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1.
J Colloid Interface Sci ; 605: 727-740, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34365309

RESUMO

Developing durable photocatalysts with highly efficient antibiotics degradation is crucial for environment purification. Herein, tetra (4-carboxyphenyl) porphyrin (TCPP) was loaded onto the surface of Bi2MoO6 microspheres to gain hierarchical organic-inorganic TCPP/Bi2MoO6 (TCPP/BMO) heterojunctions via a facile impregnation strategy. The catalytic properties of these catalysts were comprehensively investigated through the photodegradation of tetracycline hydrochloride (TC) under visible light. Among all the TCPP/BMO heterojunctions, the highest photodegradation rate constant (0.0278 min-1) was achieved with 0.25 wt% TCPP (TCPP/BMO-2), which was approximately 1.15 folds greater than that of pristine Bi2MoO6 and far superior to pure TCPP. The extremely high photocatalytic performance is attributed to the interfacial interaction between TCPP and Bi2MoO6, which favors the efficient separation of charge carriers and the enhancement of visible-light absorbance. TCPP/BMO-2 possesses high mineralization capability and good recycling performance. Photo-induced O2-, h+, and OH were mainly responsible for the degradation of TC. The degradation pathways of TC and toxicity of degradation intermediates were analyzed based on the intermediates detected by the high performance liquid chromatography-mass spectrometer (HPLC-MS) and the toxicity assessment by the quantitative structure-activity relationship (QSAR) prediction. A possible photocatalytic mechanism over TCPP/BMO is proposed. This work offers an insight in developing the porphyrin-based organic-inorganic heterojunctions for effectively remedying pharmaceutical wastewater.


Assuntos
Porfirinas , Tetraciclina , Antibacterianos/farmacologia , Bismuto , Molibdênio
2.
Spectrochim Acta A Mol Biomol Spectrosc ; 265: 120387, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34555697

RESUMO

Dye-sensitized solar cells (DSSCs) have recently received a significant attention as possible sources of renewable energy. As a result, a significant effort is being made to develop organic dyes for highly power conversion efficient DSSCs, in order to overcome the disadvantages of previous solar cell systems, such as cost reduction, weight reduction, and production methods that minimize environmental pollution. As shown by multiple recent research publications, computational techniques such as quantitative structure-property relationship (QSPR) modeling may aid in the development of suitable dyes for DSSCs satisfying many fundamental desired characteristics. The current report provides robust, externally verified QSPR models for five chemical classes of organic dyes (Triphenylamines, Phenothiazines, Indolines, Porphyrins and Coumarins) based on experimentally determined absorption maxima values. The size of the dye data points utilized to develop the models is the largest known to date. The QSPR models were constructed using only two-dimensional descriptors with clear physicochemical meaning. Using the best subset selection approach, we built 5, 3, 4, 3 and 2 descriptor models for the Triphenylamine, Phenothiazine, Indoline, Porphyrin and Coumarin classes, respectively. The models were validated both internally and externally, and then consensus predictions were made for specific categories of dyes using the developed partial least squares (PLS) models, and the "Intelligent consensus predictor" tool (http://teqip.jdvu.ac.in/QSAR_Tools/) was used to determine whether the quality of test set compound predictions can be improved through the "intelligent" selection of multiple PLS models. We identified from the insights gained from the developed models several chemical attributes that are important in enhancing the absorption maxima. Thus, our study may be utilized to predict the λmax values of novel or untested organic dyes and to give insights that will aid in the development of new dyes for use in solar cells with increased λmax values and enhanced power conversion efficiency.


Assuntos
Porfirinas , Energia Solar , Corantes , Relação Quantitativa Estrutura-Atividade , Luz Solar
3.
J Nutr Sci Vitaminol (Tokyo) ; 67(5): 339-350, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34719620

RESUMO

5-Aminolevulinic acid (ALA) is a key intermediate of heme biosynthesis, which is an essential component of the respiratory chain. Therefore, nutrients that affect ALA biosynthesis eventually affect ATP production, which is the basis of mitochondrial function. Although the effects of various non-nutrient components that affect ALA after biosynthesis have been reported, there are few reports on the effects of dietary amino acids/protein on ALA formation and the effects of dietary vitamins that are involved in amino acid metabolism. In mitochondria, ALA is synthesized from succinyl-CoA and glycine by the pyridoxal phosphate-dependent enzyme ALA synthase [EC 2.3.1.37]. In this study, the effects of dietary amino acids/protein and vitamins on the amount of ALA synthesized were investigated using mice, rats, and cultured cells. Amounts of ALA in plasma and urine, and porphyrins in plasma increased with increasing protein intake. Vitamin B1 insufficiency did not affect ALA synthesis. Vitamin B6 insufficiency increased the amount of ALA synthesized, while niacin deficiency markedly reduced ALA synthesis. Thus, for heme synthesis, an essential biological substance for life, the amounts of amino acids, as well as the pathways metabolizing amino acids to glycine and succinyl-CoA are very important. Specifically, it is important that niacin is associated with the formation of glycine and succinyl-CoA from amino acids.


Assuntos
Ácido Aminolevulínico , Porfirinas , Aminoácidos , Animais , Glicina , Heme , Camundongos , Ratos
4.
Anal Chim Acta ; 1183: 338870, 2021 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-34627528

RESUMO

Nowadays, brain natriuretic peptide (BNP-32) is fundamental to early cardiovascular clinical diagnosis, whose accurate assay is of significance by photoelectrochemistry (PEC) for the low background and high precision. Herein, a novel enhanced PEC platform was built by successive deposition of N-doped ZnO nanopolyhedra (N-ZnO NP) and protoporphyrin IX (PPIX). Specifically, the N-ZnO NP with a narrow bandgap of 2.60 eV was synthesized by direct calcination of zeolitic imidazole framework-8 (ZIF-8), and performed as the substrate to enhance the photocurrents of PPIX (as photosensitizer) whose photoelectron transfer pathway and enhanced PEC mechanism were studied in detail. Under such foundation, a label-free PEC aptasensor was developed by deposition of DNA aptamer onto the PEC platform and then ultrasensitive assay of BNP-32 based on a "signal off" model. The biosensor showed a wide linear range (1 pg mL-1- 0.1 µg mL-1) with a limit of detection (LOD) as low as 0.14 pg mL-1. This doping technique of ZnO nanomaterials provides some valuable guidelines for synthesis of advanced PEC probes in bioanalysis.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Porfirinas , Óxido de Zinco , Peptídeo Natriurético Encefálico
5.
J Biomed Nanotechnol ; 17(10): 1939-1950, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34706794

RESUMO

We prepared poly(lactide-co-glycolide) (PLGA) encapsulated with chlorin e6 (Ce6) in an effort to increase the stability and efficiency of photosensitizers for photodynamic therapy (PDT). We determined that Ce6-loaded PLGA nanoparticles (PLGA-Ce6 NPs) had drug-loading efficiency of 5%. The efficiency of encapsulation was 82%, the zeta potential was- 25 mV, and the average diameter was 130 nm. The encapsulation of Ce6 in PLGA nanoparticles showed excellent stability. The nanoparticles exhibited sustained Ce6 release profiles with 50% released at the end of 3 days, whereas free Ce6 showed rapid release within 1 day. Ce6 release patterns were controlled by encapsulation into PLGA. The uptake of PLGA-Ce6 NPs was significantly enhanced by endocytosis in the first 8 hours in the HCT-116 cell line. An intracellular reactive oxygen species assay revealed the enhanced uptake of the nanoparticles. An in vitro anti-tumor activity assay showed that the PLGA-Ce6 NPs exhibited enhanced phototoxicity toward HCT-116 cells and a slightly lower IC50 value in HCT-116 cells than Ce6 solution alone. Exposure of HCT-116 cell spheroids to PLGA-Ce6 NPs penetrated more profoundly and had better phototoxicity than pure drugs. These findings suggest that PLGA-Ce6 NPs might serve as PDT for colorectal cancer.


Assuntos
Neoplasias Colorretais , Nanopartículas , Fotoquimioterapia , Porfirinas , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Humanos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Poliglactina 910
6.
ACS Appl Mater Interfaces ; 13(42): 49754-49761, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34657424

RESUMO

A reliable and sensitive detection approach for SARS-CoV 2 is essential for timely infection diagnosis and transmission prevention. Here, a two-dimensional (2D) metal-organic framework (MOF)-based photoelectrochemical (PEC) aptasensor with high sensitivity and stability for SARS-CoV 2 spike glycoprotein (S protein) detection was developed. The PEC aptasensor was constructed by a plasmon-enhanced photoactive material (namely, Au NPs/Yb-TCPP) with a specific DNA aptamer against S protein. The Au NPs/Yb-TCPP fabricated by in situ growth of Au NPs on the surface of 2D Yb-TCPP nanosheets showed a high electron-hole (e-h) separation efficiency due to the enhancement effect of plasmon, resulting in excellent photoelectric performance. The modified DNA aptamer on the surface of Au NPs/Yb-TCPP can bind with S protein with high selectivity, thus decreasing the photocurrent of the system due to the high steric hindrance and low conductivity of the S protein. The established PEC aptasensor demonstrated a highly sensitive detection for S protein with a linear response range of 0.5-8 µg/mL with a detection limit of 72 ng/mL. This work presented a promising way for the detection of SARS-CoV 2, which may conduce to the impetus of clinic diagnostics.


Assuntos
Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , Estruturas Metalorgânicas/química , SARS-CoV-2/química , Glicoproteína da Espícula de Coronavírus/análise , Sequência de Bases , Técnicas Biossensoriais/instrumentação , COVID-19/diagnóstico , DNA/química , Técnicas Eletroquímicas/instrumentação , Técnicas Eletroquímicas/métodos , Eletrodos , Ouro/química , Ouro/efeitos da radiação , Humanos , Ácidos Nucleicos Imobilizados/química , Luz , Limite de Detecção , Nanopartículas Metálicas/química , Nanopartículas Metálicas/efeitos da radiação , Faringe/virologia , Processos Fotoquímicos , Porfirinas/química , Glicoproteína da Espícula de Coronavírus/química , Itérbio/química
7.
Water Sci Technol ; 84(7): 1813-1825, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34662315

RESUMO

In this study, zinc oxide and silver and copper-doped zinc oxide nanorods were synthesized by a simple template-free precipitation technique. In addition, meso-tetrakis-(4-sulfonatophenyl) porphyrin (TPPS4) was prepared and immobilized on ZnO nanorods (TPPS/ZnO). The synthesized photocatalysts were characterized by various techniques such as X-ray powder diffraction, scanning electron microscopy, UV-visible spectroscopy, diffuse reflectance spectroscopy, and Fourier transform Infrared spectroscopy. The potential of the obtained photocatalysts in the degradation of methylene blue was investigated under UV and visible light irradiation. The results revealed that the photocatalytic activity of TPPS/ZnO was higher than those of the pure ZnO and doped ZnO under visible light irradiation.


Assuntos
Óxido de Zinco , Catálise , Luz , Azul de Metileno , Porfirinas
8.
J Phys Chem B ; 125(41): 11432-11443, 2021 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-34634911

RESUMO

Molecular dynamics simulations based on an atomistic empirical force field have been carried out to investigate structural, thermodynamic, and dynamical properties of adlayers made of porphyrin-type molecules physisorbed on surfaces of cellulose Iß nanocrystals. The results show that low-index surfaces provide a thermally stable, weakly perturbing support for the deposition of non-hydrogen-bonded organic molecules. At submonolayer coverage, the discoidal porphyrin molecules lay flat on the surface, forming compact 2D clusters with clear elements of ordering. The adlayer grows layer-by-layer for the smallest porphyrin species on compact cellulose surfaces, while forming 3D clusters on a first relatively ordered adlayer (Stranski-Krastanov growth) in all other cases. The adsorption energy exceeds ∼1 eV per molecule, underlying the thermal stability of the adsorbate. Entropy plays a non-negligible role, destabilizing to some extent the adlayer. The in-plane dynamics of the smallest porphyrin species, i.e., porphine, on compact surfaces shows signs of superlubricity, due to the low energy and momentum exchange between the flat admolecule and the equally flat cellulose surface.


Assuntos
Nanopartículas , Porfirinas , Adsorção , Celulose , Termodinâmica
9.
Sci Rep ; 11(1): 19481, 2021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-34593970

RESUMO

The pandemic infectious disease (Covid-19) caused by the coronavirus (SARS-CoV2) is spreading rapidly around the world. Covid-19 does an irreparable harm to the health and life of people. It also has a negative financial impact on the economies of most countries of the world. In this regard, the issue of creating drugs aimed at combating this disease is especially acute. In this work, molecular docking was used to study the docking of 23 compounds with QRF3a SARS-CoV2. The performed in silico modeling made it possible to identify leading compounds capable of exerting a potential inhibitory and virucidal effect. The leading compounds include chlorin (a drug used in PDT), iron(III)protoporphyrin (endogenous porphyrin), and tetraanthraquinone porphyrazine (an exogenous substance). Having taken into consideration the localization of ligands in the QRF3a SARS-CoV2, we have made an assumption about their influence on the pathogenesis of Covid-19. The interaction of chlorin, iron(III)protoporphyrin and protoporphyrin with the viral protein ORF3a were studied by fluorescence and UV-Vis spectroscopy. The obtained experimental results confirm the data of molecular docking. The results showed that a viral protein binds to endogenous porphyrins and chlorins, moreover, chlorin is a competitive ligand for endogenous porphyrins. Chlorin should be considered as a promising drug for repurposing.


Assuntos
Antivirais/química , Antivirais/metabolismo , Compostos Heterocíclicos/química , Compostos Macrocíclicos/química , Compostos Macrocíclicos/metabolismo , Proteínas Viroporinas/química , Proteínas Viroporinas/metabolismo , Sítios de Ligação , COVID-19/tratamento farmacológico , Reposicionamento de Medicamentos , Compostos Heterocíclicos/metabolismo , Ligantes , Simulação de Acoplamento Molecular , Porfirinas/química , Porfirinas/metabolismo , Protoporfirinas/química , Protoporfirinas/metabolismo , SARS-CoV-2/efeitos dos fármacos , Proteínas Viroporinas/antagonistas & inibidores
10.
Arkh Patol ; 83(5): 13-20, 2021.
Artigo em Russo | MEDLINE | ID: mdl-34609799

RESUMO

OBJECTIVE: To evaluate the effectiveness of fluorescence navigation with chlorin e6 in surgery for malignant gliomas based on surgical material morphological and immunohistochemical data. MATERIAL AND METHODS: The surgical material obtained from patients with high-grade (Grade III-IV) anaplastic glioma was examined. Along with histological examination, the proliferation marker Ki-67, the cell cycle transcription factor protein p53, and vascular endothelial growth factor (VEGF) were determined. RESULTS: A significant direct correlation was found between the expression of Ki-67, p53, and VEGF and the fluorescence intensity of tumor tissues (p<0.05). CONCLUSION: The technique of fluorescence navigation using chlorin e6 in comparative morphopathological analysis has confirmed its effectiveness in surgery for malignant gliomas.


Assuntos
Neoplasias Encefálicas , Glioma , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/cirurgia , Fluorescência , Glioma/genética , Glioma/cirurgia , Humanos , Antígeno Ki-67/genética , Porfirinas , Proteína Supressora de Tumor p53/genética , Fator A de Crescimento do Endotélio Vascular/genética
11.
Phytomedicine ; 93: 153788, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34634745

RESUMO

BACKGROUND: Sono-photodynamic therapy (SPDT) which is the combination of photodynamic therapy (PDT) and sonodynamic therapy (SDT), could exert much better anti-cancer effects than monotherapy. The combination of chemotherapy and PDT or SDT has shown great potential for cancer treatment. However, the combination of SPDT and chemotherapy for cancer treatment is rarely explored. PURPOSE: We utilized a natural hydrophobic anti-cancer drug oleanolic acid (OA) and a photosensitizer chlorin e6 (Ce6) through self-assembly technology to form a carrier-free nanosensitizer OC for combined chemotherapy and SPDT for cancer treatment. No studies involving using carrier-free nanomedicine for combined chemotherapy/SPDT have been reported yet. STUDY DESIGN: After fully characterization of OC, the in vitro and in vivo anti-cancer activities of OC were investigated and the mechanisms of the synergistic therapeutic effects were studied. METHODS: OC were synthesized through self-assembly technology and characterized by dynamic light scattering (DLS) and an atomic force microscope (AFM). Confocal microscope was used to investigate the intracellular uptake efficiency and the penetration ability of OC. The cell viability of PC9 and 4T1 cells treated with OC under laser and ultrasound (US) irradiation was determined by MTT assay. Furthermore, flow cytometry was performed to detect the reactive oxygen species (ROS) generation, loss of mitochondrial membrane potential (MMP), cell apoptosis and cell cycle arrest. Finally, the anti-tumor therapeutic efficacy of OC was investigated in orthotopic 4T1 breast tumor-bearing mouse model. RESULTS: OC showed an average particle size of around 100 nm with excellent light stability. OC increased more than 23 times accumulation of Ce6 in cancer cells and had strong tumor penetration ability in three-dimensional (3D) multicellular tumor spheroids (MCTSs). Compared with other therapeutic options, OC showed obvious synergistic inhibitory effects under light and US irradiation in PC9 and 4T1 cells with a significant decrease in IC50 values. Mechanism studies showed that OC could generate high ROS, induce MMP loss, and cause apoptosis and cell cycle arrest. In vivo studies also approved the synergistic therapeutic effects of OC in 4T1 mouse models. CONCLUSION: Self-assembled carrier-free nanosensitizer OC could be a promising therapeutic agent for synergistic chemo/sono-photodynamic therapy for cancer treatment.


Assuntos
Nanopartículas , Neoplasias , Ácido Oleanólico , Fotoquimioterapia , Porfirinas , Animais , Linhagem Celular Tumoral , Humanos , Camundongos , Ácido Oleanólico/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/farmacologia
12.
Molecules ; 26(19)2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34641360

RESUMO

Despite the significant relevance of photodynamic therapy (PDT) as an efficient strategy for primary and adjuvant anticancer treatment, several challenges compromise its efficiency. In order to develop an "ideal photosensitizer" and the requirements applied to photosensitizers for PDT, there is still a need for new photodynamic agents with improved photophysical and photobiological properties. In this study, we performed a detailed characterization of two tetracyanotetra(aryl)porphyrazine dyes with 4-biphenyl (pz II) and 4-diethylaminophenyl (pz IV) groups in the periphery of the porphyrazine macrocycle. Photophysical properties, namely, fluorescence quantum yield and lifetime of both photosensitizers, demonstrate extremely high dependence on the viscosity of the environment, which enables them to be used as viscosity sensors. PzII and pz IV easily enter cancer cells and efficiently induce cell death under light irradiation. Using fluorescence lifetime imaging microscopy, we demonstrated the possibility of assessing local intracellular viscosity and visualizing viscosity changes driven by PDT treatment with the compounds. Thus, pz II and pz IV combine the features of potent photodynamic agents and viscosity sensors. These data suggest that the unique properties of the compounds provide a tool for PDT dosimetry and tailoring the PDT treatment regimen to the individual characteristics of each patient.


Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Glioma/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/química , Oxigênio Singlete/química , Animais , Carcinoma de Células Escamosas/patologia , Glioma/patologia , Humanos , Camundongos , Fármacos Fotossensibilizantes/química , Células Tumorais Cultivadas , Viscosidade
13.
Biomacromolecules ; 22(11): 4783-4793, 2021 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-34623134

RESUMO

Photodynamic therapy (PDT) is showing great potential in the treatment of cancer diseases, and photosensitizers play crucial roles in absorbing the energy of light and generating reactive oxygen species (ROS) during PDT. Most of the photosensitizers bearing macrocyclic structures have strong hydrophobicity and suffer from the π-π interaction and undesired aggregation caused quenching (ACQ), which severely limit the PDT efficacy. Moreover, the continuous oxygen consumption during PDT also leads to the upregulated expression of hypoxia-inducible factor-1α (HIF-1α), which can aggravate the growth of tumors. To overcome the abovementioned problems, polymerized photosensitizers repelled by flexible thioketal linkers were designed and synthesized using a multicomponent polymerization (MCP) method to afford the poly-porphyrins with high molecular weight (Mw > 20 000 g/mol) under room temperature. The ACQ effect could be significantly inhibited by introducing flexible chains and increasing Mw, leading to the improvement in the singlet oxygen quantum yield and phototoxicity simultaneously. An HIF-1α inhibitor, Lificiguat (YC-1) was synthesized as a chemodrug and codelivered with poly-porphyrins to decrease the expression of HIF-1α and inhibit tumor growth under hypoxia. With the synergistic PDT and chemotherapy, poly-porphyrin/YC-1 micelles showed excellent therapeutic antitumor efficacy both in vitro and in vivo.


Assuntos
Fotoquimioterapia , Porfirinas , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Espécies Reativas de Oxigênio , Oxigênio Singlete
14.
Molecules ; 26(19)2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34641420

RESUMO

New porphyrin-Schiff base conjugates bearing one (6) and two (7) basic amino groups were synthesized by condensation between tetrapyrrolic macrocycle-containing amine functions and 4-(3-(N,N-dimethylamino)propoxy)benzaldehyde. This approach allowed us to easily obtain porphyrins substituted by positive charge precursor groups in aqueous media. These compounds showed the typical Soret and four Q absorption bands with red fluorescence emission (ΦF ~ 0.12) in N,N-dimethylformamide. Porphyrins 6 and 7 photosensitized the generation of O2(1Δg) (ΦΔ ~ 0.44) and the photo-oxidation of L-tryptophan. The decomposition of this amino acid was mainly mediated by a type II photoprocess. Moreover, the addition of KI strongly quenched the photodynamic action through a reaction with O2(1Δg) to produce iodine. The photodynamic inactivation capacity induced by porphyrins 6 and 7 was evaluated in Staphylococcus aureus, Escherichia coli, and Candida albicans. Furthermore, the photoinactivation of these microorganisms was improved using potentiation with iodide anions. These porphyrins containing basic aliphatic amino groups can be protonated in biological systems, which provides an amphiphilic character to the tetrapyrrolic macrocycle. This effect allows one to increase the interaction with the cell wall, thus improving photocytotoxic activity against microorganisms.


Assuntos
Aminoácidos Básicos/química , Anti-Infecciosos/farmacologia , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Porfirinas/química , Bases de Schiff/farmacologia , Anti-Infecciosos/química , Antifúngicos/química , Bases de Schiff/química
15.
Rev Assoc Med Bras (1992) ; 67(5): 650-655, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34550251

RESUMO

OBJECTIVE: To assess the impact of the metoclopramide-induced hyperprolactinemia in cellular death and proliferation in the harderian gland of female mice. METHODS: Twenty female mice were divided into two groups of 10 animals each and treated: 0.2 mL of saline solution (controls, Ctr) and 200 µg of metoclopramide (experimental, hyperprolactinemia), both for 50 consecutive days and at 12:00 a.m. On the 50th day, the female were euthanized, and the harderian glands were removed and processed for immunohistochemistry for detected ki67 and TUNEL method. Data were statistically analyzed by unpaired Student's t test (p<0.05). RESULTS: The harderian gland of the hyperprolactinemia group showed increase in the immunoexpression of Ki67 and TUNEL compared to the Ctr group (p<0.05), and there was no significant difference in the amount of porphyrin in the HPrl group compared to the Ctr group. CONCLUSION: The hyperprolactinemia led to increased cell death in the acini the harderian gland and cell proliferation in the stroma glandular, fact that suggesting a reduction process of cellular activity and fibrosis, which suggests impairment in the functioning of the lacrimal harderian.


Assuntos
Glândula de Harder , Hiperprolactinemia , Aparelho Lacrimal , Porfirinas , Animais , Proliferação de Células , Feminino , Hiperprolactinemia/induzido quimicamente , Camundongos
16.
BMJ Open ; 11(9): e053325, 2021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34548368

RESUMO

INTRODUCTION: The COVID-19 pandemic has emerged worldwide. Although several medications have been approved for treating moderate-to-severe COVID-19, very few treatment strategy has been established for patients with mild COVID-19 who do not require oxygen administration. Clarithromycin is a macrolide antimicrobial agent that has been widely used for bacterial respiratory infectious diseases. Clarithromycin also acts an immunomodulating drug and suppresses cytokine storms in viral respiratory diseases, including influenza. In this study, we aim to evaluate the efficacy of clarithromycin in patients with mild COVID-19. METHODS AND ANALYSIS: This is an exploratory, multicentre, open-label, randomised controlled trial. This study was initiated in May 2021 and will end in July 2022. Patients with mild COVID-19 pneumonia who do not require oxygen administration will be enrolled and randomly assigned in a 1:1:1 ratio to group A (administration of clarithromycin 800 mg/day), group B (administration of clarithromycin 400 mg/day) or group C (standard treatment without clarithromycin). The planned number of enrolled patients is 60 (20 patients × three groups). The primary endpoint is the number of days required to improve the clinical symptoms as measured by the severity score. Secondary endpoints include days for recovery of the body temperature, proportion of patients with oxygen administration, inflammatory cytokines, viral load, serum immunoglobulins, peripheral blood lymphocytes, blood biomarkers and pneumonia infiltrations. ETHICS AND DISSEMINATION: The study protocol was approved by the Clinical Research Review Board of Nagasaki University in accordance with the Clinical Trials Act in Japan. The study will be conducted in accordance with the Declaration of Helsinki, the Clinical Trials Act and other current legal regulations in Japan. Written informed consent will be obtained from all the participants. The results of this study will be reported as journal publications. TRIAL REGISTRATION NUMBER: jRCTs071210011.


Assuntos
COVID-19 , Claritromicina , Humanos , Estudos Multicêntricos como Assunto , Oxigênio , Pandemias , Porfirinas , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2 , Resultado do Tratamento
17.
Nanoscale ; 13(38): 16197-16206, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34545903

RESUMO

Nanotheranostics for fluorescence/magnetic resonance (FL/MR) dual-modal imaging guided photodynamic therapy (PDT) are highly desirable in precision and personalized medicine. In this study, a facile non-covalent electrostatic interaction induced self-assembly strategy is developed to effectively encapsulate gadolinium porphyrin (Gd-TCPP) into homogeneous supramolecular nanoparticles (referred to as Gd-PNPs). Gd-PNPs exhibit the following advantages: (1) excellent FL imaging property, high longitudinal relaxivity (16.157 mM-1 s-1), and good singlet oxygen (1O2) production property; (2) excellent long-term colloidal stability, dispersity and biocompatibility; and (3) enhanced in vivo FL/MR imaging guided tumor growth inhibition efficiency for CT 26 tumor-bearing mice. This study provides a new strategy to design and synthesize metalloporphyrin-based nanotheranostics for imaging-guided cancer therapy with enhanced theranostic properties.


Assuntos
Nanopartículas , Fotoquimioterapia , Porfirinas , Animais , Linhagem Celular Tumoral , Gadolínio , Imageamento por Ressonância Magnética , Camundongos , Polímeros , Nanomedicina Teranóstica
18.
Biomaterials ; 277: 121061, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34508957

RESUMO

Patient-derived xenograft (PDX) models are powerful tools for understanding cancer biology and drug discovery. In this study, a polymeric nano-sized drug delivery system poly (OEGMA)-PTX@Ce6 (NPs@Ce6) composed of a photosensitizer chlorin e6 (Ce6) and a cathepsin B-sensitive polymer-paclitaxel (PTX) prodrug was constructed. The photochemical internalization (PCI) effect and enhanced chemo-photodynamic therapy (PDT) were achieved via a two-stage light irradiation strategy. The results showed that the NPs@Ce6 had great tumor targeting and rapid cellular uptake induced by PCI, thereby producing excellent anti-tumor effects on human bladder cancer PDX models with tumor growth inhibition greater than 98%. Bioinformatics analysis revealed that the combination of PTX chemotherapy and PDT up-regulated oxidative phosphorylation and reactive oxygen species (ROS) generation, blocked cell cycle and proliferation, and down-regulated the pathways related to tumor progression, invasion and metastasis, including hypoxia, TGF-ß signaling and TNF-α signaling pathways. Western blots analysis confirmed that proteins promoting apoptosis (Bax, Cleaved caspase-3, Cleaved PARP) and DNA damage (γH2A.X) were up-regulated, while those inhibiting apoptosis (Bcl-2) and mitosis (pan-actin and α/ß-tubulin) were down-regulated after chemo-PDT treatment. Therefore, this stimuli-responsive polymer-PTX prodrug-based nanomedicine with combinational chemotherapy and PDT evaluated in the PDX models could be a potential candidate for bladder cancer therapy.


Assuntos
Nanopartículas , Fotoquimioterapia , Porfirinas , Pró-Fármacos , Neoplasias da Bexiga Urinária , Linhagem Celular Tumoral , Xenoenxertos , Humanos , Fármacos Fotossensibilizantes , Neoplasias da Bexiga Urinária/tratamento farmacológico
19.
J Phys Chem B ; 125(37): 10571-10577, 2021 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-34506146

RESUMO

Photoinduced electron transfer systems can mimic certain features of natural photosynthetic reaction centers, which are crucial for solar energy production. Among other tetra-pyrroles, the versatile chemical and photophysical properties of corroles make them very promising donors applicable in donor-acceptor complexes. Here, we present a first comprehensive study of ultrafast photoinduced electron transfer in a self-assembling sulfonated aluminum corrole-methylviologen complex combining visible and mid-IR transient absorption spectroscopy. The noncovalent D-A association of the corrole-methylviologen complex has the great advantage that photoinduced charge separation becomes possible even though the back electron transfer (BET) rate is large. Initial forward electron transfer from corrole to methylviologen is observed on an ∼130 fs time scale. Subsequent back electron transfer takes place with τBET = (1.8 ± 0.5) ps, revealing very complex relaxation dynamics. Direct probing in the mid-IR allows us to unravel the back electron transfer and cooling dynamics/electronic reorganization. Upon tracing the dynamics of the methylviologen-radical marker band at 1640 cm-1 and the C═C stretching of corrole at around 1500 cm-1, we observe that large amounts of excess energy survive the back transfer, leading to the formation of hot ground state absorption. A closer examination of the signal after 300 ps, surviving the back transfer, exhibits a charge-separation yield of 10-15%.


Assuntos
Alumínio , Elétrons , Transporte de Elétrons , Paraquat , Porfirinas
20.
J Photochem Photobiol B ; 223: 112301, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34492530

RESUMO

Prostate cancer (PCa) is the second most frequent cancer diagnosed in men worldwide. Among the common treatment options, photodynamic therapy (PDT) is being considered a promising local therapy to treat this cancer. Although PDT is an established treatment modality approved for several types of cancer, the low solubility, the reduced tumor selectivity, the absorption in the therapeutic window and the poor clearance from the body of the currently approved photosensitizers (PS) hampers its wide clinical application. In this regard, herein we synthesized three fluorinated porphyrinoid derivatives and entrapped them into polyvinylpyrrolidone (PVP) to prevent their aggregation and preserve their desirable photophysical properties under the physiological environment. In vitro studies revealed the negligible dark cytotoxicity of all PVP formulations (PS1@PVP, PS2@PVP and PS3@PVP) at the tested concentrations (5.0 to 20 µM), but also confirmed the significant photodynamic effect of PS2@PVP and PS3@PVP towards the PCa cell line PC-3, upon red light irradiation at an irradiance of 17.6 mW.cm-2. To provide insight into the underlying mechanisms of cell death under PDT treatment induced by PS2@PVP and PS3@PVP, their intracellular localization in PC-3 cells was firstly investigated by confocal microscopy. Since both PS2@PVP and PS3@PVP nanoparticles were mainly localized in mitochondria, the involvement of this organelle in PDT-induced apoptosis mediated by both formulations was further explored. Western blot analysis revealed that PDT treatment of PC-3 cells with either PS2@PVP or PS3@PVP resulted in the reduction of the expression level of the anti-apoptotic protein Bcl-2. As the photodamage to Bcl-2 after PDT with PS2@PVP and PS3@PVP was accompanied by the further activation of pro-caspase-3, we assumed that upon irradiation the photogenerated reactive oxygen species (ROS) were able to activate a caspase-dependent apoptotic response as a consequence of a post-mitochondrial event. Taken together, these findings demonstrate that among the tested fluorinated porphyrinoids, PS2@PVP and, particularly, PS3@PVP, are significantly more effective in overall PC-3 cell killing than PS1@PVP, thus highlighting their great potential as therapeutic agents for PCa.


Assuntos
Apoptose/efeitos dos fármacos , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/farmacologia , Caspase 3/metabolismo , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Composição de Medicamentos , Humanos , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Nanopartículas/química , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/química , Porfirinas/uso terapêutico , Povidona/química , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo
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