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1.
Water Res ; 223: 119033, 2022 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-36058096

RESUMEN

External stimulus such as light irradiation is able to deteriorate intracellular redox homeostasis and induce photooxidative damage to non-photogenic bacteria. Exploiting effective strategies to help bacteria resisting infaust stress is meaningful for achieving a stable operation of biological treatment system. In this work, selenium-doped carbon quantum dots (Se-CQDs) were blended into anaerobic ammonia oxidation (anammox) bacteria and an inorganic nanoparticle-microbe hybrid was successfully fabricated to evaluate its nitrogen removal performance under solar-simulated irradiation. It was found that the specific anammox activity decreased by 29.7 ± 5.2% and reactive oxygen species (ROS) content increased by 134.8 ± 4.1% under 50,000 lux light. Sludge activity could be completely recovered under the optimum dosage of 0.42 mL·(g volatile suspended solid) -1 Se-CQDs. Hydroxyl radical (·OH) and superoxide anion radical (·O2-) were identified as the leading ROS inducing lipid peroxidation and antioxidase function detriment. Also, the structure of ladderane lipids located on anammoxosome was destroyed by ROS and functional genes abundances declined accordingly. Although cell surface coated Se-CQDs could absorb ultraviolet light and partially mitigated the photoinhibition, the direct scavenging of ROS by intracellular Se-CQDs primarily contributed to the cellular redox homeostasis, antioxidase activity recovery and sludge activity improvement. The findings of this work provide in-depth understanding the metabolic response mechanism of anammox consortia to light irradiation and might be valuable for a more stable and sustainable nitrogen removal technology, i.e., algal-bacterial symbiotic system, development.


Asunto(s)
Puntos Cuánticos , Selenio , Oxidación Anaeróbica del Amoníaco , Anaerobiosis , Bacterias/metabolismo , Reactores Biológicos/microbiología , Carbono/metabolismo , Radical Hidroxilo/metabolismo , Lípidos , Nitrógeno/metabolismo , Oxidación-Reducción , Especies Reactivas de Oxígeno/metabolismo , Selenio/metabolismo , Aguas del Alcantarillado/microbiología , Superóxidos
2.
BMC Vet Res ; 18(1): 347, 2022 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-36109808

RESUMEN

BACKGROUND: Cottonseed meal (CSM), a relatively rich source of protein and amino acids, is used as an inexpensive alternative to soybean meal (SBM) in poultry diets. However, the toxicity of free gossypol in CSM has been a primary concern. The present study was conducted to investigate the effects of CSM on growth performance, serum biochemical parameters, and liver redox status in goslings at 1 to 28 days of age. Three hundred 1-day-old male goslings were randomly divided into 5 groups (10 goslings/pen, 6 replicate pens/group) and subjected to a 28-day experiment. Five isonitrogenous and isoenergetic diets were formulated such that 0% (control), 25% (CSM25), 50% (CSM50), 75% (CSM75), and 100% (CSM100) of protein from SBM was replaced by protein from CSM. The free gossypol contents in the five diets were 0, 56, 109, 166, and 222 mg/kg, respectively. RESULTS: The results showed that dietary CSM was associated with linear decreases in body weight, average daily feed intake and average daily gain and linear increases in the feed-to-gain ratio from 1 to 28 days of age (P < 0.001). As the dietary CSM concentration increased, a numerical increase was found in the mortality of goslings. According to a single-slope broken-line model, the breakpoints for the average daily gain of dietary free gossypol concentration on days 1 to 14, 15 to 28, and 1 to 28 occurred at 23.63, 14.78, and 18.53 mg/kg, respectively. As the dietary CSM concentration increased, serum albumin (P < 0.001) concentrations decreased linearly and serum uric acid (P = 0.011) increased linearly. The hydroxyl radical scavenging ability (P = 0.002) and catalase (P < 0.001) and glutathione peroxidase (P = 0.001) activities of the liver decreased linearly with increasing dietary CSM. However, dietary CSM did not affect the concentrations of reactive oxygen metabolites, malondialdehyde, or protein carbonyl in the liver. CONCLUSIONS: The increasing dietary CSM increased the concentration of free gossypol and altered the composition of some amino acids in the diet. A high concentration of CSM reduced the growth performance of goslings aged 1 to 28 days by decreasing feed intake, liver metabolism, and antioxidant capacity. From the primary concern of free gossypol in CSM, the tolerance of goslings to free gossypol from CSM is low, and the toxicity of free gossypol has a cumulative effect over time.


Asunto(s)
Aceite de Semillas de Algodón , Gosipol , Aminoácidos/metabolismo , Alimentación Animal/análisis , Animales , Antioxidantes/metabolismo , Catalasa , Aceite de Semillas de Algodón/análisis , Aceite de Semillas de Algodón/metabolismo , Aceite de Semillas de Algodón/farmacología , Gansos/metabolismo , Glutatión Peroxidasa , Gosipol/análisis , Gosipol/metabolismo , Gosipol/farmacología , Radical Hidroxilo/análisis , Radical Hidroxilo/metabolismo , Radical Hidroxilo/farmacología , Hígado/metabolismo , Masculino , Malondialdehído/metabolismo , Oxidación-Reducción , Oxígeno/metabolismo , Albúmina Sérica/análisis , Glycine max/metabolismo , Ácido Úrico/análisis
3.
ACS Appl Mater Interfaces ; 14(34): 38604-38616, 2022 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-35979620

RESUMEN

Chemodynamic therapy (CDT) is a highly tumor-specific and minimally invasive treatment that is widely used in cancer therapy. However, its therapeutic effect is limited by the poor efficiency of hydroxyl radical generation. In colon cancer in particular, the high expression of hydrogen sulfide (H2S), which has strong reducibility, results in the consumption of generated hydroxyl radicals, further weakening the efficacy of CDT. To overcome this problem, we developed a novel two-dimensional (2D) Cu-bipyridine metal-organic framework (MOF) nanosheet [Cu(bpy)2(OTf)2] for colon cancer CDT. The therapeutic effect of Cu(bpy)2(OTf)2 is enhanced based on three factors. First, the developed 2D Cu-MOF rapidly consumes H2S to inhibit the consumption of generated hydroxyl radicals. Second, the ultrasmall CuS generated after H2S depletion facilitates Fenton-like reactions. Third, the generated CuS exhibits good photothermal performance in the second near-infrared window, allowing for photothermal-enhanced CDT. The ability of Cu(bpy)2(OTf)2 to improve the CDT effect was demonstrated through both in vitro and in vivo experiments. This work demonstrates the applicability of 2D Cu-MOF in the CDT of colon cancer and provides a novel strategy for constructing CDT agents for colon cancer.


Asunto(s)
Neoplasias del Colon , Hipertermia Inducida , Estructuras Metalorgánicas , Nanopartículas , Neoplasias , Línea Celular Tumoral , Neoplasias del Colon/tratamiento farmacológico , Humanos , Peróxido de Hidrógeno/metabolismo , Radical Hidroxilo/metabolismo , Hipertermia Inducida/métodos , Estructuras Metalorgánicas/farmacología , Estructuras Metalorgánicas/uso terapéutico , Nanopartículas/uso terapéutico , Neoplasias/tratamiento farmacológico , Fototerapia/métodos
4.
Arch Toxicol ; 96(7): 1915-1920, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35416515

RESUMEN

The toxic potential of H2O2 is limited, even if intracellular concentrations of H2O2 under conditions of oxidative stress increase to the micromolar concentration range. Its toxicity is mostly restricted to the oxidation of highly reactive thiol groups, some of which are functionally very important. Subsequently, the HO· radical is generated spontaneously from H2O2 in the Fenton reaction. The HO· radical is extremely toxic and destroys any biological structure. Due to the high reactivity, its action is limited to a locally restricted site of its generation. On the other hand, H2O2 with its stability and long half-life can reach virtually any site and distribute its toxic effect all over the cell. Thereby HO·, in spite of its ultra-short half-life (10-9 s), can execute its extraordinary toxic action at any target of the cell. In this oxidative stress scenario, H2O2 is the pro-radical, that spreads the toxic action of the HO· radical. It is the longevity of the H2O2 molecule allowing it to distribute its toxic action from the site of origin all over the cell and may even mediate intercellular communication. Thus, H2O2 acts as a spreader by transporting it to sites where the extremely short-lived toxic HO· radical can arise in the presence of "free iron". H2O2 and HO· act in concert due to their different complementary chemical properties. They are dependent upon each other while executing the toxic effects in oxidative stress under diabetic metabolic conditions in particular in the highly vulnerable pancreatic beta cell, which in contrast to many other cell types is so badly protected against oxidative stress due to its extremely low H2O2 inactivating enzyme capacity.


Asunto(s)
Radical Hidroxilo , Células Secretoras de Insulina , Peróxido de Hidrógeno/metabolismo , Peróxido de Hidrógeno/toxicidad , Radical Hidroxilo/química , Radical Hidroxilo/metabolismo , Células Secretoras de Insulina/metabolismo , Hierro/metabolismo , Oxidación-Reducción
5.
Adv Healthc Mater ; 11(14): e2200041, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35481899

RESUMEN

As a typical tumor microenvironment-responsive therapy, chemodynamic therapy (CDT), producing hydroxyl radicals (• OH) to eliminate tumor cells, has demonstrated great promise. Nevertheless, there are still major challenges: • OH generated from endogenous H2 O2 is usually insufficient; the CDT effect is strongly dependent on the pre-reaction with glutathione. Addressing the challenges, Au@MnSe2 core-shell nanoagent for synergetic chemodynamic-photothermo-photocatalytic therapy combined with tetramodal imaging, including magnetic resonance imaging, computed tomography, photoacoustic, and infrared thermal imaging is reported. Distinct from the reported glutathione-depleting agents, Mn2+ in MnSe2 allows immediate generation of • OH, independent of pre-reaction. Meanwhile, Mn3+ consumes glutathione by its conversion to Mn2+ . The Au-MnSe2 combination promotes photothermal conversion and photocatalytic reaction, resulting in largely enhanced • OH generation from endogenous H2 O2 and significant hyperthermia. Meanwhile, immune response is effectively activated: the intratumoral expression of programmed cell death-1 and proinflammatory cytokines increase to 4-7 folds; the cytotoxic and helper T lymphocytes cells in the tumor area increase to more than 2.5-folds; an evident, temporary systemic immunostimulatory effect is demonstrated. High tumor inhibition rate (≈97.3%) and greatly prolonged survival are obtained. This highly-integrated design coordinating three different therapies with four different imaging modals provide new possibilities for high-performance theranostic nanoagents.


Asunto(s)
Hipertermia Inducida , Nanopartículas , Línea Celular Tumoral , Glutatión/metabolismo , Radical Hidroxilo/metabolismo , Inmunidad
6.
ACS Appl Mater Interfaces ; 14(5): 6453-6464, 2022 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-35094518

RESUMEN

The unrestrained use of antibiotics accelerates the development of drug-resistant bacteria and leads to an increasing threat to human health. Therefore, there is an urgent need to explore novel and effective strategies for the treatment of bacterial infections. Herein, zeolite imidazole framework-8 (ZIF-8) material was utilized to construct biomineralized nanomaterial (GOx&HRP@ZIF-8/ASO) by encapsulating biological cascade enzymes and combining with antisense oligonucleotides (ASOs), which achieved effective and synergistic antidrug-resistant bacteria therapy. Various in vitro assays confirmed that GOx&HRP@ZIF-8/ASO exhibited excellent antibacterial properties against Escherichia coli, Staphylococcus aureus, methicillin-resistant S. aureus (MRSA) during catalysis of glucose (Glu), especially the minimum inhibitory concentration (MIC) against MRSA was only 16 µg/mL. Compared with simple ZIF-8 (32.85%) and ftsZ ASO (58.65%), GOx&HRP@ZIF-8/ASO+Glu exhibited superb biofilm destruction ability, and the bacteria removal efficiency of the MRSA biofilm could be as high as 88.2%, indicating that the reactive oxygen species (ROS) produced by the cascade enzyme reaction imparted the main synergistic antibacterial capability, and simultaneously, ftsZ ASO significantly enhanced the antibacterial effect by inhibiting the expression of the ftsZ gene. In vivo anti-infection treatment experiments revealed that GOx&HRP@ZIF-8/ASO exhibited the best wound repairing performance and excellent biocompatibility in the presence of Glu. These findings suggested that GOx&HRP@ZIF-8/ASO has favorably realized high-efficiency treatment of MRSA infection and filled the gap in the antibacterial application of biological enzymes.


Asunto(s)
Glucosa Oxidasa/química , Peroxidasa de Rábano Silvestre/química , Imidazoles/química , Estructuras Metalorgánicas/química , Nanopartículas/química , Oligonucleótidos Antisentido/química , Animales , Proteínas Bacterianas/antagonistas & inhibidores , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Biopelículas/efectos de los fármacos , Proteínas del Citoesqueleto/antagonistas & inhibidores , Proteínas del Citoesqueleto/genética , Proteínas del Citoesqueleto/metabolismo , Escherichia coli/efectos de los fármacos , Glucosa Oxidasa/metabolismo , Peroxidasa de Rábano Silvestre/metabolismo , Radical Hidroxilo/metabolismo , Imidazoles/farmacología , Estructuras Metalorgánicas/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/fisiología , Ratones , Pruebas de Sensibilidad Microbiana , Nanopartículas/uso terapéutico , Nanopartículas/toxicidad , Oligonucleótidos Antisentido/metabolismo , Oligonucleótidos Antisentido/farmacología , Especies Reactivas de Oxígeno/metabolismo , Enfermedades de la Piel/tratamiento farmacológico , Enfermedades de la Piel/patología , Enfermedades de la Piel/veterinaria , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/veterinaria , Staphylococcus aureus/efectos de los fármacos
7.
Yakugaku Zasshi ; 141(10): 1185-1194, 2021.
Artículo en Japonés | MEDLINE | ID: mdl-34602515

RESUMEN

Plasma medicine is a rapidly expanding new field of interdisciplinary research that combines physics, chemistry, biology, and medicine. Non-thermal atmospheric pressure plasma (NTAPP) has recently been applied to living cells and tissues, and has emerged as a novel technology for medical applications, such as wound healing, blood coagulation, and cancer treatment. NTAPP was found to affect cells indirectly through the treatment of cells with previously prepared medium irradiated by NTAPP, termed plasma-activated medium (PAM). The treatment of culture media with NTAPP results in the generation of a large amount of reactive oxygen species and reactive nitrogen species, and their derived species. We found that PAM triggered a spiral apoptotic cascade in the mitochondrial-nuclear network in A549 cancer cells. This process induced the depletion of total cellular NAD+ and elevations in intracellular calcium ion, ultimately leading to cell death. We also detected the production of hydroxyl radical and elevations in intracellular ferrous ions in PAM-treated cells. The elevations observed in ferrous ions may have been due to their release from the intracellular iron store, ferritin. However, difficulties are associated with applying PAM to the clinical phase because culture media cannot be used for medical treatments. The anti-tumor activity of plasma-activated Ringer's solution was significantly stronger than that of PAM. At the end, we herein demonstrated the advantages of the combined application of plasma-activated acetate Ringer's solution and hyperthermia, a heat treatment at 42℃, for A549 cancer cell death and elucidated the underlying mechanisms.


Asunto(s)
Gases em Plasma , Células A549 , Apoptosis , Coagulación Sanguínea , Calcio/metabolismo , Medios de Cultivo , Humanos , Radical Hidroxilo/metabolismo , Hipertermia Inducida , Hierro/metabolismo , Mitocondrias/metabolismo , Mitocondrias/patología , NAD/metabolismo , Neoplasias/patología , Neoplasias/terapia , Gases em Plasma/farmacología , Gases em Plasma/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo , Solución de Ringer/farmacología , Solución de Ringer/uso terapéutico , Soluciones , Cicatrización de Heridas
8.
Adv Sci (Weinh) ; 8(20): e2102422, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34390202

RESUMEN

Sonodynamic therapy (SDT) triggered by ultrasound represents an emerging tumor therapy approach with minimally invasive treatment featuring nontoxicity and deep tissue-penetration, and its efficacy sensitively depends on the sonosensitizer which determines the generation of reactive oxygen species (ROS). Herein, for the first time covalently functionalized few-layer black phosphorus nanosheets (BPNSs) are applied as novel sonosensitizers in SDT, achieving not only boosted SDT efficacy but also inhibited cytotoxicity relative to the pristine BPNSs. Three different covalently functionalized-BPNSs are synthesized, including the first fullerene-functionalized BPNSs with C60 covalently bonded onto the surface of BPNSs (abbreviated as C60 -s-BP), surface-functionalized BPNSs by benzoic acid (abbreviated as BA-s-BP), and edge-functionalized BPNSs by C60 (abbreviated as C60 -e-BP), and the role of covalent functionalization pattern of BPNSs on its SDT efficacy is systematically investigated. Except C60 -e-BP, both surface-functionalized BPNSs (C60 -s-BP, BA-s-BP) exhibit higher SDT efficacies than the pristine BPNSs, while the highest SDT efficacy is achieved for BA-s-BP due to its strongest capability of generating the hydroxyl (·OH) radicals, which act as the dominant ROS to kill the tumor cells.


Asunto(s)
Neoplasias/terapia , Fósforo/farmacología , Fotoquimioterapia , Terapia por Ultrasonido , Animales , Apoptosis/efectos de la radiación , Proliferación Celular/efectos de la radiación , Células HeLa , Humanos , Radical Hidroxilo/metabolismo , Ratones , Células 3T3 NIH , Nanopartículas/química , Neoplasias/patología , Fósforo/química , Especies Reactivas de Oxígeno/metabolismo
9.
ACS Appl Mater Interfaces ; 13(34): 40302-40314, 2021 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-34412471

RESUMEN

Nanozyme has been regarded as one of the antibacterial agents to kill bacteria via a Fenton-like reaction in the presence of H2O2. However, it still suffers drawbacks such as insufficient catalytic activity in near-neutral conditions and the requirement of high H2O2 levels, which would minimize the side effects to healthy tissues. Herein, a mesoporous ceria hollow sphere/enzyme nanoreactor is constructed by loading glucose oxidase in the mesoporous ceria hollow sphere nanozyme. Due to the mesoporous framework, large internal voids, and high specific surface area, the obtained nanoreactor can effectively convert the nontoxic glucose into highly toxic hydroxyl radicals via a cascade catalytic reaction. Moreover, the generated glucose acid can decrease the localized pH value, further boosting the peroxidase-like catalytic performance of mesoporous ceria. The generated hydroxyl radicals could damage severely the cell structure of the bacteria and prevent biofilm formation. Moreover, the in vivo experiments demonstrate that the nanoreactor can efficiently eliminate 99.9% of bacteria in the wound tissues and prevent persistent inflammation without damage to normal tissues in mice. This work provides a rational design of a nanoreactor with enhanced catalytic activity, which can covert glucose to hydroxyl radicals and exhibits potential applications in antibacterial therapy.


Asunto(s)
Antibacterianos/uso terapéutico , Nanopartículas del Metal/uso terapéutico , Infecciones Cutáneas Estafilocócicas/tratamiento farmacológico , Antibacterianos/química , Antibacterianos/farmacología , Biocatálisis , Biopelículas/efectos de los fármacos , Cerio/química , Cerio/uso terapéutico , Enzimas Inmovilizadas/química , Enzimas Inmovilizadas/uso terapéutico , Escherichia coli/efectos de los fármacos , Escherichia coli/fisiología , Glucosa/química , Glucosa Oxidasa/química , Glucosa Oxidasa/uso terapéutico , Peróxido de Hidrógeno/química , Radical Hidroxilo/metabolismo , Nanopartículas del Metal/química , Pruebas de Sensibilidad Microbiana , Porosidad , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/fisiología
10.
Theranostics ; 11(1): 379-396, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33391481

RESUMEN

Photodynamic therapy (PDT) holds a number of advantages for tumor therapy. However, its therapeutic efficiency is limited by non-sustainable reactive oxygen species (ROS) generation and heterogeneous distribution of photosensitizer (PS) in tumor. Herein, a "Sustainable ROS Generator" (SRG) is developed for efficient antitumor therapy. Methods: SRG was prepared by encapsulating small-sized Mn3O4-Ce6 nanoparticles (MC) into dendritic mesoporous silica nanoparticles (DMSNs) and then enveloped with hyaluronic acid (HA). Due to the high concentration of HAase in tumor tissue, the small-sized MC could be released from DMSNs and homogeneously distributed in whole tumor. Then, the released MC would be uptaken by tumor cells and degraded by high levels of intracellular glutathione (GSH), disrupting intracellular redox homeostasis. More importantly, the released Ce6 could efficiently generate singlet oxygen (1O2) under laser irradiation until the tissue oxygen was exhausted, and the manganese ion (Mn2+) generated by degraded MC would then convert the low toxic by-product (H2O2) of PDT to the most harmful ROS (·OH) for sustainable and recyclable ROS generation. Results: MC could be homogeneously distributed in whole tumor and significantly reduced the level of intracellular GSH. At 2 h after PDT, obvious intracellular ROS production was still observed. Moreover, during oxygen recovery in tumor tissue, ·OH could be continuously produced, and the nanosystem could induce 82% of cell death comparing with 30% of cell death induced by free Ce6. For in vivo PDT, SRG achieved a complete inhibition on tumor growth. Conclusion: Based on these findings, we conclude that the designed SRG could induce sustainable ROS generation, homogeneous intratumoral distribution and intracellular redox homeostasis disruption, presenting an efficient strategy for enhanced ROS-mediated anti-tumor therapy.


Asunto(s)
Apoptosis/efectos de los fármacos , Neoplasias de la Mama/terapia , Terapia por Luz de Baja Intensidad , Compuestos de Manganeso/farmacología , Nanopartículas , Óxidos/farmacología , Fotoquimioterapia , Porfirinas/farmacología , Fármacos Sensibilizantes a Radiaciones/farmacología , Especies Reactivas de Oxígeno/metabolismo , Animales , Apoptosis/efectos de la radiación , Línea Celular Tumoral , Clorofilidas , Portadores de Fármacos , Glutatión/metabolismo , Disulfuro de Glutatión/metabolismo , Humanos , Ácido Hialurónico , Peróxido de Hidrógeno , Radical Hidroxilo/metabolismo , Ratones , Dióxido de Silicio , Oxígeno Singlete/metabolismo , Distribución Tisular
11.
ACS Appl Mater Interfaces ; 12(39): 43456-43465, 2020 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-32880166

RESUMEN

Cancer deaths are mainly caused by tumor metastases. However, tumor ablation therapies can only target the primary tumor but not inhibit tumor metastasis. Herein, a multifunctional covalent organic framework (COF)-based nanocomposite is designed for synergetic photo-, chemodynamic- and immunotherapies. Specifically, the synthesized COF possesses the ability to produce singlet oxygen under the 650 nm laser irradiation. After being metallized with FeCl3, p-phenylenediamine is polymerized on the surface of COF with Fe3+ as the oxidant. The obtained poly(p-phenylenediamine) can be used for photothermal therapy. Meanwhile, the overexpressed H2O2 in the tumor would be further catalyzed and decomposed into hydroxyl radicals (•OH) by the Fe3+/Fe2+ redox couple via Fenton reaction. Intriguingly, the increase of temperature caused by photothermal therapy can accelerate the production of •OH. Moreover, the tumor-associated antigen induced a robust antitumor immune response and effectively inhibited tumor metastasis in the presence of anti-PD-L1 checkpoint blockade. Such a COF-based multifunctional nanoplatform provides an efficacious treatment strategy for both the primary tumor and tumor metastasis.


Asunto(s)
Antineoplásicos/farmacología , Neoplasias del Colon/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/farmacología , Estructuras Metalorgánicas/farmacología , Nanocompuestos/química , Fármacos Fotosensibilizantes/farmacología , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/metabolismo , Línea Celular Tumoral , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Compuestos Férricos/química , Compuestos Férricos/farmacología , Radical Hidroxilo/análisis , Radical Hidroxilo/metabolismo , Inhibidores de Puntos de Control Inmunológico/síntesis química , Inhibidores de Puntos de Control Inmunológico/química , Inmunoterapia , Estructuras Metalorgánicas/síntesis química , Estructuras Metalorgánicas/química , Ratones , Tamaño de la Partícula , Fenilendiaminas/química , Fenilendiaminas/farmacología , Fotoquimioterapia , Fármacos Fotosensibilizantes/síntesis química , Fármacos Fotosensibilizantes/química , Fototerapia , Propiedades de Superficie
12.
Int J Med Mushrooms ; 22(5): 431-444, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32749098

RESUMEN

Three water-soluble glucans (PELPS-A1, PELPS-A2, and PELPS-A3) purified from the hot water extract of the basidiomata of an edible mushroom Pleurotus eryngii var. elaeoselini by chromatography on DEAE-cellulose 32 and Sephadex G-100 column were found to consist of only D-glucose as monosaccharide constituent. Structural investigation was carried out by acid hydrolysis, periodate oxidation, and NMR experiments (1H-NMR, 13C-NMR, DQF-COSY, TOCSY, ROESY, HMQC, and HMBC). On the basis of these experiments, the structures of the repeating unit of the three isolated polysaccharides were established as follows: (1) PELPS-A1: {[→3)-α-D-Glcp-(1→]3→4)-α-D-Glcp-(1→2)-α-D-Glcp-(1→6)-α-D-Glcp-(1[→6)-ß-D-Glcp-(1→]2}n 6 ↑ 1 α-D-Glcp (2) PELPS-A2: [→6)-ß-D-Glcp-(1→6)-ß-D-Glcp-(1→6)-ß-D-Glcp-(1→]n 3 ↑ 1 ß-D-Glcp (3) PELPS-A3: [→6)-α-D-Glcp-(1→6)-α-D-Glcp-(1→6)-α-D-Glcp-(1→]n The dried basidiomata of P. eryngii var. elaoselini were tested for their antioxidant activity by DPPH and hydroxyl radical scavenging assays. The crude extract has shown a SC50 of 1.4 mg/mL for DPPH test while a SC50 of 5.7 mg/mL was observed for hydroxyl radical scavenging activity test. The antioxidant activity of PELPS-A1, PELPS-A2, and PELPS-A3, evaluated as hydroxyl radical scavenging activity, was similar and significant, suggesting their use as antioxidants.


Asunto(s)
Antioxidantes/química , Glucanos/química , Pleurotus/química , Radical Hidroxilo/metabolismo , Espectroscopía de Resonancia Magnética
13.
PLoS One ; 15(6): e0234435, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32574221

RESUMEN

This study was designed to investigate the antioxidant properties of the extracts and subfractions of various polarities from Clerodendrum cyrtophyllum Turcz leaves and the related phenolic compound profiles. The ethyl acetate fraction (EAF) showed the most potent radical-scavenging activity for DPPH radicals, ABTS radicals, and superoxide anion (O2·-) radicals as well as the highest reducing power of the fractions tested; the n-butyl alcohol fraction (BAF) was the most effective in scavenging hydroxyl radical (OH·), and the dichloromethane fraction (DMF) exhibited the highest ferrous ion chelating activity. Twelve phenolic components were identified from the EAF of C. cyrtophyllum. Additionally, acteoside (1) was found to be a major component (0.803 g, 0.54%) and show DPPH and ABTS radical scavenging activities with IC50 values of 79.65±3.4 and 23.00±1.5 µg/ml, indicating it is principally responsible for the significant total antioxidant effect of C. cyrtophyllum. Our work offers a theoretical basis for further utilization of C. cyrtophyllum as a potential source of natural, green antioxidants derived from plants.


Asunto(s)
Antioxidantes/farmacología , Clerodendrum/química , Glucósidos/farmacología , Fenoles/farmacología , Extractos Vegetales/farmacología , Antioxidantes/análisis , Antioxidantes/aislamiento & purificación , Glucósidos/análisis , Glucósidos/aislamiento & purificación , Radical Hidroxilo/metabolismo , Fenoles/análisis , Fenoles/aislamiento & purificación , Extractos Vegetales/análisis , Extractos Vegetales/aislamiento & purificación , Hojas de la Planta/química , Superóxidos/metabolismo
14.
ACS Appl Mater Interfaces ; 12(18): 20321-20330, 2020 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-32293862

RESUMEN

Metal-organic frameworks (MOFs) have been identified as promising materials for the delivery of therapeutics to cure cancer owing to their intrinsic porous structure. However, in a majority of cases, MOFs act as only a delivery cargo for anticancer drugs while little attention has been focused on the utilization of their intriguing physical and chemical properties for potential anticancer purposes. Herein for the first time, an ultrathin (16.4 nm thick) ferrocene-based MOF (Zr-Fc MOF) nanosheet has been synthesized for synergistic photothermal therapy (PTT) and Fenton reaction-based chemodynamic (CDT) therapy to cure cancer without additional drugs. The Zr-Fc MOF nanosheet acts not only as an excellent photothermal agent with a prominent photothermal conversion efficiency of 53% at 808 nm but also as an efficient Fenton catalyst to promote the conversion of H2O2 into hydroxyl radical (•OH). As a consequence, an excellent therapeutic performance has been achieved in vitro as well as in vivo through this combinational effect. This work aims to construct an "all-in-one" MOF nanoplatform for PTT and CDT treatments without incorporating any additional therapeutics, which may launch a new era in the investigation of MOF-based synergistic therapy platforms for cancer therapy.


Asunto(s)
Antineoplásicos/uso terapéutico , Estructuras Metalorgánicas/uso terapéutico , Nanoestructuras/uso terapéutico , Neoplasias/tratamiento farmacológico , Animales , Antineoplásicos/química , Antineoplásicos/efectos de la radiación , Catálisis , Línea Celular Tumoral , Terapia Combinada/métodos , Compuestos Ferrosos/química , Compuestos Ferrosos/efectos de la radiación , Compuestos Ferrosos/uso terapéutico , Radical Hidroxilo/metabolismo , Hipertermia Inducida/métodos , Rayos Infrarrojos , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/efectos de la radiación , Metalocenos/química , Metalocenos/efectos de la radiación , Metalocenos/uso terapéutico , Ratones , Nanoestructuras/química , Nanoestructuras/efectos de la radiación , Fotoquimioterapia/métodos , Circonio/química , Circonio/efectos de la radiación , Circonio/uso terapéutico
15.
ACS Appl Mater Interfaces ; 12(17): 19285-19294, 2020 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-32249558

RESUMEN

Magnetite (Fe3O4) nanoparticles have been extensively used in noninvasive cancer treatment, for example, magnetic hyperthermia (MH) and chemodynamic therapy (CDT). However, how to achieve a highly efficient MH-CDT synergistic therapy based only on a single component of Fe3O4 still remains a challenge. Herein, hollow Fe3O4 mesocrystals (MCs) are constructed via a modified solvothermal method. Owing to the distinctive magnetic property of the mesocrystalline structure, Fe3O4 MCs show excellent magnetothermal conversion efficiency with a specific absorption rate of 722 w g-1 at a Fe concentration of 0.6 mg mL-1, much higher than that of Fe3O4 polycrystals (PCs). Moreover, Fe3O4 MCs also exhibit higher peroxidase-like activity than Fe3O4 PCs, which may be ascribed to the higher ratio of Fe2+/Fe3+ and more oxygen defects in the Fe3O4 MCs. Detailed in vivo results confirm that Fe3O4 MCs can instantly initiate CDT by producing the detrimental •OH, and such boosted reactive oxygen levels not only induces cell apoptosis but also reduces the expression of heat shock proteins, thus enabling low-temperature-mediated MH. More importantly, the in situ rising temperature resulted from MH in turn facilitates CDT, thus achieving a self-augmented synergistic effect between MH and CDT.


Asunto(s)
Antineoplásicos/uso terapéutico , Óxido Ferrosoférrico/uso terapéutico , Hipertermia Inducida/métodos , Neoplasias/tratamiento farmacológico , Neoplasias/terapia , Animales , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Catálisis , Femenino , Óxido Ferrosoférrico/química , Radical Hidroxilo/metabolismo , Fenómenos Magnéticos , Ratones Endogámicos BALB C , Neoplasias/patología , Ensayos Antitumor por Modelo de Xenoinjerto
16.
Sci Rep ; 10(1): 1588, 2020 01 31.
Artículo en Inglés | MEDLINE | ID: mdl-32005913

RESUMEN

Rhythms in the pseudo-steady state (PSS) levels of reactive species (RS), particularly superoxide and hydroxyl radicals, exist in cancer cells. The RS rhythm characteristics, particularly frequency and amplitude, are entrained (reset) by the anticancer compounds/drugs. In this work, we show for the first time that the phase of the RS rhythm at which the drug is added is significantly important in determining the cytotoxicity of anticancer compounds/drugs such as menadione and curcumin, in two different cancer cell lines. Curcumin, the more effective of the two drugs (IC50 = 15 µM, SiHa; 6 µM, HCT116) induced reset of superoxide and hydroxyl rhythms from 15.4 h to 9 h, and 25 h to 11 h respectively, as well as caused increases in these radical levels. However, menadione (IC50 = 20 µM, SiHa; 17 µM, HCT116) affected only the superoxide levels. Drug treatment at different time points/phase of the RS rhythm resulted in a maximum of 27% increase in cytotoxicity, which is significant. Further, we report for the first time, an unexpected absence of a correlation between the intracellular PSS RS and antioxidant levels; thus, the practice of using antioxidant enzyme levels as surrogate markers of intracellular oxidative stress levels may need a re-consideration. Therefore, the RS rhythm could be a fundamental/generic target to manipulate for improved cancer therapy.


Asunto(s)
Antineoplásicos/uso terapéutico , Curcumina/uso terapéutico , Neoplasias/tratamiento farmacológico , Oxidación-Reducción/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Vitamina K 3/uso terapéutico , Antioxidantes/metabolismo , Línea Celular Tumoral , Células HCT116 , Humanos , Radical Hidroxilo/metabolismo , Neoplasias/metabolismo , Superóxidos/metabolismo
17.
Photochem Photobiol Sci ; 19(6): 831-843, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33856681

RESUMEN

Solar radiation in the ultraviolet (UV), visible (VIS), and infrared (IR) ranges produces different biological effects in humans. Most of these, particularly those derived from ultraviolet radiation (UVR) are harmful to the skin, and include cutaneous aging and increased risk of cutaneous diseases, particularly skin cancer. Pharmacological photoprotection is mostly topical, but it can also be systemic. Oral photoprotectives constitute a new generation of drugs to combat the deleterious effects of solar radiation. Among these, an extract of Polypodium leucotomos (PL/Fernblock®, IFC Group, Spain) contains a high content of phenolic compounds that endow it with antioxidant activity. PL can administered orally or topically and is completely safe. PL complements and enhances endogenous antioxidant systems by neutralizing superoxide anions, hydroxyl radicals, and lipoperoxides. In addition to its antioxidant activity, PL also improves DNA repair and modulates immune and inflammatory responses. These activities are likely due to its ability to inhibit the generation and release of reactive oxygen species (ROS) by UVR, VIS, and IR radiation. PL also prevents direct DNA damage by accelerating the removal of induced photoproducts and decreasing UV-induced mutations. Oral PL increases the expression of active p53, decreases cell proliferation, and inhibits UV-induced COX-2 enzyme levels. PL has been used to treat skin diseases such as photodermatoses and pigmentary disorders and recently as a complement of photodynamic phototherapy in actinic keratoses. The photoprotective capability of PL has been proven in a multitude of in vitro and in vivo studies, which include animal models and clinical trials with human subjects. Based on this evidence, PL is a new generation photoprotector with antioxidant and anti-inflammatory properties that also protects DNA integrity and enhances the immune response.


Asunto(s)
Antioxidantes/farmacología , Extractos Vegetales/farmacología , Polypodium/química , Sustancias Protectoras/farmacología , Administración Oral , Animales , Antioxidantes/administración & dosificación , Antioxidantes/química , Daño del ADN , Humanos , Radical Hidroxilo/antagonistas & inhibidores , Radical Hidroxilo/metabolismo , Rayos Infrarrojos , Peróxidos Lipídicos/antagonistas & inhibidores , Peróxidos Lipídicos/metabolismo , Ratones , Ratones Noqueados , Estrés Oxidativo/efectos de los fármacos , Procesos Fotoquímicos , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Sustancias Protectoras/administración & dosificación , Sustancias Protectoras/química , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Especies Reactivas de Oxígeno/metabolismo , Piel/efectos de los fármacos , Superóxidos/antagonistas & inhibidores , Superóxidos/metabolismo , Rayos Ultravioleta , Agua/química
18.
Neuromolecular Med ; 22(1): 150-158, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31628580

RESUMEN

The present study demonstrates the efficacies of synthetic 1,8-cineole and an 1,8-cineole-rich supercritical carbon dioxide (SC-CO2) extract of small cardamom seeds in preventing oligomerization of amyloid beta peptide (Aß42) and inhibiting iron-dependent oxyradical production in vitro. The oligomerization of Aß42 was monitored by thioflavin T assay and MALDI-TOF analysis of the oligomers. The iron-dependent production of oxygen free radicals was detected by fluorometric benzoate hydroxylation assay. We observed that both pure 1,8-cineole and 1,8-cineole-rich extract of small cardamom seeds at concentrations of 50 µM and 100 µM prevented the production of reactive hydroxyl radicals from a mixture of Fe2+ and ascorbate. However, the 1,8-cineole-rich extract of small cardamom seeds prevented in vitro Aß42 oligomerization more effectively vis-à-vis the synthetic (99% pure) 1,8-cineole. Additional study on SHSY5Y cells indicated that both pure 1,8-cineole and 1,8-cineole-rich SC-CO2 extract of small cardamom seeds prevented iron-dependent cell death. Since oxidative damage, Aß42 aggregation and loss of cell viability (iron-induced) are characteristics of onset of Alzheimer's disease pathology, our results suggest a putative therapeutic role of 1,8-cineole-rich extract of small cardamom seeds over pure 1,8-cineole in preventing this neurodegenerative disease.


Asunto(s)
Enfermedad de Alzheimer/prevención & control , Elettaria/química , Eucaliptol/uso terapéutico , Ferroptosis/efectos de los fármacos , Extractos Vegetales/uso terapéutico , Semillas/química , Péptidos beta-Amiloides/metabolismo , Ácido Ascórbico/farmacología , Línea Celular Tumoral , Evaluación Preclínica de Medicamentos , Sinergismo Farmacológico , Eucaliptol/administración & dosificación , Compuestos Ferrosos/farmacología , Cromatografía de Gases y Espectrometría de Masas , Humanos , Radical Hidroxilo/metabolismo , Neuroblastoma/patología , Fragmentos de Péptidos/metabolismo , Fitoterapia , Extractos Vegetales/administración & dosificación , Especies Reactivas de Oxígeno/metabolismo , Especias
19.
Pak J Pharm Sci ; 32(5): 1949-1956, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31813857

RESUMEN

The caryopses (seeds) of Echinochloa colona Link of family Poaceae are traditionally used for the treatment of jaundice. The methanolic extract of caryopses of Echinochloa colona (ECME) was evaluated for its hepatoprotective activity in paracetamol (3g/kg per oral) and ethanol (5g/kg per oral) intoxicated rats while its antihepatotoxic activity against D-galactosamine (400mg/kg body weight intra peritoneal). The activity of the extract was assessed on the basis of improvement in the altered level of various serum biochemical parameters and in the changes occurred in the histology of liver of the rats. The extract was also investigated for its antioxidant potential by employing different in vitro methods. The extract exhibited ferrous ion reducing power, 1,1 Diphenyl-1-picryl hydrazyl (DPPH), superoxide, nitric oxide and hydroxyl radical scavenging activities. The significant (p<0.001) hepatoprotective and antioxidant activities exhibited by the extract ECME, in different in vivo models and in vitro studies respectively may be attributed to the flavonoids and phenolic compounds present in the extract.


Asunto(s)
Echinochloa/química , Hígado/efectos de los fármacos , Extractos Vegetales/farmacología , Sustancias Protectoras/farmacología , Semillas/química , Animales , Antioxidantes/química , Antioxidantes/farmacología , Compuestos de Bifenilo/farmacología , Flavonoides/farmacología , Galactosamina/farmacología , Radical Hidroxilo/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Metanol/química , Óxido Nítrico/metabolismo , Fenoles/farmacología , Picratos/farmacología , Extractos Vegetales/química , Hojas de la Planta/química , Sustancias Protectoras/química , Ratas , Superóxidos/metabolismo
20.
Int J Med Mushrooms ; 21(7): 657-669, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31679300

RESUMEN

The yield and efficacy of bioactive compounds from Cordyceps militaris fruiting bodies and its fermented grains usually vary with the strain used. In this study, we compared the antiproliferative, apoptotic, and antioxidative properties of ethanolic extracts of fruiting bodies and solid-stated fermented rice (FRE) from two wild-type strains of C. militaris applied to human breast cancer cell lines. We observed that FRE of the Zhangzhou strain (FRE-Z) produced a high level of cordycepin and exhibited comprehensive in vitro antioxidant activity against the oxidation of 2,2-diphenyl-1-picrylhydrazyl, superoxide, and hydroxyl radicals and low-density lipoprotein. Only FRE-Z exhibited dose-dependent inhibition of cell proliferation in MCF-7 (0.7 mg/mL) and MDA-MB-231 cells (1 mg/mL) after culturing for 24 h. The antiproliferative effects of FRE-Z were associated with an early stage of apoptosis induction at 4 h of treatment with 0.5 mg/mL FRE-Z in MCF-7 cells. The antiproliferative effect was determined to occur through p53 activation but not through the release of mitochondrial apoptosis-inducing factor or caspase-9 activation for an initial culture period of 16 h. In addition to a transient increase in cellular antioxidant enzyme, Cu/Zn superoxide dismutase was identified in MCF-7 cells after 2 h of treatment with FRE-Z. Therefore, FRE-Z, which exhibits various dose- and exposure time-dependent activities, has potential application in breast cancer chemoprevention.


Asunto(s)
Proliferación Celular/efectos de los fármacos , Mezclas Complejas/farmacología , Cordyceps/química , Cuerpos Fructíferos de los Hongos/química , Micelio/química , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Mezclas Complejas/química , Etanol , Femenino , Fermentación , Humanos , Radical Hidroxilo/metabolismo , Células MCF-7 , Oryza , Superóxido Dismutasa/metabolismo
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