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1.
Heliyon ; 10(9): e30373, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38765108

RESUMO

In the vanguard of oncological advancement, this investigation delineates the integration of deep learning paradigms to refine the screening process for Anticancer Peptides (ACPs), epitomizing a new frontier in broad-spectrum oncolytic therapeutics renowned for their targeted antitumor efficacy and specificity. Conventional methodologies for ACP identification are marred by prohibitive time and financial exigencies, representing a formidable impediment to the evolution of precision oncology. In response, our research heralds the development of a groundbreaking screening apparatus that marries Natural Language Processing (NLP) with the Pseudo Amino Acid Composition (PseAAC) technique, thereby inaugurating a comprehensive ACP compendium for the extraction of quintessential primary and secondary structural attributes. This innovative methodological approach is augmented by an optimized BERT model, meticulously calibrated for ACP detection, which conspicuously surpasses existing BERT variants and traditional machine learning algorithms in both accuracy and selectivity. Subjected to rigorous validation via five-fold cross-validation and external assessment, our model exhibited exemplary performance, boasting an average Area Under the Curve (AUC) of 0.9726 and an F1 score of 0.9385, with external validation further affirming its prowess (AUC of 0.9848 and F1 of 0.9371). These findings vividly underscore the method's unparalleled efficacy and prospective utility in the precise identification and prognostication of ACPs, significantly ameliorating the financial and temporal burdens traditionally associated with ACP research and development. Ergo, this pioneering screening paradigm promises to catalyze the discovery and clinical application of ACPs, constituting a seminal stride towards the realization of more efficacious and economically viable precision oncology interventions.

2.
J Chromatogr A ; 1713: 464523, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38041974

RESUMO

Protein A affinity chromatography is widely used as a capture step for monoclonal antibodies (mAb) and molecules that possess an Fc-domain, such as fusion proteins and bispecific antibodies. However, the use of low pH (3.0-4.0) to elute the molecule and achieve acceptable yield (>85 %) can lead to product degradation (e.g. fragmentation, aggregation) for molecules sensitive to low pH. In this paper, we describe a comprehensive evaluation of two protein A resins with ligands designed to elute at a milder pH as a result of modified sequences in their Fc and VH3 binding regions. One of the evaluated resins has been made commercially available by Purolite and named Praesto Jetted A50 HipH. Results demonstrated that Jetted A50 HipH could elute the Fc-fusion protein and most mAbs evaluated with an elution pH at or above 4.6. Elution and wash optimization determined run conditions for high recovery (>90 % monomer yield), reduction of high molecular weight (HMW) species (>50 %), and significant host cell protein (HCP) clearance at the mildest elution pH possible. For a pH-stable mAb and a pH-sensitive fusion protein, cell culture material was purified with optimized conditions and demonstrated the mild elution pH resins' ability to purify product with acceptable yield, comparable or better impurity clearance, and significantly milder native eluate pH compared to traditional resins. The benefits of the mild elution pH resins were clearly exemplified for the pH-sensitive protein, where a milder elution buffer and native eluate pH resulted in only 2 % HMW in the eluate that remained stable over 48 h. In contrast, a traditional protein A resin requiring low pH elution led to eluate HMW levels of 8 %, which increased to 16 % over the same hold time. Additionally, these resins have high dynamic binding capacity and allow the use of traditional HCP washes. Therefore, Jetted A50 HipH is an ideal candidate for a platform protein A resin and provides flexibility for pH-sensitive proteins and stable mAbs, while preserving product quality, recovery, and seamless integration into a downstream process.


Assuntos
Anticorpos Biespecíficos , Proteína Estafilocócica A , Cricetinae , Animais , Proteína Estafilocócica A/química , Anticorpos Monoclonais/química , Técnicas de Cultura de Células , Concentração de Íons de Hidrogênio , Cromatografia de Afinidade/métodos , Células CHO
3.
Toxics ; 11(12)2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-38133398

RESUMO

With rapid economic development, soil heavy metal (HM) pollution has emerged as a global environmental concern. Because the toxicity of HMs differs dramatically among various fractions, risk assessments based on these fractions are of great significance for environmental management. This study employed a modified Hakanson index approach to evaluate the possible ecological impacts of soil HMs in a gold mine tailings pond in Shaanxi Province, China. A modified Hakanson-Monte Carlo model was built to perform a probabilistic risk assessment. The results showed that: (1) the exceedance rates of chromium (Cr) and zinc (Zn) were 68.75% and 93.75%, respectively. Moreover, the overall concentrations of nickel (Ni), copper (Cu), arsenic (As), and lead (Pb) were higher than the background soil environmental values in China. (2) HMs with the lowest oxidizable fraction were mostly present in the residual fraction. The oxidizable portions of Cr, Cu, and Pb and the reducible and residual fractions of As were notably distinct. (3) The risk degrees of Cr, Ni, Cu, and Zn were low; those of As and Pb were very high and moderate; and the comprehensive ecological hazard index was very high. This study offers a solid scientific foundation for ecological risk notification and environmental management.

4.
Toxics ; 11(12)2023 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-38133426

RESUMO

Arsenic (As) contamination of gold mine tailings poses major threats to the natural environment and human health, necessitating adequate management measures. To investigate the soil As contamination level and the potential of pioneer plants for As remediation, the soil and plants of an abandoned gold mine tailings in the Qinling Mountains were analyzed. The level of As contamination was assessed using the single-factor pollution index and potential ecological risk index, and its bioeffectiveness was analyzed. The enrichment capability of plants was investigated using the bioaccumulation factor and translocation factor. Redundancy analysis and partial least squares regression were employed to investigate factors affecting the distribution of As in soil and plants. The results show that As in soil mainly existed in the difficult-available state, with serious contamination and extremely high ecological risk. Lythrum salicaria L. and Equisetum ramosissimum Desf. are the preferred plants for remediation of As contamination through screening pioneer plants. Soil total nitrogen (STN) and available phosphorus (SAP) are the main factors influencing the characteristics of As distribution in the soil. Soil available potassium (SAK), water content (SWC), and SAP promote the accumulation of As by plants. This study provides plant materials and new ideas for mine ecological remediation.

5.
Toxics ; 10(7)2022 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-35878290

RESUMO

Soil-heavy metal pollution in mining areas is one of the problems in the comprehensive treatment of soil environmental pollution. To explore the degree of soil-heavy metal pollution and the human health risk in mining areas, the contents of soil As, Cd, Cu, Cr, Hg, Ni, Pb, and Cr(VI) in an abandoned gold mining area were determined. The geoaccumulation index (Igeo), single-factor pollution index (SPI), Nemerow comprehensive pollution index (NCPI), potential ecological risk index (PERI), and the human health risk assessment model were used to assess the pollution degree and the risk of soil-heavy metal pollution. Finally, the assessment results were used to provide remediation guidance. The results showed that (1) the average contents of As, Cd, Cr, Cu, Hg, and Ni in the mining area exceeded the background values of the soil elements. (2) The mining area was polluted by heavy metals to different degrees and had strong potential ecological hazards. (3) The total carcinogenic risk of heavy metals exceeded the health risk standard. The main components of pollution in the mining area were As, Cd, Cr, and Hg. Results from this study are expected to play a positive role in pollution treatment and the balance between humans and ecology.

6.
Int J Infect Dis ; 122: 921-929, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35908723

RESUMO

OBJECTIVES: This study aimed to evaluate the clinical value of metagenomic next-generation sequencing (mNGS) in patients with suspected lower respiratory tract infections. METHODS: This retrospective study reviewed patients with suspected lower respiratory tract infections at the Wuhan Union Hospital. Data including demographic, laboratory, and radiological profiles; treatment; and outcomes were recorded and analyzed. RESULTS: mNGS identified pathogenic microbes in 100/140 (71.4%) patients, although 135 (96.4%) had received empiric antibiotic treatment before the mNGS tests. Single bacterial infection (35/100, 35%) was the most common type of infection in patients with positive mNGS results, followed by single fungal infection (14/100, 14%), bacterial-viral coinfection (14/100, 14%), single viral infection (12/100, 12%), bacterial-fungal coinfection (9/100, 9%), fungal-viral coinfection (9/100, 9%), and bacterial-fungal-viral coinfection (7/100, 7%). Moreover, compared with culture test, mNGS showed higher sensitivity (63/85, 74.1% vs 22/85, 25.9% P = 0.001) and lower processing time (24 hours vs 48 hours). Antibiotic treatment was adjusted or confirmed based on the mNGS results in 123 (87.9%) patients, including five (3.6%), 33 (23.6%), and 85 (60.7%) patients, in whom treatment was downgraded, upgraded, and unchanged, respectively. Almost all patients, regardless of escalation, de-escalation, or no change in treatment, showed significant improvement in clinical symptoms and inflammatory indicators. In addition, 17 (12.1%) patients were referred to Wuhan Pulmonary Hospital for further treatment because of confirmed or suspected tuberculosis. CONCLUSION: mNGS could be a promising technique for microbiological diagnosis and antibiotic management, potentially improving outcomes for patients.


Assuntos
Coinfecção , Infecções Respiratórias , Antibacterianos/uso terapêutico , Coinfecção/diagnóstico , Coinfecção/tratamento farmacológico , Coinfecção/microbiologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Metagenômica/métodos , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/tratamento farmacológico , Estudos Retrospectivos , Sensibilidade e Especificidade
9.
Nat Biomed Eng ; 4(1): 69-83, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31844155

RESUMO

Exosomes are attractive as nucleic-acid carriers because of their favourable pharmacokinetic and immunological properties and their ability to penetrate physiological barriers that are impermeable to synthetic drug-delivery vehicles. However, inserting exogenous nucleic acids, especially large messenger RNAs, into cell-secreted exosomes leads to low yields. Here we report a cellular-nanoporation method for the production of large quantities of exosomes containing therapeutic mRNAs and targeting peptides. We transfected various source cells with plasmid DNAs and stimulated the cells with a focal and transient electrical stimulus that promotes the release of exosomes carrying transcribed mRNAs and targeting peptides. Compared with bulk electroporation and other exosome-production strategies, cellular nanoporation produced up to 50-fold more exosomes and a more than 103-fold increase in exosomal mRNA transcripts, even from cells with low basal levels of exosome secretion. In orthotopic phosphatase and tensin homologue (PTEN)-deficient glioma mouse models, mRNA-containing exosomes restored tumour-suppressor function, enhanced inhibition of tumour growth and increased survival. Cellular nanoporation may enable the use of exosomes as a universal nucleic-acid carrier for applications requiring transcriptional manipulation.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Eletroporação/métodos , Exossomos/metabolismo , Glioma/tratamento farmacológico , RNA Mensageiro/uso terapêutico , Animais , Células Cultivadas , Modelos Animais de Doenças , Células HEK293 , Humanos , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , MicroRNAs/uso terapêutico , Nanotecnologia , RNA Mensageiro/metabolismo , Transdução de Sinais
10.
Toxicol Sci ; 174(1): 133-146, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31879758

RESUMO

Chemical warfare nerve agents (CWNAs) present a global threat to both military and civilian populations. The acute toxicity of CWNAs stems from their ability to effectively inhibit acetylcholinesterase (AChE). This inhibition can lead to uncontrolled cholinergic cellular signaling, resulting in cholinergic crisis and, ultimately, death. Although the current FDA-approved standard of care is moderately effective when administered early, development of novel treatment strategies is necessary. Butyrylcholinesterase (BChE) is an enzyme which displays a high degree of structural homology to AChE. Unlike AChE, the roles of BChE are uncertain and possibilities are still being explored. However, BChE appears to primarily serve as a bioscavenger of toxic esters due to its ability to accommodate a wide variety of substrates within its active site. Like AChE, BChE is also readily inhibited by CWNAs. Due to its high affinity for binding CWNAs, and that null-BChE yields no apparent health effects, exogenous BChE has been explored as a candidate therapeutic for CWNA intoxication. Despite years of research, minimal strides have been made to develop a catalytic bioscavenger. Furthermore, BChE is only in early clinical trials as a stoichiometric bioscavenger of CWNAs, and large quantities must be administered to treat CWNA toxicity. Here, we describe previously unidentified mutations to residues within and adjacent to the acyl binding pocket (positions 282-285 were mutagenized from YGTP to NHML) of BChE that confer catalytic degradation of the CWNA, sarin. These mutations, along with corresponding future efforts, may finally lead to a novel therapeutic to combat CWNA intoxication.


Assuntos
Butirilcolinesterase/metabolismo , Substâncias para a Guerra Química/metabolismo , Inibidores da Colinesterase/metabolismo , Sarina/metabolismo , Sítios de Ligação , Butirilcolinesterase/genética , Catálise , Células HEK293 , Humanos , Mutação , Ligação Proteica , Especificidade por Substrato
11.
Cent Eur J Immunol ; 44(3): 226-236, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31933533

RESUMO

INTRODUCTION: Recent studies suggested that sulfur dioxide (SO2) can be produced endogenously by pulmonary vessels and attenuate acute lung injury (ALI) with vasorelaxant effects. This study was conducted to determine whether SO2 can inhibit lung inflammation and relax pulmonary arteries via inhibition of the mitogen-activated protein kinase (MAPK) pathway. MATERIAL AND METHODS: Forty-eight adult male Sprague Dawley rats (250~300 g) were randomly divided into six treatment groups: control (n = 8), control + SO2 (n = 8), control + L-aspartic acid-ß-hydroxamate (HDX) (n = 8), LPS (n = 8), LPS + SO2 (n = 8) and LPS + HDX (n = 8). RESULTS: Six hours after LPS treatment, rats exhibited elevated pulmonary artery hypertension (PAH), marked pulmonary structure injury with elevated pulmonary myeloperoxidase (MPO) activity and increased expression of intercellular adhesion molecule 1 (ICAM-1) and CD11b, along with decreased pulmonary SO2 production and reduced pulmonary aspartate aminotransferase (AAT) activity. Pretreatment with SO2 saline solution significantly reduced, while HDX (AAT inhibitor) aggravated, the pathogenesis of LPS-induced ALI. Moreover, SO2 saline solution significantly down-regulated expression of Raf-1, MEK-1 and phosphorylated ERK (p-ERK). It also prevented pulmonary hypertension in association with an up-regulated SO2/AAT pathway. However, HDX advanced pulmonary hypertension and inflammatory responses in the lung were associated with a down-regulated SO2/AAT pathway. CONCLUSIONS: Our results suggest that SO2 markedly relieved inflammatory responses, in association with Raf-1, MEK-1 and p-ERK during ALI induced by LPS. The down-regulation of the SO2/AAT pathway may be involved in the mechanism(s) of LPS-induced lung injury.

12.
Polymers (Basel) ; 10(5)2018 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-30966502

RESUMO

Conventional column chromatography processes to purify recombinant proteins are associated with high production costs and slow volumetric throughput at both laboratory and large scale. Non-chromatographic purifications based on selective aggregating tags have the potential to reduce costs with acceptable protein yields. A significant drawback, however, is that current proteolytic approaches for post-purification tag removal after are expensive and non-scalable. To address this problem, we have developed two non-chromatographic purification strategies that use either the elastin-like polypeptide (ELP) tag or the ß-roll tag (BRT17) in combination with an engineered split intein for tag removal. The use of the split intein eliminates premature cleavage during expression and provides controlled cleavage under mild conditions after purification. These self-cleaving aggregating tags were used to efficiently purify ß-lactamase (ß-lac), super-folder green fluorescent protein (sfGFP), streptokinase (SK) and maltose binding protein (MBP), resulting in increased yields compared to previous ELP and BRT17-based methods. Observed yields of purified targets for both systems typically ranged from approximately 200 to 300 micrograms per milliliter of cell culture, while overall recoveries ranged from 10 to 85 percent and were highly dependent on the target protein.

13.
Dalton Trans ; 46(34): 11250-11258, 2017 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-28799589

RESUMO

Novel two-dimensional (2D) metal-free few-layer BN/graphene-like g-C3N4 (2D BN/g-C3N4) composites have been synthesized by a simple hydrothermal method. The construction of a 2D/2D structure between BN and g-C3N4 could shorten the migration distance of charge transfer, and provide a large contact surface. By introducing few-layer BN nanosheets into g-C3N4, the as-prepared 2D BN/g-C3N4 composites exhibited a much enhanced photocatalytic performance than that of pure g-C3N4. The 0.5% 2D BN/g-C3N4 composite possessed the most wonderful ability towards Rhodamine B (RhB) degradation irradiated by visible light, which could achieve a highest degradation efficiency of 98.2% within 120 min. Further studies revealed that modifying g-C3N4 with few-layer BN could not only facilitate the separation and transfer of photo-induced holes and electrons, but also exposed the fact that the (002) facet edges of BN terminated with -OH groups could act as catalytic sites, and thus enhance the photocatalytic activities. Moreover, the successful preparation of 2D BN/g-C3N4 composites may pave the way for fabricating other 2D composites with a layer-by-layer architecture.

14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 24(3): 707-11, 2016 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-27342495

RESUMO

OBJECTIVE: To explore the diagnostic values of interleukin-12 (IL-12) and interferon-γ (IFN-γ) for the patients with acute leukemia (AL). METHODS: A total of 76 cases of AL were enrolled in this study, and the 40 healthy persons were used as control group. The levels of IL-12 and IFN-γ were determined by enzyme linked immunosorbent assay (ELISA). The results were analyzed. RESULTS: The levels of IL-12 and IFN-γ in the untreated AL group, ALL and ANLL groups were lower significantly than those in the control group (P<0.05), there was no significant difference between untreated AL and ANLL groups (P>0.05). The levels of IL-12 and IFN-γ in CR patients of AL group after treatment obviously higher than that of patients before treatment (P<0.05), but there was no significant difference as campared with that in control. The levels of IL-12 and IFN-γ in NR patients of AL group after treatment were obviously lower than that in control group (P<0.05), but there was no significant difference in comparision with patients before treatment (P>0.05). The levels of IL-12 and IFN-γ of AL-CR and AL-NR patients before treatment were not significant difference before treatment (P>0.05). The levels of IL-12 and IFN-γ of AL-CR patients obviously higher than that in AL-NR patients (P<0.05). According to immure classification, the levels of IL-12 and IFN-γ of patients in untreated group were not significant difference. In regard to the clinical risk degree, the level of IL-12 of patients in untreated group was not obvious difference (P>0.05), but the level of IFN-γ of patients in untreated group was obvious different (P<0.05). The level of IL-12 of patients in untreated group positively correlated with level of IFN-γ (r=0.735, P<0.05), but the level of IL-12 did not significantly correlated with the level of IFN-γ (r=0.292, P>0.05). CONCLUSION: The serum levels of both IL-12 and IFN-γ are lower, but the changes of both serum levels may be helpful to diagnose and treatment of AL patients.


Assuntos
Interferon gama/sangue , Interleucina-12/sangue , Leucemia/sangue , Doença Aguda , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Humanos , Interleucina-4/sangue , Leucemia/diagnóstico , Indução de Remissão
15.
Environ Sci Pollut Res Int ; 22(18): 14358-66, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26139394

RESUMO

A health risk assessment of food crops contaminated with heavy metals (Cu, Zn, Pb, As, Cd, and Cr) through the intake of cereals and vegetables grown from biogas slurry irrigated sites was conducted. In the vegetable soils and cereal soils, the concentrations of Zn, Pb, and Cd were far higher than Chinese agricultural standards. The pollution conditions of the aforementioned heavy metals varied with the seasons. Typically, the pollution was more serious in summer than in autumn. Furthermore, the accumulative properties of the heavy metals were different in the cereals and vegetables. In particular, Cu, Zn, and Pb tended to accumulate in rice with concentrations of 6.70, 36.58, and 4.14 mg kg(-1), respectively. Pb and Cd in cereals and vegetables exceeded the maximum permissible concentrations in China. The health risk assessment revealed that the daily intake (DI) and target hazard quotients (THQs) of Pb, As, and Cd in cereals and vegetables also exceeded the FAO/WHO limit. The results indicated that heavy metal contamination posed a severe health risk to local humans.


Assuntos
Produtos Agrícolas/química , Metais Pesados/química , Poluentes do Solo/química , Agricultura , Biocombustíveis , China , Humanos , Metais Pesados/análise , Medição de Risco , Estações do Ano , Solo/química , Poluentes do Solo/análise , Verduras
16.
Exp Mol Pathol ; 98(2): 268-76, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25746665

RESUMO

AIMS: Although hydrogen has been proved to be a novel therapeutic medical gas in several lung injury animal models, to our knowledge, it has not been tested yet in acute lung injury (ALI) induced by cecal ligation and puncture (CLP). This study was to investigate the hypothesis that hydrogen could ameliorate CLP-induced lung injury in rats. METHODS AND RESULTS: Our experiments exhibited that gas exchange dysfunction and lung tissue inflammation were observed in animals exposed to CLP. Hydrogen-rich saline treatment significantly attenuated lung injury as indicated by significantly improved gas exchange and histological changes in the lung and significantly reduced lung water content (LWC) and neutrophil infiltration 8h after CLP. Lipid peroxidation and DNA oxidation in the lung tissue were significantly reduced along with a decreased nitrotyrosine content and maintained superoxide dismutase activity in the presence of hydrogen, demonstrating antioxidant role of hydrogen in CLP-induced ALI. Importantly, hydrogen-rich saline treatment significantly inhibited the activation of p-p38 and NF-κB while suppressing the production of several proinflammatory mediators. CONCLUSIONS: This observation indicated that hydrogen-rich saline peritoneal injection improves histological and functional assessment in rat model of CLP-induced ALI. The therapeutic effects of hydrogen-rich saline may be related to antioxidant and anti-inflammatory actions.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Hidrogênio/farmacologia , Cloreto de Sódio/farmacologia , Animais , Ceco/cirurgia , DNA/metabolismo , Modelos Animais de Doenças , Ativação Enzimática/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Pulmão/patologia , Masculino , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Infiltração de Neutrófilos/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Punções , Ratos , Ratos Sprague-Dawley , Sepse , Superóxido Dismutase/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
17.
AIChE J ; 60(4): 1236-1244, 2014 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-25843955

RESUMO

Amyloidogenesis is the process of formation of protein aggregates with fibrillar morphology. Because amyloidogenesis is linked to neurodegenerative disease, there is interest in understanding the mechanism of fibril growth. Kinetic models of amyloidogenesis require data on the number concentration and size distribution of aggregates, but this information is difficult to obtain using conventional methods. Nanoparticle tracking analysis (NTA) is a relatively new technique that may be uniquely suited for obtaining these data. In NTA, the two-dimensional (2-D) trajectory of individual particles is tracked, from which the diffusion coefficient, and, hence, hydrodynamic radius is obtained. Here we examine the validity of NTA in tracking number concentration and size of DNA, as a model of a fibrillar macromolecule. We use NTA to examine three amyloidogenic materials: beta-amyloid, transthyretin, and polyglutamine-containing peptides. Our results are instructive in demonstrating the advantages and some limitations of single-particle diffusion measurements for investigating aggregation in protein systems.

18.
Sheng Li Xue Bao ; 64(6): 666-72, 2012 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-23258330

RESUMO

To investigate the influence of hydrogen sulfide (H2S) on p38 MAPK signaling pathway during acute lung injury (ALI) caused by lipopolysaccharide (LPS), the rats were randomly divided into six groups: control group, LPS group, LPS + NaHS group, LPS + PPG (cystathionine-γ-lyase inhibitor) group, NaHS group and PPG group. The rats were sacrificed 6 h after injection and lung tissues were obtained. The structure of lung tissues and the number of polymorphonuclear leucocyte (PMN) was observed under optical microscope; the lung myeloperoxidase (MPO) activity, superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were tested; intercellular adhesion molecule-1 (ICAM-1) protein expression changes were detected by immunohistochemical staining; phosphorylated p38 MAPK (p-p38 MAPK) protein expression was detected by Western blotting. The results showed that the lung injury in LPS group was observed, at the same time the MPO activity, the content of MDA, ICAM-1 and p-p38 MAPK protein expressions, the number of PMN were all higher than those in control group (all P < 0.05). Pre-injection of NaHS alleviated the changes induced by LPS, while pre-injection of PPG aggravated those alterations (all P < 0.05). ICAM-1 and p-p38 MAPK protein expressions in lung tissue were positively correlated (r = 0.923, P < 0.01). The results suggest that H2S may reduce LPS-induced ALI through inhibiting the conjugation of p38 MAPK and reducing the expression of ICAM-1.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Sulfeto de Hidrogênio/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Molécula 1 de Adesão Intercelular/metabolismo , Lipopolissacarídeos , Pulmão/metabolismo , Pulmão/patologia , Malondialdeído/farmacologia , Neutrófilos , Peroxidase/metabolismo , Fosforilação , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
19.
Acta Pharmacol Sin ; 33(8): 983-90, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22796764

RESUMO

AIM: We speculated that the enhanced apoptosis of polymorphonuclear neutrophil (PMN) might be responsible for the inhibition of PMN infiltration in the lung. This study was designed to investigate the effects of sulfur dioxide (SO(2)) on PMN apoptosis in vivo and in vitro, which may mediate the protective action of SO(2) on pulmonary diseases. METHODS: Acute lung injury (ALI) was induced by intratracheally instillation of lipopolysaccharide (LPS, 100 µg/100 g, in 200 µL saline) in adult male SD rats. SO(2) solution (25 µmol/kg) was administered intraperitoneally 30 min before LPS treatment. The rats were killed 6 h after LPS treatment. Lung tissues were collected for histopathologic study and SO(2) concentration assay. Bronchoalveolar lavage fluid (BALF) was collected for the measurement of PMN apoptosis. For in vitro experiments, rat peripheral blood PMNs were cultured and treated with LPS (30 mg/L) and SO(2) (10, 20 and 30 µmol/L) for 6 h, and apoptosis-related protein expression was detected by Western blotting, and apoptosis rate was measured with flow cytometry. RESULTS: LPS treatment significantly reduced the SO(2) concentrations in the lung tissue and peripheral blood, as compared with the control group. Pretreatment with SO(2) prevented LPS-induced reduction of the SO(2) concentration in the lung tissue and peripheral blood. LPS treatment significantly reduced PMN apoptosis both in vivo and in vitro, which could be prevented by the pretreatment with SO(2). The protein levels of Caspase-3 and Bax was significantly increased, but Bcl-2 was decreased by the pretreatment with SO(2), as compared with LPS administration alone. CONCLUSION: SO(2) plays an important role as the modulator of PMN apoptosis during LPS-induced ALI, which might be one of the mechanisms underlying the protective action of SO(2) on pulmonary diseases.


Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Apoptose/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Neutrófilos/efeitos dos fármacos , Dióxido de Enxofre/uso terapêutico , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/patologia , Animais , Apoptose/fisiologia , Masculino , Neutrófilos/patologia , Ratos , Ratos Sprague-Dawley , Dióxido de Enxofre/farmacologia
20.
Zhongguo Zhong Yao Za Zhi ; 37(2): 250-4, 2012 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-22737862

RESUMO

To explore the role of heme oxygenase (HO)-1 experimental system in dachengqitang (DD) ameliorating ALI induced by lipopolysaccharide (LPS) in mice. Seventy-five male Kunming mice were randomly divided into control group (normal saline was instilled intratracheally(50 microL/per mouse), LPS group (LPS was instilled intratracheally to replicate ALI model), DD + LPS group, DD + LPS + ZnPP (ZnPP, HO-1 specific inhibitor) group and the DD group. Mice were killed at 6 h after administration. Lung indexes were tested; lung histomorphological changes were observed under microscope, and neutrophils (PMN) number and protein content of bronchoalveolar lavage fluid (BALF) were measured; HO-1 mRNA and protein expression in lung tissue were detected by RT-PCR and Western blot. The results showed that intratracheal instillation of LPS in mice can cause significant morphological changes in lung tissue. Both PMN numbers and protein content in BALF were increased. meanwhile the expressions of HO-1 mRNA and protein in lung tissue were increased. Pretreated with DD and then intratracheally instillated LPS coulde ameliorat lung tissue injury, reduced PMN BALF number and protein content, but increase HO-1 mRNA and protein expression in the lung tissue when compared with LPS. HO-1 inhibitor ZnPP coulde inhibite the ameliorative effect of DD. The results suggest that the ameliorative effect of DD on ALI induced by LPS in mice were related with upregulation HO-1 mRNA and protein.


Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Heme Oxigenase-1/metabolismo , Pulmão/efeitos dos fármacos , Extratos Vegetais/farmacologia , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Western Blotting , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Heme Oxigenase-1/antagonistas & inibidores , Heme Oxigenase-1/genética , Contagem de Leucócitos , Lipopolissacarídeos , Pulmão/enzimologia , Pulmão/patologia , Masculino , Camundongos , Neutrófilos/citologia , Neutrófilos/efeitos dos fármacos , Fitoterapia/métodos , Proteínas/metabolismo , Protoporfirinas/farmacologia , Distribuição Aleatória , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Resultado do Tratamento
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