects might be related to the Cys and Trp in WCPFSRSF. Moreover, WCPFSRSF could improve spatial memory impairment in sleep-deprived mice. Thus, this work provided evidence for WCPFSRSF as a potential candidate against neurotoxicity and memory deficits.


Assuntos
Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Fármacos Neuroprotetores , Animais , Antioxidantes/farmacologia , Camundongos , Fator 2 Relacionado a NF-E2/genética , Neuroproteção , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio , Transdução de Sinais
5.
Nat Commun ; 12(1): 5243, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475406

RESUMO

Peroxisome, a special cytoplasmic organelle, possesses one or more kinds of oxidases for hydrogen peroxide (H2O2) production and catalase for H2O2 degradation, which serves as an intracellular H2O2 regulator to degrade toxic peroxides to water. Inspired by this biochemical pathway, we demonstrate the reactive oxygen species (ROS) induced tumor therapy by integrating lactate oxidase (LOx) and catalase (CAT) into Fe3O4 nanoparticle/indocyanine green (ICG) co-loaded hybrid nanogels (designated as FIGs-LC). Based on the O2 redistribution and H2O2 activation by cascading LOx and CAT catalytic metabolic regulation, hydroxyl radical (·OH) and singlet oxygen (1O2) production can be modulated for glutathione (GSH)-activated chemodynamic therapy (CDT) and NIR-triggered photodynamic therapy (PDT), by manipulating the ratio of LOx and CAT to catalyze endogenous lactate to produce H2O2 and further cascade decomposing H2O2 into O2. The regulation reactions of FIGs-LC significantly elevate the intracellular ROS level and cause fatal damage to cancer cells inducing the effective inhibition of tumor growth. Such enzyme complex loaded hybrid nanogel present potential for biomedical ROS regulation, especially for the tumors with different redox state, size, and subcutaneous depth.


Assuntos
Antineoplásicos/farmacologia , Nanogéis/química , Peroxissomos/enzimologia , Fotoquimioterapia/métodos , Animais , Antineoplásicos/química , Catalase/química , Catalase/metabolismo , Catálise , Linhagem Celular Tumoral , Óxido Ferroso-Férrico/química , Glutationa/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Verde de Indocianina/química , Camundongos , Oxigenases de Função Mista/química , Oxigenases de Função Mista/metabolismo , Nanopartículas/química , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Oxigênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Microambiente Tumoral/efeitos dos fármacos
6.
Nanoscale ; 13(34): 14525-14537, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34473816

RESUMO

Radiotherapy (RT) is one of the main treatments for men with prostate cancer (PCa). To date, numerous sophisticated nano-formulations as radiosensitizers have been synthesized with inspiring therapeutic effects both in vitro and in vivo; however, almost all the attention has been paid on the enhanced dose deposition effect by secondary electrons of nanomaterials with high atomic numbers (Z); despite this, cell-cycle arrest, DNA damage, and also reactive oxygen species (ROS) production are critical working mechanisms that account for radiosensitization. Herein, an 'all-purpose' nanostrategy based on dose deposition enhancement, cell cycle arrest, and ROS production as prostate cancer radiosensitizer for potential clinical translation was proposed. The rather simple structure of docetaxel-loaded Au nanoparticles (NPs) with prostate specific membrane antigen (PSMA) ligand conjugation have been successfully synthesized. Enhanced cellular uptake achieved via the selective internalization of the NPs by PCa cells with positive PSMA expression could guarantee enhanced dose deposition. Moreover, the as-synthesized nanosystem could effectively arrest the cell cycle at G2/M phases, which would reduce the ability of DNA damage repair for more irradiation sensitive of the PCa cells. Moreover, the G2/M phase arrest would further promote cascade retention and the enrichment of NPs within the cells. Furthermore, ROS generation and double strand breaks greatly promoted by NPs under irradiation (IR) could also provide an underlying basis for effective radiosensitizers. In vitro and in vivo investigations confirmed the as-synthesized NPs as an effective nano-radiosensitizer with ideal safety. More importantly, all moieties within the present nanosystem have been approved by FDA for the purpose of PCa treatment, thus making it highly attractive for clinical translation.


Assuntos
Nanopartículas Metálicas , Neoplasias da Próstata , Pontos de Checagem do Ciclo Celular , Dano ao DNA , Ouro , Humanos , Masculino , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Neoplasias da Próstata/radioterapia , Espécies Reativas de Oxigênio
7.
Mater Sci Eng C Mater Biol Appl ; 128: 112308, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474859

RESUMO

Gold nanoparticles are emerging as promising nanomaterials to create nanoscale therapeutic delivery systems. The aim of the study was to synthesis of highly monodisperse and stable gold nanoparticles functionalized with polyethyleneimine (PEI) and polyethylene glycol (PEG), multiparametric investigation of their neuronal toxicological effects and evaluation of the cellular/suborgan biodistribution. Gold nanoparticles (AuNP20 and AuNP50) were synthesized and their surfaces were electrostatically modified by PEI and PEG. Dorsal root ganglion (DRG) sensory neurones were isolated from BALB/c mice. Cell viability, apoptosis and ROS production were evaluated in vitro. Cellular and suborgan biodisribution of the AuNPs were investigated using inductively coupled plasma mass spectrometry (ICP-MS) technique. PEI and PEG surface coating increased both biocompatibility and biodistribution of the AuNPs. ICP-MS measurements showed the presence of gold in liver, spleen, kidney, heart, blood and brain within a 30 days period. The size and surface chemistry of the AuNPs are important parameters for potential nanoteranostic applications in the future studies.


Assuntos
Ouro , Nanopartículas Metálicas , Animais , Apoptose , Nanopartículas Metálicas/toxicidade , Camundongos , Camundongos Endogâmicos BALB C , Tamanho da Partícula , Polietilenoglicóis , Espécies Reativas de Oxigênio , Distribuição Tecidual
8.
Langmuir ; 37(36): 10818-10826, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34470217

RESUMO

Direct visualization of the dynamic events in lysosomes during drug-mediated programmed cell death (apoptosis) is a great challenge. This is due to the lack of resolving power of a conventional microscope and also the unavailability of a suitable multimodal probe that simultaneously can carry the drug with high loading capacity and ensure its specific internalization into lysosomes. In this work, using super-resolution microscopy, we observed the lysosomal expansion during apoptosis that was treated with epigallocatechin gallate (EGCG) conjugated to bovine serum albumin (BSA). Albumin protein is known to internalize into lysosomes via endocytosis, thus helping in the specific delivery of EGCG to the lysosomal compartment. The conjugation of EGCG to BSA not only helped in increasing the killing efficiency of cancer cells but it also reduces the side effects and produces minimal reactive oxygen species. The decrease in local viscosity helped in lysosomal expansion during apoptosis.


Assuntos
Catequina , Microscopia , Apoptose , Catequina/análogos & derivados , Lisossomos , Espécies Reativas de Oxigênio
9.
J Hazard Mater ; 416: 126158, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492938

RESUMO

Graphene oxide (GO) nanomaterials have significant advantages for drug delivery and electrode materials in neural science, however, their exposure risks to the central nervous system (CNS) and toxicity concerns are also increased. The current studies of GO-induced neurotoxicity remain still ambiguous, let alone the mechanism of how complicated GO chemistry affects its biological behavior with neural cells. In this study, we characterized the commercially available GO in detail and investigated its biological adverse effects using cultured SH-SY5Y cells. We found that ultrasonic processing in medium changed the oxidation status and surface reactivity on the planar surface of GO due to its hydration activity, causing lipid peroxidation and cell membrane damage. Subsequently, ROS-disrupted mitochondrial homeostasis, resulting from the activation of NOX2 signaling, was observed following GO internalization. The autophagy-lysosomal network was initiated as a defensive reaction to obliterate oxidative damaged mitochondria and foreign nanomaterials, which was ineffective due to reduced lysosomal degradation capacity. These sequential cellular responses exacerbated mitochondrial stress, leading to apoptotic cell death. These data highlight the importance of the structure-related activity of GO on its biological properties and provide an in-depth understanding of how GO-derived cellular redox signaling induces mitochondrion-related cascades that modulate cell functionality and survival.


Assuntos
Autofagia , Lisossomos , Apoptose , Linhagem Celular Tumoral , Grafite , Homeostase , Lisossomos/metabolismo , Mitocôndrias , Oxirredução , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo
10.
BMC Plant Biol ; 21(1): 410, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493227

RESUMO

BACKGROUND: Water deficit is an abiotic stress that retards plant growth and destabilizes crop production. Long non coding RNAs (lncRNAs) are a class of non-coding endogenous RNAs that participate in diverse cellular processes and stress responses in plants. lncRNAs could function as competing endogenous RNAs (ceRNA) and represent a novel layer of gene regulation. However, the regulatory mechanism of lncRNAs as ceRNA in drought stress response is yet unclear. RESULTS: In this study, we performed transcriptome-wide identification of drought-responsive lncRNAs in rice. Thereafter, we constructed a lncRNA-mediated ceRNA network by analyzing competing relationships between mRNAs and lncRNAs based on ceRNA hypothesis. A drought responsive ceRNA network with 40 lncRNAs, 23 miRNAs and 103 mRNAs was obtained. Network analysis revealed TCONS_00021861/miR528-3p/YUCCA7 regulatory axis as a hub involved in drought response. The miRNA-target expression and interaction were validated by RT-qPCR and RLM-5'RACE. TCONS_00021861 showed significant positive correlation (r = 0.7102) with YUCCA7 and negative correlation with miR528-3p (r = -0.7483). Overexpression of TCONS_00021861 attenuated the repression of miR528-3p on YUCCA7, leading to increased IAA (Indole-3-acetic acid) content and auxin overproduction phenotypes. CONCLUSIONS: TCONS_00021861 could regulate YUCCA7 by sponging miR528-3p, which in turn activates IAA biosynthetic pathway and confer resistance to drought stress. Our findings provide a new perspective of the regulatory roles of lncRNAs as ceRNAs in drought resistance of rice.


Assuntos
Oryza/genética , RNA Longo não Codificante/genética , Desidratação/genética , Secas , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Redes Reguladoras de Genes , Células do Mesofilo/ultraestrutura , MicroRNAs/genética , Folhas de Planta/genética , RNA Mensageiro/genética , RNA de Plantas , Espécies Reativas de Oxigênio/metabolismo
11.
Klin Lab Diagn ; 66(9): 552-557, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34543534

RESUMO

Bacterial rhinosinusitis (BRS) is a complicated form of rhinosinusitis, characterized by its acute course and tendency to chronicity. A significant role in pathogenetic mechanisms of HRS is played by functional state of neutrophils responsible for inflammation development at HRS. Investigation of neutrophils metabolic activity on external stimuli by chemiluminescence method in patients with acute and chronic forms of the disease will enable to develop method of differential diagnostics of BRS forms. The examination of 65 patients with BRS which were divided into patients with acute form (n=35) and chronic form of the disease (n=30) was carried out. The control group consisted of 30 healthy subjects. Functional activity of neutrophils was studied in whole blood by chemiluminescence with double stimulation (phorbol-12-myristate-13-acetate (PMA) and N-formylmethionyl-leucyl-phenylalanine (fMLP). In patients with the acute form of BRS we found an increase in parameters of specific maximum intensity of neutrophils luminescence, light sum of spontaneous and stimulated luminol-dependent chemiluminescence and a decrease in time to maximum output. Patients with the chronic form of BRS revealed a decrease in the luminescence of spontaneous, stimulated neutrophil production and maximum luminescence intensity. On the basis of significant differences in chemiluminescence indices of neutrophils, a method of differential diagnosis of the BRS forms was developed. The results obtained testify to increased production of reactive oxygen species (ROS) by neutrophils in the process of killing in patients with acute form of LRS and depletion of cell function and reserve in patients with the chronic form. Developed on the basis of the studied indicators method of diagnosing the forms of BRS by chemiluminescence will allow to differentiate acute and chronic forms of the disease, which will increase the effectiveness of treatment of patients.


Assuntos
Medições Luminescentes , Neutrófilos , Humanos , Luminol , N-Formilmetionina Leucil-Fenilalanina , Espécies Reativas de Oxigênio
12.
J Biomed Nanotechnol ; 17(8): 1654-1667, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34544542

RESUMO

Oxidized low density lipoprotein (Ox-LDL) is a known biomarker of inflammation and atherosclerosis, a leading cause of death worldwide. As a new class of nanomaterials, carbon nanodots (CNDs) are widely used in bioimaging, diagnostics, and drug delivery. However, there is no current report on how these CNDs affect the cardiovascular system, particularly their potential in mediating endothelial inflammatory dysfunction. This study examined effects of CNDs on Ox-LDL-mediated endothelial dysfunction. CNDs significantly inhibited Ox-LDL-mediated adhesion of monocytes to human microvascular endothelial cells (HMEC-1), in human microvascular endothelial cells (HMEC-1). CNDs significantly inhibited Ox-LDL-mediated adhesion of monocytes to endothelial cells, which is an essential step in the development of atherosclerosis. Further, CNDs significantly inhibited OxLDL-induced expression of interleukin-8 (IL-8), a vital cytokine on monocyte adhesion to the endothelial cells. These results demonstrate CNDs possess anti-inflammatory properties. CNDs also protect cells against Ox-LDL-induced cytotoxicity. Electron paramagnetic resonance (EPR) spectroscopy studies demonstrated direct reactive oxygen species-scavenging by CNDs. This result indicates that the anti-inflammatory properties of CNDs are most likely due to their direct scavenging of reactive oxygen species. Animal studies involving mice did not show any morphological or physical changes between the CNDs and control groups. Our study provides evidence of potential of CNDs in reducing Ox-LDL-mediated inflammation and cytotoxicity in HMEC-1.


Assuntos
Células Endoteliais , Monócitos , Animais , Carbono , Lipoproteínas LDL , Camundongos , Espécies Reativas de Oxigênio
13.
Braz J Med Biol Res ; 54(10): e11207, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34378677

RESUMO

Reactive oxygen species (ROS) are involved in neuropathic pain, a complicated condition after nerve tissue lesion. Vitamin D appears to improve symptoms of pain and exhibits antioxidant properties. We investigated the effects of oral administration of vitamin D3, the active form of vitamin D, on nociception, the sciatic functional index (SFI), and spinal cord pro-oxidant and antioxidant markers in rats with chronic constriction injury (CCI) of the sciatic nerve, a model of neuropathic pain. Vitamin D3 (500 IU/kg per day) attenuated the CCI-induced decrease in mechanical withdrawal threshold and thermal withdrawal latency (indicators of antinociception) and SFI. The vitamin prevented increased lipid hydroperoxide levels in injured sciatic nerve without change to total antioxidant capacity (TAC). Vitamin D3 prevented increased lipid hydroperoxide, superoxide anion generation (SAG), and hydrogen peroxide (H2O2) levels in the spinal cord, which were found in rats without treatment at 7 and 28 days post-CCI. A significant negative correlation was found between mechanical threshold and SAG and between mechanical threshold and H2O2 at day 7. Vitamin D3 also prevented decreased spinal cord total thiols content. There was an increase in TAC in the spinal cord of vitamin-treated CCI rats, compared to CCI rats without treatment only at 28 days. No significant changes were found in body weight and blood parameters of hepatic and renal function. These findings demonstrated, for first time, that vitamin D modulated pro-oxidant and antioxidant markers in the spinal cord. Since antinociception occurred in parallel with oxidative changes in the spinal cord, the oxidative changes may have contributed to vitamin D-induced antinociception.


Assuntos
Antioxidantes , Neuralgia , Animais , Peróxido de Hidrogênio , Hiperalgesia/tratamento farmacológico , Neuralgia/tratamento farmacológico , Nociceptividade , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio , Nervo Isquiático , Medula Espinal , Vitamina D , Vitaminas
14.
Nano Lett ; 21(16): 6998-7004, 2021 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-34339204

RESUMO

Solar-driven reactive oxygen species (ROS) generation is an attractive disinfection technique for cell death and water purification. However, most photocatalysts require high stability in the water environment and the production of ROS with a sufficient amount and diffusion length to damage pathogens. Here, a ROS generation system was developed consisting of tapered crystalline silicon microwires coated with anatase titanium dioxide for a conformal junction. The system effectively absorbed >95% of sunlight over 300-1100 nm, resulting in effective ROS generation. The system was designed to produce various ROS species, but a logistic regression analysis with cellular survival data revealed that the diffusion length of the ROS is ∼9 µm, implying that the most dominant species causing cell damage is H2O2. Surprisingly, a quantitative analysis showed that only 15 min of light irradiation on the system would catalyze a local bactericidal effect comparable to the conventional germicidal level of H2O2 (∼3 mM).


Assuntos
Peróxido de Hidrogênio , Luz Solar , Morte Celular , Espécies Reativas de Oxigênio , Titânio
16.
Int J Mol Sci ; 22(15)2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34361036

RESUMO

Hinokitiol is a natural tropolone derivative that is present in the heartwood of cupressaceous plants, and has been extensively investigated for its anti-inflammatory, antioxidant, and antitumor properties in the context of various diseases. To date, the effects of hinokitiol on endometrial cancer (EC) has not been explored. The purpose of our study was to investigate the anti-proliferative effects of hinokitiol on EC cells. Cell viability was determined with an MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, and the quantification of apoptosis and reactive oxygen species (ROSs) was performed by using flow cytometry, while protein expression was measured with the Western blotting technique. Hinokitiol significantly suppressed cell proliferation through the inhibition of the expression of cell-cycle mediators, such as cyclin D1 and cyclin-dependent kinase 4 (CDK4), as well as the induction of the tumor suppressor protein p53. In addition, hinokitiol increased the number of apoptotic cells and increased the protein expression of cleaved-poly-ADP-ribose polymerase (PARP) and active cleaved-caspase-3, as well as the ratio of Bcl-2-associated X protein (Bax) to B-cell lymphoma 2 (Bcl-2). Interestingly, except for KLE cells, hinokitiol induced autophagy by promoting the accumulation of the microtubule-associated protein light chain 3B (LC3B) and reducing the sequestosome-1 (p62/SQSTM1) protein level. Furthermore, hinokitiol triggered ROS production and upregulated the phosphorylation of extracellular-signal-regulated kinase (p-ERK1/2) in EC cells. These results demonstrate that hinokitiol has potential anti-proliferative and pro-apoptotic benefits in the treatment of endometrial cancer cell lines (Ishikawa, HEC-1A, and KLE).


Assuntos
Antineoplásicos Fitogênicos/toxicidade , Apoptose , Pontos de Checagem do Ciclo Celular , Neoplasias do Endométrio/metabolismo , Monoterpenos/toxicidade , Tropolona/análogos & derivados , Autofagia , Linhagem Celular Tumoral , Ciclina D1/metabolismo , Quinase 4 Dependente de Ciclina/metabolismo , Feminino , Humanos , Poli(ADP-Ribose) Polimerases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Tropolona/toxicidade , Proteína Supressora de Tumor p53/metabolismo
17.
Int J Mol Sci ; 22(15)2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34361042

RESUMO

Various neurodegenerative disorders are associated with human NTE/PNPLA6 dysfunction. Mechanisms of neuropathogenesis in these diseases are far from clearly elucidated. Hereditary spastic paraplegia belongs to a type of neurodegeneration associated with NTE/PNLPLA6 and is implicated in neuron death. In this study, we used Drosophila melanogaster to investigate the consequences of neuronal knockdown of swiss cheese (sws)-the evolutionarily conserved ortholog of human NTE/PNPLA6-in vivo. Adult flies with the knockdown show longevity decline, locomotor and memory deficits, severe neurodegeneration progression in the brain, reactive oxygen species level acceleration, mitochondria abnormalities and lipid droplet accumulation. Our results suggest that SWS/NTE/PNPLA6 dysfunction in neurons induces oxidative stress and lipid metabolism alterations, involving mitochondria dynamics and lipid droplet turnover in neurodegeneration pathogenesis. We propose that there is a complex mechanism in neurological diseases such as hereditary spastic paraplegia, which includes a stress reaction, engaging mitochondria, lipid droplets and endoplasmic reticulum interplay.


Assuntos
Encéfalo/metabolismo , Proteínas de Drosophila/metabolismo , Gotículas Lipídicas/metabolismo , Mitocôndrias/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Encéfalo/citologia , Proteínas de Drosophila/deficiência , Proteínas de Drosophila/genética , Drosophila melanogaster , Metabolismo dos Lipídeos , Mitocôndrias/ultraestrutura , Proteínas do Tecido Nervoso/deficiência , Proteínas do Tecido Nervoso/genética , Neurônios/metabolismo , Estresse Oxidativo
18.
Artigo em Inglês | MEDLINE | ID: mdl-34444340

RESUMO

Mancozeb (MZ) and zoxamide (ZOX) are fungicides commonly used in pest control programs to protect vineyards. Their toxic and genotoxic potential were investigated in vitro on HepG2 and A549 cell lines at environmentally relevant concentrations. Cytotoxicity, apoptosis, necrosis and intracellular reactive oxygen species (ROS), comet assay and a micronucleus test with CREST immunofluorescence were used. The expression of a panel of genes involved in apoptosis/necrosis (BAX/BCL2), oxidative stress (NRF2), drug metabolism (CYP1A1) and DNA repair (ERCC1/OGG1) was evaluated by real-time PCR. Both fungicides were cytotoxic at the highest tested concentrations (295.7 and 463.4 µM, respectively); MZ induced necrosis, ZOX did not increase apoptosis but modulated BAX and BCL2 expression, suggesting a different mechanism. Both compounds did not increase ROS, but the induction of CYP1A1 and NRF2 expression supported a pro-oxidant mechanism. The comet assay evidenced MZ genotoxicity, whereas no DNA damage due to ZOX treatment was observed. Positive micronuclei were increased in both cell lines treated with MZ and ZOX, supporting their aneugenic potential. ERCC1 and OGG1 were differently modulated, indicating the efficient activation of the nucleotide excision repair system by both fungicides and the inhibition of the base excision repair system by MZ. Overall, MZ confirmed its toxicity and new ZOX-relevant effects were highlighted.


Assuntos
Fungicidas Industriais , Maneb , Zineb , Amidas , Ensaio Cometa , Dano ao DNA , Fungicidas Industriais/toxicidade , Maneb/toxicidade , Estresse Oxidativo , Espécies Reativas de Oxigênio , Zineb/toxicidade
19.
Int J Mol Sci ; 22(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34360819

RESUMO

Photodynamic therapy (PDT) has become an alternative to standard cancer treatment methods such as surgery, chemotherapy and radiotherapy. The uniqueness of this method relies on the possibility of using various photosensitizers (PS) that absorb and convert light emission in radical oxygen-derived species (ROS). They can be present alone or in the presence of other compounds such as metal organic frameworks (MOFs), non-tubules or polymers. The interaction between DNA and metal-based complexes plays a key role in the development of new anti-cancer drugs. The use of coordination compounds in PDT has a significant impact on the amount ROS generated, quantum emission efficiency (Φem) and phototoxic index (PI). In this review, we will attempt to systematically review the recent literature and analyze the coordination complexes used as PS in PDT. Finally, we compared the anticancer activities of individual coordination complexes and discuss future perspectives. So far, only a few articles link so many transition metal ion coordination complexes of varying degrees of oxidation, which is why this review is needed by the scientific community to further expand this field worldwide. Additionally, it serves as a convenient collection of important, up-to-date information.


Assuntos
Neoplasias/tratamento farmacológico , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Linhagem Celular Tumoral , Humanos , Estruturas Metalorgânicas/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo
20.
Int J Mol Sci ; 22(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34360825

RESUMO

Metal oxide nanoparticles (MONPs) are inorganic materials that have become a valuable tool for many industrial sectors, especially in healthcare, due to their versatility, unique intrinsic properties, and relatively inexpensive production cost. As a consequence of their wide applications, human exposure to MONPs has increased dramatically. More recently, their use has become somehow controversial. On one hand, MONPs can interact with cellular macromolecules, which makes them useful platforms for diagnostic and therapeutic interventions. On the other hand, research suggests that these MONPs can cross the blood-testis barrier and accumulate in the testis. Although it has been demonstrated that some MONPs have protective effects on male germ cells, contradictory reports suggest that these nanoparticles compromise male fertility by interfering with spermatogenesis. In fact, in vitro and in vivo studies indicate that exposure to MONPs could induce the overproduction of reactive oxygen species, resulting in oxidative stress, which is the main suggested molecular mechanism that leads to germ cells' toxicity. The latter results in subsequent damage to proteins, cell membranes, and DNA, which ultimately may lead to the impairment of the male reproductive system. The present manuscript overviews the therapeutic potential of MONPs and their biomedical applications, followed by a critical view of their potential risks in mammalian male fertility, as suggested by recent scientific literature.


Assuntos
Genitália Masculina/efeitos dos fármacos , Nanopartículas Metálicas/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Óxidos/efeitos adversos , Espermatogênese/efeitos dos fármacos , Animais , Humanos , Masculino , Compostos Orgânicos/efeitos adversos , Espécies Reativas de Oxigênio/metabolismo
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