Background Tumor necrosis factor （TNF）-α plays an important role in mediating inflammatory state in obesity and related disorders.Lipopolysaccharides （LPS）-induced TNF-α factor （LITAF） is recently verified as ...Background Tumor necrosis factor （TNF）-α plays an important role in mediating inflammatory state in obesity and related disorders.Lipopolysaccharides （LPS）-induced TNF-α factor （LITAF） is recently verified as a regulator of TNF-α and other inflammatory cytokines,and maybe act as a transcriptional factor.The aim of this study was to confirm the association between LITAF and obesity and insulin resistance.Methods Forty-seven subjects with a wide range of body mass index （BMI） were included.Subjects were divided intothree groups according to the criteria of normal weight,overweight and obese.Anthropometrics and metabolic profile were tested for all the subjects.Peripheral monocytes were isolated and purified.LITAF transcription was detected by real time PCR,and the protein expression in whole cell and nucleus extracts was detected by Western blotting analysis;transcriptional activity of LITAF was detected by ELISA like assay using a probe containing the DNA binding sequence of LITAF.Plasma TNF-α and interleukin （IL）-6 concentrations were determined with ELISA kit.Results The LITAF mRNA and protein expression in whole cell were higher in overweight （P 〈0.05） and obese group （P 〈0.05） compared with that in normal weight group.The LITAF protein expression in the nucleus and transcriptional activity could not be detected.LITAF protein expression was positively correlated with BMI （r=0.541,P 〈0.001）,waist circumference （r=0.391,P=0.007）,the homeostasis model assessment for insulin resistance （r=0.372,P=0.011） and fasting insulin levels （r=0.359,P=0.013）.As a regulator of inflammatory cytokines,LITAF protein expression was positively correlated with plasma TNF-α （r=0.621,P=0.002） and IL-6 （r=0.407,P=0.039） concentration.Multiple variant regression analysis indicated that BMI （P=0.002） and waist circumference （P=0.017） were independent predictors of LITAF protein expression.Conclusions LITAF is associated with obesity and insulin resistance,as well as inflammatory cytokine secretion.The results indicate LITAF to be a new mediator between inflammation and the obesity related disorders.展开更多
Tumor necrosis factor α （TNF-α） and interferon-γ （IFN-γ） are cytokines with strong antitumor activities. They were reacted with a photoactive arylazide-4-azidobenzoic acid, resulting in photoactive TNF-α and ...Tumor necrosis factor α （TNF-α） and interferon-γ （IFN-γ） are cytokines with strong antitumor activities. They were reacted with a photoactive arylazide-4-azidobenzoic acid, resulting in photoactive TNF-α and IFN-γ. The infrared （IR） spectra of these products showed the characteristic absorption of an azido group at 2127 cm^-1. By photo-immobilization, this modified TNF-α and IFN-γ were immobilized on polystyrene membranes for cell culture to prepare biomaterials. The micro-morphology of photoactive cytokines was observed with a scanning electron microscope （SEM）. The inhibitory effect on growth of Hela cells and inducing apoptosis activity of these two cytokines were analyzed by growth curve, transmission electron microscope （TEM） and fluorescence active cell sorter （FACS）. The results showed that co-immobilization of IFN-γ and TNF-α had significant inhibitory effect on growth of Hela cells, inhibitory rate up to 82%, and IFN-γ had obviously synergistic action.展开更多
Mixed lineage kinase 3 （MLK3） is a mitogen-activated protein kinase kinase kinase that is activated by tumor necrosis factor-α （TNF-α） and specifically activates c-Jun N-terminal kinase （JNK） on TNF-a stimulat...Mixed lineage kinase 3 （MLK3） is a mitogen-activated protein kinase kinase kinase that is activated by tumor necrosis factor-α （TNF-α） and specifically activates c-Jun N-terminal kinase （JNK） on TNF-a stimulation. The mecha- nism by which TNF-α activates MLK3 is still not known. TNF receptor-associated factors （TRAFs） are adapter molecules that are recruited to cytoplasmic end of TNF receptor and mediate the downstream signaling, including activation of JNK. Here, we report that MLK3 associates with TRAF2, TRAF5 and TRAF6; however only TRAF2 can significantly induce the kinase activity of MLK3. The interaction domain of TRAF2 maps to the TRAF domain and for MLK3 to its C-terminal half （amino acids 511-847）. Endogenous TRAF2 and MLK3 associate with each other in response to TNF-α treatment in a time-dependent manner. The association between MLK3 and TRAF2 mediates MLK3 activation and competition with the TRAF2 deletion mutant that binds to MLK3 attenuates MLK3 kinase activity in a dose-dependent manner, on TNF-α treatment. Furthermore the downstream target of MLK3, JNK was activated by TNF-α in a TRAF2-dependent manner. Hence, our data show that the direct interaction between TRAF2 and MLK3 is required for TNF-α-induced activation of MLK3 and its downstream target, JNK.展开更多
Objective： Even though radiotherapy plays a major role in the local treatment of non-small cell lung cancer （NSCLC）, little is known about the molecular effects of irradiation in this tumor. In the present study, w...Objective： Even though radiotherapy plays a major role in the local treatment of non-small cell lung cancer （NSCLC）, little is known about the molecular effects of irradiation in this tumor. In the present study, we examined two NSCLC cell lines for their endogenous production of TNF-α after irradiation. To investigate the radiation-induced TNF-α production in NSCLC cell lines. Methods： Two human NSCLC cell lines （A549： squamous; NCI-H596： adenosquamous） were investigated for their TNF-α mRNA （real-time RT-PCR） after exposure to different irradiation doses （2, 5, 10, 20, 30, 40 Gy） and time intervals （1, 3, 6, 12, 24, 48 or 72 h）. The TNF-α mRNA expression was quantified by real-time RT-PCR. The clonogenic survival was evaluated after irradiation with 2, 4, 6 and 8 Gy. Results： Non-irradiated NSCLC cells exhibited no or very low TNF-α expression. For the NCI-H596 cell line, TNF-α expression was significantly elevated 1～12 h （maximum 6h： 568fold increase relative to unirradiated cells） in a time-dependent manner. The radiation-induced increase could be observed after irradiation with 2 Gy reaching maximal at 40 Gy, with 83 times higher than normal controls. The clonogenic survival of these cell lines was nearly identical. Conclusion： NCI-H596 cells produce significant quantities of TNF-α following irradiation in a time- and dose-dependent manner. The pro-inflammatory cytokine TNF-α is a key mediator for the pathogenesis of radiation pneumonitis. Radiation-induced endogenous TNF-α expression in NSCLC cells may affect the normal lung adjacent to the tumor and may be associated with an adverse clinical outcome of the patient.展开更多
Objective： To observe the expression of TGF-β and TNF-α in the spinal cord injured rat model and discuss the significance of the articular cartilage metabolism. Methods： 36 SD female rats were randomly divided int...Objective： To observe the expression of TGF-β and TNF-α in the spinal cord injured rat model and discuss the significance of the articular cartilage metabolism. Methods： 36 SD female rats were randomly divided into 2 groups： Rats models of spinal cord injury were implemented by Allen method. T10 laminectomy was performed in the control group. Both groups of rats were killed respectively in 1w, 3w and 6w. Hematoxylin-eosin stain was given to each slice in the model group and control group. Immunohistochemical stain was applied by using ABC method in the expression of TGF-β and TNF-α. Those expressed level were performed in image analysis and statistics process. Results： TGF-β and TNF-α were mainly distributed on the surface layer of the articular cartilage, with a weak expression in control group. The expression of TNF-α in the model group was more significant than that in the control group in the lw, and still remained an evident difference with that in control group until the 6w（P 〈 0.05）. TGF-β expression of the model group had no remarkable difference with the control group in the lw （P 〉 0.05） and prominently became stronger at 6w（P 〈 0.05）. Conclusion： The expression of TNF-α occurred early in the development of spinal cord injury, and the expression of TGF-β became stronger with the revival of spinal neural function. Both expressions were strengthened in articular cartilage in the 3rd week.展开更多
Objective： To study the effects of kadsurenone on inflammatory mediators Platelet-activating factor （PAF）, tumor necrosis factor-α（TNF-α） and interleukin-6（IL-6） in rat model of acute pancreatitis（AP）. Meth...Objective： To study the effects of kadsurenone on inflammatory mediators Platelet-activating factor （PAF）, tumor necrosis factor-α（TNF-α） and interleukin-6（IL-6） in rat model of acute pancreatitis（AP）. Methods： SD male rats （104） were randomly divided into sham group （n = 24）, AP group （n = 40） and kadsurenone group （n = 40）. The rats were killed 3, 6, 12 and 24 hours after operation. The serum level of PAF, TNF-α and IL-6 was measured. Results： The serum level of PAF, TNF-α and IL-6 of AP group was significantly increased（P 〈 0.01 ）compared with control group. The serum level of TNF-α got to a peak 6 hours after operation, and the serum IL-6 getting to a peak 12 hours after operation in AP group. After kadsurenone was administered to AP rats, pancreas and lung myeloperoxidase （MPO）, serum amylase activity was reduced. Histology showed a trend toward improvement. The serum level of PAF, TNF-α and IL-6 was significantly decreased （P 〈 0.05）. Conclusion. Kadsurenone can reduce the severity of systemic inflammation in rats with AP and relieve the damage of the pancreas and lung in AP rats. These results suggested that kadsurenone may be useful in the treatment of acute pancreatitis.展开更多
Objective To investigate the relationship between peritoneal macrophages(PMAs)and inflammatory reaction in a rat model of severe acute pancreatitis(SAP).Methods Sprague-Dawley rats were randomly divided into control g...Objective To investigate the relationship between peritoneal macrophages(PMAs)and inflammatory reaction in a rat model of severe acute pancreatitis(SAP).Methods Sprague-Dawley rats were randomly divided into control group and SAP group.To induce SAP in rats,40 g/L sodium taurocholate(0.1 mL/100 g)was injected into the pancreatic duct through retrograde exposure of pancreatic bile duct in hepatic porta.One-third of rats were sacrificed at 3,6 or 12 h after modeling.PMAs were extracted,and incubated for 24 h in a humidified 5% carbon dioxide incubator.The expressions of tumor necrosis factor alpha(TNF-α)and interleukin-1β(IL-1β)mRNA in PMAs were measured by semi-quantitative RT-PCR.The levels of TNF-α and IL-1β in culture medium and serum were evaluated.The histological changes of pancreas were examined.Results The expressions of TNF-α mRNA and IL-1β mRNA in PMAs were significantly higher in SAP group than in control group at each time point(P<0.01).The concentrations of TNF-α and IL-1β in culture medium and serum were significantly elevated in SAP group compared with control group(P<0.01).The histological analysis of pancreas indicated that the damage was more severe in SAP group than in control group(P<0.01).Conclusion PMAs secrete cytokines into pancreatitis-associated ascitic fluid,and this study demonstrates a correlation between SAP and the activation of PMAs.展开更多
Objective： To explore the regulating effects of cefodizime on cytokines expression of neutrophil response to Klebsiella pneumoniae （Kle. p） treatment. Methods： We detected the types and expression of cytokines sec...Objective： To explore the regulating effects of cefodizime on cytokines expression of neutrophil response to Klebsiella pneumoniae （Kle. p） treatment. Methods： We detected the types and expression of cytokines secreted by neutrophils by cDNA array and RT-PCR. We also analyzed the changes of signal transduction in this process by detecting the expression of toll like receptor 4 （TLR4） and the inhibitor factor of κBα （I-κBα） expressed by neutrophils. The activity of NF-κB DNA-binding in neutrophils was measured by electrophoretic mobility shift assay （EMSA）. Results： Cefodizime increased the neutrophils production of TNF-α, IL-β3 and the mRNA expression of TLR4 in the early stage of Kle. p stimulation in mice, which seemed corresponding to the enhanced NF-κB DNA-binding activity. Conclusion： Cefodizime regulates the cytokines expression of neutrophils through the LPS-TLR4-NF-κB pathway by affecting the expression of TLR4 mRNA and the DNA binding activities of NF-κB in mice with the challenge of Kle. p.展开更多
Objective This systematic review was conducted to investigate the efficacy and safety of thalidomide in metastatic breast cancer(MBC).Methods Based on pre-defined inclusion and exclusion criteria,data were independent...Objective This systematic review was conducted to investigate the efficacy and safety of thalidomide in metastatic breast cancer(MBC).Methods Based on pre-defined inclusion and exclusion criteria,data were independently collected from different databases by three investigators.Overall,three studies were included.Results The included studies indicated that no patient achieved a partial or complete response from different thalidomide dose levels.Thalidomide was well-tolerated at doses of 100 mg,200 mg,and 400 mg.In all three studies,common side effects included constipation,somnolence,fatigue,peripheral neuropathy,and dry mouth.Circulating angiogenic factors were not significantly correlated with disease progression.Conclusion The available evidence indicates that single-agent thalidomide has little or no activity in patients with MBC.展开更多
Nanopartide （NP） drug delivery systems have been successfully designed and implemented to orally deliver small interfering RNAs （siRNAs） for inflammatory disorders. However, the influence of surface charge on oral...Nanopartide （NP） drug delivery systems have been successfully designed and implemented to orally deliver small interfering RNAs （siRNAs） for inflammatory disorders. However, the influence of surface charge on orally administered siRNA nanocarriers has not been investigated. In this study, we prepared structurally related poly（ethylene glycol）-block-poly（lactic-co-glycolic acid） （PEG5K-b-PLGA10K） NPs with the assistance of a synthesized lipid featuring surface amine groups for subsequent charge tuning. NPs were prepared by a double emulsion method, and their surface charge could be tuned and controlled by a succinylation reaction to yield NPs with different surface charges, while maintaining their size and composition. The prepared NPs were termed as aminated NPs （ANPs）, plain NPs （PNPs）, or carboxylated NPs （CNPs） based on their surface charge. All NPs exhibited the desired structural stability and siRNA integrity after enzymatic degradation. In vivo studies showed that ANPs significantly accumulated in inflamed colons, and they were successful in decreasing TNF-α secretion and mRNA expression levels while maintaining colonic histology in a murine model of acute ulcerative colitis （UC）. This study described a methodology to modify the surface charge of siRNA-encapsulating polymeric NPs and highlighted the influence of surface charge on oral delivery of siRNA for localized inflammatory disorders.展开更多
Psoriatic arthritis(PsA) is a rheumatoid factor(RF)-seronegative systemic inflammatory disorder associated with psoriasis.Current treatment for PsA in China is still focused on disease modifying anti-rheumatic drugs(D...Psoriatic arthritis(PsA) is a rheumatoid factor(RF)-seronegative systemic inflammatory disorder associated with psoriasis.Current treatment for PsA in China is still focused on disease modifying anti-rheumatic drugs(DMARDs).In this paper,we report two Chinese patients with active longstanding PsA treated with infliximab,a human-mouse chimeric monoclonal antibody against tumor necrosis factor alpha(TNF-α).The results show that infliximab acted quickly and effectively in relieving peripheral and axial symptoms and refractory skin lesions,even in recombinant human TNF-α receptor(rhTNFR)-resistant case.The take-home message from our cases is that infliximab is a useful therapeutic option for refractory PsA,especially when a patient has a combination of psoriasis and psoriatic arthritis.Further local evidence and experience must be accumulated in order to make anti-TNF-α therapy more accessible to PsA patients in China.展开更多
基金This work was supported by a grant from the National Natural Science Foundation of China （No. 30871188）.
文摘Background Tumor necrosis factor （TNF）-α plays an important role in mediating inflammatory state in obesity and related disorders.Lipopolysaccharides （LPS）-induced TNF-α factor （LITAF） is recently verified as a regulator of TNF-α and other inflammatory cytokines,and maybe act as a transcriptional factor.The aim of this study was to confirm the association between LITAF and obesity and insulin resistance.Methods Forty-seven subjects with a wide range of body mass index （BMI） were included.Subjects were divided intothree groups according to the criteria of normal weight,overweight and obese.Anthropometrics and metabolic profile were tested for all the subjects.Peripheral monocytes were isolated and purified.LITAF transcription was detected by real time PCR,and the protein expression in whole cell and nucleus extracts was detected by Western blotting analysis;transcriptional activity of LITAF was detected by ELISA like assay using a probe containing the DNA binding sequence of LITAF.Plasma TNF-α and interleukin （IL）-6 concentrations were determined with ELISA kit.Results The LITAF mRNA and protein expression in whole cell were higher in overweight （P 〈0.05） and obese group （P 〈0.05） compared with that in normal weight group.The LITAF protein expression in the nucleus and transcriptional activity could not be detected.LITAF protein expression was positively correlated with BMI （r=0.541,P 〈0.001）,waist circumference （r=0.391,P=0.007）,the homeostasis model assessment for insulin resistance （r=0.372,P=0.011） and fasting insulin levels （r=0.359,P=0.013）.As a regulator of inflammatory cytokines,LITAF protein expression was positively correlated with plasma TNF-α （r=0.621,P=0.002） and IL-6 （r=0.407,P=0.039） concentration.Multiple variant regression analysis indicated that BMI （P=0.002） and waist circumference （P=0.017） were independent predictors of LITAF protein expression.Conclusions LITAF is associated with obesity and insulin resistance,as well as inflammatory cytokine secretion.The results indicate LITAF to be a new mediator between inflammation and the obesity related disorders.
基金This work was supported by the China Postdoctoral Science Foundation under grant No.2004035588.
文摘Tumor necrosis factor α （TNF-α） and interferon-γ （IFN-γ） are cytokines with strong antitumor activities. They were reacted with a photoactive arylazide-4-azidobenzoic acid, resulting in photoactive TNF-α and IFN-γ. The infrared （IR） spectra of these products showed the characteristic absorption of an azido group at 2127 cm^-1. By photo-immobilization, this modified TNF-α and IFN-γ were immobilized on polystyrene membranes for cell culture to prepare biomaterials. The micro-morphology of photoactive cytokines was observed with a scanning electron microscope （SEM）. The inhibitory effect on growth of Hela cells and inducing apoptosis activity of these two cytokines were analyzed by growth curve, transmission electron microscope （TEM） and fluorescence active cell sorter （FACS）. The results showed that co-immobilization of IFN-γ and TNF-α had significant inhibitory effect on growth of Hela cells, inhibitory rate up to 82%, and IFN-γ had obviously synergistic action.
文摘Mixed lineage kinase 3 （MLK3） is a mitogen-activated protein kinase kinase kinase that is activated by tumor necrosis factor-α （TNF-α） and specifically activates c-Jun N-terminal kinase （JNK） on TNF-a stimulation. The mecha- nism by which TNF-α activates MLK3 is still not known. TNF receptor-associated factors （TRAFs） are adapter molecules that are recruited to cytoplasmic end of TNF receptor and mediate the downstream signaling, including activation of JNK. Here, we report that MLK3 associates with TRAF2, TRAF5 and TRAF6; however only TRAF2 can significantly induce the kinase activity of MLK3. The interaction domain of TRAF2 maps to the TRAF domain and for MLK3 to its C-terminal half （amino acids 511-847）. Endogenous TRAF2 and MLK3 associate with each other in response to TNF-α treatment in a time-dependent manner. The association between MLK3 and TRAF2 mediates MLK3 activation and competition with the TRAF2 deletion mutant that binds to MLK3 attenuates MLK3 kinase activity in a dose-dependent manner, on TNF-α treatment. Furthermore the downstream target of MLK3, JNK was activated by TNF-α in a TRAF2-dependent manner. Hence, our data show that the direct interaction between TRAF2 and MLK3 is required for TNF-α-induced activation of MLK3 and its downstream target, JNK.
基金This work was supported by a grant fromChina Scholarship Council (No.20842007).
文摘Objective： Even though radiotherapy plays a major role in the local treatment of non-small cell lung cancer （NSCLC）, little is known about the molecular effects of irradiation in this tumor. In the present study, we examined two NSCLC cell lines for their endogenous production of TNF-α after irradiation. To investigate the radiation-induced TNF-α production in NSCLC cell lines. Methods： Two human NSCLC cell lines （A549： squamous; NCI-H596： adenosquamous） were investigated for their TNF-α mRNA （real-time RT-PCR） after exposure to different irradiation doses （2, 5, 10, 20, 30, 40 Gy） and time intervals （1, 3, 6, 12, 24, 48 or 72 h）. The TNF-α mRNA expression was quantified by real-time RT-PCR. The clonogenic survival was evaluated after irradiation with 2, 4, 6 and 8 Gy. Results： Non-irradiated NSCLC cells exhibited no or very low TNF-α expression. For the NCI-H596 cell line, TNF-α expression was significantly elevated 1～12 h （maximum 6h： 568fold increase relative to unirradiated cells） in a time-dependent manner. The radiation-induced increase could be observed after irradiation with 2 Gy reaching maximal at 40 Gy, with 83 times higher than normal controls. The clonogenic survival of these cell lines was nearly identical. Conclusion： NCI-H596 cells produce significant quantities of TNF-α following irradiation in a time- and dose-dependent manner. The pro-inflammatory cytokine TNF-α is a key mediator for the pathogenesis of radiation pneumonitis. Radiation-induced endogenous TNF-α expression in NSCLC cells may affect the normal lung adjacent to the tumor and may be associated with an adverse clinical outcome of the patient.
基金This work was supported by the national nature science fundation(30400163)
文摘Objective： To observe the expression of TGF-β and TNF-α in the spinal cord injured rat model and discuss the significance of the articular cartilage metabolism. Methods： 36 SD female rats were randomly divided into 2 groups： Rats models of spinal cord injury were implemented by Allen method. T10 laminectomy was performed in the control group. Both groups of rats were killed respectively in 1w, 3w and 6w. Hematoxylin-eosin stain was given to each slice in the model group and control group. Immunohistochemical stain was applied by using ABC method in the expression of TGF-β and TNF-α. Those expressed level were performed in image analysis and statistics process. Results： TGF-β and TNF-α were mainly distributed on the surface layer of the articular cartilage, with a weak expression in control group. The expression of TNF-α in the model group was more significant than that in the control group in the lw, and still remained an evident difference with that in control group until the 6w（P 〈 0.05）. TGF-β expression of the model group had no remarkable difference with the control group in the lw （P 〉 0.05） and prominently became stronger at 6w（P 〈 0.05）. Conclusion： The expression of TNF-α occurred early in the development of spinal cord injury, and the expression of TGF-β became stronger with the revival of spinal neural function. Both expressions were strengthened in articular cartilage in the 3rd week.
文摘目的：研究老年口腔溃疡患者血清肿瘤坏死因子（ TNF-α）变化并讨论其临床意义。方法：老年口腔溃疡患者102例，年龄69．1±11．6岁。选择体检健康人26例作正常对照，年龄66．3±6．4岁。血清TNF-α含量用双抗体夹心ELISA法测定，8例重型患者进行病理组织学检查。结果：老年口腔溃疡血清TNF-α含量（g/L）明显高于正常对照（46．1±11．7 vs 25．3±10．4，P＜0．01），重型（n＝14，53．7±19．1，P＜0．01）和中型（n＝53，43．1±10．5， P＜0．01）明显高于轻型（n＝35，34．1±9．6，P＜0．01），即重型TNF-α含量＞中型＞轻型。8例组织病理学检查包括5例是淋巴细胞、浆细胞和单核巨噬细胞浸润的炎症，3例是炎症伴有增生。结论：老年口腔溃疡血清TNF-α含量可明显增高，病变越重增加越明显，且病理改变是炎症或伴增生，疾病发生发展与TNF-α变化有关。
基金By the Science Fund of health department of Shan xi Province (NO.2004D41)
文摘Objective： To study the effects of kadsurenone on inflammatory mediators Platelet-activating factor （PAF）, tumor necrosis factor-α（TNF-α） and interleukin-6（IL-6） in rat model of acute pancreatitis（AP）. Methods： SD male rats （104） were randomly divided into sham group （n = 24）, AP group （n = 40） and kadsurenone group （n = 40）. The rats were killed 3, 6, 12 and 24 hours after operation. The serum level of PAF, TNF-α and IL-6 was measured. Results： The serum level of PAF, TNF-α and IL-6 of AP group was significantly increased（P 〈 0.01 ）compared with control group. The serum level of TNF-α got to a peak 6 hours after operation, and the serum IL-6 getting to a peak 12 hours after operation in AP group. After kadsurenone was administered to AP rats, pancreas and lung myeloperoxidase （MPO）, serum amylase activity was reduced. Histology showed a trend toward improvement. The serum level of PAF, TNF-α and IL-6 was significantly decreased （P 〈 0.05）. Conclusion. Kadsurenone can reduce the severity of systemic inflammation in rats with AP and relieve the damage of the pancreas and lung in AP rats. These results suggested that kadsurenone may be useful in the treatment of acute pancreatitis.
基金supported by the National Natural Science Foundation of China(No.30772745)the Doctoral Foundation of Ministry of Education of China(No.20070698070)Science and Technology Project of Shaanxi Province(2006K16-G14)
文摘Objective To investigate the relationship between peritoneal macrophages(PMAs)and inflammatory reaction in a rat model of severe acute pancreatitis(SAP).Methods Sprague-Dawley rats were randomly divided into control group and SAP group.To induce SAP in rats,40 g/L sodium taurocholate(0.1 mL/100 g)was injected into the pancreatic duct through retrograde exposure of pancreatic bile duct in hepatic porta.One-third of rats were sacrificed at 3,6 or 12 h after modeling.PMAs were extracted,and incubated for 24 h in a humidified 5% carbon dioxide incubator.The expressions of tumor necrosis factor alpha(TNF-α)and interleukin-1β(IL-1β)mRNA in PMAs were measured by semi-quantitative RT-PCR.The levels of TNF-α and IL-1β in culture medium and serum were evaluated.The histological changes of pancreas were examined.Results The expressions of TNF-α mRNA and IL-1β mRNA in PMAs were significantly higher in SAP group than in control group at each time point(P<0.01).The concentrations of TNF-α and IL-1β in culture medium and serum were significantly elevated in SAP group compared with control group(P<0.01).The histological analysis of pancreas indicated that the damage was more severe in SAP group than in control group(P<0.01).Conclusion PMAs secrete cytokines into pancreatitis-associated ascitic fluid,and this study demonstrates a correlation between SAP and the activation of PMAs.
基金the Natural Science Foundation of GuangdongProvince (5300983)
文摘Objective： To explore the regulating effects of cefodizime on cytokines expression of neutrophil response to Klebsiella pneumoniae （Kle. p） treatment. Methods： We detected the types and expression of cytokines secreted by neutrophils by cDNA array and RT-PCR. We also analyzed the changes of signal transduction in this process by detecting the expression of toll like receptor 4 （TLR4） and the inhibitor factor of κBα （I-κBα） expressed by neutrophils. The activity of NF-κB DNA-binding in neutrophils was measured by electrophoretic mobility shift assay （EMSA）. Results： Cefodizime increased the neutrophils production of TNF-α, IL-β3 and the mRNA expression of TLR4 in the early stage of Kle. p stimulation in mice, which seemed corresponding to the enhanced NF-κB DNA-binding activity. Conclusion： Cefodizime regulates the cytokines expression of neutrophils through the LPS-TLR4-NF-κB pathway by affecting the expression of TLR4 mRNA and the DNA binding activities of NF-κB in mice with the challenge of Kle. p.
文摘Objective This systematic review was conducted to investigate the efficacy and safety of thalidomide in metastatic breast cancer(MBC).Methods Based on pre-defined inclusion and exclusion criteria,data were independently collected from different databases by three investigators.Overall,three studies were included.Results The included studies indicated that no patient achieved a partial or complete response from different thalidomide dose levels.Thalidomide was well-tolerated at doses of 100 mg,200 mg,and 400 mg.In all three studies,common side effects included constipation,somnolence,fatigue,peripheral neuropathy,and dry mouth.Circulating angiogenic factors were not significantly correlated with disease progression.Conclusion The available evidence indicates that single-agent thalidomide has little or no activity in patients with MBC.
基金This work was supported by the National Basic Research Program of China （No. 2015CB932100）, the National Natural Science Foundation of China （Nos. 51503195, 51390482 and 51633008）, the National Key R＆D Program of China （No. 2017YFA0205600）, the Fundamental Research Funds for the Central Universities, and 111 Project （No. B17018）. S. I. is also grateful for the CAS-TWAS president fellowship.
文摘Nanopartide （NP） drug delivery systems have been successfully designed and implemented to orally deliver small interfering RNAs （siRNAs） for inflammatory disorders. However, the influence of surface charge on orally administered siRNA nanocarriers has not been investigated. In this study, we prepared structurally related poly（ethylene glycol）-block-poly（lactic-co-glycolic acid） （PEG5K-b-PLGA10K） NPs with the assistance of a synthesized lipid featuring surface amine groups for subsequent charge tuning. NPs were prepared by a double emulsion method, and their surface charge could be tuned and controlled by a succinylation reaction to yield NPs with different surface charges, while maintaining their size and composition. The prepared NPs were termed as aminated NPs （ANPs）, plain NPs （PNPs）, or carboxylated NPs （CNPs） based on their surface charge. All NPs exhibited the desired structural stability and siRNA integrity after enzymatic degradation. In vivo studies showed that ANPs significantly accumulated in inflamed colons, and they were successful in decreasing TNF-α secretion and mRNA expression levels while maintaining colonic histology in a murine model of acute ulcerative colitis （UC）. This study described a methodology to modify the surface charge of siRNA-encapsulating polymeric NPs and highlighted the influence of surface charge on oral delivery of siRNA for localized inflammatory disorders.
文摘Psoriatic arthritis(PsA) is a rheumatoid factor(RF)-seronegative systemic inflammatory disorder associated with psoriasis.Current treatment for PsA in China is still focused on disease modifying anti-rheumatic drugs(DMARDs).In this paper,we report two Chinese patients with active longstanding PsA treated with infliximab,a human-mouse chimeric monoclonal antibody against tumor necrosis factor alpha(TNF-α).The results show that infliximab acted quickly and effectively in relieving peripheral and axial symptoms and refractory skin lesions,even in recombinant human TNF-α receptor(rhTNFR)-resistant case.The take-home message from our cases is that infliximab is a useful therapeutic option for refractory PsA,especially when a patient has a combination of psoriasis and psoriatic arthritis.Further local evidence and experience must be accumulated in order to make anti-TNF-α therapy more accessible to PsA patients in China.
