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As a type of emerging pollutant, organophosphate esters (OPEs) have the characteristics of toxicity, persistence, and bioaccumulation. Due to their wide use in production and life, OPEs pose potential risks to ecosystems when they enter the environment. In this study, the concentrations of 14 species of OPEs in surface water were determined using UPLC-MS/MS, and the spatial distribution of the OPEs in the surface water of the estuary of the Yellow River basin was further analyzed. The pollution sources were analyzed using correlation analysis and principal component analysis, and the ecological risk was evaluated. The results indicated that the concentration of Σ14OPEs in surface water ranged from 183.81 to 1674.52 ng·L-1, with an average concentration of 638.25 ng·L-1. Tris(2-chloroethyl) phosphate (TCEP) and tris(1-chloro-2-propanyl) phosphate (TCPP) were the main OPEs. The Xiaoqing River flowing through the urban area differed from the main stream of the Yellow River and other branches in terms of OPEs composition characteristics, which showed a greater impact from human activities. The distribution of Σ14OPEs showed an obvious regional pattern, with a trend of increasing and then decreasing along the direction of the Yellow River inlet. The results of source analysis revealed that human activities such as industrial wastewater discharge from different industries, transportation, and atmospheric deposition were the sources of OPEs in surface water. The ecological risk assessment results indicated that TCEP posed a high risk to aquatic organisms in the main stream of the Yellow River, Xiaoqing River, and Zhimai River, and tri-n-butyl phosphate (TnBP) and triphenyl phosphate (TPhP) posed a low risk at some sites.
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Human bone marrowderived mesenchymal stromal cells (hBMSCs) have been revealed to be beneficial for the regeneration of tissues and cells in several diseases. The present study aimed to elucidate the mechanisms underlying the effect of hBMSC transplantation on neuron regeneration in a rat model of middle cerebral artery occlusion (MCAO). The hBMSCs were isolated, cultured and identified. A rat model of MCAO was induced via the modified Longa method. Neurological severity scores (NSS) were adopted for the evaluation of neuronal function in the model rats after cell transplantation. Next, the expression levels of nestin, ßIIItubulin (ßIIITub), glial fibrillary acidic protein (GFAP), HNA and neuronal nuclear antigen (NeuN) were examined, as well as the positive expression rates of human neutrophil alloantigen (HNA), nestin, NeuN, ßIIITub and GFAP. The NSS, as well as the mRNA and protein expression of nestin, decreased at the 1st, 2nd, 4 and 8th weeks, while the mRNA and protein expression of NeuN, ßIIITub and GFAP increased with time. In addition, after treatment, the MCAO rats showed decreased NSS and mRNA and protein expression of nestin, but elevated mRNA and protein expression of NeuN, ßIIITub and GFAP at the 2nd, 4 and 8th weeks, and decreased positive expression of HNA and nestin with enhanced expression of NeuN, ßIIITub and GFAP. Therefore, the present findings demonstrated that hBMSC transplantation triggered the formation of nerve cells and enhanced neuronal function in a rat model of MCAO.
Assuntos
Células da Medula Óssea , Infarto da Artéria Cerebral Média , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Neurônios , Regeneração , Animais , Células da Medula Óssea/metabolismo , Células da Medula Óssea/patologia , Modelos Animais de Doenças , Xenoenxertos , Humanos , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , Infarto da Artéria Cerebral Média/fisiopatologia , Infarto da Artéria Cerebral Média/terapia , Masculino , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/patologia , Neurônios/metabolismo , Neurônios/patologia , Ratos , Ratos Sprague-DawleyRESUMO
Pulmonary adenoid cystic carcinoma is a rare and indolent lung malignancy, characterized by a protracted but unpredictable growth behavior. Currently, the treatment of PACC relies on surgery and local radiotherapy. However, treatment options for advanced PACC patients are limited. A larger number of studies demonstrated that advanced PACC patients obtained limited benefit from chemotherapy. Moreover, only a few case reports revealed PACC patients were candidates for target therapy. Therefore, there is an urgent need to develop novel therapies. Due to its rareness, its mutational landscape remains largely elusive. In this study, we performed capture-based ultra-deep sequencing on multiregional surgical specimens obtained from 8 PACC patients using a panel consisting of 295 cancer-related genes. Our data revealed distinctive mutational spectrum of PACC, which differed from non-small cell lung cancer and adenoid cystic carcinomas originated from other anatomical sites. PACC, lacking mutations in a majority of non-small cell lung cancer driver genes, has frequent mutations in genes participating in chromatin remodeling and NOTCH signaling pathway. We also elucidated spatial intra-tumoral heterogeneity, which varied among cases. Most mutations in chromatin remodelers were subclonal. Collectively, our findings elucidated molecular signature associated with PACC and highlighted the potential for epigenetic therapy in this disease.
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Biomarcadores Tumorais , Carcinoma Adenoide Cístico/genética , Evolução Clonal/genética , Heterogeneidade Genética , Neoplasias Pulmonares/genética , Mutação , Adulto , Carcinoma Adenoide Cístico/metabolismo , Carcinoma Adenoide Cístico/patologia , Montagem e Desmontagem da Cromatina , Análise Mutacional de DNA , Epigênese Genética , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Receptores Notch/metabolismo , Transdução de Sinais , Carga Tumoral , Adulto JovemRESUMO
PURPOSE:: To investigate the effect of chitosan oligosaccharides (COS) against osteoarthritis (OA) and preliminarily discuss the osteoprotegerin (OPG), receptor activator of NF-κB ligand (RANKL) and RANK expression in a rat OA model. METHODS:: Thirty-six 6-week-old Male SD rats were randomly divided into three groups: sham-operated group(CON), OA-induction group(OA), COS intervention group(n=12/group). At 4 weeks after the operation, COS (50 ul) intervention weekily for consecutive 5 weeks. The OA and CON groups received an injection of 50 ul physiological saline. At death, 11 weeks following surgery, cartilage was harvested and total RNA and protein were extracted. Both the morphological changes of the cartilage were observed and harvested the total RNA and protein. Meanwhile, the expression of OPG, RANKL and RANK in cartilage were determined. RESULTS:: The expression of OPG and RANKL were both enhanced in the cartilage of the OA model. Compared with the OA group, COS treatment improved the cartilage damage (both extent and grade). Furthermore, the COS group showed highly OPG and lower RANKL. Simultaneously, COS treatment upregulated the ratio of OPG/RANKL and downregulated the RANKL/RANK. CONCLUSION:: Chitosan oligosaccharides may be used as a unique biological agent to prevent and treat osteoarthritis, and this effect is associated with modulation of the expression of osteoprotegerin and receptor activator of NF-κB ligand.
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Cartilagem Articular/efeitos dos fármacos , Quitosana/farmacologia , Oligossacarídeos/farmacologia , Osteoartrite/metabolismo , Osteoprotegerina/metabolismo , Ligante RANK/metabolismo , Animais , Cartilagem Articular/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica , Masculino , Osteoprotegerina/efeitos dos fármacos , Ratos , Ratos Sprague-DawleyRESUMO
Abstract Purpose: To investigate the effect of chitosan oligosaccharides (COS) against osteoarthritis (OA) and preliminarily discuss the osteoprotegerin (OPG), receptor activator of NF-κB ligand (RANKL) and RANK expression in a rat OA model. Methods: Thirty-six 6-week-old Male SD rats were randomly divided into three groups: sham-operated group(CON), OA-induction group(OA), COS intervention group(n=12/group). At 4 weeks after the operation, COS (50 ul) intervention weekily for consecutive 5 weeks. The OA and CON groups received an injection of 50 ul physiological saline. At death, 11 weeks following surgery, cartilage was harvested and total RNA and protein were extracted. Both the morphological changes of the cartilage were observed and harvested the total RNA and protein. Meanwhile, the expression of OPG, RANKL and RANK in cartilage were determined. Results: The expression of OPG and RANKL were both enhanced in the cartilage of the OA model. Compared with the OA group, COS treatment improved the cartilage damage (both extent and grade). Furthermore, the COS group showed highly OPG and lower RANKL. Simultaneously, COS treatment upregulated the ratio of OPG/RANKL and downregulated the RANKL/RANK. Conclusion: Chitosan oligosaccharides may be used as a unique biological agent to prevent and treat osteoarthritis, and this effect is associated with modulation of the expression of osteoprotegerin and receptor activator of NF-κB ligand.
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Animais , Masculino , Ratos , Oligossacarídeos/farmacologia , Osteoartrite/metabolismo , Cartilagem Articular/efeitos dos fármacos , Quitosana/farmacologia , Ligante RANK/metabolismo , Osteoprotegerina/metabolismo , Cartilagem Articular/metabolismo , Regulação da Expressão Gênica , Ratos Sprague-Dawley , Modelos Animais de Doenças , Osteoprotegerina/efeitos dos fármacosRESUMO
The preventive and therapeutic effects of chitosan oligosaccharides (COS) on osteoarthritis (OA) have been rarely investigated. In this study, the protective effects of COS against IL-1ß-induced chondrocyte apoptosis were evaluated and the underlying mechanisms were elucidated. Results showed that COS not only inhibited cell apoptosis in a dose-dependent manner but also ameliorated IL-1ß-induced nuclear chromatin damage and mitochondrial membrane potential in chondrocytes. In IL-1ß-treated chondrocytes, COS downregulated the expression of Bax and caspase-3 but upregulated the expression of Bcl-2 by inhibiting the phosphorylated p38 mitogen-activated protein kinase (MAPK). COS inhibited the mRNA expression of inducible nitric oxide synthase (iNOS) and matrix metalloproteinase-13 (MMP-13) and enhanced the mRNA expression of the tissue inhibitor of metalloproteinase-1 (TIMP-1). These results suggested that COS effectively inhibits the IL-1ß-induced apoptosis of chondrocytes by activating the p38 MAPK signaling pathway. COS may also be used as a unique biological agent to prevent and treat OA.
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Apoptose/efeitos dos fármacos , Quitosana/farmacologia , Condrócitos/metabolismo , Interleucina-1beta/biossíntese , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Oligossacarídeos/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Metaloproteinase 13 da Matriz/biossíntese , Óxido Nítrico Sintase Tipo II/biossíntese , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Ratos , Ratos Sprague-Dawley , Inibidor Tecidual de Metaloproteinase-1/biossíntese , Proteína X Associada a bcl-2/biossínteseRESUMO
Chondrocyte apoptosis is an important mechanism involved in osteoarthritis (OA). Berberine (BBR), a plant alkaloid derived from Chinese medicine, is characterized by multiple pharmacological effects, such as anti-inflammatory and anti-apoptotic activities. This study aimed to evaluate the chondroprotective effect and underlying mechanisms of BBR on sodium nitroprusside (SNP)-stimulated chondrocyte apoptosis and surgically-induced rat OA model. The in vitro results revealed that BBR suppressed SNP-stimulated chondrocyte apoptosis as well as cytoskeletal remodeling, down-regulated expressions of inducible nitric oxide synthase (iNOS) and caspase-3, and up-regulated Bcl-2/Bax ratio and Type II collagen (Col II) at protein levels, which were accompanied by increased adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and decreased phosphorylation of p38 mitogen-activated protein kinase (MAPK). Furthermore, the anti-apoptotic effect of BBR was blocked by AMPK inhibitor Compound C (CC) and adenosine-9-ß-D-arabino-furanoside (Ara A), and enhanced by p38 MAPK inhibitor SB203580. In vivo experiment suggested that BBR ameliorated cartilage degeneration and exhibited an anti-apoptotic effect on articular cartilage in a rat OA model, as demonstrated by histological analyses, TUNEL assay and immunohistochemical analyses of caspase-3, Bcl-2 and Bax expressions. These findings suggest that BBR suppresses SNP-stimulated chondrocyte apoptosis and ameliorates cartilage degeneration via activating AMPK signaling and suppressing p38 MAPK activity.
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Proteínas Quinases Ativadas por AMP/metabolismo , Apoptose/efeitos dos fármacos , Berberina/farmacologia , Cartilagem Articular/metabolismo , Osteoartrite/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Alcaloides/farmacologia , Animais , Animais Recém-Nascidos , Proteínas Reguladoras de Apoptose/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Condrócitos/citologia , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Citoesqueleto/metabolismo , Modelos Animais de Doenças , Imidazóis/farmacologia , Articulação do Joelho/citologia , Masculino , Óxido Nítrico/metabolismo , Nitroprussiato/farmacologia , Fosforilação/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Piridinas/farmacologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Vidarabina/farmacologiaRESUMO
Berberine chloride (BBR) is an isoquinoline alkaloid that possesses promising protective efficacies against osteoarthritis (OA). Nevertheless, the therapeutic agent of this substance in OA is limited by its poor aqueous solubility, low bioavailability and short biological half-life. In this study, chitosan (CS)-based nanoparticles were prepared for the sustained release of BBR. Novel BBR-loaded chitosan nanoparticles (CNs) were successfully synthesized by the ionic cross-linking method. BBR-loaded CNs were spherical and homogeneous in shape. Moreover, they exhibited good stability and had ideal releasing profile in vitro. After intra-articular injection of BBR-loaded CNs, the level of BBR in rat plasma decreased and the retention time in synovial fluid increased compared with free BBR solution. In vivo evaluation of BBR-loaded CNs further showed higher anti-apoptosis activity in the treatment of OA compared with BBR solution at equivalent concentration. This result was evidenced by the changes of gross morphology and histological analyses in rat articular cartilage, TUNEL assay, quantitative real-time polymerase chain reaction, Western blot, and immunohistochemical analyses of caspase-3, Bcl-2 and Bax expressions. Given these results, BBR-loaded CNs are potential therapeutic agents for OA.
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Apoptose/efeitos dos fármacos , Berberina/farmacologia , Osteoartrite/tratamento farmacológico , Animais , Berberina/administração & dosagem , Berberina/farmacocinética , Cartilagem Articular/patologia , Quitosana/química , Condrócitos/efeitos dos fármacos , Reagentes de Ligações Cruzadas , Citocinas/biossíntese , Citocinas/genética , Estabilidade de Medicamentos , Injeções Intra-Articulares , Articulações/patologia , Masculino , Nanopartículas/química , Osteoartrite/patologia , Ratos , Ratos Sprague-Dawley , Líquido Sinovial/metabolismoRESUMO
OBJECTIVE: To evaluate the clinical therapeutic effects of anterior decompression on spinal osteoporotic fracture and inflammatory cytokines. METHODS: A total of 140 patients with spinal osteoporotic fracture were selected and randomly divided into a treatment group and a control group (n=70). The control group was treated by central corpectomy, and the control group was treated by anterior decompression. RESULTS: The rate of excellent and good outcomes in the treatment group was 94.3%, and that of the control group was 78.6%, which differed significantly (P<0.05). Cobb angle and cord occupancy in the spinal canal of both groups significantly decreased (P<0.05), while height ratio of the injured vertebral body significantly increased (P<0.05). Meanwhile, there were statistically significant inter-group differences (P<0.05). During the three-month follow-up period, the treatment group was significantly less prone to complications such as superficial infection, spinal instability and screw breakage compared with the control group (P<0.05). The postoperative serum MMP-3 and IL-6 levels of both groups significantly decreased compared with those before surgeries (P<0.05), with statistically significant inter-group differences (P<0.05). CONCLUSION: Compared with central corpectomy, anterior decompression exerted better effects on spinal osteoporotic fracture by improving the prognosis and stabilizing the spine safely, which may be associated with the effectively reduced serum MMP-3 and IL-6 levels.
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The protective and promotion effects of Carboxymethylated chitosan (CMCS) on peripheral nerve and cultured Schwann cells (SCs) have been demonstrated, but few studies discussed the protective roles of CMCS on SCs apoptosis. We explored the anti-apoptotic activities of CMCS in SCs to enhance cells survival in this present study. Rat SCs were isolated and cultured in vitro, hydrogen peroxide (H2O2) was used to establish the apoptosis models of SCs. Cells proliferative activity was assessed by CCK-8 assay. The apoptosis of SCs was detected by flow cytometry (FCM) analysis. Superoxide dismutase (SOD) and malondialdehyde (MDA) activities were detected by the corresponding assay kit. The nuclear appearance of apoptotic SCs was observed by nuclear staining with Hoechst 33342. The real-time PCR was performed to detect the levels of Bcl-2, Bax, Caspase-3 and -9 mRNA. Detection of caspase-3 and -9 was fulfilled by using Western blot analysis. FCM assay and Hoechst33342 staining results indicated that CMCS could protect SCs from apoptosis with dose and time-dependent manner. SOD and MDA analysis results indicated that CMCS could promote SOD activity and reduce the MDA levels in H2O2 induced SCs. The decreased caspase-3, -9 and Bax activities and increased Bcl-2 activity were observed in CMCS treated SCs. The present study indicates CMCS has the neuroprotective effect on peripheral nerves and inhibit SCs apoptosis.
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Quitosana/análogos & derivados , Quitosana/farmacologia , Fármacos Neuroprotetores/farmacologia , Células de Schwann/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Caspase 3/genética , Caspase 9/genética , Células Cultivadas , Peróxido de Hidrogênio , Malondialdeído/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Células de Schwann/metabolismo , Superóxido Dismutase/metabolismo , Proteína X Associada a bcl-2/genéticaRESUMO
Heat stress decreases natural immunity making cows more vulnerable to diseases. A previous study reported that daidzein can enhance animal resistance to heat stress and regulate animal immunocompetence. However, it is unclear whether daidzein regulates the immune performance of late lactation cows under heat stress. In this study, late lactation cows in four groups were raised in hot weather and fed with basic diet, basic diet plus 200, 300, 400 mg/day daidzein, respectively, and the experimental period was 60 days. Blood was collected to examine the changes of serum total protein (TP), albumin (ALB), immunoglobulin G (IgG), interferon alpha (IFN-α), and interleukin-2 (IL-2). We found the levels of serum IgG and INF-α were significantly higher in late lactation cows after 300 and 400 mg/day daidzein treatment compared to those in the control group and 200 mg/day daidzein treatment (P < 0.05 or P < 0.01). Moreover, 300 and 400 mg/day daidzein treatment markedly increased serum IL-2 (P < 0.01), while the levels of serum TP and ALB were not changed by any concentration of daidzein treatment (P > 0.05). Daidzein can enhance the immunocompetence of late lactation cows and strengthen cow resistance to heat stress.
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Bovinos/imunologia , Bovinos/fisiologia , Temperatura Alta/efeitos adversos , Imunidade Inata/efeitos dos fármacos , Imunidade Inata/imunologia , Imunocompetência/efeitos dos fármacos , Isoflavonas/administração & dosagem , Isoflavonas/farmacologia , Lactação/imunologia , Fitoestrógenos/administração & dosagem , Fitoestrógenos/farmacologia , Estresse Fisiológico/imunologia , Animais , Proteínas Sanguíneas/metabolismo , Relação Dose-Resposta a Droga , Feminino , Imunoglobulina G/sangue , Interferon-alfa/sangue , Interleucina-2/sangue , Albumina Sérica/metabolismo , Estimulação QuímicaRESUMO
OBJECTIVE: To explore the technique and therapeutic effect of bridge wire splint fixation with ankle dorsiflexion for the treatment of femoral shaft fractures in young children. Methods:From June 2006 to June 2012,45 young children with femoral shaft fractures were treated by bridge wire splint fixation with ankle dorsiflexion,which was designed according to arch bridge mechanical principle and structure. There were 31 males and 14 females with an average age of 3.2 years old ranging from 8 months to 5.5 years old; 14 cases were upper 1/3 femoral fractures,26 cases were middle 1/3 femoral fractures,5 cases were lower 1/3 femoral fractures; 20 cases were transverse fractures, 14 cases were oblique fractures,6 cases were spiral frac- tures, and 5 cases were comminuted fractures. X-ray, follow-up imaging changes,clinical curative effect and complications were assessed. RESULTS: Forty-five patients were followed up for 6 to 21 months (averaged 12 months). All fractures were reached clinical bone healing after 5 to 7 weeks (averaged 6 weeks) fixation. Seven cases appearred limb soft tissue complications, including buttocks bedsore,dorsal foot and Achilles tendon epidermal necrosis, and healed after dressing and removal of external fixation. During follow-up,the original overlap angle and lateral displacement were remodeled, and limbs were restored to the normal line of force and bone structure. According to Flynn standard, 35 cases got excellent results, 8 cases good, 2 cases fair. CONCLUSION: The bridge wire splint fixation with ankle dorsiflexion for the treatment of femoral. shaft fractures in young children (less than 6 years old) is safe,feasible, simple,and has raliable effect, which can be applied in primary hospitals.
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Fraturas do Fêmur/cirurgia , Fixação Intramedular de Fraturas , Tornozelo/cirurgia , Fios Ortopédicos , Criança , Pré-Escolar , Feminino , Fêmur/cirurgia , Seguimentos , Fixação Intramedular de Fraturas/instrumentação , Humanos , Lactente , Masculino , Resultado do TratamentoRESUMO
The proliferation of Schwann cells around injured peripheral nerves supports the process of Wallerian degeneration and is critical for axonal regeneration. In this publication, carboxymethylated chitosan (CMCS) was studied to determine its capacity (i) to induce proliferation and secretion of nerve growth factor (NGF) and (ii) to activate Wingless-type(Wnt) protein/ß-catenin signaling pathways in rat Schwann cells. CMCS was found to induce Schwann cell proliferation and NGF synthesis in Schwann cell in a dose and time dependent manner. CMCS was shown to activate factors in the Wnt/ß-catenin signaling pathway, including Dvl-1, ß-catenin, Tcf4, Lef1, C-myc, and Cyclin D1 which are active in the proliferation of Schwann cells and biosynthesis of NGF of Schwann cell. Overall, this study suggests that CMCS can promote the proliferation of cultured Schwann cells and synthesis of NGF by activating the Wnt/ß-catenin signaling pathway.
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Quitosana/análogos & derivados , Quitosana/farmacologia , Fator de Crescimento Neural/biossíntese , Células de Schwann/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Proliferação de Células/efeitos dos fármacos , Proteínas de Ligação a DNA/metabolismo , Proteínas Desgrenhadas , Fator 1 de Ligação ao Facilitador Linfoide/metabolismo , Fosfoproteínas/genética , Ratos , Ratos Sprague-Dawley , Células de Schwann/citologia , Células de Schwann/metabolismo , Fator de Transcrição 4 , Fatores de Transcrição/metabolismo , beta Catenina/metabolismoRESUMO
OBJECTIVE(S): Protein kinase C (PKCα) is involved in modulating articular chondrocytes apoptosis induced by nitric oxide (NO). Hyaluronic acid (HA) inhibits nitric oxide-induced apoptosis of articular chondrocytes by protecting PKCα, but the mechanism remains unclear. The present study was performed to investigate the effects and mechanisms of PKCα regulate protective effect of hyaluronic acid. Materials and Methods The ratio of apoptotic cell and cell viability was surveyed by PCNA and MTT assay. The expression of caspase-3 was determined by real-time PCR and western blot. RESULTS: It was showed that HA was able to reduce the nuclei fragment and PCNA expression, and NO-induced articular apoptosis blocked by HA, pretreated chondrocytes with PMA, HA significantly inhibits the activation of caspase-3 induced by NO, but pretrement with CHR, HA significantly incresed the expression of caspase-3. CONCLUSION: The results may be showed that PKCa regulate the expresion of caspase-3, which contribute to the apoptosis of chondrocytes induced by NO. PKC α agonists enhance the protective effect of hyaluronic acid on nitric oxide-induced articular chondrocytes apoptosis.
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OBJECTIVE: To investigate the effects of pyrroloquinoline quinine (PQQ) on proliferation and expression of c-fos, c-jun, CREB and PCNA in cultured Schwann cells. METHODS: Schwann cells were cultured and purified in vitro. The purity of Schwann cells was identified by immunofluorescence of S-100. After synchronization of cell cycle by serum-free medium, different concentration of PQQ (0,1, 10, 100, 1,000, 10,000 nmol/L) were added into culture medium for 72 h. Flow cytometry was used to determine cell cycle. The content of c-fos, c-jun, and CREB mRNA were detected by RT-PCR, and the expression of PCNA protein was detected by Western blot. RESULTS: After PQQ treatment, the percentage of cells in G0/G1 phase decreased and the percentage of cells in S and G2/M phase increased. After treated by PQQ at concentration of 1-10,000nmol/L, content of c-fos,c-jun,CREB mRNA was increased by 0.33,0.42 and 0. 52 fold (P < 0. 05). However, at concentration of 1 000 nmol/L, there was no difference in mRNAs content when compare to control (P >0.05). And it showed a decline at concentration of 10,000 nmol/L (P < 0.05). PCNA protein expression was up-regulated at PQQ concentration of 1-100 nmol/L. At 100 nmol/L, the expression increased by 1.17 fold (P < 0.05); However, at 1,000 nmol/L, there was no difference in PCNA expression when compared to control. And 10,000 nmol/L of PQQ inhibited the expression of PCNA (P < 0.05). CONCLUSIONS: When treated with PQQ at concentration of 10-100 nmol/L, the proliferation of Schwann cells increased and the expression of c-fos,c-jun, CREB and PCNA was up-regulated.
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Proliferação de Células/efeitos dos fármacos , Cofator PQQ/farmacologia , Células de Schwann/efeitos dos fármacos , Células de Schwann/metabolismo , Animais , Células Cultivadas , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Genes fos , Genes jun , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos , Ratos Sprague-Dawley , Células de Schwann/citologiaRESUMO
OBJECTIVE: To explore the effects of debridement combined with vacuum sealing drainage (VSD) technique in treatment of high-pressure paint injection injuries of hand. METHODS: From April 2005 to August 2010,14 patients with high-pressure paint injection injuries of hand were treated with debridement and VSD technique within 6 hours after injury. All the patients were male,ranging in age from 23 to 47 years with an average of 36.5 years. All injuries occurred left hand,thumb injured in 5 cases,index finger in 3 cases, middle finger in 2 cases and palm in 4 cases. Injured hands swelled obviously with poor blood circulation. When the wounds were covered with fresh granulation tissue without inflammatory effusion after operation of 3-4 times, the skingrafting (9 cases) or transfer flap (5 cases) were done on the wounds. RESULTS: All the patients were followed up from 8 to 16 months with an average of 12 months. All the wounds obtained good healing. Therapeutic effects were estimated according to TAM criteria, 7 cases were excellent,6 good and 1 fair. CONCLUSION: In high-pressure paint injection injuries of hands,debridement combined with VSD technique can avoid wound infection,promote the growth of granulation tissue. It is beneficial to wound healing.
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Desbridamento/métodos , Drenagem/métodos , Traumatismos da Mão/cirurgia , Adulto , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , PinturaRESUMO
Proliferation of Schwann cell in the injured peripheral nerve supports axonal regeneration and also is critical for the regeneration of injured nerves. In this publication, carboxymethylated chitosan (CMCS) was studied to determine its capacity (i) to induce proliferation and synthesis of proliferating cell nuclear antigen (PCNA) and (ii) to activate mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK/ERK) and phosphatidylinositil-3 kinase (PI3K)/Akt signaling pathways in rat Schwann cells. CMCS was found to induce proliferation and PCNA synthesis in Schwann cells in a dose and time dependent manner. CMCS was shown to phosphorylate ERK1/2 and Akt in Schwann cell proliferation. The phosphorylation of ERK1/2 and Akt in Schwann cells was blocked by the MEK inhibitor PD98059 and the PI3K inhibitor wortmannin. In addition, inhibition of the MEK/ERK or the PI3K/Akt signaling pathways significantly decreased the proliferative effects of CMCS in Schwann cells. Overall, the above results indicate that CMCS stimulates proliferation of Schwann cells by activating the intracellular signaling cascades of ERK1/2 and PI3K/Akt.
Assuntos
Quitosana/química , Quitosana/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células de Schwann/citologia , Células de Schwann/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Metilação , Fosfatidilinositol 3-Quinases/metabolismo , Antígeno Nuclear de Célula em Proliferação/biossíntese , Antígeno Nuclear de Célula em Proliferação/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Células de Schwann/metabolismoRESUMO
AIM: To review the application of nutrition support in patients after surgery for colorectal cancer, and to propose appropriate nutrition strategies. METHODS: A total of 202 consecutive surgical patients admitted to our hospital with a diagnosis of colon cancer or rectal cancer from January 2010 to July 2010, meeting the requirements of Nutrition Risk Screening 2002, were enrolled in our study. Laboratory tests were performed to analyze the nutrition status of each patient, and the clinical outcome variables, including postoperative complications, hospital stay, cost of hospitalization and postoperative outcome, were analyzed. RESULTS: The "non-risk" patients who did not receive postoperative nutrition support had a higher rate of postoperative complications than patients who received postoperative nutrition support (2.40 ± 1.51 vs. 1.23 ± 0.60, P = 0.000), and had a longer postoperative hospital stay (23.00 ± 15.84 d vs. 15.27 ± 5.89 d, P = 0.009). There was higher cost of hospitalization for patients who received preoperative total parenteral nutrition (TPN) than for patients who did not receive preoperative TPN (62 713.50 ± 5070.66 RMB Yuan vs. 43178.00 ± 3596.68 RMB Yuan, P = 0.014). Applying postoperative enteral nutrition significantly shortened postoperative fasting time (5.16 ± 1.21 d vs. 6.40 ± 1.84 d, P = 0.001) and postoperative hospital stay (11.92 ± 4.34 d vs. 15.77 ± 6.03 d, P = 0.002). The patients who received postoperative TPN for no less than 7 d had increased serum glucose levels (7.59 ± 3.57 mmol/L vs. 6.48 ± 1.32 mmol/L, P = 0.006) and cost of hospitalization (47 724.14 ± 16 945.17 Yuan vs. 38 598.73 ± 8349.79 Yuan, P = 0.000). The patients who received postoperative omega-3 fatty acids had a higher rate of postoperative complications than the patients who did not (1.33 ± 0.64 vs. 1.13 ± 0.49, P = 0.041). High level of serum glucose was associated with a high risk of postoperative complications of infection. CONCLUSION: Appropriate and moderate nutritional intervention can improve the postoperative outcome of colorectal cancer patients.