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1.
J Am Chem Soc ; 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39141924

RESUMO

Anisotropic nanoparticles such as worm-like micelles have aroused much attention due to their promising applications from templates to drug delivery. The fabrication of worm-like micelles with tunable structural stability and control over their diameter and length is of great importance but still challenging. Herein, we report a kinetically controlled ring-opening metathesis polymerization-induced self-assembly (ROMPISA) for the robust preparation of kinetically trapped worm-like micelles with tunable diameter/length at enlarged experimental windows by the rational manipulation of kinetic factors, including solvent property, temperature, and π-π stacking effects. The resultant worm structures were thermodynamically metastable and capable of excellent structural stability at room temperature due to the kinetic trapping effect. At elevated temperatures, these thermodynamically metastable worms could undergo morphology evolution into vesicular structures in a controlled manner. Moreover, the structural stability of worms could also be significantly enhanced by in situ cross-linking. Overall, this kinetically controlled ROMPISA opens a new avenue for PISA chemistry that is expected to prepare "smart" polymer materials by manipulating kinetic factors.

2.
Med Sci Monit ; 30: e940146, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38234086

RESUMO

BACKGROUND Limited research has been conducted on laparoscopic partial nephrectomy for kidney tuberculosis. This study aimed to evaluate the effectiveness of the skirted continuous suture technique in laparoscopic partial nephrectomy for localized renal tuberculosis. MATERIAL AND METHODS Five patients with kidney tuberculosis underwent standard retroperitoneal laparoscopic partial nephrectomy after computed tomography evaluation. The skirted continuous suture technique was utilized during the procedure. This retrospective study analyzed the outcomes of these patients who received treatment between January 2011 and December 2020 at Beijing Tsinghua Changgung Hospital and Eighth Medical Center of Chinese People's Liberation Army General Hospital. RESULTS The surgical success rate was 100%. Renal function was well preserved, with a decrease of glomerular filtration rate by 9.6±9.0 ml/min. Only 1 patient experienced postoperative urinous infiltration and lymphatic fistula, while the others did not have any surgical complications. Antituberculous therapy was continued postoperatively, and 1 patient had recurrence during follow-up. CONCLUSIONS The laparoscopic continuous suturing technique offers a reliable and straightforward method for extensively closing incision edges of the renal parenchyma in laparoscopic surgery. It contributes to the improved efficacy and safety of treating localized renal tuberculosis with exceptional application.


Assuntos
Neoplasias Renais , Laparoscopia , Nefrectomia , Tuberculose Renal , Humanos , Neoplasias Renais/cirurgia , Laparoscopia/métodos , Nefrectomia/métodos , Estudos Retrospectivos , Técnicas de Sutura , Resultado do Tratamento , Tuberculose Renal/cirurgia , Tuberculose Renal/etiologia
3.
Molecules ; 29(6)2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38543035

RESUMO

To investigate the influence of deashing on fusion characteristics, a combined method of water and acid washing with different sequences (water washing followed by acid washing, and acid washing followed by water washing) was used to treat the biochar of bamboo shoot shells (BBSSs). The results show that deashing decreased the K content of the biochar from 50.3% to 1.08% but increased the Si content from 33.48% to 89.15%. The formation of silicates and aluminosilicates from alkali metal oxides with silicon was an inevitable result of ash phase transformation at the high temperatures used to improve the fusion temperature (>1450 °C). The thermochemical behavior of ash mainly occurs at 1000 °C. The deashing treatment significantly reduced the reaction intensity during the high-temperature process. This significantly increased the thermal stability of the ash. The adjustment of the washing sequence had a slight impact on the chemical compositions, but the differences in ash micromorphology were obvious. Deashing treatments with different washing sequences can significantly improve ash fusion properties effectively and reduce the risk of scaling, slagging, and corrosion. This study provides a new and reasonable strategy for the deashing of biochar to commercially utilize bamboo shoot shell resources.


Assuntos
Álcalis , Carvão Vegetal , Carvão Vegetal/química , Temperatura , Água , Cinza de Carvão
4.
Opt Express ; 31(8): 13195-13210, 2023 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-37157462

RESUMO

The high-precision measurement of the six degrees-of-freedom (6DoF) relative position and pose deformation of satellites on the ground in vacuum and high-/low-temperature environments plays a critical role in ensuring the on-orbit mapping accuracy of satellites. To meet the strict measurement requirements for a satellite of a high accuracy, high stability, and a miniaturized measurement system, this paper proposes a laser measurement method for simultaneously measuring 6DoF relative position and attitude. In particular, a miniaturized measurement system was developed and a measurement model was established. The problem of error crosstalk between the 6DoF relative position and pose measurements was solved by conducting a theoretical analysis and OpticStudio software simulation, and the measurement accuracy was improved. Laboratory experiments and field tests were then conducted. The experimental results revealed that the measurement accuracy of the developed system for the relative position and relative attitude reached 0.2 µm and 0.4", within the measurement ranges of 500 mm along the X axis, ±100 µm along Y and Z axes, and ±100", and the 24-h measurement stabilities were superior to 0.5 µm and 0.5", respectively, which meets the ground measurement requirements for the satellite. The developed system was successfully applied on site, and the 6Dof relative position and pose deformation of the satellite were obtained via a thermal load test. This novel measurement method and system provides an experimental means for satellite development, in addition to a method for the high-precision measurement of the relative 6DoF position and pose between two points.

5.
Chemistry ; 29(12): e202203460, 2023 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-36445789

RESUMO

Insulin, a main medication to control glycemia of type 1 and advanced type 2 diabetes, faces problems of a short half-life and poor stability during its clinical use. Zwitterionic polymer shows unique properties of antifouling and low immunogenicity. Here, we have synthesized a new insulin-zwitterionic polymer conjugate (INS-PMPC) through grafting-from strategy by controlled radical polymerization. Apart from showing excellent stability upon mechanical agitation, the resulting INS-PMPC conjugate provided over 20 h of glycemic control due to improved pharmacokinetics in diabetic mice with one single subcutaneous injection. Most importantly, this insulin-zwitterionic polymer conjugate significantly decreases the incidence of hypoglycemia.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Hipoglicemia , Animais , Camundongos , Insulina de Ação Prolongada , Polímeros , Hipoglicemia/epidemiologia , Insulina
6.
Int J Mol Sci ; 24(3)2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36768806

RESUMO

This study systematically investigated the differences in allergenicity of casein in cow milk (CM), goat milk (GM), camel milk (CAM), and mare milk (MM) from protein structures using bioinformatics. Primary structure sequence analysis reveals high sequence similarity between the α-casein of CM and GM, while all allergenic subtypes are likely to have good hydrophilicity and thermal stability. By analyzing linear B-cell epitope, T-cell epitope, and allergenic peptides, the strongest casein allergenicity is observed for CM, followed by GM, and the casein of MM has the weakest allergenicity. Meanwhile, 7, 9, and 16 similar or identical amino acid fragments in linear B-cell epitopes, T-cell epitopes, and allergenic peptides, respectively, were observed in different milks. Among these, the same T-cell epitope FLGAEVQNQ was shared by κ-CN in all four different species' milk. Epitope results may provide targets of allergenic fragments for reducing milk allergenicity through physical or/and chemical methods. This study explained the underlying secrets for the high allergenicity of CM to some extent from the perspective of casein and provided new insights for the dairy industry to reduce milk allergy. Furthermore, it provides a new idea and method for comparing the allergenicity of homologous proteins from different species.


Assuntos
Camelus , Caseínas , Animais , Feminino , Cavalos , Bovinos , Caseínas/química , Alérgenos/metabolismo , Cabras/metabolismo , Epitopos de Linfócito T , Imunoglobulina E , Peptídeos , Epitopos de Linfócito B , Proteínas do Leite
7.
Molecules ; 28(8)2023 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-37110642

RESUMO

To effectively remove methylene blue (MB) from dye wastewater, a novel activated carbon (BAC) was manufactured through co-pyrolysis of bamboo shoot shell and K2FeO4. The activation process was optimized to a temperature of 750 °C and an activation time of 90 min based on its excellent adsorption capacity of 560.94 mg/g with a yield of 10.03%. The physicochemical and adsorption properties of BACs were investigated. The BAC had an ultrahigh specific surface area of 2327.7 cm2/g and abundant active functional groups. The adsorption mechanisms included chemisorption and physisorption. The Freundlich model could be used to describe the isothermal adsorption of MB. The kinetics confirmed that the adsorption of MB belonged to the pseudo-second-order model. Intra-particle diffusion was the main rate-limiting step. The thermodynamic study showed that the adsorption process was endothermic and temperature was beneficial for the improvement of adsorption property. Furthermore, the removal rate of MB was 63.5% after three cycles. The BAC will have great potential for commercial development for purifying dye wastewater.

8.
Angew Chem Int Ed Engl ; 62(43): e202310401, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37661193

RESUMO

The development of lipid nanoparticles (LNPs) has enabled a successful clinical application of mRNA vaccines. However, disclosure of design principles for the core component-ionizable lipids (ILs), improving the delivery efficacy and organ targeting of LNPs, remains a formidable challenge. Herein, we report a powerful strategy to modulate ILs in one-step chemistry using the Ugi four-component reaction (Ugi-4CR) under mild conditions. A large IL library of new structures was established simply and efficiently through a multidimensional approach, allowing us to identify the top-performing ILs in delivering mRNA via the formulated LNPs. Adjusting the skeleton of ILs has transformed the organ-specific and robust transfection in mRNA delivery from the liver to the spleen following different administration routes. Of note, a series of isomeric ILs were prepared and we found that the isomers mattered greatly in the performance of LNPs for mRNA delivery. Furthermore, owing to the bis-amide bonds formed in the Ugi-4CR reaction, the ILs within LNPs may form hydrogen bonding intermolecularly, facilitating the colloidal stabilization of LNPs. This work provides clues to the rapid discovery and rational design of IL candidates, assisting the application of mRNA therapeutics.

9.
Can J Physiol Pharmacol ; 100(1): 5-11, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34779659

RESUMO

The optimal cutoff point for evaluating the prognosis of localized renal cell carcinoma (LRCC) remains unclear. This study aimed to verify the efficacy of tumor diameter in the 2010 American Joint Committee on Cancer (AJCC) TNM staging system and contribute to the modification of TNM staging on the prognosis of this disease. A total of 3748 patients with LRCC were enrolled and grouped according to the 2010 AJCC TNM staging system. COX analysis was used to stratify the prognosis. The optimal cutoff point of the tumor diameter in the T1 and T2 prognosis was explored. There were 3330 (88.9%) patients in stage T1 and 418 (11.1%) in stage T2. The cancer-specific mortality rate was 2.7% (100/3748). The mean follow-up was 49.8 months. A tumor diameter of 7 cm can determine the prognosis of patients at stages T1 and T2; however, 4.5 cm and 11 cm as the cutoff points for T1 and T2 sub-classification of patients with LRCC might show better recognition ability than 4 cm and 10 cm, respectively. The 2010 AJCC TNM stage can predict the prognosis of LRCC in stages T1 and T2. In addition, a tumor diameter of 4.5 cm and 11 cm might be the optimal cutoff points for the sub-classification of stages T1 and T2.


Assuntos
Carcinoma de Células Renais/classificação , Carcinoma de Células Renais/patologia , Neoplasias Renais/classificação , Neoplasias Renais/patologia , Estadiamento de Neoplasias/classificação , Estadiamento de Neoplasias/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/mortalidade , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Adulto Jovem
10.
Zhongguo Zhong Yao Za Zhi ; 47(8): 2064-2073, 2022 Apr.
Artigo em Zh | MEDLINE | ID: mdl-35531722

RESUMO

To study the protective effect of Ershiwuwei Zhenzhu Pills on ischemic stroke rats. Ninety 4-weeks-old SPF male SD rats were randomly divided into 6 groups(n=15):sham operation group, model group, nimodipine group(12 mg·kg~(-1)), Ershiwuwei Zhenzhu Pills high-dose group(400 mg·kg~(-1)), Ershiwuwei Zhenzhu Pills medium-dose group(200 mg·kg~(-1)), Ershiwuwei Zhenzhu Pills low-dose group(100 mg·kg~(-1)).The permanent middle cerebral artery occlusion model(PMCAO) was established in the model group, nimodipine group, and Ershiwuwei Zhenzhu Pills groups by the improved thread plug method, while the sham operation group did not insert the thread plug.Nimodipine group and Ershiwuwei Zhenzhu Pills groups were given intragastric administration once a day for 24 days before the modeling operation, and once 1 hour before the modeling operation, while sham operation group and model group were given equal volumes of distilled water.The neuroethology of the surviving rats was measured; The volume of cerebral infarction in rats was measured by TTC method; The histopathology of rat brain was observed by HE method; The expression levels of tumor necrosis factor α(TNF-α),interleukin-1ß(IL-1ß),interleukin-6(IL-6),malondialdehyde(MDA),superoxide dismutase(SOD) and catalase(CAT) in serum were detected by ELISA;The mRNA expressions of Notch 1,Jagged 1,Hes 1 and Bcl-2 in rat brain were detected by RT-PCR;Western blot was used to detect the expression levels of caspase-3 protein in rat brain; the expression levels of vascular endothelial growth factor(VEGF) and CD34 positive cells in rat brain were detected by immunofluorescence.The low, medium and high dose groups of Ershiwuwei Zhenzhu Pills and nimodipine group could significantly reduce the neurobehavioral score and cerebral infarction volume of rats with permanent middle cerebral artery occlusion, reduce the morphological changes of nerve cells, decrease the expression of TNF-α,IL-1ß and IL-6 in rat serum, increase the activity of SOD and CAT,and reduce the level of MDA.Furthermore, the expression levels of Notch l, Jagged l, Hes l and Bcl-2 mRNA were significantly increased, and the expression level of caspase-3 protein was decreased.Meanwhile, the number of VEGF and CD34 positive cells increased in the treatment group.The differences were statistically significant. Ershiwuwei Zhenzhu Pills has a protective effect on ischemic stroke rats, and its mechanism may be related to anti-inflammation, anti-oxidation, promotion of nerve cell proliferation, inhibition nerve cell apoptosis and promotion of angiogenesis.


Assuntos
Medicamentos de Ervas Chinesas , Infarto da Artéria Cerebral Média , AVC Isquêmico , Animais , Caspase 3/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Infarto da Artéria Cerebral Média/tratamento farmacológico , Interleucina-6/metabolismo , AVC Isquêmico/tratamento farmacológico , Masculino , Nimodipina/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Mensageiro , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
11.
Appl Opt ; 60(4): 809-814, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33690387

RESUMO

Ghost imaging (GI) can reconstruct the image of an object when the light traveling from the object to the detector is scattered or distorted. It is usually used in complicated environments, where the environmental light may heavily impact measurement. However, the traditional GI algorithm will be seriously affected if the environmental light changes during the measurement. In this paper, we analyze the frequency of environmental light and the light source, and introduce a digital filtering method that can improve the image quality of the traditional GI algorithm. Compared to the traditional GI algorithm, the digital filtering method can obtain an image even if the environmental light changes seriously.

12.
Mol Pharm ; 17(3): 757-768, 2020 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-32011888

RESUMO

Salmon calcitonin (sCT) is a potent calcium-regulating peptide hormone and widely applied for the treatment of some bone diseases clinically. However, the therapeutic usefulness of sCT is hindered by the frequent injection required, owing to its short plasma half-life and therapeutic need for a high dose. Oral delivery is a popular modality of administration for patients because of its convenience to self-administration and high patient compliance, while orally administered sCT remains a great challenge currently due to the existence of multiple barriers in the gastrointestinal (GI) tract. Here, we introduced an orally targeted delivery system to increase the transport of sCT across the intestine through both the paracellular permeation route and the bile acid pathway. In this system, sCT-based glycol chitosan-taurocholic acid conjugate (GC-T)/dextran sulfate (DS) ternary nanocomplexes (NC-T) were produced by a flash nanocomplexation (FNC) process in a kinetically controlled mode. The optimized NC-T exhibited well-controlled properties with a uniform and sub-60 nm hydrodynamic diameter, high batch-to-batch reproducibility, good physical or chemical stability, as well as sustained drug release behaviors. The studies revealed that NC-T could effectively improve the intestinal uptake and permeability, owing to its surface functionalization with the taurocholic acid ligand. In the rat model, orally administered NC-T showed an obvious hypocalcemia effect and a relative oral bioavailability of 10.9%. An in vivo assay also demonstrated that NC-T induced no observable side effect after long-term oral administration. As a result, the orally targeted nanocomplex might be a promising candidate for improving the oral transport of therapeutic peptides.


Assuntos
Calcitonina/administração & dosagem , Hormônios e Agentes Reguladores de Cálcio/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Absorção Intestinal/efeitos dos fármacos , Nanocompostos/química , Administração Oral , Animais , Disponibilidade Biológica , Transporte Biológico , Células CACO-2/efeitos dos fármacos , Células CACO-2/metabolismo , Calcitonina/efeitos adversos , Calcitonina/sangue , Calcitonina/farmacocinética , Cálcio/sangue , Hormônios e Agentes Reguladores de Cálcio/efeitos adversos , Hormônios e Agentes Reguladores de Cálcio/sangue , Hormônios e Agentes Reguladores de Cálcio/farmacocinética , Quitosana/química , Sulfato de Dextrana/química , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Meia-Vida , Humanos , Hipocalcemia/induzido quimicamente , Injeções Subcutâneas , Masculino , Ratos , Ratos Sprague-Dawley , Ácido Taurocólico/química
13.
Biomacromolecules ; 21(2): 556-565, 2020 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-31804804

RESUMO

Near-infrared (NIR) light-responsive, injectable hydrogels are among the most promising drug delivery systems for localized anticancer therapy owing to its minimally invasive administration and remote-controlled manner. However, most currently reported NIR-responsive hydrogels were usually generated through physical mixing of thermosensitive polymers and photothermal conversion agents. In this study, a novel type of dynamic-covalent hydrogel (GelPV-DOX-DBNP) with NIR light-triggered drug release behavior was rationally designed for chemo-photothermal combination treatment of tumors. Concretely, this NIR-responsive hydrogel was formed by specific benzoxaborole-carbohydrate interactions between benzoxaborole (BOB)-modified hyaluronic acid (BOB-HA) and fructose-based glycopolymer (PolyFru), where photosensitizer perylene diimide zwitterionic polymer (PDS), reductant ascorbic acid (Vc), anticancer drug doxorubicin (DOX) as well as photothermal nanoparticles (DB-NPs) were encapsulated, simultaneously. Upon 660 nm light irradiation, both PDS and Vc within the designed hydrogel can convert oxygen into hydrogen peroxide, which could make hydrogel be degraded through the breakage of dynamic covalent bonds based on benzoxaborole-carbohydrate interactions, leading to NIR light-activatable release of DOX and DB-NPs from GelPV-DOX-DBNP. Furthermore, the released DB-NPs can convert 915 nm light irradiation into heat, enabling the application of GelPV-DOX-DBNP as a NIR-responsive drug delivery platform for both chemotherapy and photothermal therapy (PTT). In vivo results prove that GelPV-DOX-DBNP exhibited a markedly enhanced chemo-photothermal synergistic therapy for 4T1 tumor model mice, compared to chemotherapy alone or PTT. This work presents a new strategy to construct NIR light-responsive hydrogel as one alternative drug delivery system for anticancer applications.


Assuntos
Doxorrubicina/administração & dosagem , Hidrogéis/química , Nanopartículas/química , Terapia Fototérmica/métodos , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacocinética , Ácido Ascórbico/administração & dosagem , Ácido Ascórbico/química , Doxorrubicina/farmacocinética , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Humanos , Ácido Hialurônico/química , Hidrogéis/administração & dosagem , Imidas/química , Luz , Camundongos Endogâmicos BALB C , Nanopartículas/administração & dosagem , Perileno/análogos & derivados , Perileno/química , Fármacos Fotossensibilizantes/química , Polímeros/química , Ratos Sprague-Dawley , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Waste Manag Res ; 38(8): 896-902, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31868133

RESUMO

To evaluate the combustion characteristics of raw or torrefied bamboo wastes and coal blends, the co-firing process determined by cone and pollutant emission was investigated by thermogravimetric analysis coupled with Fourier transform infrared spectroscopy. The results showed that torrefaction improved the fuel properties of bamboo wastes. Torrefied bamboo had a lower volatile fuel ratio, H/C and O/C ratios, pollutant emission and a higher heating value. They further affected the co-firing process of raw or torrefied bamboo and coal. All blends had a lower ignition temperature and a more stable flame than coal. Torrefied bamboo and coal blends had a lower percentage of quality loss, a higher heat release rate (HRR), total heat release (THR) and total smoke release (TSR). With an increase in the proportion of torrefied bamboo in the blends, the HRR, THR, TSR and percentage of quality loss increased. The main pollutant emissions included CO2, CO, SO2 and NOx. All blends of torrefied bamboo and coal had a lower pollutant emission. The optimum blend suggested was 20% torrefied bamboo/80% coal.


Assuntos
Carvão Mineral/análise , Biomassa , Calorimetria , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura
15.
J Cell Physiol ; 234(12): 23495-23506, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31173361

RESUMO

Mitochondrial fusion is linked to heart and liver ischemia-reperfusion (IR) insult. Unfortunately, there is no report to elucidate the detailed influence of mitochondrial fusion in renal IR injury. This study principally investigated the mechanism by which mitochondrial fusion protected kidney against IR injury. Our results indicated that sirtuin 3 (Sirt3) was inhibited after renal IR injury in vivo and in vitro. Overexpression of Sirt3 improved kidney function, modulated oxidative injury, repressed inflammatory damage, and reduced tubular epithelial cell apoptosis. The molecular investigation found that Sirt3 overexpression attenuated IR-induced mitochondrial damage in renal tubular epithelial cells, as evidenced by decreased reactive oxygen species production, increased antioxidants sustained mitochondrial membrane potential, and inactivated mitochondria-initiated death signaling. In addition, our information also illuminated that Sirt3 maintained mitochondrial homeostasis against IR injury by enhancing optic atrophy 1 (OPA1)-triggered fusion of mitochondrion. Inhibition of OPA1-induced fusion repressed Sirt3 overexpression-induced kidney protection, leading to mitochondrial dysfunction. Further, our study illustrated that OPA1-induced fusion could be affected through ERK; inhibition of ERK abolished the regulatory impacts of Sirt3 on OPA1 expression and mitochondrial fusion, leading to mitochondrial damage and tubular epithelial cell apoptosis. Altogether, our results suggest that renal IR injury is closely associated with Sirt3 downregulation and mitochondrial fusion inhibition. Regaining Sirt3 and/or activating mitochondrial fission by modifying the ERK-OPA1 cascade may represent new therapeutic modalities for renal IR injury.


Assuntos
Injúria Renal Aguda/enzimologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , GTP Fosfo-Hidrolases/metabolismo , Rim/enzimologia , Mitocôndrias/enzimologia , Dinâmica Mitocondrial , Traumatismo por Reperfusão/enzimologia , Sirtuína 3/metabolismo , Injúria Renal Aguda/genética , Injúria Renal Aguda/patologia , Animais , Apoptose , Modelos Animais de Doenças , Ativação Enzimática , Rim/patologia , Células LLC-PK1 , Camundongos Transgênicos , Mitocôndrias/patologia , Estresse Oxidativo , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/patologia , Transdução de Sinais , Sirtuína 3/genética , Suínos
16.
Biomacromolecules ; 20(1): 528-538, 2019 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-30537806

RESUMO

Oral drug delivery is a more favored mode of administration because of its ease of administration, high patient compliance, and low healthcare costs. However, no oral protein formulations are commercially available currently due to hostile gastrointestinal (GI) barriers resulting in insignificant oral bioavailability of macromolecular drugs. Herein, we used insulin as a model protein drug; insulin-loaded N-(2-hydroxy)-propyl-3-trimethylammonium chloride modified chitosan (HTCC)/sodium tripolyphosphate (TPP) nanocomplex (NC) as a nanocore was further encapsulated into enteric Eudragit L100-55 material, through a two-step flash nanocomplexation (FNC) process in a reliable and scalable manner, forming our NC-in-Eudragit composite particles (NE). Particle size and surface properties of our optimized NE were tailored to protect the loaded insulin from acidic degradation in the hostile stomach environment and to achieve intestinal site-specific drug release as well as the improvement of oral delivery efficiency of insulin. In addition, the oral administration of the optimized NE to type 1 diabetic rats could induce a very significant hypoglycemic effect with a relative oral bioavailability of 13.3%. Our results demonstrated that enteric encapsulation of nanotherapeutics using a FNC apparatus could cause drug formulations to possess better size controllability, batch-mode reproducibility, and homogeneous surface coating and then significantly enhance their oral bioavailability of insulin, indicating its great potential for clinical translation of oral protein therapeutics.


Assuntos
Absorção Gastrointestinal , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Nanocápsulas/química , Resinas Acrílicas/química , Administração Oral , Animais , Células CACO-2 , Quitosana/análogos & derivados , Células HT29 , Humanos , Hipoglicemiantes/farmacocinética , Insulina/farmacocinética , Masculino , Nanocápsulas/efeitos adversos , Polifosfatos/química , Ratos , Ratos Sprague-Dawley
17.
Molecules ; 24(16)2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31434214

RESUMO

Bamboo shoots, a promising renewable biomass, mainly consist of carbohydrates and other nitrogen-related compounds, such as proteins, amino acids and nucleotides. In this work, nitrogen self-doped activated carbons derived from bamboo shoots were prepared via a simultaneous carbonization and activation process. The adsorption properties of the prepared samples were evaluated by removing methylene blue from waste water. The factors that affect the adsorption process were examined, including initial concentration, contact time and pH of methylene blue solution. The resulting that BSNC-800-4 performed better in methylene blue removal from waste water, due to its high specific surface area (2270.9 m2 g-1), proper pore size (2.19 nm) and relatively high nitrogen content (1.06%). Its equilibrium data were well fitted to Langmuir isotherm model with a maximum monolayer adsorption capacity of 458 mg g-1 and a removal efficiency of 91.7% at methylene blue concentration of 500 mg L-1. The pseudo-second-order kinetic model could be used to accurately estimate the carbon material's (BSNC-800-4) adsorption process. The adsorption mechanism between methylene blue solution and BSNC-800-4 was controlled by film diffusion. This study provides an alternative way to develop nitrogen self-doped activated carbons to better meet the needs of the adsorption applications.


Assuntos
Carvão Vegetal/química , Azul de Metileno/isolamento & purificação , Nitrogênio/química , Sasa/química , Poluentes Químicos da Água/isolamento & purificação , Adsorção , Corantes/química , Concentração de Íons de Hidrogênio , Cinética , Azul de Metileno/química , Microscopia Eletrônica de Varredura , Modelos Químicos , Brotos de Planta/química , Porosidade , Fatores de Tempo , Poluentes Químicos da Água/química
18.
Stroke ; 49(1): 184-192, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29212744

RESUMO

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is a devastating disease without effective treatment. As a key component of the innate immune system, the NOD-like receptor (NLR) family, NLRP3 (pyrin domain-containing protein 3) inflammasome, when activated after ICH, promotes neuroinflammation and brain edema. MCC950 is a potent, selective, small-molecule NLRP3 inhibitor that blocks NLRP3 activation at nanomolar concentrations. Here, we examined the effect of MCC950 on brain injury and inflammation in 2 models of ICH in mice. METHODS: In mice with ICH induced by injection of autologous blood or bacterial collagenase, we determined the therapeutic potential of MCC950 and its mechanisms of neuroprotection. RESULTS: MCC950 reduced IL-1ß (interleukin-1ß) production and attenuated neurodeficits and perihematomal brain edema after ICH induction by injection of either autologous blood or collagenase. In mice with autologous blood-induced ICH, the protection of MCC950 was associated with reduced leukocyte infiltration into the brain and microglial production of IL-6. MCC950 improved blood-brain barrier integrity and diminished cell death. Notably, the protective effect of MCC950 was abolished in mice depleted of either microglia or Gr-1+ myeloid cells. CONCLUSIONS: These results indicate that the NLRP3 inflammasome inhibitor, MCC950, attenuates brain injury and inflammation after ICH. Hence, NLRP3 inflammasome inhibition is a potential therapy for ICH that warrants further investigation.


Assuntos
Lesões Encefálicas/tratamento farmacológico , Hemorragia Cerebral/tratamento farmacológico , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Animais , Lesões Encefálicas/etiologia , Lesões Encefálicas/metabolismo , Lesões Encefálicas/patologia , Hemorragia Cerebral/complicações , Hemorragia Cerebral/metabolismo , Hemorragia Cerebral/patologia , Feminino , Interleucina-1beta/metabolismo , Masculino , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo
19.
Metab Brain Dis ; 32(5): 1395-1402, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28303450

RESUMO

Traumatic brain injury (TBI) results in severe neurological impairments without effective treatments. Inflammation appears to be an important contributor to key pathogenic events such as secondary brain injury following TBI and therefore serves as a promising target for novel therapies. We have recently demonstrated the ability of a molecular construct comprised of the human leukocyte antigen (HLA)-DRα1 domain linked covalently to mouse (m)MOG-35-55 peptide (DRα1-MOG-35-55 construct) to reduce CNS inflammation and tissue injury in animal models of multiple sclerosis and ischemic stroke. The aim of the current study was to determine if DRα1-MOG-35-55 treatment of a fluid percussion injury (FPI) mouse model of TBI could reduce the lesion size and improve disease outcome measures. Neurodeficits, lesion size, and immune responses were determined to evaluate the therapeutic potential and mechanisms of neuroprotection induced by DRα1-MOG-35-55 treatment. The results demonstrated that daily injections of DRα1-MOG-35-55 given after FPI significantly reduced numbers of infiltrating CD74+ and CD86+ macrophages and increased numbers of CD206+ microglia in the brain concomitant with smaller lesion sizes and improvement in neurodeficits. Conversely, DRα1-MOG-35-55 treatment of TBI increased numbers of circulating CD11b+ monocytes and their expression of CD74 but had no detectable effect on cell numbers or marker expression in the spleen. These results demonstrate that DRα1-MOG-35-55 therapy can reduce CNS inflammation and significantly improve histological and clinical outcomes after TBI. Future studies will further examine the potential of DRα1-MOG-35-55 for treatment of TBI.


Assuntos
Lesões Encefálicas Traumáticas/tratamento farmacológico , Doenças do Sistema Nervoso/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Animais , Antígenos de Diferenciação de Linfócitos B/metabolismo , Encéfalo/patologia , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/patologia , Antígeno CD11b/metabolismo , Clonagem Molecular , Antígenos de Histocompatibilidade Classe II/metabolismo , Contagem de Leucócitos , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Doenças do Sistema Nervoso/etiologia , Fármacos Neuroprotetores/síntese química , Proteínas Recombinantes de Fusão/síntese química , Resultado do Tratamento
20.
Waste Manag Res ; 35(12): 1220-1225, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29090659

RESUMO

Significant quantities of bamboo waste are generated in Zhejiang province, China. Many small businesses in this area convert this waste to biochar for use as a cooking fuel (in residential barbecues). This case study was conducted to evaluate the potential economic benefits of building and operating an industrial-sized plant in this province, yielding 500 tonnes per year. The researchers developed a conceptual design for a hypothetical biochar plant and then calculated net present value (NPV), investment payback period (PBP), internal rate of return (IRR), and sensitivity analysis. Results show that the static investment PBP would be 2.58 years, the IRR would be 38.8%, and the NPV would be US$ 486,700. The IRR would be higher than the forestry industry benchmark (11%), indicating that a production line of bamboo-biochar with the stated yield not only could generate higher profits, but also could achieve a better return on investment. Thus, this study indicates that there are good market prospects for the bamboo-biochar industry in this region. The influence of sales prices on the IRR was more than that of operational costs, indicating that a large-scale plant should be designed to produce a high-quality bamboo-biochar. Supply chain issues such as transportation distances between locations where bamboo wastes are generated and the biochar plant should be considered in advance when siting new bamboo-biochar plants. The results from this research provide guidance to those considering development of bamboo-biochar plants in other parts of China.


Assuntos
Carvão Vegetal , Sasa , China , Gerenciamento de Resíduos
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