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1.
Molecules ; 29(7)2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38611812

RESUMEN

Antibiotic resistance has emerged as a grave threat to global public health, leading to an increasing number of treatment failures. Antimicrobial peptides (AMPs) are widely regarded as potential substitutes for traditional antibiotics since they are less likely to induce resistance when used. A novel AMP named Brevinin-1BW (FLPLLAGLAASFLPTIFCKISRKC) was obtained by the Research Center of Molecular Medicine of Yunnan Province from the skin of the Pelophylax nigromaculatus. Brevinia-1BW had effective inhibitory effects on Gram-positive bacteria, with a minimum inhibitory concentration (MIC) of 3.125 µg/mL against Enterococcus faecalis (ATCC 29212) and 6.25 µg/mL against both Staphylococcus aureus (ATCC 25923) and multidrug-resistant Staphylococcus aureus (ATCC 29213) but had weaker inhibitory effects on Gram-negative bacteria, with a MIC of ≥100 µg/mL. Studies using scanning electron microscopy (SEM) and flow cytometry have revealed that it exerts its antibacterial activity by disrupting bacterial membranes. Additionally, it possesses strong biofilm inhibitory and eradication activities as well as significant lipopolysaccharide (LPS)-binding activity. Furthermore, Brevinin-1BW has shown a significant anti-inflammatory effect in LPS-treated RAW264.7 cells. In conclusion, Brevinin-1BW is anticipated to be a promising clinical agent with potent anti-Gram-positive bacterial and anti-inflammatory properties.


Asunto(s)
Lipopolisacáridos , Staphylococcus aureus Resistente a Meticilina , China , Antibacterianos/farmacología , Antiinflamatorios/farmacología , Péptidos Antimicrobianos
2.
Artículo en Inglés | MEDLINE | ID: mdl-37883762

RESUMEN

Cerebral infarction is characterized by a high morbidity, disability, and fatality rate. This study explored the relationship between serum ß2 microglobulin (ß2-MG), HGF, lipoprotein-associated phospholipase A2 (Lp-PLA2) and carotid atherosclerosis in patients with hypertension combined with cerebral infarction and their prognostic value. A total of 320 patients with cerebral infarction complicated with hypertension who were hospitalized from January 2015 to January 2020 were collected. HGF, Lp-PLA2 and ß2-MG levels were detected. Plaque score (Crouse score) was the patient's cumulative plaque thickness measurements. Additionally, the maximum plaque thickness and the number of plaques were measured.. The correlation was found between high ß2-MG levels and the poor prognosis (HR: 1.29, 95% CI: 1.03-1.52, P = .022). Patients who had elevated levels of HGF were also less likely to have a positive outcome (HR: 1.38, 95% CI: 1.26-1.56, P = .015). High Lp-PLA2 levels were associated with a worse prognosis than low levels (HR: 1.74, 95% CI: 1.29-2.32, P = .015). In conclusion, the levels of ß2-MG, HGF, and Lp-PLA2 in patients with hypertension combined with cerebral infarction were substantially linked with carotid plaques.

3.
Int J Mol Sci ; 24(23)2023 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-38069041

RESUMEN

Gastrointestinal cancer is a common clinical malignant tumor disease that seriously endangers human health and lacks effective treatment methods. As part of the innate immune defense of many organisms, antimicrobial peptides not only have broad-spectrum antibacterial activity but also can specifically kill tumor cells. The positive charge of antimicrobial peptides under neutral conditions determines their high selectivity to tumor cells. In addition, antimicrobial peptides also have unique anticancer mechanisms, such as inducing apoptosis, autophagy, cell cycle arrest, membrane destruction, and inhibition of metastasis, which highlights the low drug resistance and high specificity of antimicrobial peptides. In this review, we summarize the related studies on antimicrobial peptides in the treatment of digestive tract tumors, mainly oral cancer, esophageal cancer, gastric cancer, liver cancer, pancreatic cancer, and colorectal cancer. This paper describes the therapeutic advantages of antimicrobial peptides due to their unique anticancer mechanisms. The length, net charge, and secondary structure of antimicrobial peptides can be modified by design or modification to further enhance their anticancer effects. In summary, as an emerging cancer treatment drug, antimicrobial peptides need to be further studied to realize their application in gastrointestinal cancer diseases.


Asunto(s)
Antineoplásicos , Neoplasias Gastrointestinales , Neoplasias Gástricas , Humanos , Péptidos Antimicrobianos , Péptidos Catiónicos Antimicrobianos/farmacología , Péptidos Catiónicos Antimicrobianos/uso terapéutico , Péptidos Catiónicos Antimicrobianos/química , Neoplasias Gastrointestinales/tratamiento farmacológico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Antineoplásicos/química , Neoplasias Gástricas/tratamiento farmacológico , Antibacterianos/farmacología
4.
J Environ Manage ; 255: 109859, 2020 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-32063319

RESUMEN

China's paper industry development is rapid, but the recycling rate of China's waste paper has been low all the time. Meanwhile, material flow analysis can help determine the flow of waste paper, and life cycle assessment (LCA) is the methodological framework for quantifying greenhouse gas emissions. Therefore, present study integrates these two methods into the model construction of China's waste paper recycling decision system. Present study constructs a benchmark model of China's waste paper recycling decision system in 2017, focusing on the impact of nonstandard waste paper recycling on the economic and environmental benefits of China's domestic waste paper recycling system. This model construction is followed by sensitivity analysis of the relevant parameters affecting the efficiency of the waste paper recycling system. Finally, present study forecasts the system's economic benefits and greenhouse gas (GHG) emissions in the context of integrating and regulating nonstandard recycling vendors. The results show that the economic benefit of China's waste paper recycling in 2017 is approximately 458.3 yuan/t and that the GHG emissions are 901.1 kgCO2eq. The standard recovery rate and nonstandard recovery acceptance rate will both have a significant impact on the system's economic benefits and improve the GHG emissions structure. In the context of integrating nonstandard recycling enterprises and individual recycling vendors, the economic benefits will rise to 3312.5 yuan/t in 2030, while GHG emissions will rise to 942.9 kgCO2eq. Present study can play a certain guiding role for policy makers in formulating waste paper recycling industry specifications and formulating relevant policies.


Asunto(s)
Gases de Efecto Invernadero , Reciclaje , China , Efecto Invernadero , Industrias
5.
Open Life Sci ; 19(1): 20220918, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39071491

RESUMEN

Pseudohypoparathyroidism (PHP) type 1a (PHP 1a) is a rare hereditary disorder characterized by target organ resistance to hormonal signaling and the Albright hereditary osteodystrophy (AHO) phenotype, which features round facial features, short fingers, subcutaneous calcifications, short stature, obesity, and intellectual disability. Progressive osseous heteroplasia (POH) is another rare disorder characterized by heterotopic ossification (HO) that progressively affects skin, subcutaneous tissues, and deep skeletal muscle. PHP 1a is inherited maternally due to a GNAS mutation, while pure POH is inherited paternally. This case study presented a Chinese boy with congenital hypothyroidism, tonic-clonic seizures, hypoparathyroidism, AHO, POH, and joint fixation deformity. Sequencing analysis of GNAS-Gsα revealed a heterozygous C.432+2T>C(P.?) variant (NM_000516.7) affecting the canonical splice donor site of intron 5 in the boy and his mother, indicating maternal inheritance of a GNAS mutation. The patient was diagnosed with POH overlap syndrome (POH/PHP 1a). Following calcium and calcitriol supplementation, he experienced a reduction in seizures, and surgery was performed to correct the joint fixation deformity caused by HO. This case report provided valuable insights into the genotype-phenotype correlations of POH overlap syndrome and underscored the significance of genetic testing in diagnosing rare diseases.

6.
Micromachines (Basel) ; 14(7)2023 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-37512731

RESUMEN

A high-precision current-mode bandgap reference (BGR) circuit with a high-order temperature compensation is presented in this paper. In order to achieve a high-precision BGR circuit, the equation of the nonlinear current has been modified and the high-order term of the current flowing into the nonlinear compensation bipolar junction transistor (NLCBJT) is compensated further. According to the modified equation, two solutions are designed to improve the output accuracy of BGR circuits. The first solution is to divide the NLCBJT branch into two branches to reduce the coefficient of the nonlinear temperature compensation current. The second solution is to inject the nonlinear current into the two branches based on the first one to further eliminate the temperature coefficient (TC) of the current flowing into the NLCBJT. The proposed BGR circuit has been designed using the Semiconductor Manufacturing International Corporation (SMIC) 55 nm CMOS process. The simulation results show that the variations in currents flowing into NLCBJTs improved from 148.41 nA to 69.35 nA and 7.4 nA, respectively, the TC of the output reference current of the proposed circuit is approximately 3.78 ppm/°C at a temperature range of -50 °C to 120 °C with a supply voltage of 3.3 V, the quiescent current consumption of the entire BGR circuit is 42.13 µA, and the size of the BGR layout is 0.044 mm2, leading to the development of a high-precision BGR circuit.

7.
J Gastroenterol Hepatol ; 27(5): 966-73, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-21913985

RESUMEN

BACKGROUND AND AIM: (Z)2-(5-(4-methoxybenzylidene)-2, 4-dioxothiazolidin-3-yl) acetic acid (MDA) is an aldose reductase (AR) inhibitor. Recent studies suggest that AR contributes to the pathogenesis of inflammation by affecting the nuclear factor κB (NF-κB)-dependent expression of cytokines and chemokines and therefore could be a novel therapeutic target for inflammatory pathology. The current study evaluated the in vivo role of MDA in protecting the liver against injury and fibrogenesis caused by CCl(4) in rats, and the underlying mechanisms. METHODS: A single injection of CCl(4) induced acute hepatitis, and repeated injections were used to induce hepatic fibrosis in rats. Therapeutic efficacy was assessed by comparison of the severity of hepatic injury and fibrosis in MDA-treated rats versus untreated controls. RESULTS: MDA significantly protected the liver from injury by reducing the activity of serum alanine aminotransferase, and improving the histological architecture of the liver. MDA modulated NF-κB-dependent activation of inflammatory cytokines by reducing hepatic mRNA levels of tumor necrosis factor-α, interleukin-1ß, inducible nitric oxide (NO) synthase and transforming growth factor-ß. In addition, MDA attenuated oxidative stress by increasing the content of hepatic glutathione. These favorable changes were associated with suppressed hepatic NF-κB activation by MDA. MDA treatment improved liver fibrosis in rats that received repeated CCl(4) injections. In vitro, MDA attenuated phosphorylation of IκB and activation of NF-κB, and thus prevented biosynthesis of NO in lipopolysaccharide-activated RAW264.7 cells. CONCLUSIONS: The present study suggests that AR is a novel therapeutic anti-inflammatory target for the treatment of hepatitis and liver fibrosis.


Asunto(s)
Aldehído Reductasa/antagonistas & inhibidores , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Inhibidores Enzimáticos/uso terapéutico , Cirrosis Hepática Experimental/metabolismo , Cirrosis Hepática Experimental/prevención & control , Tiazolidinedionas/uso terapéutico , Alanina Transaminasa/sangre , Animales , Tetracloruro de Carbono , Células Cultivadas , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Inhibidores Enzimáticos/farmacología , Glutatión/metabolismo , Proteínas I-kappa B/metabolismo , Interleucina-1beta/metabolismo , Hígado/metabolismo , Hígado/patología , Cirrosis Hepática Experimental/patología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , FN-kappa B/efectos de los fármacos , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Estrés Oxidativo/efectos de los fármacos , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Tiazolidinedionas/farmacología , Factor de Crecimiento Transformador beta/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
8.
Open Life Sci ; 17(1): 1519-1530, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36448063

RESUMEN

Ischemic stroke (IS), usually caused due to an abrupt blockage of an artery, is the leading cause of disability and the second leading cause of death worldwide. The association of the C-reactive protein (CRP) gene (s3093059 T/C and rs1205 C/T) polymorphisms and IS susceptibility has been widely studied, but the results remain inconsistent. Our study aimed to assess the association between CRP gene (s3093059 T/C and rs1205 C/T) polymorphisms and IS risk. PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, and WanFang databases were searched up to April 2022 to identify eligible studies. The Newcastle-Ottawa scale (NOS) score was calculated to assess study quality. The odd ratios (ORs) with a 95% confidence interval (CI) were calculated to assess the association between CRP gene (rs3093059 T/C and rs1205 C/T) polymorphisms and IS risk. Eighteen case-control studies with 6339 cases and 29580 controls were identified. We found that CRP (s3093059 T/C and rs1205 C/T) polymorphism was not significantly associated with the risk of IS in any genetic model (recessive model: OR 1.00, 95% CI 0.79-1.26; OR 1.06, 95% CI 0.90-1.25). When stratified analysis by country, genotype method, source of controls, and NOS score, still no statistically significant association was found. Our study indicated that the CRP (rs3093059 T/C and rs1205 C/T) polymorphisms were not associated with the susceptibility to IS.

9.
J Neurol ; 269(11): 5787-5797, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35829759

RESUMEN

Sarcopenia has an insidious start that can induce physical malfunction, raise the risk of falls, disability, and mortality in the old, severely impair the aged persons' quality of life and health. More and more studies have demonstrated that sarcopenia is linked to neurological diseases in recent years. This review examines the advancement of sarcopenia and neurological illnesses research.


Asunto(s)
Personas con Discapacidad , Enfermedades del Sistema Nervioso , Sarcopenia , Accidentes por Caídas , Anciano , Humanos , Enfermedades del Sistema Nervioso/complicaciones , Enfermedades del Sistema Nervioso/epidemiología , Enfermedades del Sistema Nervioso/terapia , Calidad de Vida , Sarcopenia/epidemiología , Sarcopenia/etiología , Sarcopenia/terapia
10.
Micromachines (Basel) ; 13(10)2022 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-36295947

RESUMEN

A novel output-capacitorless low-dropout regulator (OCL-LDO) with an embedded slew-rate-enhancement (SRE) circuit is presented in this paper. The SRE circuit adopts a transient current-boost strategy to improve the slew rate at the gate of the power transistor when a large voltage spike at the output is detected. In addition, a feed-forward transconductance cell is introduced to form a push−pull output structure with the power transistor. The simulation results show that the maximum transient output voltage variation is 23.5 mV when the load current ILOAD is stepped from 0 to 100 mA in 100 ns with a load capacitance of 100 pF, and the settling time is 1.2 µs. The proposed OCL-LDO consumes a quiescent current of 30 µA and has a dropout voltage of 200 mV for the maximum output current of 100 mA.

11.
Micromachines (Basel) ; 13(10)2022 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-36296021

RESUMEN

A fully integrated low-dropout (LDO) regulator with improved load regulation and transient responses in 40 nm technology is presented in this paper. Combining adjustable threshold push-pull stage (ATPS) and master-slave power transistors topology, the proposed LDO maintains a three-stage structure within the full load range. The proposed structure ensures the steady-state performance of LDO and achieves 0.017 mV/mA load regulation. The ATPS consumes little quiescent current at light load current condition, and the turn-on threshold of the ATPS can be adjusted by a current source. Once the value of current source is set, the turn-on threshold is also determined. A benefit of the proposed structure is that the LDO can be stable from 0 to 100 mA load current with a maximum 100 pF parasitic load capacitance and a 0.7 pF compensation capacitor. It also shows good figure of merit (FOM) without an extra transient enhanced circuit. For the maximum 100 mA load transient with 100 ns edge time, the undershoot and overshoot are less than 33 mV. The dropout voltage of the regulator is 200 mV with input voltage of 1.1 V. The total current consumption of the LDO was 24.6 µA at no load.

12.
Front Bioeng Biotechnol ; 10: 977159, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36425652

RESUMEN

Background and Purpose: Chronic wound infections and the development of antibiotic resistance are serious clinical problems that affect millions of people worldwide. Cathelicidin-DM, an antimicrobial peptide from Duttaphrynus melanostictus, has powerful antimicrobial activity and wound healing efficacy. So, it could be a potential candidate to address this problem. In this paper, we investigate the wound healing mechanism of cathelicidin-DM to establish a basis for preclinical studies of the drug. Experimental Approach: The effects of cathelicidin-DM on cell proliferation and migration, cytokines, and mitogen-activated protein kinase (MAPK) signaling pathways were examined. Then mice whole skin wound model was constructed to evaluate the wound healing activity of cathelicidin-DM, and further histological changes in the wounds were assessed by hematoxylin-eosin staining (H&E) and immunohistochemical assays. Key Results: Cathelicidin-DM promotes the proliferation of HaCaT, HSF, and HUVEC cells in a concentration-dependent manner and the migration of HSF, HUVEC, and RAW.264.7 cells. Moreover,cathelicidin-DM can involve in wound healing through activation of the MAPK signaling pathway by upregulating phosphorylation of ERK, JNK, and P38. However, cathelicidin-DM didn't affect the secretion of IL-6 and TNF-α. At the animal level, cathelicidin-DM accelerated skin wound healing and early debridement in mice as well as promoted re-epithelialization and granulation tissue formation, α-SMA expression, and collagen I deposition in mice. Conclusion and Implications: Our data suggest that cathelicidin-DM can be engaged in the healing of infected and non-infected wounds through multiple pathways, providing a new strategy for the treatment of infected chronic wounds.

13.
Biol Pharm Bull ; 34(2): 219-25, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21415531

RESUMEN

Idiopathic pulmonary fibrosis is regarded as a lethal chronic disease accompanied with excessive collagen disposition. In the early stage, monocyte chemotactic protein-1 (MCP-1) plays a crucial role in the process. Our previously screening with a vitro assay through inhibition of chemotaxis of RAW264.7 cells stimulated by MCP-1 proved that several analogues of thiazolidinediones, especially (Z)-5-(4-methoxybenzylidene)thiazolidine-2,4-dione (SKLB010), had potency of protecting acute liver injury in vivo without obvious toxicity. The present study aimed to investigate the preventive effect of SKLB010 in bleomycin-induced pulmonary fibrosis and further explore the underlying mechanisms. Bleomycin (BLM) was injected intratracheally at a single dose of 5 U kg(-1) for pulmonary fibrosis induction. SKLB010 (25, 50 mg/kg/d) was respectively administrated by gavages 1 d prior to BLM administration and continued to the end of the study (for 4 weeks). Our results demonstrated that SKLB010 diminished the increase of macrophage, neutrophil and lymphocyte counts as well as the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, and IL-6 in bronchoalveolar lavage fluid on day 14 (p<0.05). Moreover, oral gavages of SKLB010 also ameliorated histological changes and significantly suppressed collagen deposition on day 28. The treatment with SKLB010 exerted approximately 34.6% the hydroxyproline content reduction for 25 mg/kg dose and 56.7% reduction for 50 mg/kg dose in contrast to bleomycin-induced group (p<0.05). Meanwhile, SKLB010 inhibited the overexpression of tumor growth factor (TGF)-ß1 and Smad3 in a dose-dependent manner. In conclusion, our results showed that SKLB010 could attenuate the BLM-induced pulmonary fibrosis in vivo and therefore be a promising anti-fibrogenic candidate.


Asunto(s)
Colágeno/metabolismo , Citocinas/metabolismo , Hidroxiprolina/metabolismo , Pulmón/efectos de los fármacos , Fibrosis Pulmonar/prevención & control , Tiazolidinedionas/uso terapéutico , Animales , Bleomicina , Líquido del Lavado Bronquioalveolar , Línea Celular , Relación Dosis-Respuesta a Droga , Pulmón/inmunología , Pulmón/metabolismo , Pulmón/patología , Linfocitos/metabolismo , Macrófagos/metabolismo , Ratones , Neutrófilos/metabolismo , Fibrosis Pulmonar/inmunología , Proteína smad3/metabolismo , Tiazolidinedionas/farmacología , Factor de Crecimiento Transformador beta1/metabolismo
14.
Dalton Trans ; 50(34): 11804-11813, 2021 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-34369502

RESUMEN

Two-phase Ca2+-doped LaVO4:Eu3+ nanocrystals were prepared through a hydrothermal method with the help of SOD CITR and EDTA surfactants. The phase and morphology of the products were characterized by XRD and TEM, and the fluorescence performances were also recorded. The results indicated that Ca2+ ions were doped into the LaVO4:Eu3+ host lattice, impeding the aggregation of the nanocrystals and enhancing the luminescence intensity. The morphology transformation process and luminescence enhancement were systematacially investigated. The fluorescence intensity of the two selected samples could be completely quenched by Fe3+ ions without the disturbance of other ions, with the mechanism being due to the adsorption of Fe3+ ions onto the grains and a subsequent energy transfer from Eu3+ to Fe3+. Therefore, the present two Ca2+-doped LaVO4:Eu3+ samples can be applied as appropriate candidates for detecting Fe3+ ions with agility and sensitivity in aqueous solution.

15.
Biochem Biophys Res Commun ; 397(2): 311-7, 2010 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-20510675

RESUMEN

Phosphoinositide 3-kinase-gamma (PI3Kgamma) has been identified to play the critical roles in inflammatory cells activation and recruitment in multiply inflammatory diseases and it promised to be a prospective target for relevant inflammatory diseases therapy. AS605240, a selective PI3Kgamma inhibitor, has been proved effective on several inflammatory diseases. In this study, we investigated the protective effect of AS605240 on bleomycin-induced pulmonary fibrosis in rats. Our results showed that orally administration of AS605240 significantly prevented lung inflammation and reduced collagen deposition. AS605240 also inhibited augmented expression of TNF-alpha and IL-1beta induced by bleomycin instillation. Moreover, the mRNA levels of TNF-alpha and IL-1beta in lung were remarkably suppressed. Histological assessment found that AS605240 reduced the expression of TGF-beta(1) and prevented T lymphocytes infiltration to lung. Phospho-Akt level in inflammatory cells by blocking PI3Kgamma was down-regulated and the inhibition of Akt phosphorylation was further confirmed by Western blot. Our findings illustrated that AS605240 was effective for preventing pulmonary fibrosis by suppressing inflammatory cells recruitment and production of inflammatory cytokines. These findings also suggest that PI3Kgamma may be a useful target in treating inflammation diseases and AS605240 may represent a promising novel agent for the future therapy of pulmonary fibrosis.


Asunto(s)
Inhibidores Enzimáticos/administración & dosificación , Inhibidores de las Quinasa Fosfoinosítidos-3 , Fibrosis Pulmonar/prevención & control , Quinoxalinas/administración & dosificación , Tiazolidinedionas/administración & dosificación , Animales , Bleomicina/toxicidad , Femenino , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/patología , Ratas , Ratas Sprague-Dawley
16.
J Pharmacol Exp Ther ; 332(1): 46-56, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19828878

RESUMEN

The critical role of phosphoinositide 3-kinase gamma (PI3Kgamma) in inflammatory cell activation and recruitment makes it an attractive target for immunomodulatory therapy. 5-Quinoxilin-6-methylene-1,3-thiazolidine-2,4-dione (AS605240), a potent PI3Kgamma inhibitor, has been reported to ameliorate chronic inflammatory disorders including rheumatoid arthritis, systemic lupus erythematosus, and atherosclerosis. However, its in vivo effect on intestinal inflammation remains unknown. Here we evaluated the protective and therapeutic potentials of AS605240 in mice with dextran sodium sulfate (DSS)-induced acute and chronic colitis. Our results showed that AS605240 improved survival rate, disease activity index, and histological damage score in mice administered DSS in both preventive and therapeutic studies. AS605240 treatment also significantly inhibited the increase in myeloperoxidase levels, macrophage infiltration, and CD4(+) T-cell number in the colon of DSS-fed mice. The DSS-induced overproduction of colonic proinflammatory cytokines including interleukin (IL)-1beta, tumor necrosis factor-alpha, and interferon-gamma was significantly suppressed in mice undergoing AS605240 therapy, whereas colonic anti-inflammatory cytokines such as IL-4 were up-regulated. The down-regulation of the phospho-Akt level in immunological cells from the inflamed colon tissue and spleen of AS605240-treated mice was detected both by immunohistochemical analysis and Western blotting. These findings demonstrate that AS605240 may represent a promising novel agent for the treatment of inflammatory bowel disease by suppressing leukocyte infiltration as well as by immunoregulating the imbalance between proinflammatory and anti-inflammatory cytokines.


Asunto(s)
Colitis/prevención & control , Inhibidores Enzimáticos/uso terapéutico , Inhibidores de las Quinasa Fosfoinosítidos-3 , Quinoxalinas/uso terapéutico , Tiazolidinedionas/uso terapéutico , Enfermedad Aguda , Animales , Western Blotting , Recuento de Linfocito CD4 , Linfocitos T CD4-Positivos/citología , Enfermedad Crónica , Colitis/inducido químicamente , Colitis/enzimología , Colitis/inmunología , Colitis/patología , Colon/efectos de los fármacos , Colon/enzimología , Colon/inmunología , Colon/patología , Citocinas/biosíntesis , Citocinas/inmunología , Sulfato de Dextran , Modelos Animales de Enfermedad , Inhibidores Enzimáticos/administración & dosificación , Inhibidores Enzimáticos/farmacología , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Inmunohistoquímica , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/enzimología , Mucosa Intestinal/inmunología , Mucosa Intestinal/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Tamaño de los Órganos , Quinoxalinas/administración & dosificación , Quinoxalinas/farmacología , Índice de Severidad de la Enfermedad , Bazo/efectos de los fármacos , Bazo/inmunología , Tiazolidinedionas/administración & dosificación , Tiazolidinedionas/farmacología
17.
Waste Manag ; 117: 81-92, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32818811

RESUMEN

China's automobile industry is developing rapidly, but the recycling rate of end-of-life vehicles has been low. In 2018, the recovery rate of end-of-life passenger vehicles was less than 18% of the scrapped amount. Dynamic material flow analysis can predict the amount of end-of-life passenger cars in China in the future, and analyze the flow of materials in recycling system. Life cycle assessment can be used to quantify greenhouse gas emissions. Therefore, this paper integrates these two methods into the model construction of recycling decision system. Meanwhile, sensitivity analysis of the important factors affecting the efficiency of the recovery system is carried out. Finally, the main recovery indexes of the system are predicted under three scenarios: low-speed, medium speed and high-speed development, which are set based on scrap volume, standard recovery rate, proportion of assembly into remanufacturing and carbon tax price. The research results show that in 2018, 656.9 kg/vehicle of iron, 150.2 kg/vehicle of aluminum and 7.9 kg/vehicle of copper are recovered from end-of-life passenger car in China, and the carbon emission during the recovery process is 651.1 kg of CO2eq/vehicle, with a total emission reduction of 3816.1 kgCO2eq/vehicle compared with the original production, and the economic benefit is about 5055.5 yuan/vehicle. The scenario prediction results show that by 2050, from the low-speed development scenario to the high-speed development scenario, the total amount of iron, aluminum and copper recovered rise from 3.96 million tons, 915 thousand tons and 46 thousand tons to 697 thousand tons, 1.61 million tons and 80 thousand tons respectively throughout the year. The carbon emission in the recovery process rise from 4.98 thousand tons to 9.32 million tons. Compared with the original production, the carbon emission reduction increases from 2.21 million tons to 38.3 million tons, the economic benefit increases from 58.9 billion yuan to 118.8 billion yuan, and the comprehensive benefit increases from 57 billion yuan to 111.6 billion yuan.


Asunto(s)
Gases de Efecto Invernadero , Reciclaje , Automóviles , China , Industrias
18.
Biochem Biophys Res Commun ; 386(4): 569-74, 2009 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-19538942

RESUMEN

A pivotal role of phosphoinositide 3-kinase-gamma (PI3Kgamma) in inflammatory cell activation and recruitment makes it an attractive target for immunomodulatory therapy. In present study we investigated the therapeutic efficiency of AS605240, a selective PI3Kgamma inhibitor, on hepatitis and liver fibrosis in murine models induced by concanavalin A (ConA). Orally administration of AS605240 significantly improved survival, decreased the serum levels of alanine aminotransaminase (ALT), prevented inflammatory infiltration to liver in ConA-induced hepatitis. TNF-alpha and IFN-gamma at protein levels in serum and mRNA levels in liver were markedly reduced. Downregulated phospho-Akt level of inflammatory cells infiltrating the liver by AS605240 treatment was detected by immunohistochemistry analysis in liver and further confirmed by Western blotting analysis in splenocytes. In ConA-induced chronic liver fibrosis model, accumulation of smooth-muscle actin (SMA)-expressing cells was partially inhibited by AS605240 treatment. These observations suggest that AS605240 might be of therapeutic value for the treatment of ConA-induced hepatic injury.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Inhibidores Enzimáticos/uso terapéutico , Hígado/enzimología , Inhibidores de las Quinasa Fosfoinosítidos-3 , Quinoxalinas/uso terapéutico , Tiazolidinedionas/uso terapéutico , Enfermedad Aguda , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/complicaciones , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Fosfatidilinositol 3-Quinasa Clase Ib , Concanavalina A/toxicidad , Citocinas/biosíntesis , Isoenzimas/antagonistas & inhibidores , Hígado/efectos de los fármacos , Hígado/patología , Cirrosis Hepática/etiología , Cirrosis Hepática/patología , Cirrosis Hepática/prevención & control , Ratones , Mitógenos/toxicidad , Fosforilación/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo
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