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1.
Theranostics ; 11(16): 7869-7878, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335969

RESUMO

Goals: Chemotherapy, the most conventional modality for cancer therapy, usually brings serious side effects because of the low cancer-therapeutic specificity and bioavailability. It is of great significance for cancer treatment to develop new effective strategies to regulate biochemical reactions in organelles, enhance the specificity of chemotherapeutic drugs and reduce their side effects. Methods: We report herein a zeolitic imidazole framework-90 (ZIF-90) based nanoplatform, which was used to initiate a series of mitochondrial cascade reactions using ATP as a molecular switch for cancer therapy. The thioketal linked camptothecin (camptothecin prodrug, TK-CPT) and 2-Methoxyestradiol (2-ME) were encapsulated into the pores of ZIF-90 nanoparticles using a simple one-pot method, and the nanoplatform was finally coated with a layer of homologous cell membrane. Results: Mitochondrial ATP can efficiently degrade ZIF-90 and then release the loaded 2-ME and CPT prodrugs. 2-ME can inhibit the activity of superoxide dismutase (SOD), which induces the up-regulation of reactive oxygen species (ROS) in situ. The thioketal linkers in CPT prodrug can respond to ROS, thereby achieving subsequent release of parent CPT drug. This cascade of reactions can lead to prolonged high oxidative stress and cause continuous cancer cell apoptosis, due to the increased ROS level and the liberation of CPT. Conclusion: We constructed an ATP-triggered strategy using nanoscale ZIF-90 to initiate mitochondrial cascade reactions for cancer therapy. The ZIF-90 based nanoplatform exhibited low cytotoxicity, good mitochondria-targeting ability, and excellent therapeutic effect. In vivo experiments demonstrated that the growth of tumor can be efficiently inhibited in a mouse model. This ATP-triggered strategy to induce mitochondrial biochemical reactions offers more possibilities for developing organelle-targeted therapeutic platforms.


Assuntos
Antineoplásicos/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Zeolitas/química , Trifosfato de Adenosina/química , Trifosfato de Adenosina/metabolismo , Animais , Antineoplásicos/farmacologia , Disponibilidade Biológica , Linhagem Celular Tumoral , China , Liberação Controlada de Fármacos/fisiologia , Imidazóis/química , Imidazóis/metabolismo , Imidazóis/farmacologia , Camundongos , Mitocôndrias/metabolismo , Nanopartículas/administração & dosagem , Neoplasias/metabolismo , Pró-Fármacos/química , Espécies Reativas de Oxigênio/metabolismo , Zeolitas/metabolismo , Zeolitas/farmacologia
2.
Biomed Res Int ; 2021: 5529368, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34368350

RESUMO

The aim of this study was to evaluate the biocompatibility and osteogenic potential of a Zeolite Socony Mobil-5 (ZSM-5) coating on a Ti-24 Nb-4 Zr-7.9 Sn (Ti-2448) surface. ZSM-5-modified Ti-2448 (ZSM-5/Ti-2448) and Ti-2448 (control) groups were employed. The physical and chemical properties of the two types of samples were evaluated by scanning electron microscopy, Fourier-transform infrared spectroscopy, nitrogen adsorption/desorption, and contact angle methods. The surface of the ZSM-5/Ti-2448 was rougher than that of the original Ti-2448, while the contact angle of the ZSM-5/Ti-2448 was smaller than that of Ti-2448. In addition, the ZSM-5/Ti-2448 largely increased the specific surface area and introduced silanol groups. A bone-like apatite layer could be formed on the surface of ZSM-5/Ti-2448 after 14 days of incubation in a simulated body fluid. ZSM-5/Ti-2448 was not cytotoxic. The number and alkaline phosphatase (ALP) activity of osteoblasts on ZSM-5/Ti-2448 were significantly higher than those on Ti-2448 surfaces, obtained in vitro using 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide and ALP activity assays. Few inflammatory cells were observed around ZSM-5/Ti-2448 after insertion into the femurs of Japanese white rabbits after 4, 12, and 26 weeks through hematoxylin-eosin staining. The average gray scale of transforming growth factor-ß1 (TGF-ß1) on ZSM-5/Ti-2448 peaked earlier than that on Ti-2448, according to immunohistochemical staining. These results indicate that ZSM-5/Ti-2448 has a good biocompatibility and improved early osteogenic potential compared to a noncoated Ti-2448.


Assuntos
Ligas/farmacologia , Materiais Revestidos Biocompatíveis/farmacologia , Osteogênese/efeitos dos fármacos , Zeolitas/farmacologia , Fosfatase Alcalina/metabolismo , Animais , Biomineralização/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Implantes Experimentais , Masculino , Camundongos , Coelhos , Propriedades de Superfície , Fator de Crescimento Transformador beta/metabolismo
3.
Molecules ; 26(11)2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34073510

RESUMO

Broad industrial application of zeolites increases the opportunity of inhalation. However, the potential impact of different types and compositions of zeolite on cytotoxicity is still unknown. Four types of synthetic zeolites have been prepared for assessing the effect on lung fibroblast: two zeolite L (LTL-R and LTL-D), ZSM-5 (MFI-S), and faujasite (FAU-S). The cytotoxicity of zeolites on human lung fibroblast (IMR-90) was assessed using WST1 cell proliferation assay, mitochondrial function, membrane leakage of lactate dehydrogenase, reduced glutathione levels, and mitochondrial membrane potential were assessed under control. Intracellular changes were examined using transmission electron microscopy (TEM). Toxicity-related gene expressions were evaluated by PCR array. The result showed significantly higher toxicity in IMR-90 cells with FAU-S than LTL-R, LTL-D and MFI-S exposure. TEM showed FAU-S, spheroidal zeolite with a low Si/Al ratio, was readily internalized forming numerous phagosomes in IMR-90 cells, while the largest and disc-shaped zeolites showed the lowest toxicity and were located in submembranous phagosomes in IMR-90 cells. Differential expression of TNF related genes was detected using PCR arrays and confirmed using qRT-PCR analysis of selected genes. Collectively, the exposure of different zeolites shows different toxicity on IMR-90 cells.


Assuntos
Fibroblastos/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Potencial da Membrana Mitocondrial , Zeolitas/toxicidade , Linhagem Celular , Proliferação de Células , Sobrevivência Celular/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Glutationa/metabolismo , Humanos , Nanoestruturas , Reação em Cadeia da Polimerase , Difração de Raios X , Zeolitas/farmacologia
4.
Colloids Surf B Biointerfaces ; 205: 111920, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34144324

RESUMO

Poly-ether-ether-ketone (PEEK) is a promising material in oral repair and orthopedic implantation field due to its stability and proper elastic modulus. However, the lack of simple but effective strategy to functionalize PEEK and improve its antibacterial function hinders its further biomedical application. In this study, a sulfonated 3D porous PEEK is fabricated via sulfonation treatment, and then decorated with the in situ synthesized zeolitic imidazolate framework-8 (ZIF-8), in which Ag+ ions were loaded with high loading capacity. Surface morphology, roughness, chemical composition and hydrophilicity of all the substrates were evaluated in details, suggesting Ag+ ions loaded ZIF-8 on sulfonated PEEK (SPZA) was successfully prepared. The antibacterial activity of pristine and functionalized PEEK was evaluated by inhibition zone test, spread plate assay, growth curve, and morphology of bacteria. Experimental results demonstrate that the SPZA has effectively bacteriostatic performance against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The excellent antimicrobial activity is attributed to the synergistic effect of Ag+ and Zn2+ ions released continuously from SPZA. This work provides a promising route for surface modification of PEEK and offer a potential candidate for biomedical implants.


Assuntos
Anti-Infecciosos , Estruturas Metalorgânicas , Zeolitas , Antibacterianos/farmacologia , Escherichia coli , Éter , Éteres/farmacologia , Cetonas/farmacologia , Estruturas Metalorgânicas/farmacologia , Polietilenoglicóis , Porosidade , Prata , Staphylococcus aureus , Zeolitas/farmacologia
5.
Angew Chem Int Ed Engl ; 60(28): 15472-15481, 2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-33964189

RESUMO

Although reactive oxygen species (ROS)-mediated tumor treatments are predominant in clinical applications, ROS-induced protective autophagy promotes cell survival, especially in hypoxic tumors. Herein, X-ray triggered nitrite (NO2 - ) is used for hypoxic prostate cancer therapy by inhibiting autophagy and inducing nitrosative stress based on an electrophilic zeolitic imidazole framework (ZIF-82-PVP). After internalization of pH-responsive ZIF-82-PVP nanoparticles, electrophilic ligands and Zn2+ are delivered into cancer cells. Electrophilic ligands can not only consume GSH under hypoxia but also capture low-energy electrons derived from X-rays to generate NO2 - , which inhibits autophagy and further elevates lethal nitrosative stress levels. In addition, dissociated Zn2+ specifically limits the migration and invasion of prostate cancer cells through ion interference. In vitro and in vivo results indicate that ZIF-82-PVP nanoparticles under X-ray irradiation can effectively promote the apoptosis of hypoxic prostate cancer cells. Overall, this nitrosative stress-mediated tumor therapy strategy provides a novel approach targeting hypoxic tumors.


Assuntos
Antineoplásicos/farmacologia , Autofagia/efeitos dos fármacos , Imidazóis/farmacologia , Estruturas Metalorgânicas/farmacologia , Nanopartículas/química , Neoplasias da Próstata/tratamento farmacológico , Zeolitas/farmacologia , Antineoplásicos/química , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Imidazóis/química , Masculino , Estruturas Metalorgânicas/química , Estresse Nitrosativo/efeitos dos fármacos , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Raios X , Zeolitas/química
6.
PLoS One ; 16(5): e0252211, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34043688

RESUMO

Clostridioides difficile (C. difficile) infection is a major public health problem worldwide. The current treatment of C. difficile-associated diarrhea relies on the use of antibacterial agents. However, recurrences are frequent. The main virulence factors of C. difficile are two secreted cytotoxic proteins toxin A and toxin B. Alternative research exploring toxin binding by resins found a reduced rate of recurrence by administration of tolevamer. Hence, binding of exotoxins may be useful in preventing a relapse provided that the adsorbent is innocuous. Here, we examined the toxin binding capacity of G-PUR®, a purified version of natural clinoptilolite-tuff. Our observations showed that the purified clinoptilolite-tuff adsorbed clinically relevant amounts of C. difficile toxins A and B in vitro and neutralized their action in a Caco-2 intestinal model. This conclusion is based on four independent sets of findings: G-PUR® abrogated toxin-induced (i) RAC1 glucosylation, (ii) redistribution of occludin, (iii) rarefaction of the brush border as visualized by scanning electron microscopy and (iv) breakdown of the epithelial barrier recorded by transepithelial electrical resistance monitoring. Finally, we confirmed that the epithelial monolayer tolerated G-PUR® over a wide range of particle densities. Our findings justify the further exploration of purified clinoptilolite-tuff as a safe agent in the treatment and/or prevention of C. difficile-associated diarrhea.


Assuntos
Proteínas de Bactérias/metabolismo , Toxinas Bacterianas/metabolismo , Clostridioides difficile/imunologia , Infecções por Clostridium/prevenção & controle , Enterotoxinas/metabolismo , Fatores de Virulência/metabolismo , Zeolitas/farmacologia , Células CACO-2 , Humanos , Ligação Proteica
7.
Parasit Vectors ; 14(1): 268, 2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34016175

RESUMO

BACKGROUND: Malaria vector control approaches that rely on mosquito releases such as the sterile insect technique (SIT) and suppression or replacement strategies relying on genetically modified mosquitoes (GMM) depend on effective mass production of Anopheles mosquitoes. Anophelines typically require relatively clean larval rearing water, and water management techniques that minimise toxic ammonia are key to achieving optimal rearing conditions in small and large rearing facilities. Zeolites are extensively used in closed-system fish aquaculture to improve water quality and reduce water consumption, thanks to their selective adsorption of ammonia and toxic heavy metals. The many advantages of zeolites include low cost, abundance in many parts of the world and environmental friendliness. However, so far, their potential benefit for mosquito rearing has not been evaluated. METHODS: This study evaluated the independent effects of zeolite and daily water changes (to simulate a continuous flow system) on the rearing of An. coluzzii under two feed regimes (powder and slurry feed) and larval densities (200 and 400 larvae per tray). The duration of larval development, adult emergence success and phenotypic quality (body size) were recorded to assess the impact of water treatments on mosquito numbers, phenotypic quality and identification of optimal feeding regimes and larval density for the use of zeolite. RESULTS: Overall, mosquito emergence, duration of development and adult phenotypic quality were significantly better in treatments with daily water changes. In treatments without daily water changes, zeolite significantly improved water quality at the lower larval rearing density, resulting in higher mosquito emergence and shorter development time. At the lower larval rearing density, the adult phenotypic quality did not significantly differ between zeolite treatment without water changes and those with daily changes. CONCLUSIONS: These results suggest that treating rearing water with zeolite can improve mosquito production in smaller facilities. Zeolite could also offer cost-effective and environmentally friendly solutions for water recycling management systems in larger production facilities. Further studies are needed to optimise and assess the costs and benefits of such applications to Anopheles gambiae (s.l.) mosquito-rearing programmes.


Assuntos
Amônia/farmacologia , Anopheles/crescimento & desenvolvimento , Água Doce/química , Zeolitas/farmacologia , Animais , Anopheles/efeitos dos fármacos , Tamanho Corporal/efeitos dos fármacos , Feminino , Água Doce/parasitologia , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Masculino , Mosquitos Vetores/efeitos dos fármacos , Mosquitos Vetores/crescimento & desenvolvimento , Fenótipo , Qualidade da Água
8.
Int J Biol Macromol ; 179: 206-216, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33675827

RESUMO

Chitosan/zeolite-A nanocomposite (CH/ZA) was synthesized as a potential carrier for levofloxacin (LVOX) of enhanced technical properties. The CH/ZA composite displayed enhanced loading capacity (425 mg/g) as compared to chitosan (188.8 mg/g) and zeolite-A (234.6 mg/g). The loading behavior follows Pseudo-Second-order and Langmuir as kinetic and isotherm models. The equilibrium studies, Gaussian energy (8.15 KJ/mol), and thermodynamic parameters demonstrate homogenous and monolayer loading by complex chemical and physical reactions that are of spontaneous and exothermic nature. The CH/ZA composite is of slow and continuous release profile (200h) with 94.3% as the maximum release percentage. The release reactions are of non-Fickian behavior involving both diffusion and erosion mechanisms. The loading of LVOX into CH/ZA induced its anti-inflammatory effect against the cytokine production (IL-6 and IL-8) within the human bronchial epithelia cells (NL20). The cytotoxicity studies on the normal cells demonstrated a high safety value for the composite.


Assuntos
Anti-Inflamatórios , Quitosana , Portadores de Fármacos , Levofloxacino , Nanocompostos , Zeolitas , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacocinética , Anti-Inflamatórios/farmacologia , Linhagem Celular , Quitosana/química , Quitosana/farmacocinética , Quitosana/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Humanos , Levofloxacino/química , Levofloxacino/farmacocinética , Levofloxacino/farmacologia , Teste de Materiais , Nanocompostos/química , Nanocompostos/uso terapêutico , Zeolitas/química , Zeolitas/farmacocinética , Zeolitas/farmacologia
9.
Acta Vet Hung ; 69(1): 23-30, 2021 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-33764891

RESUMO

The purpose of the present study was to use oxidative stress markers for investigating the effect of zeolite (315 mg/kg of complete feed) in the case of aflatoxin B1 contamination (92 µg/kg complete feed). In a 21-day feeding trial with broiler chickens, oxidative stress parameters such as conjugated dienes, conjugated trienes, malondialdehyde, reduced glutathione content and glutathione peroxidase activity were not changed significantly by supplementation with this mycotoxin absorbent. The relative gene expression of transcription factors KEAP1 and NRF2 was not modified by the absorbent either. Still, the expression of GSS, GSR and GPX4 genes increased significantly due to the aluminosilicate supplementation. The results suggest that zeolite reduced lipid peroxidation in the blood plasma but not in the red blood cell haemolysate or the kidney. The relative expression of the genes encoding the glutathione redox system also changed as a result of zeolite supplementation, but these changes were not found at the protein level.


Assuntos
Aflatoxina B1 , Zeolitas , Aflatoxina B1/toxicidade , Ração Animal , Animais , Galinhas/metabolismo , Genes Reguladores , Glutationa/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fígado , Fator 2 Relacionado a NF-E2/genética , Zeolitas/farmacologia
10.
Br Poult Sci ; 62(4): 601-610, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33595390

RESUMO

1. The aim of the present study was to test the ability of an in-feed modified clinoptilolite zeolite-based mycotoxin binding substance (Minazel® Plus, Patent Co, Misicevo, Serbia; MP) to prevent gastrointestinal absorption of aflatoxin B1 (AFB1) and ochratoxin A (OTA) and its effects on health status and performance parameters of broilers.2. A total of 375, 1 d old male broiler chickens (Cobb 500) were used for a total trial period of 42 d (from hatch to 42 d of age). Animals were randomly allocated to five treatment groups (T1-T5), in 25 pens (15 male broilers per pen, five pens per treatment). T1 was the control maize-based diet without the addition of mycotoxins, or the test product. T2 and T3 groups received contaminated maize in the diet containing 0.02 mg AFB1/kg feed and 0.1 mg OTA/kg feed, whereas T4 and T5 groups received 0.05 mg AFB1/kg feed and 0.5 mg OTA/kg feed. The MP was added to T3 (1 g/kg feed), and T5 (2 g/kg feed) groups.3. Results showed that exposure to AFB1 and OTA at low or moderate levels, as used in this study, did not markedly affect growth performance, blood profile or organ weights. Improvements in feed conversion ratio (FCR) were observed in birds receiving MP, whereby FCR of T3 group was improved in comparison with T2 group, although there was no significant difference between T5 and T4 groups. However, average body weight gain (ABWG) was improved in the T5 group compared to T4, but not in the T3 versus T2 group comparison.4. For serum biochemical parameters, glutamate-dehydrogenase (GLDH) was significantly improved in T5 birds in comparison with T4. The addition of MP significantly decreased residue levels of AFB1 in liver and OTA in the spleen of the treated groups.5. The improvements in productive performance and reduction of mycotoxin residue levels in tissues demonstrated a beneficial effect of MP in cases of concurrent AFB1 and OTA ingestion by broilers.


Assuntos
Galinhas , Zeolitas , Aflatoxina B1 , Ração Animal/análise , Animais , Nível de Saúde , Masculino , Ocratoxinas , Zeolitas/farmacologia
11.
Mater Sci Eng C Mater Biol Appl ; 120: 111721, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33545872

RESUMO

Zeolites have attractive features making them suitable carriers for drug delivery systems (DDS). As such, we loaded the anticancer drug 5-fluorouracil (5-FU), into two different zeolite structures, faujasite (NaY) and Linde Type L (LTL), to obtain different DDS. The prepared DDS were tested in vitro using breast cancer, colorectal carcinoma, and melanoma cell lines and in vivo using the chick embryo chorioallantoic membrane model (CAM). Both assays showed the best results for the Hs578T breast cancer cells, with a higher potentiation for 5-FU encapsulated in the zeolite LTL. To unveil the endocytic mechanisms involved in the internalization of the zeolite nanoparticles, endocytosis was inhibited pharmacologically in breast cancer and epithelial mammary human cells. The results suggest that a caveolin-mediated process was responsible for the internalized zeolite nanoparticles. Aiming to boost the DDS efficacy, the disc-shaped zeolite LTL outer surface was functionalized using amino (NH2) or carboxylic acid (COOH) groups and coated with poly-l-lysine (PLL). Positively functionalized surface LTL nanoparticles revealed to be non-toxic to human cells and, importantly, their internalization was faster and led to a higher tumor reduction in vivo. Overall, our results provide further insights into the mechanisms of interaction between zeolite-based DDS and cancer cells, and pave the way for future studies aiming to improve DDS anticancer activity.


Assuntos
Antineoplásicos , Nanopartículas , Zeolitas , Animais , Antineoplásicos/farmacologia , Embrião de Galinha , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Fluoruracila/farmacologia , Humanos , Zeolitas/farmacologia
12.
ACS Appl Mater Interfaces ; 13(5): 6034-6042, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33499584

RESUMO

MicroRNA (miRNA) represents a promising class of therapeutic nucleic acid drugs, while delivery challenges remain that impede the advancement of miRNA therapy, largely because of in vivo instability and low delivery efficiency. Herein, we discover the dual roles of metal-organic framework (MOF) nanoparticles (ZIF-8) as nanocarriers for miRNA delivery and adjuvants for chemodynamic therapy. The miR-34a-m@ZIF-8 complex demonstrated efficient cellular uptake and lysosomal stimuli-responsive miRNA release. Zn2+ triggered the generation of reactive oxygen species, which consequently induced apoptosis of tumor cells. Released miR-34a-m led to a remarkable decrease in expression of Bcl-2 at both mRNA and protein levels and enhanced cancer cell apoptosis. In vivo experiments showed high efficacy of using miR-34a-m@ZIF-8 to suppress tumor growth via synergistic gene/chemodynamic therapy in a mouse model of triple-negative breast cancer. Our work demonstrates MOFs as a promising nanoplatform for efficient synergetic gene/chemodynamic therapy.


Assuntos
Adjuvantes Farmacêuticos/farmacologia , Antibióticos Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Estruturas Metalorgânicas/química , MicroRNAs/farmacologia , Nanopartículas/química , Adjuvantes Farmacêuticos/química , Animais , Antibióticos Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/química , Portadores de Fármacos/química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Neoplasias Mamárias Experimentais/diagnóstico por imagem , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/metabolismo , Camundongos , MicroRNAs/química , Tamanho da Partícula , Espécies Reativas de Oxigênio/metabolismo , Propriedades de Superfície , Zeolitas/química , Zeolitas/farmacologia
13.
Exp Biol Med (Maywood) ; 246(5): 529-537, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33183068

RESUMO

The severity of osteoporosis in humans manifests in its high incidence and by its complications that diminish quality of life. A societal consequence of osteoporosis is the substantial burden that it inflicts upon patients and their families. Several bone-modifying drugs have been prescribed to patients with osteoporosis. However, evidence for their anti-fracture efficacy remains inconclusive. To the contrary, long-term use of anti-osteoporotic drugs such as bisphosphonates and Denosumab, an RANKL inhibitor, have resulted in adverse events. We now present an alternative and adjuvant approach for treatment of osteoporosis. The data derive from in vivo studies in an ovariectomized rat model and from a randomized double blind, placebo-controlled human clinical study. Both studies involved treatment with Panaceo Micro Activation (PMA)-zeolite-clinoptilolite, a defined cation exchange clinoptilolite, which clearly improved all bone histomorphometric parameters examined from ovariectomized animals, indicative for increased bone formation. Moreover, intervention with PMA-zeolite-clinoptilolite for one year proved safe in humans. Furthermore, patients treated with PMA-zeolite-clinoptilolite showed an increase in bone mineral density, an elevated level of markers indicative of bone formation, a significant reduction in pain, and significantly improved quality of life compared with patients in the control (placebo) group. These encouraging positive effects of PMA-zeolite-clinoptilolite on bone integrity and on osteoporosis warrant further evaluation of treatment with PMA-zeolite-clinoptilolite as a new alternative adjuvant therapy for osteoporosis.


Assuntos
Osteoporose/tratamento farmacológico , Zeolitas/uso terapêutico , Idoso , Animais , Biomarcadores/metabolismo , Densidade Óssea/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/diagnóstico por imagem , Osteoporose/patologia , Osteoporose/fisiopatologia , Ovariectomia , Ratos Wistar , Tíbia/diagnóstico por imagem , Tíbia/efeitos dos fármacos , Tíbia/patologia , Tíbia/fisiopatologia , Microtomografia por Raio-X , Zeolitas/farmacologia
14.
Biol Trace Elem Res ; 199(4): 1405-1413, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32607765

RESUMO

This experiment was conducted to investigate the effects of zinc oxide/zeolite on growth performance, serum biochemistry, intestinal morphology, and microflora of weaned piglets. Two hundred and fifty-six weaned piglets (Duroc × Landrace × Large) at 21 days of age were randomly assigned to 2 groups with 8 replicates and 16 piglets in each pen. The diets of high dose of zinc oxide group (HD-ZnO) supplemented with 1500 mg/kg zinc as zinc oxide, but the diet of experimental group supplemented with 500 mg/kg zinc as zinc oxide that supported on zeolite (SR-ZnO). The experiment was conducted for 2 weeks after weanling. The results showed replacement of high-dosed zinc oxide by SR-ZnO had no significant effects on growth performance and intestinal morphology. However, the dietary supplementation of SR-ZnO reduced the diarrhea rate (P < 0.05), increased the activity of serum alkaline phosphatase (ALP) (P < 0.01), and tended to reduce zinc release in stomach (P = 0.06) and increase serum total protein (TP) (P = 0.07). Although there were no significant effects in ileal microflora on α diversity, the abundance of Campylobacters was found significantly decreased (P < 0.05), whereas the abundance of Clostridium was increased (P < 0.05) after lower-dosed SR-ZnO replacement. It is revealed that replacement of HD-ZnO (1500 mg/kg) by SR-ZnO (500 mg/kg) in creep feed could improve the zinc bioavailability, regulate the intestinal flora, and alleviate the postweaning diarrhea in weaned piglets. Accordingly, the application of SR-ZnO would reduce the zinc in feed and therefore benefits for the ecological environment.


Assuntos
Microbioma Gastrointestinal , Zeolitas , Óxido de Zinco , Animais , Diarreia/prevenção & controle , Diarreia/veterinária , Suplementos Nutricionais , Suínos , Desmame , Zeolitas/farmacologia , Óxido de Zinco/farmacologia
15.
Environ Geochem Health ; 43(5): 2037-2048, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33244649

RESUMO

Helicobacter pylori can be found in the stomach of about half of the humans, and a large population can be associated with serious diseases. To survive in the stomach H. pylori increases the pH locally by producing ammonia which binds to H+ becoming ammonium. This work investigated the effects on the in-vitro growth of H. pylori of a natural cation-exchanger mainly composed (≈70%) of clinoptilolite and mordenite. The zeolitized material from Cuba was evaluated in its original form (M), as well as in its Na- (M-Na) and Zn-exchanged (M-Zn) counterparts. In the preliminary agar cup diffusion test, H. pylori revealed susceptibility only to M-Zn, with a direct relationship between concentration and width of inhibition halo. Further experiments evidenced that bacterium replication increases when ammonium is supplied to the growth medium and decreases when zeolites subtract NH4+ via ion exchange. Due to the multi-cationic population of its zeolites M was not effective enough in removing ammonium and, in the Minimum Inhibitory Concentration (MIC) test, allowed bacterial growth even at a concentration of 50 mg/mL. Inhibition was achieved with M-Na because it contained sodium zeolites capable of maximizing NH4+ subtraction, although the MIC was high (30 mg/mL). M-Zn evidenced a more effective inhibitory capacity, with a MIC of 4 mg/mL. Zinc has antimicrobial properties and H. pylori growth was affected by Zn2+ released from clinoptilolite and mordenite. These zeolites, being more selective towards NH4+ than Zn2+, can also subtract ammonium to the bacterium, thus enhancing the efficacy of M-Zn.


Assuntos
Silicatos de Alumínio/farmacologia , Antibacterianos/farmacologia , Helicobacter pylori/efeitos dos fármacos , Zeolitas/farmacologia , Zinco/farmacologia , Silicatos de Alumínio/química , Compostos de Amônio/metabolismo , Compostos de Amônio/farmacologia , Antibacterianos/química , Cuba , Helicobacter pylori/crescimento & desenvolvimento , Troca Iônica , Testes de Sensibilidade Microbiana , Sódio/química , Zeolitas/química , Zinco/química
16.
J Dairy Res ; 87(4): 429-435, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33261672

RESUMO

This research paper addresses the hypothesis that an oral supplementation with organically modified clinoptilolite will improve colostrum quality in primiparous dairy cows whilst having no adverse effects on the cows' health. A total of 36 pregnant Holstein primiparous dairy cattle were randomly assigned to receive daily oral drenching, two hours following morning feeding, with 1 l of water containing either 0 g/l (n = 16) or 150 g/l (n = 20) of clinoptilolite. Treatment lasted from 24 ± 4 d prior to expected parturition until two days postpartum (pp). Colostrum was collected at 2 to 3 h, 12, 24 and 36 h pp and blood samples were collected at 24 ± 4 and 4 ± 2 d prior to parturition and 1, 2 and 7 d pp. Overall mean dry matter, fat and total protein percentage as well as IgG concentration and mass were significantly greater in colostrum collected from cattle drenched with clinoptilolite (total protein increased by 15% and IgG concentration and mass by 21 and 38% respectively at first sampling and further at second sampling). Total γ globulin and most other blood serum biochemistry parameters did not differ between cattle treated and not treated with clinoptilolite, the only exception being the fast anionic γ globulin fraction that was 17% greater at 4 ± 2 d prior to parturition and 10% lower on the 1st day pp in treated cattle. These results showed that organically modified oral clinoptilolite supplementation at 150 g/d significantly increases the IgG concentration in colostrum and has no adverse effects on the energy status, protein, lipid, and mineral metabolism in primiparous dairy cattle during prepartum period.


Assuntos
Bovinos/fisiologia , Colostro/química , Dieta/veterinária , Suplementos Nutricionais , Zeolitas/farmacologia , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Esquema de Medicação , Feminino , Paridade , Gravidez , Fenômenos Fisiológicos da Nutrição Pré-Natal , Zeolitas/administração & dosagem , gama-Globulinas/metabolismo
17.
Bioconjug Chem ; 31(10): 2439-2445, 2020 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-33040528

RESUMO

The serious threat of antibiotic-resistant bacterial infections has brought an urgent need for the development of new antibacterial nanomaterials. We encapsulate glutathione (GSH)-protected gold nanoclusters (AuNCs) in zeolitic imidazolate frameworks-8 (ZIF-8) and present their potential in antibacterial capabilities. Under white light irradiation, AuNCs-embedded ZIF-8 nanocomposites show assembly-enhanced emission and reactive oxygen species (ROS) generation. AuNCs@ZIF-8 exhibit almost complete inactivation of bacterial growth within 60 min of light irradiation. Scanning electron microscopic results show that AuNCs@ZIF-8 nanocomposites are captured by bacterial cells, and the leakage of alkaline phosphatase and nucleotides from bacteria demonstrate that the photoinduced ROS can easily destroy the bacterial surface and totally kill the bacteria. Herein, our antibacterial nanocomposites have photoenhanced bactericidal capability and show promising applications for sterilization.


Assuntos
Antibacterianos/farmacologia , Glutationa/farmacologia , Ouro/farmacologia , Imidazóis/farmacologia , Estruturas Metalorgânicas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Zeolitas/farmacologia , Antibacterianos/química , Bactérias/efeitos dos fármacos , Bactérias/efeitos da radiação , Infecções Bacterianas/prevenção & controle , Glutationa/química , Ouro/química , Humanos , Imidazóis/química , Luz , Nanopartículas Metálicas/química , Estruturas Metalorgânicas/química , Esterilização , Zeolitas/química
18.
Molecules ; 25(15)2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32752039

RESUMO

The present studies were conducted to show the potential of 2D zeolites as effective and non-toxic carriers of drugs. Layered zeolites exhibit adjustable interlayer porosity which can be exploited for controlled drug delivery allowing detailed investigation of the drug release because the structure of the carrier is known exactly. This study was conducted with model drugs ciprofloxacin and piracetam, and ZSM-55 with ca 1 nm thick layers, in detemplated and pillared forms. The release profiles differed from the commercial, crystalline forms of drugs-the release rate increased for ciprofloxacin and decreased for piracetam. To understand the dissolution mechanisms the release data were fitted to Korsmeyer-Peppas equation, showing Fickian (for pillared) and anomalous (for detemplated sample) transport. FT-IR studies showed that strong interaction carrier-drug may be responsible for the modified, slowed down release of piracetam while better solubility and faster release of ciprofloxacin was attributed to formation of the protonated form resulting in weaker interaction with the zeolite than in the pure crystalline form. Two independent tests on L929 mice fibroblasts (ToxiLight and PrestoBlue) showed that ZSM-55, in moderate concentrations may be safely used as a carrier of drug molecules, not having negative effect on the cells viability or proliferation rate.


Assuntos
Ciprofloxacina/química , Portadores de Fármacos/química , Zeolitas/química , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ciprofloxacina/metabolismo , Portadores de Fármacos/farmacologia , Liberação Controlada de Fármacos , Camundongos , Piracetam/química , Piracetam/metabolismo , Zeolitas/farmacologia
19.
Angew Chem Int Ed Engl ; 59(50): 22537-22543, 2020 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-32856362

RESUMO

Redox homeostasis is one of the main reasons for reactive oxygen species (ROS) tolerance in hypoxic tumors, limiting ROS-mediated tumor therapy. Proposed herein is a redox dyshomeostasis (RDH) strategy based on a nanoplatform, FeCysPW@ZIF-82@CAT Dz, to disrupt redox homeostasis, and its application to improve ROS-mediated hypoxic tumor therapy. Once endocytosed by tumor cells, the catalase DNAzyme (CAT Dz) loaded zeolitic imidazole framework-82 (ZIF-82@CAT Dz) shell can be degraded into Zn2+ as cofactors for CAT Dz mediated CAT silencing and electrophilic ligands for glutathione (GSH) depletion under hypoxia, both of which lead to intracellular RDH and H2 O2 accumulation. These "disordered" cells show reduced resistance to ROS and are effectively killed by ferrous cysteine-phosphotungstate (FeCysPW) induced chemodynamic therapy (CDT). In vitro and in vivo data demonstrate that the pH/hypoxia/H2 O2 triple stimuli responsive nanocomposite can efficiently kill hypoxic tumors. Overall, the RDH strategy provides a new way of thinking about ROS-mediated treatment of hypoxic tumors.


Assuntos
Antineoplásicos/farmacologia , Cisteína/farmacologia , DNA Catalítico/metabolismo , Compostos Ferrosos/farmacologia , Ácido Fosfotúngstico/farmacologia , Hipóxia Tumoral/efeitos dos fármacos , Zeolitas/farmacologia , Animais , Antineoplásicos/química , Sobrevivência Celular/efeitos dos fármacos , Cisteína/química , DNA Catalítico/química , Compostos Ferrosos/química , Células HeLa , Homeostase/efeitos dos fármacos , Humanos , Camundongos , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Oxirredução , Tamanho da Partícula , Ácido Fosfotúngstico/química , Fotoquimioterapia , Espécies Reativas de Oxigênio/metabolismo , Propriedades de Superfície , Zeolitas/química
20.
Molecules ; 25(15)2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32731423

RESUMO

In this study, a layer of a pure and dense phase of FAU-type zeolite was synthesized directly on the surface of α-Al2O3 plane macroporous support. Before hydrothermal synthesis, a step of cleaning of the support by an anionic detergent was performed, a roughness surface is created, allowing the anchoring of the zeolite nuclei and then their growth, favoring in this sense the formation of a homogeneous zeolite layer. The obtained membranes were fully characterized using X-ray diffraction analysis (XRD), nitrogen sorption, scanning electron microscopy (SEM), and mercury porosimetry. After 24 h of thermal treatment at 75 °C, a homogeneous zeolite layer composed of bipyramidal crystals of FAU-type zeolite is obtained with a thickness of about 2.5 µm. No obvious defects or cracks can be observed. It was found that the increase in heating temperature could lead to the appearance of an impurity phase, GIS-type zeolite. Then the ideal zeolite membrane was exchanged with Ag+ or Zn2+ cations to studies their antimicrobial properties. Zeolites membranes exchanged with Ag+ showed an agar-diffusive bactericidal activity against gram negative Escherichia coli (E. coli) bacteria. Zn2+ exchanged zeolite membrane presented a bacteriostatic activity that is less diffusive in agar. As expected, non-exchanged zeolite membrane (in its Na+ form) have no effect on bacterial activity. This process is particularly interesting for the synthesis of a good quality FAU-type zeolite membranes with antimicrobial properties.


Assuntos
Antibacterianos , Escherichia coli/crescimento & desenvolvimento , Membranas Artificiais , Zeolitas , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Zeolitas/síntese química , Zeolitas/química , Zeolitas/farmacologia
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