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The biological oxidation of elemental sulfur (S0) to sulfate and the reduction of S0 to sulfide provide a potential route for extracting and reclaiming phosphorus (P) from anaerobically digested sludge (ADS). However, the treatment performance, stability, and cost-effectiveness of the two opposing bioprocesses based on S° for selective P recovery from ADS remain unclear. This study aimed to compare the roles of S0-oxidizing bacteria (S0OB) and S0-reducing bacteria (S0RB) in liberating insoluble P from ADS through single-batch and consecutive multibatch experiments. Changes in P speciation in the sludge during the biological extraction processes were analyzed by using complementary sequential extraction and P X-ray absorption near-edge spectroscopy. Results showed that S0OB treatment extracted more phosphate from the sludge compared with S0RB treatment, but it also released a considerable amount of metal cations (e.g., heavy metals, Mg2+, Al3+, Ca2+) and negatively affected sludge dewaterability due to intense sludge acidification and cell lysis. At pH 1.2, the S0OB treatment released 92.9% of P from the sludge, with the dissolution of HAP, Fe-PO4, Mg3(PO4)2, and P-fehrrihy contributing 26.8%, 22.1%, 12.8%, and 10.5%, respectively. The S0RB treatment released 63.6% of P from the sludge at pH 7.0, with negligible dissolution of metal cations, thereby avoiding costly purification of the extract and alkali neutralization for pH adjustment. This treatment involved the replacement of phosphates bounded with Fe-PO4 (FePO4 and P-fehrrihy) and Al-PO4 (P-Alumina and AlPO4) with biogenic sulfides, with contributions of 72.7%, and 20.9%, respectively. Consecutive bioprocesses for P extraction were achieved by recirculating the treated sludge. Both S0OB and S0RB treatments did not affect the extent of sludge dewatering but considerably weakened the dewatering rate. The S0OB-treated sludge exhibited prolonged filtration time (from 3010 s to 9150 s) and expressing time (from 795 s to 4690 s) during compression dewatering. After removing metal cations using cation exchange resin (CER) and neutralizing using NaOH, a vivianite product Fe3(PO4)2·8H2O (purity: 84%) was harvested from the S0OB-treated extract through precipitation with FeSO4·7H2O. By contrast, a vivianite product Fe3(PO4)2·8H2O (purity: 81%) was directly obtained from the S0RB-treated extract through precipitation with FeSO4·7H2O. Ultimately, 79.8 and 57.9wt% of P were recovered from ADS through S0OB extraction-CER purification-alkali neutralization-vivianite crystallization, and S0RB extraction-vivianite crystallization, respectively. Collectively, biological S0 reduction is more applicable than biological S0 oxidation for selectively reclaiming P from Fe/Al-associated phosphate-rich ADS due to better cost-effectiveness and process simplicity. These findings are of significance for developing sludge management strategies to improve P reclamation with minimal process inputs.
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Fósforo , Aguas del Alcantarillado , Fósforo/química , Aguas del Alcantarillado/química , Hierro/química , Fosfatos/química , Azufre , Sulfuros , Cationes , Oxidación-Reducción , Álcalis , Eliminación de Residuos Líquidos/métodosRESUMEN
Micro-/nanorobots have attracted great interest in the field of drug delivery and treatment, while preparations for biocompatible robots are extremely challenging. Here, a self-driving yeast micro-/nanorobot (Cur@CaY-robot) is designed via dual biomineralization and acid catalysis of calcium carbonate (CaCO3). Inner nano-CaCO3 inside yeast cells (CaY) is biomineralized through cell respiration and provides nanoscaffolds for highly encapsulating curcumin (Cur). Meanwhile, the CaCO3 crystals outside yeast cells (outer-CaCO3) through uniaxial growth offer an asymmetric power source for self-propelled motility. The Cur@CaY-robot displays an efficient motion in gastric acid, with the potential for deep penetration to the thick gastric mucus, which significantly improves the accumulation of drug agents in the stomach wall tissue for robust gastritis therapy. More importantly, Ca2+ cations released from the Cur@CaY-robot also synergistically repair the gastric motility of gastritis mice. Such yeast micro-/nanorobots exhibit desirable biocompatibility and biodegradability with a good loading capacity for drugs. This work provides an idea for the design of micro-/nanorobots through an environmentally friendly biosynthesis strategy for active drug delivery and precise therapy.
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Curcumina , Gastritis , Nanopartículas , Ratones , Animales , Saccharomyces cerevisiae , Sistemas de Liberación de Medicamentos , Curcumina/química , Gastritis/tratamiento farmacológico , Nanopartículas/químicaRESUMEN
Upper limb motor dysfunction after stroke is a serious threat to the living quality of patients and their families. Recovery of upper limb motor function after stroke largely relies on the activation and remodeling of neural circuits. rTMS (repetitive transcranial magnetic stimulation) has been proved to promote the reconstruction of neural synapses and neural circuits. However, there are still a large number of patients who cannot fully recover and leave behind varying degrees of dysfunction. Considering the systemic pathology after stroke, in addition to focal brain injury, stroke can also cause extensive dysfunction of peripheral organs. The rehabilitation strategy for stroke should combine the treatment of primary brain lesions with the intervention of secondary systemic damage. The aim of this trial is to verify the efficacy of rTMS synergize with Tui Na (Chinese Massage) on upper limb motor function after ischemic stroke, and to explore the mechanism of activation and remodeling of sensorimotor neural circuits with functional near-infrared spectroscopy. Ninety patients will be randomly assigned to either rTMS + Tui Na + conventional rehabilitation group (the experimental group) or rTMS + conventional rehabilitation group (the control group) in 1:1 ratio. Intervention is conducted five sessions a week, with a total of twenty sessions. The primary outcome is Fugl-Meyer Assessment, and the secondary outcomes include Muscle Strength, Modified Ashworth Assessment, Modified Barthel Index Assessment, motor evoked potentials and functional near-infrared spectroscopy. There are four time points for the evaluation, including baseline, 2 weeks and 4 weeks after the start of treatment, and 4 weeks after the end of treatment. This study is a randomized controlled trial. This study was approved by Institutional Ethics Committee of Shanghai Third Rehabilitation Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (approval No. SH3RH-2021-EC-012) on December, 16th, 2021. The protocol was registered with Chinese Clinical Trial Registry (ChiCTR2200056266), on February 3th, 2022. Patient recruitment was initiated on February 10th, 2022, and the study will be continued until December 2023.
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The distribution, composition, sources, and potential ecological risks of polycyclic aromatic hydrocarbons (PAHs) in the sediments of the Lanzhou Reach of the Yellow River, China were investigated. The total concentration of the 18 individual PAHs (∑18PAHs) in the sediments ranged from 638 to 1620 ng/g, with a mean value of 901 ng/g. The pollution level of PAHs in the sediments was low to moderate. Spatially, the distribution of PAHs in the sediments showed an increasing trend along the direction of water flow. ∑18PAHs predominantly consisted of low molecular weight PAHs. The principal component analysis and isomer ratios of PAHs suggested the mixed sources of petroleum and those from the combustion of petroleum, coal, and biomass. The results showed that the PAHs in the sediments of the Lanzhou Reach of the Yellow River have a low ecological risk. However, the BaP equivalent exposure values suggested a potential cancer risk.
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Monitoreo del Ambiente , Hidrocarburos Policíclicos Aromáticos/análisis , Contaminantes Químicos del Agua/análisis , Biomasa , China , Carbón Mineral/análisis , Sedimentos Geológicos/análisis , Petróleo/análisis , Análisis de Componente Principal , Medición de Riesgo , RíosRESUMEN
As the predominant treatment approach of acid mine drainage (AMD), lime neutralization often exhibits inefficiencies since the abundance of iron and sulfate in AMD usually form iron hydroxide and gypsum precipitate coatings on the surface of lime. In this study, a novel approach of biomineralization prior to lime neutralization for treating AMD was proposed, in which iron and sulfate were biologically precipitated as schwertmannite through iron biological reduction-oxidation driven by a culture mixed with Acidiphilium multivorum JZ-6 and Acidithiobacillus ferrooxidans LX5. It was found that only five cycles of iron reduction by A. multivorum JZ-6 followed by iron oxidation by A. ferrooxidans LX5 could remove completely iron and nearly 40% of sulfate in AMD, while non-ferrous metals (Al, Mn, Cu, Ni, and Zn) were hardly removed. Consequently, the amounts of lime required and sludge generated in the subsequent lime neutralization process were reduced by 56% and 68%, respectively. As a result, the content of non-ferrous metals in the sludge was increased by 3.2 folds. The level of Al was increased surprisingly to 19% (wt/wt), a level similar to the commercially valuable bauxite. The novel process of biomineralization prior to lime neutralization provides a sustainable way for AMD treatment.
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Acidithiobacillus , Compuestos de Hierro , Acidiphilium , Compuestos de Calcio , Oxidación-Reducción , ÓxidosRESUMEN
Chemotherapy is an important modality available for cancer treatment. However, the present chemotherapy is still far from being satisfactory mainly owing to the severe side effects of the chemotherapeutic agents and drug resistance of cancer cells. Thus, reversing drug resistance by constructing an ideal chemotherapeutic strategy with the least side effects and the best efficacy is greatly needed. Here, we designed a smart nanosystem of thermo-sensitive liposome coated gold nanocages with doxorubicin (DOX) loading (LAD) for near-infrared (NIR)-triggered drug release and chemo-photothermal combination therapy. The biocompatible liposomes coating facilitated the cellular uptake of LAD and meanwhile avoided drug leakage during the circulation. More importantly, LAD exhibited controllable photothermal conversion property and produced mild heat under NIR irradiation, which not only triggered DOX release and transferred DOX from lysosome to nucleus, but also elicited the mild heat cell killing effect to improve the curative efficiency. Further mechanism study revealed that mild heat could reverse drug resistance by down-regulation of the chemoresistance-related markers (e.g., HSF-1, p53, P-gp), and inhibited DOX export and increased drug sensitiveness, thereby prominently increased the anticancer efficiency. This versatile nanoplatform with enhanced curative efficacy and lower side effect is promising to apply in the field of drug controlled release and combination tumor therapy.
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Oro , Hipertermia Inducida , Línea Celular Tumoral , Doxorrubicina , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Resistencia a Antineoplásicos , Calor , FototerapiaRESUMEN
Diabetes mellitus (DM) is a chronic inflammatory disease, and the rapidly increasing DM is becoming a major problem of global public health. Traditional Chinese medicine (TCM) has a long history of treating diabetes. It has been developed and utilized because of its good efficacy and no toxic side effects. Lobelia chinensis is a traditional whole grass herbal. With the continuous deepening of pharmacological research on TCM, the active ingredients of L. chinensis are continuously revealed, which contained the alkaloids, flavonoids, flavonoid glycosides and amino acids that have the good effects of anti-inflammatory, anti-viral and anti-diabetic. In order to further explore the targets of active ingredients and its anti-diabetic mechanism, a feasible network pharmacology analysis model based on chemical, pharmacokinetic and pharmacological data was developed by network construction method to clarify the anti-diabetic mechanism of L. chinensis. The present study conducted by gas chromatography-mass spectrometer (GC/MS), which identified 208 metabolites of L. chinensis, of which 23 ingredients may have effective pharmacological effects after absorption, distribution, metabolism, and excretion (ADME) screening. Network pharmacological analysis on the active ingredients revealed that 5-hydroxymethylfurfural in L. chinensis affects the insulin resistance signaling pathway by acting on GSK3B, TNF, and MAPK1, acacetin affects the diabetic pathway by acting on INSR, DPP4, and GSK3B, that regulate type 2 diabetes, non-insulin-dependent DM, and inflammatory diseases. These results successfully indicated the potential anti-diabetic mechanism of the active ingredients of L. chinensis.
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Advanced colorectal cancer has a high mortality rate since conventional treatments have limited therapeutic effects and poor prognosis with high risks of metastasis and recurrence. Photodynamic therapy (PDT) is a promising treatment modality for the eradication of colorectal cancer, but its curative efficacy is severely affected by tumor hypoxia. Herein, we developed a core-shell gold nanocage coated with manganese dioxide and hyaluronic acid (AMH) for targeted delivery to colorectal tumors and oxygenation-boosted immunogenic phototherapy in situ. The AMH nanoparticles can generate abundant oxygen from mild acidic/H2O2 medium, which can further enhance the PDT efficacy of AMH itself under near infrared (NIR) irradiation. Meanwhile, AMH-based PDT induced immunogenic cell death (ICD) of tumor cells with damage-associated molecular patterns (DAMPs) release and facilitated the dendritic cells (DCs) maturation to further potentiate the systematic antitumor immunity against advanced tumors. In vivo experiment results exhibited that AMH nanoparticles not only had the ability of targeting tumor but also in situ produced sufficient oxygen to relieve the tumor hypoxia. Furthermore, AMH-mediated oxygen-boosted immunogenic PDT effectively inhibited the tumor growth and recurrence. Thus, this work provides a potent targeted delivery nanoplatform for enhanced immunogenic PDT against advanced cancers. STATEMENT OF SIGNIFICANCE: Local hypoxic tumor microenvironment not only greatly limits the photodynamic therapy (PDT) efficacy, but also has an association with tumor invasiveness and metastasis. This study provides an AMH nanoparticle for targeted delivery to colorectal tumors and oxygenation-boosted immunogenic PDT in situ. AMH nanoparticle exhibits a good tumor-targeted ability to in situ produce abundant oxygen to relieve the tumor hypoxia, and initiates the potent oxygen-boosted immunogenic PDT effect under NIR irradiation to effectively inhibit the growth and recurrence of colorectal tumor. This oxygen-boosted immunogenic PDT nanosystem can be a promising candidate for advanced tumor treatment.
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Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/terapia , Nanopartículas/química , Oxígeno/farmacología , Fototerapia , Animales , Línea Celular Tumoral , Neoplasias Colorrectales/patología , Células Dendríticas/metabolismo , Femenino , Oro/química , Ácido Hialurónico/química , Compuestos de Manganeso/química , Ratones Endogámicos BALB C , Nanopartículas/ultraestructura , Óxidos/química , Fotoquimioterapia , Distribución TisularRESUMEN
BACKGROUND: Recently, many studies have reported that some botanicals and natural products were able to regulate NOD-like receptor signaling. NOD-like receptors (NLRs) have been established as crucial regulators in inflammation-associated tumorigenesis, angiogenesis, cancer cell stemness and chemoresistance. NLRs specifically sense pathogen-associated molecular patterns and respond by activating other signaling regulators, including Rip2 kinase, NF-κB, MAPK and ASC/caspase-1, leading to the secretion of various cytokines. PURPOSE: The aim of this article is to review the molecular mechanisms of NOD-like receptor signaling in inflammation-associated cancers and the NLRs-targeted botanicals and synthetic small molecules in cancer intervention. RESULTS: Aberrant activation of NLRs occurs in various cancers, orchestrating the tissue microenvironment and potentiating neoplastic risk. Blocking NLR inflammasome activation by botanicals or synthetic small molecules may be a valuable way to prevent cancer progression. Moreover, due to the roles of NLRs in regulating cytokine production, NLR signaling may be correlated with senescence-associated secretory phenotype. CONCLUSION: In this review, we discuss how NLR signaling is involved in inflammation-associated cancers, and highlight the NLR-targeted botanicals and synthetic small molecules in cancer intervention.
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Inflamasomas/efectos de los fármacos , Inflamación/tratamiento farmacológico , Proteínas NLR/metabolismo , Neoplasias/tratamiento farmacológico , Transducción de Señal , Productos Biológicos/farmacología , Carcinogénesis/efectos de los fármacos , Senescencia Celular , Citocinas/metabolismo , Humanos , Peroxidación de Lípido/efectos de los fármacos , Terapia Molecular Dirigida , Neoplasias/patología , Neovascularización Patológica/tratamiento farmacológico , Fitoquímicos/farmacologíaRESUMEN
To investigate the cell cycle and cellular mechanisms of leukocyte elevation by laser acupuncture in rats with cyclophosphamide (CTX)-induced leukopenia. Sixty-six rats were randomized into six groups: normal, model control group, sham treatment group, 10.6 µm laser treatment group, 650 nm laser treatment group, and 10.6 µm-650 nm compound laser treatment group. Eleven rats were used in the normal group and 55 were models that were injected with cyclophosphamide to induce leukopenia. For the three laser treatment groups, 10.6-µm and 650-nm lasers, and 10.6-µm-650-nm compound lasers were used to irradiate the DU14 (Dazhui) and bilateral ST36 (Zusanli) for 5 min each. The sham laser group received the same operation as the laser group but without irradiation. The normal group and model group were not treated. Differences in the number of nucleated cells in the femoral bone marrow, and cell cycle and cellular apoptosis of peripheral leukocytes in rats in various groups were compared. Compared with the model group and the sham laser group, the number of nucleated cells in the femoral bone marrow in the 10.6-µm laser, 650-nm laser, and 10.6-µm-650-nm compound laser group was significantly increased after treatment (P = 0.001, 0.002, 0.034, respectively) and did not show any significant difference with the normal group (P = 0.964, P = 0.838, P = 0.287, respectively). The number of cells in G2 phase in the 10.6 µm laser group was similar to that of the normal group (P = 0.973). The number of cells in G2 phase in the model, sham, 650-nm laser group, and 10.6-µm-650-nm compound laser group were significantly lower than in the normal group and 10.6-µm laser group (P = 0.016, P = 0.023, P = 0.044, P = 0.039, respectively). In the model group and the sham treatment group, the apoptosis rates of peripheral leukocytes were increased compared with the normal group (P = 0.001), while the proportion of cells in the G2 phase was significantly lower than in the normal group (P = 0.016), and the proportion of cells in S phase was higher than in the normal group (P = 0.014). The incidence of apoptosis in peripheral blood cells in the three laser treatment groups did not show any statistically significant difference when compared with the normal group (P > 0.05). Treatment with the 10.6-µm, 650-nm, and 10.6-µm-650-nm compound lasers increased the number of nucleated cells in the bone marrow, decreased the unfavorable effects of cyclophosphamide on the cell cycle, induced the cell cycle towards proliferation, decreased apoptosis, improved the intramedullary hematopoietic system, and increased peripheral leukocyte count.
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Terapia por Acupuntura , Rayos Láser , Leucocitos/patología , Moxibustión , Animales , Apoptosis/efectos de los fármacos , Células de la Médula Ósea/citología , Células de la Médula Ósea/efectos de la radiación , Recuento de Células , Ciclo Celular/efectos de la radiación , Fémur/citología , Leucocitos/efectos de la radiación , Masculino , Ratas Sprague-DawleyRESUMEN
Mulberry leaves are one of the most commonly used medicinal and herbaceous traditional Chinese medicines that are currently considered for the treatment of diabetes mellitus and its complications. The alkaloids, flavonoids, and polysaccharides in mulberry leaves impart regulatory effects on blood sugar levels. To identify the hypoglycemia-related active components in mulberry leaves and their targets, the present study conducted gas chromatography-mass spectrometer (GC/MS), which identified 202 components of mulberry leaf, of which 22 components may have significant curative effects on diabetes mellitus and its complications and chronic inflammation. The network-based pharmacological analysis platform was used to identify target proteins related to diabetes. Finally, the interaction networks of these target proteins were identified using STRING and Cytoscape. The results showed that mulberry leaf powder contains tricetin, gallic acid, chlorogenic acid, and other drug components that can regulate tumor necrosis factor (TNF), peroxisome proliferator-activated receptor gamma (PPARG), glycogen synthase kinase-3 beta (GSK3B), insulin receptor substrate 1 (IRS1), interleukin 6 (IL-6) and other proteins, which are related to the insulin and inflammatory signaling pathways, glucose metabolism and other related pathways, chronic inflammatory diseases, obesity, diabetic nephropathy, non-insulin-dependent diabetes mellitus and other diseases.
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Hipoglucemiantes/análisis , Morus , Fitoquímicos/análisis , Extractos Vegetales/análisis , Diabetes Mellitus/tratamiento farmacológico , Ontología de Genes , Hipoglucemiantes/farmacología , Fitoquímicos/farmacología , Extractos Vegetales/farmacología , Hojas de la Planta , Mapas de Interacción de ProteínasRESUMEN
One approach to cancer immunotherapy is the repolarization of immunosuppressive tumor-associated macrophages (TAMs) to antitumor M1 macrophages. The present study developed galactose-functionalized zinc protoporphyrin IX (ZnPP) grafted poly(l-lysine)- b-poly(ethylene glycol) polypeptide micelles (ZnPP PM) for TAM-targeted immunopotentiator delivery, which aimed at in vivo repolarization of TAMs to antitumor M1 macrophages. The outcomes revealed that ROS-inducing ZnPP PM demonstrated specificity for the in vitro and in vivo targeting of macrophages, elevated the level of ROS, and lowered STAT3 expression in BM-TAMs. Poly I:C (PIC, a TLR3 agonist)-loaded ZnPP PM (ZnPP PM/PIC) efficiently repolarized TAMs to M1 macrophages, which were reliant on ROS generation. Further, ZnPP PM/PIC substantially elevated the activated NK cells and T lymphocytes in B16-F10 melanoma tumors, which caused vigorous tumor regression. Therefore, the TAM-targeted transport of an immunologic adjuvant with ZnPP-grafted nanovectors may be a potential strategy to repolarize TAMs to M1 macrophages in situ for effective cancer immunotherapy.
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Inmunoterapia , Macrófagos/inmunología , Melanoma , Micelas , Poli I-C/farmacología , Especies Reactivas de Oxígeno/metabolismo , Receptor Toll-Like 3/inmunología , Animales , Línea Celular Tumoral , Inmunidad Celular/efectos de los fármacos , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/patología , Melanoma/inmunología , Melanoma/patología , Melanoma/terapia , Ratones , Células RAW 264.7 , Linfocitos T/inmunología , Linfocitos T/patologíaRESUMEN
As a result of rapid economic growth over the previous three decades, China has become the second largest economy worldwide since 2010. However, as a developing country with the largest population, this rapid economic growth primarily based on excessive consumption and waste of resources. Thus, China has been facing particularly severe ecological and environmental problems in speeding up industrialization and urbanization. The impact of the health risk factors is complex and difficult to accurately predict. Therefore, it is critical to investigate potential threats in the context of the human-animal-environment interface to protect human and animal health. The "One Health" concept recognizes that human health is connected to animal and environmental health. This review primarily discusses specific health problems in China, particularly zoonoses, and explains the origin and development of the One Health approach, as well as the importance of a holistic approach in China.
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An active cell membrane-camouflaged nanoparticle, owning to membrane antigens and membrane structure, can achieve special properties such as specific recognition, long blood circulation, and immune escaping. Herein, we reported a cancer cell membrane-cloaked nanoparticle system as a theranostic nanoplatform. The biomimetic nanoparticles (indocyanine green (ICG)-loaded and cancer cell membrane-coated nanoparticles, ICNPs) exhibit a core-shell nanostructure consisting of an ICG-polymeric core and cancer cell membrane shell. ICNPs demonstrated specific homologous targeting to cancer cells with good monodispersity, preferable photothermal response, and excellent fluorescence/photoacoustic (FL/PA) imaging properties. Benefited from the functionalization of the homologous binding adhesion molecules from cancer cell membranes, ICNPs significantly promoted cell endocytosis and homologous-targeting tumor accumulation in vivo. Moreover, ICNPs were also good at disguising as cells to decrease interception by the liver and kidney. Through near-infrared (NIR)-FL/PA dual-modal imaging, ICNPs could realize real-time monitored in vivo dynamic distribution with high spatial resolution and deep penetration. Under NIR laser irradiation, ICNPs exhibited highly efficient photothermal therapy to eradicate xenografted tumor. The robust ICNPs with homologous properties of cancer cell membranes can serve as a bionic nanoplatform for cancer-targeted imaging and phototherapy.
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Biomimética , Membrana Celular/química , Nanopartículas , Fototerapia , Sistemas de Liberación de Medicamentos , Nanomedicina TeranósticaRESUMEN
Calcium oxide was added into ferrous ion oxidation system in the presence of Acidithiobacillus ferrooxidans at concentrations of 0-4.00 g/L. The pH, ferrous ion oxidation efficiency, total iron precipitation efficiency, and phase of the solid minerals harvested from different treatments were investigated during the ferrous ion oxidation process. In control check (CK) system, pH of the solution decreased from 2.81 to 2.25 when ferrous ions achieved complete oxidation after 72 h of Acidithiobacillus ferrooxidans incubation without the addition of calcium oxide, and total iron precipitation efficiency reached 20.2%. Efficiency of ferrous ion oxidation and total iron precipitation was significantly improved when the amount of calcium oxide added was ≤1.33 g/L, and the minerals harvested from systems were mainly a mixture of jarosite and schwertmannite. For example, the ferrous ion oxidation efficiency reached 100% at 60 h and total iron precipitation efficiency was increased to 32.1% at 72 h when 1.33 g/L of calcium oxide was added. However, ferrous ion oxidation and total iron precipitation for jarosite and schwertmannite formation were inhibited if the amount of calcium oxide added was above 2.67 g/L, and large amounts of calcium sulfate dihydrate were generated in systems.
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Acidithiobacillus/metabolismo , Compuestos de Calcio/química , Compuestos Ferrosos/química , Minería , Óxidos/química , Acidithiobacillus/química , Reactores Biológicos , Sulfato de Calcio/química , Concentración de Iones de Hidrógeno , Residuos Industriales , Hierro/farmacología , Oxidación-Reducción , SolucionesRESUMEN
MHC class I (MHC I) antigen presentation of exogenous antigens (so called "cross presentation") is a central mechanism of CD8(+) cytotoxic T lymphocyte (CTL) responses essential for successful vaccine-based cancer immunotherapy. The present study constructed amphiphilic pH-sensitive galactosyl dextran-retinal (GDR) nanogels for cancer vaccine delivery, in which dextran was conjugated with all-trans retinal (a metabolite of vitamin A) through a pH-sensitive hydrazone bond, followed by galactosylation to acquire dendritic cell (DC)-targeting ability. Our results showed that pH-sensitive GDR nanogel was a self-adjuvanted vaccine carrier that not only promoted DC maturation through activating retinoic acid receptor (RAR) signaling, but also facilitated antigen uptake and cytosolic antigen release in DCs. Furthermore, pH-sensitive GDR nanogel effectively augmented MHC I antigen presentation and evoked potent anti-cancer immune responses in vivo. More importantly, we first reported that nanoparticle-triggered lysosome rupture could directly induce ROS production in DCs, which was found to be essential for augmenting proteasome activity and downstream MHC I antigen presentation. Hence, DC-targeted pH-sensitive GDR nanogels could be a potent delivery system for cancer vaccine development. Triggering lyososomal rupture in DCs with pH-sensitive nanoparticles might be a plausible strategy to elevate intracellular ROS production for promoting antigen cross presentation, thereby improving cancer vaccine efficacy.
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Vacunas contra el Cáncer/administración & dosificación , Antígenos de Histocompatibilidad Clase I/inmunología , Lisosomas/química , Nanocápsulas/administración & dosificación , Neoplasias Experimentales/terapia , Especies Reactivas de Oxígeno/inmunología , Animales , Células Cultivadas , Quimioterapia Adyuvante/métodos , Preparaciones de Acción Retardada/administración & dosificación , Preparaciones de Acción Retardada/química , Células Dendríticas/efectos de los fármacos , Células Dendríticas/inmunología , Concentración de Iones de Hidrógeno , Inmunoterapia/métodos , Ratones , Ratones Endogámicos C57BL , Nanocápsulas/química , Neoplasias Experimentales/inmunología , Distribución Tisular , Resultado del TratamientoRESUMEN
Bio-oxidation of ferrous ions prior to lime neutralization exhibits great potential for acid mine drainage (AMD) treatment, while slow ferrous ion bio-oxidation or total iron precipitation is a bottleneck in this process. In this study, neutralized solid waste (NSW) harvested in an AMD lime neutralization procedure was added as a crystal seed in AMD for iron oxyhydroxysulfate bio-synthesis. The effect of this waste on ferrous ion oxidation efficiency, total iron precipitation efficiency, and iron oxyhydroxysulfate minerals yield during ferrous ion bio-oxidation by Acidithiobacillus ferrooxidans was investigated. Ferrous ion oxidation efficiency was greatly improved by adding NSW. After 72 h incubation, total iron precipitation efficiency in treatment with 24 g/L of NSW was 1.74-1.03 times higher than in treatment with 0-12 g/L of NSW. Compared with the conventional treatment system without added NSW, the iron oxyhydroxysulfate minerals yield was increased by approximately 21.2-80.9% when 3-24 g/L of NSW were added. Aside from NSW, jarosite and schwertmannite were the main precipitates during ferrous ion bio-oxidation with NSW addition. NSW can thus serve as the crystal seed for iron oxyhydroxysulfate mineral bio-synthesis in AMD, and improve ferrous ion oxidation and total iron precipitation efficiency significantly.
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Compuestos de Calcio/química , Compuestos Ferrosos/química , Minería , Óxidos/química , Residuos Sólidos , Contaminantes Químicos del Agua/metabolismo , Acidithiobacillus/metabolismo , Concentración de Iones de Hidrógeno , Microscopía Electrónica de Rastreo , Oxidación-Reducción , Difracción de Rayos XRESUMEN
Objective. To assess the effect of different lasers on cyclophosphamide- (CTX-) induced leucopenia in rats. Methods. 11 rats were normal control and 55 rats were injected with a dose of 80 mg/kg CTX for the first time and 40 mg/kg on the 6th and the 11th days to establish a leucopenia model. Rats of the irradiation groups received a 5-minute laser irradiation with either single 10.6 µ m or 650 nm laser or alternatively 10.6 µ m-650 nm laser irradiation, besides a sham treatment on acupoint Dazhui (DU 14) and acupoint Zusanli (ST 36) of both sides, 8 times for 16 days. Normal and model control group received no treatment. Results. On day 16 after the first CTX injection, the WBC counts from all the laser irradiation groups were significantly higher than those from the model control and the sham group (P < 0.05), while there were no significant differences compared with the normal control (P > 0.05). The TI of 10.6 µ m-650 nm laser irradiation group was significantly higher than that of the model control group (P < 0.05). Conclusions. The single and combined 10.6 µ m and 650 nm laser irradiation on ST36 and DU14 accelerated the recovery of the WBC count in the rats with leucopenia.
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Although the etiology of PD remains unclear, increasing evidence has shown that oxidative stress plays an important role in its pathogenesis and that of other neurodegenerative disorders. The phenolic glucoside gastrodin, a main constituent of a Chinese herbal medicine Gastrodia elata (GE) Blume, has been known to display antioxidant activity. The present study aimed to investigate the protective effects of gastrodin on 1-methyl-4-phenylpyridinium (MPP(+))-induced oxidative cytotoxicity in human dopaminergic SH-SY5Y cells and the underlying mechanism for this neuroprotection. Results indicate that pre-treatment with gastrodin for 1h significantly reduced the MPP(+)-induced viability loss, apoptotic rate and attenuated MPP(+)-mediated ROS production. In addition, gastrodin inhibited MPP(+)-induced lowered membrane potential, decreased Bcl-2/Bax ratio. Moreover, we have revealed the gastrodin increased Nrf2 nuclear translocation, which is upstream of heme oxygenase-1 (HO-1) expression and for the first time revealed gastrodin could increased antioxidant enzyme HO-1 expression in concentration-dependent and time-dependent manners. HO-1 siRNA transfection was employed, and confirmed gastrodin could active the expression of HO-1. And the increase in HO-1 expression was correlated with the protective effect of gastrodin against MPP(+)-induced injury. Because the inhibitor of HO-1 activity, ZnPP reversed the protective effect of gastrodin against MPP(+)-induced cell death. We also demonstrated that the specific p38 MAPK inhibitor, SB203580, concentration-dependently blocked on gastrodin-induced HO-1 expression, and meanwhile SB203580 reversed the protective effect of gastrodin against MPP(+)-induced cell death. Taken together, these findings suggest that gastrodin can induce HO-1 expression through activation of p38 MAPK/Nrf2 signaling pathway, thereby protecting the SH-SY5Y cells from MPP(+)-induced oxidative cell death. Thus our study indicates that gastrodin has a partial cytoprotective role in dopaminergic cell culture systems and could be of importance for the treatment of PD and other oxidative stress-related diseases.
Asunto(s)
1-Metil-4-fenilpiridinio/farmacología , Alcoholes Bencílicos/farmacología , Dopamina/metabolismo , Glucósidos/farmacología , Hemo-Oxigenasa 1/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacos , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Secuencia de Bases , Línea Celular Tumoral , Cartilla de ADN , Gastrodia/química , Humanos , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Although polysaccharide nanogels have emerged as a novel antigen delivery system for vaccine development, whether modulating the redox sensitivity of nanogels could improve vaccine efficacy remains unclear. In the present study, we generated bioreducible cationic alginate-polyethylenimine (PEI) nanogels as a novel vaccine delivery system. Briefly, nanogels were prepared by the electrostatic interaction of negatively charged alginate sodium with branched PEI2k, followed by disulfide cross-linking to generate bioreducible nanogels (AP-SS). The AP-SS nanogels demonstrated great antigen-loading capacity and minimal cytotoxicity. The in vitro study showed that reducible AP-SS nanogels not only facilitated antigen uptake by mouse bone marrow dendritic cells (BMDCs), but also promoted intracellular antigen degradation and cytosolic release. Moreover, AP-SS nanogels significantly enhanced both MHC class I and II antigen presentation by BMDCs. Compared with the non-reducible nanogels, AP-SS nanogels more potently enhanced vaccine-induced antibody production and CD8+ T cell-mediated tumor cell lysis. Hence, the bioreducible alginate-PEI nanogels could serve as a potent adjuvant to improve vaccine-elicited humoral and cellular immune responses.