AIM: To investigate the molecular mechanisms of berberine inhibition of hepatic gluconeogenesis in a diabetic rat model.METHODS: The 40 rats were randomly divided into five groups. One group was selected as the normal...AIM: To investigate the molecular mechanisms of berberine inhibition of hepatic gluconeogenesis in a diabetic rat model.METHODS: The 40 rats were randomly divided into five groups. One group was selected as the normal group. In the remaining groups(n = 8 each), the rats were fed on a high-fat diet for 1 mo and received intravenous injection of streptozotocin for induction of the diabetic models. Berberine(156 mg/kg per day)(berberine group) or metformin(184 mg/kg per day)(metformin group) was intragastrically administered to the diabetic rats and 5-aminoimidazole-4-carboxamide1-β-D-ribofuranoside(AICAR)(0.5 mg/kg per day)(AICAR group) was subcutaneously injected to the diabetic rats for 12 wk. The remaining eight diabetic rats served as the model group. Fasting plasma glucose and insulin levels as well as lipid profile were tested.The expressions of proteins were examined by western blotting. The nuclear translocation of CREB-regulated transcription co-activator(TORC)2 was observed by immunohistochemical staining. RESULTS: Berberine improved impaired glucose tolerance and decreased plasma hyperlipidemia. Moreover, berberine decreased fasting plasma insulin and homeostasis model assessment of insulin resistance(HOMA-IR). Berberine upregulated protein expression of liver kinase(LK)B1, AMP-activated protein kinase(AMPK) and phosphorylated AMPK(p-AMPK). The level of phophorylated TORC2(p-TORC2) protein in the cytoplasm was higher in the berberine group than in the model group, and no significant difference in total TORC2 protein level was observed. Immunohistochemical staining revealed that more TORC2 was localized in the cytoplasm of the berberine group than in the model group. Moreover, berberine treatment downregulated protein expression of the key gluconeogenic enzymes(phosphoenolpyruvate carboxykinase and glucose-6-phosphatase) in the liver tissues. CONCLUSION: Our findings revealed that berberine inhibited hepatic gluconeogenesis via the regulation of the LKB1-AMPK-TORC2 signaling pathway.展开更多
AIM: To investigate the effects and molecular mechanisms of berberine on improving insulin resistance induced by free fatty acids (FFAs) in 3T3-L1 adipocytes. METHODS: The model of insulin resistance in 3T3-L1 adipocy...AIM: To investigate the effects and molecular mechanisms of berberine on improving insulin resistance induced by free fatty acids (FFAs) in 3T3-L1 adipocytes. METHODS: The model of insulin resistance in 3T3-L1 adipocytes was established by adding palmic acid (0.5 mmol/L) to the culture medium. Berberine treatment was performed at the same time. Glucose uptake rate was determined by the 2-deoxy-[3H]-D-glucose method. The levels of IkB kinase beta (IKKβ) Ser181 phosphorylation, insulin receptor substrate-1(IRS-1) Ser307 phosphorylation, expression of IKKβ, IRS-1, nuclear transcription factor kappaB p65 (NF-κB p65), phosphatidylinositol-3-kinase p85 (PI-3K p85) and glucose transporter 4 (GLUT4) proteins were detected by Western blotting. The distribution of NF-κB p65 proteins inside the adipocytes was observed through confocal laser scanning microscopy (CLSM). RESULTS: After the intervention of palmic acid for 24 h, the insulin-stimulated glucose transport in 3T3-L1 adipocytes was inhibited by 67%. Meanwhile, the expression of IRS-1 and PI-3K p85 protein was reduced, while the levels of IKKβ Ser181 and IRS-1 Ser307 phosphorylation, and nuclear translocation of NF-κB p65 protein were increased. However, the above indexes, which indicated the existence of insulin resistance, were reversed by berberine although the expression of GLUT4, IKKβ and total NF-κB p65 protein were not changed during this study. CONCLUSION: Insulin resistance induced by FFAs in 3T3-L1 adipocytes can be improved by berberine. Berberine reversed free-fatty-acid-induced insulin resistance in 3T3-L1 adipocytes through targeting IKKβ.展开更多
Decompression is the major therapeutic strategy for acute spinal cord injury,but there is some debate about the time window for decompression following spinal cord injury.An important goal and challenge in the treatme...Decompression is the major therapeutic strategy for acute spinal cord injury,but there is some debate about the time window for decompression following spinal cord injury.An important goal and challenge in the treatment of spinal cord injury is inhibiting or reversing secondary injury.Governor Vessel electroacupuncture can improve symptoms of spinal cord injury by inhibiting cell apoptosis and improving the microenvironment of the injured spinal cord.In this study,Governor Vessel electroacupuncture combined with decompression at different time points was used to treat acute spinal cord injury.The rat models were established by inserting a balloon catheter into the atlanto-occipital space.The upper cervical spinal cord was compressed for 12 or 48 hours prior to decompression.Electroacupuncture was conducted at the acupoints Dazhui(GV14) and Baihui(GV 20)(2 Hz,15 minutes) once a day for 14 consecutive days.Compared with decompression alone,hind limb motor function recovery was superior after decompression for 12 and 48 hours combined with electroacupuncture.However,the recovery of motor function was not significantly different at 14 days after treatment in rats receiving decompression for 12 hours.Platelet-activating factor levels and caspase-9 protein expression were significantly reduced in rats receiving electroacupuncture compared with decompression alone.These findings indicate that compared with decompression alone,Governor Vessel electroacupuncture combined with delayed decompression(48 hours) is more effective in the treatment of upper cervical spinal cord injury.Governor Vessel electroacupuncture combined with early decompression(12 hours) can accelerate the recovery of nerve movement in rats with upper cervical spinal cord injury.Nevertheless,further studies are necessary to confirm whether it is possible to obtain additional benefit compared with early decompression alone.展开更多
Saliva is secreted from the salivary glands and has multiple functions, including mouth cleaning and protection, antibacterial effects and digestion. With the rapid advancement in salivaomics, saliva is well recognize...Saliva is secreted from the salivary glands and has multiple functions, including mouth cleaning and protection, antibacterial effects and digestion. With the rapid advancement in salivaomics, saliva is well recognized as a pool of biological markers.Saliva, as a non-invasive and safe source, could be a substitute for blood in the diagnosis and prognosis of diseases. This review summarizes the latest advancements in saliva-related studies and addresses the potential value of saliva in the early diagnosis of oral diseases, such as dental caries and periodontal disease, as well as cancer, diabetes and other systemic disorders. Saliva biomarkers range from changes in the biochemical indices of DNA, RNA and proteins to the diversi?cation of microbiota structures. This study integrates data reported in the recent literature and discusses the clinical signi?cance and prospects for the application of saliva in the early diagnosis of diseases, translational medicine and precision medicine.展开更多
In the last decade, three dimensional discontinuous deformation analyses (3D DDA) has attracted more and more attention of researchers and geotechnical engineers worldwide. The original DDA formulation utilizes a line...In the last decade, three dimensional discontinuous deformation analyses (3D DDA) has attracted more and more attention of researchers and geotechnical engineers worldwide. The original DDA formulation utilizes a linear displacement function to describe the block movement and deformation, which would cause block expansion under rigid body rotation and thus limit its capability to model block deformation. In this paper, 3D DDA is coupled with tetrahedron finite elements to tackle these two problems. Tetrahedron is the simplest in the 3D domain and makes it easy to implement automatic discretization, even for complex topology shape. Furthermore, element faces will remain planar and element edges will remain straight after deformation for tetrahedron finite elements and polyhedral contact detection schemes can be used directly. The matrices of equilibrium equations for this coupled method are given in detail and an effective contact searching algorithm is suggested. Validation is conducted by comparing the results of the proposed coupled method with that of physical model tests using one of the most common failure modes, i.e., wedge failure. Most of the failure modes predicted by the coupled method agree with the physical model results except for 4 cases out of the total 65 cases. Finally, a complex rockslide example demonstrates the robustness and versatility of the coupled method.展开更多
The effect and potential molecular mechanisms of berberine on gluconeogenesis in skeletal muscles and adipose tissues were investigated.After adaptive feeding for one week,8 rats were randomly selected as the normal g...The effect and potential molecular mechanisms of berberine on gluconeogenesis in skeletal muscles and adipose tissues were investigated.After adaptive feeding for one week,8 rats were randomly selected as the normal group and fed on a standard diet.The remaining 32 rats were fed on a high-fat diet and given an intravenous injection of streptozotocin(STZ)for 2 weeks to induce the diabetic models.The diabetic rat models were confirmed by oral glucose tolerance test(OGTT)and randomly divided into 4 groups(n=8 each),which were all fed on a high-fat diet.Berberine(3 g/kg per day)or metformin(183 mg/kg per day)was intragastrically administered to the diabetic rats for 12 weeks,serving as berberine group and metformin group respectively.5-aminoimidazole-4-carboxamide1-β-D-ribofuranoside[AICAR,an agonist of AMP-activated protein kinase(AMPK),0.5 mg/kg per day]was subcutaneously injected to the diabetic rats for 12 weeks,serving as AICAR group.The remaining 8 diabetic rats served as the model group,which was given a 0.5%carboxyl methylcellulose solution by oral gavage.Fasting serum insulin(FINS),OGTT as well as lipid parameters were tested by commercial kit.The protein levels of liver kinase B1(LKB1),AMPK,phosphorylated AMP-activated protein kinase(p-AMPK),transducer of regulated CREB activity 2(TORC2),phosphorylated transducer of regulated CREB activity 2(p-TORC2),phosphoenolpyruvate carboxykinase(PEPCK),and glucose-6-phosphatase(G6Pase)in skeletal muscles and adipose tissues were examined by Western blotting.The results showed that berberine significantly decreased the body weight,plasma glucose,insulin levels,and homeostatic model assessment for insulin resistance(HOMA-IR)of diabetic rats compared with those in the model group.Meanwhile,the serum total triglyceride(TG),total cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C)levels were markedly decreased and high-density lipoprotein cholesterol(HDL-C)level was significantly increased after the treatment with berberine.In addition,we found that berberine significantly increased the expression of p-AMPK and LKB1,while decreasing the p-TORC2 levels in skeletal muscles and adipose tissues.Moreover,the expression of PEPCK and G6Pase was significantly down-regulated after the treatment with berberine compared to the model group.It was suggested that the mechanism by which berberine inhibited peripheral tissue gluconeogenesis may be attributed to the activation of the LKB1-AMPK-TORC2 signaling pathway.展开更多
Proteases are important molecules that are involved in many physiological and pathological processes of the human body,such as growth,apoptosis and metastasis cancer cells.They are potential targets in cancer diagnosi...Proteases are important molecules that are involved in many physiological and pathological processes of the human body,such as growth,apoptosis and metastasis cancer cells.They are potential targets in cancer diagnosis and biotherapy.In this study,we analyzed the salivary protease spectrum of patients with oral squamous cell carcinoma (OSCC),oral benign masses and chronic periodontitis,as well as that of health,using human protease array kits,enzyme-linked immunosorbent assay,western blot and immunofluorescence.The salivary protease spectrum was found to be associated with oral diseases.For example,the saliva of patients with OSCC contained increased numbers of proteases than those of other oral diseases and health.The levels of matrix metalloproteinase (MMP)-1,MMP-2,MMP-10,MMP-12,A disintegrin and metalloprotease (ADAM)9,A disintegrin and metalloprotease with thrombospondin type 13 motifs (ADAMST13),cathepsin V and kallikrein 5 in the saliva of patients with OSCC were significantly increased compared with those of other groups.Taking MMP-1,cathepsin V,kallikrein 5 and ADAM9 as biomarkers of OSCC,cutoff values were199,11.34,9.29 and 202.55 pg·mL?1,respectively.From the area under the curve,sensitivity and specificity,the combination of cathepsin V/kallikrein5/ADAM9 was an optimal biomarker for diagnosing OSCC.Thus,analysis of the salivary protease spectrum may be an innovative and cost-efficient approach to evaluating the health status of the oral cavity.Specifically,increases in cathepsin V,kallikrein 5 and ADAM9 may be useful biomarkers in the screening and diagnosis of OSCC.展开更多
Due to their characteristics of dynamic topology, wireless channels and limited resources, mobile ad hoc networks are particularly vulnerable to a denial of service (DoS) attacks launched by intruders. The effects of ...Due to their characteristics of dynamic topology, wireless channels and limited resources, mobile ad hoc networks are particularly vulnerable to a denial of service (DoS) attacks launched by intruders. The effects of flooding attacks in network simulation 2 (NS2) and measured performance parameters are investigated, including packet loss ratio, average delay, throughput and average number of hops under different numbers of attack nodes, flooding frequency, network bandwidth and network size. Simulation results show that with the increase of the flooding frequency and the number of attack nodes, network performance sharply drops. But when the frequency of flooding attacks or the number of attack nodes is greater than a certain value, performance degradation tends to a stable value.展开更多
Background: Helicobacter species are best known for their roles in the pathology of gastritis;however, several Helicobacter species also colonize the intestine, and less is known about effects of Helicobacter on the d...Background: Helicobacter species are best known for their roles in the pathology of gastritis;however, several Helicobacter species also colonize the intestine, and less is known about effects of Helicobacter on the development of intestinal inflammation. To evaluate contributions of Helicobacter in inflammatory bowel disease, we investigated whether and how pre-existing intestinal colonization would affect disease severity and biomarkers of inflammation in experimental IBD. Materials and Methods: Mice were infected with H. muridarum 2 weeks prior to induction of colitis mediated by 3% dextran sulfate (DSS). Disease activity index, stool blood and consistency, colon length, myeloperoxidase, histopathology, blood and lymphatic vessels, and numbers of dilated mucosal crypts were measured in control, DSS-only, H. muridarum-infected, and H. muridarum-infected + DSS mice. Results: Prior to DSS challenge, H. muridarum-infected mice showed little distal gut injury by several indices of colon inflammation with decreased blood vessel density in the submucosa, and lower lymphatic density in the mucosa and submucosa. However, after DSS colitis, H. muridarum-infected mice exhibited significantly greater disease. Weight change, stool bleeding, diarrhea, and angiogenesis were all increased in H. muridarum-infected mice in DSS colitis compared to DSS controls. Conclusions: Our data show that Helicobacter colonization of the intestine, unlike that of the stomach, lowers basal gut inflammatory scores, but increases disease activity and inflammation in an acute colitis model. Intestinal Helicobacter infection may therefore represent a significant sub-clinical factor which predisposes the gut to inflammatory injury.展开更多
基金Supported by National Natural Science Foundation of China,No.30973836
文摘AIM: To investigate the molecular mechanisms of berberine inhibition of hepatic gluconeogenesis in a diabetic rat model.METHODS: The 40 rats were randomly divided into five groups. One group was selected as the normal group. In the remaining groups(n = 8 each), the rats were fed on a high-fat diet for 1 mo and received intravenous injection of streptozotocin for induction of the diabetic models. Berberine(156 mg/kg per day)(berberine group) or metformin(184 mg/kg per day)(metformin group) was intragastrically administered to the diabetic rats and 5-aminoimidazole-4-carboxamide1-β-D-ribofuranoside(AICAR)(0.5 mg/kg per day)(AICAR group) was subcutaneously injected to the diabetic rats for 12 wk. The remaining eight diabetic rats served as the model group. Fasting plasma glucose and insulin levels as well as lipid profile were tested.The expressions of proteins were examined by western blotting. The nuclear translocation of CREB-regulated transcription co-activator(TORC)2 was observed by immunohistochemical staining. RESULTS: Berberine improved impaired glucose tolerance and decreased plasma hyperlipidemia. Moreover, berberine decreased fasting plasma insulin and homeostasis model assessment of insulin resistance(HOMA-IR). Berberine upregulated protein expression of liver kinase(LK)B1, AMP-activated protein kinase(AMPK) and phosphorylated AMPK(p-AMPK). The level of phophorylated TORC2(p-TORC2) protein in the cytoplasm was higher in the berberine group than in the model group, and no significant difference in total TORC2 protein level was observed. Immunohistochemical staining revealed that more TORC2 was localized in the cytoplasm of the berberine group than in the model group. Moreover, berberine treatment downregulated protein expression of the key gluconeogenic enzymes(phosphoenolpyruvate carboxykinase and glucose-6-phosphatase) in the liver tissues. CONCLUSION: Our findings revealed that berberine inhibited hepatic gluconeogenesis via the regulation of the LKB1-AMPK-TORC2 signaling pathway.
基金The National Natural Science Foundation of China, No. 30371816
文摘AIM: To investigate the effects and molecular mechanisms of berberine on improving insulin resistance induced by free fatty acids (FFAs) in 3T3-L1 adipocytes. METHODS: The model of insulin resistance in 3T3-L1 adipocytes was established by adding palmic acid (0.5 mmol/L) to the culture medium. Berberine treatment was performed at the same time. Glucose uptake rate was determined by the 2-deoxy-[3H]-D-glucose method. The levels of IkB kinase beta (IKKβ) Ser181 phosphorylation, insulin receptor substrate-1(IRS-1) Ser307 phosphorylation, expression of IKKβ, IRS-1, nuclear transcription factor kappaB p65 (NF-κB p65), phosphatidylinositol-3-kinase p85 (PI-3K p85) and glucose transporter 4 (GLUT4) proteins were detected by Western blotting. The distribution of NF-κB p65 proteins inside the adipocytes was observed through confocal laser scanning microscopy (CLSM). RESULTS: After the intervention of palmic acid for 24 h, the insulin-stimulated glucose transport in 3T3-L1 adipocytes was inhibited by 67%. Meanwhile, the expression of IRS-1 and PI-3K p85 protein was reduced, while the levels of IKKβ Ser181 and IRS-1 Ser307 phosphorylation, and nuclear translocation of NF-κB p65 protein were increased. However, the above indexes, which indicated the existence of insulin resistance, were reversed by berberine although the expression of GLUT4, IKKβ and total NF-κB p65 protein were not changed during this study. CONCLUSION: Insulin resistance induced by FFAs in 3T3-L1 adipocytes can be improved by berberine. Berberine reversed free-fatty-acid-induced insulin resistance in 3T3-L1 adipocytes through targeting IKKβ.
基金supported by the Capital Characteristic Clinical Application Research Projects of Beijing Municipal Science and Technology Plan of China,No.Z16110000516009
文摘Decompression is the major therapeutic strategy for acute spinal cord injury,but there is some debate about the time window for decompression following spinal cord injury.An important goal and challenge in the treatment of spinal cord injury is inhibiting or reversing secondary injury.Governor Vessel electroacupuncture can improve symptoms of spinal cord injury by inhibiting cell apoptosis and improving the microenvironment of the injured spinal cord.In this study,Governor Vessel electroacupuncture combined with decompression at different time points was used to treat acute spinal cord injury.The rat models were established by inserting a balloon catheter into the atlanto-occipital space.The upper cervical spinal cord was compressed for 12 or 48 hours prior to decompression.Electroacupuncture was conducted at the acupoints Dazhui(GV14) and Baihui(GV 20)(2 Hz,15 minutes) once a day for 14 consecutive days.Compared with decompression alone,hind limb motor function recovery was superior after decompression for 12 and 48 hours combined with electroacupuncture.However,the recovery of motor function was not significantly different at 14 days after treatment in rats receiving decompression for 12 hours.Platelet-activating factor levels and caspase-9 protein expression were significantly reduced in rats receiving electroacupuncture compared with decompression alone.These findings indicate that compared with decompression alone,Governor Vessel electroacupuncture combined with delayed decompression(48 hours) is more effective in the treatment of upper cervical spinal cord injury.Governor Vessel electroacupuncture combined with early decompression(12 hours) can accelerate the recovery of nerve movement in rats with upper cervical spinal cord injury.Nevertheless,further studies are necessary to confirm whether it is possible to obtain additional benefit compared with early decompression alone.
基金supported by the National Natural Science Foundation of China (81430011 to Xue-Dong Zhou and 81371135 to Ji-Yao Li)Clinical Advanced Technique Award of West China Hospital of Stomatology (LCXJS2015 to Xin Xu)the Brilliant Young Investigator Award,Sichuan University (2015SCU04A16 to Xin Xu)
文摘Saliva is secreted from the salivary glands and has multiple functions, including mouth cleaning and protection, antibacterial effects and digestion. With the rapid advancement in salivaomics, saliva is well recognized as a pool of biological markers.Saliva, as a non-invasive and safe source, could be a substitute for blood in the diagnosis and prognosis of diseases. This review summarizes the latest advancements in saliva-related studies and addresses the potential value of saliva in the early diagnosis of oral diseases, such as dental caries and periodontal disease, as well as cancer, diabetes and other systemic disorders. Saliva biomarkers range from changes in the biochemical indices of DNA, RNA and proteins to the diversi?cation of microbiota structures. This study integrates data reported in the recent literature and discusses the clinical signi?cance and prospects for the application of saliva in the early diagnosis of diseases, translational medicine and precision medicine.
基金supported by the Key Project of Chinese National Programs for Fundamental Research and Development(2010CB731502)the National Natural Science Foundation of China(50978745)
文摘In the last decade, three dimensional discontinuous deformation analyses (3D DDA) has attracted more and more attention of researchers and geotechnical engineers worldwide. The original DDA formulation utilizes a linear displacement function to describe the block movement and deformation, which would cause block expansion under rigid body rotation and thus limit its capability to model block deformation. In this paper, 3D DDA is coupled with tetrahedron finite elements to tackle these two problems. Tetrahedron is the simplest in the 3D domain and makes it easy to implement automatic discretization, even for complex topology shape. Furthermore, element faces will remain planar and element edges will remain straight after deformation for tetrahedron finite elements and polyhedral contact detection schemes can be used directly. The matrices of equilibrium equations for this coupled method are given in detail and an effective contact searching algorithm is suggested. Validation is conducted by comparing the results of the proposed coupled method with that of physical model tests using one of the most common failure modes, i.e., wedge failure. Most of the failure modes predicted by the coupled method agree with the physical model results except for 4 cases out of the total 65 cases. Finally, a complex rockslide example demonstrates the robustness and versatility of the coupled method.
基金This project was supported by the National Natural Science Foundation of China(No.81673757 and No.81603652).
文摘The effect and potential molecular mechanisms of berberine on gluconeogenesis in skeletal muscles and adipose tissues were investigated.After adaptive feeding for one week,8 rats were randomly selected as the normal group and fed on a standard diet.The remaining 32 rats were fed on a high-fat diet and given an intravenous injection of streptozotocin(STZ)for 2 weeks to induce the diabetic models.The diabetic rat models were confirmed by oral glucose tolerance test(OGTT)and randomly divided into 4 groups(n=8 each),which were all fed on a high-fat diet.Berberine(3 g/kg per day)or metformin(183 mg/kg per day)was intragastrically administered to the diabetic rats for 12 weeks,serving as berberine group and metformin group respectively.5-aminoimidazole-4-carboxamide1-β-D-ribofuranoside[AICAR,an agonist of AMP-activated protein kinase(AMPK),0.5 mg/kg per day]was subcutaneously injected to the diabetic rats for 12 weeks,serving as AICAR group.The remaining 8 diabetic rats served as the model group,which was given a 0.5%carboxyl methylcellulose solution by oral gavage.Fasting serum insulin(FINS),OGTT as well as lipid parameters were tested by commercial kit.The protein levels of liver kinase B1(LKB1),AMPK,phosphorylated AMP-activated protein kinase(p-AMPK),transducer of regulated CREB activity 2(TORC2),phosphorylated transducer of regulated CREB activity 2(p-TORC2),phosphoenolpyruvate carboxykinase(PEPCK),and glucose-6-phosphatase(G6Pase)in skeletal muscles and adipose tissues were examined by Western blotting.The results showed that berberine significantly decreased the body weight,plasma glucose,insulin levels,and homeostatic model assessment for insulin resistance(HOMA-IR)of diabetic rats compared with those in the model group.Meanwhile,the serum total triglyceride(TG),total cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C)levels were markedly decreased and high-density lipoprotein cholesterol(HDL-C)level was significantly increased after the treatment with berberine.In addition,we found that berberine significantly increased the expression of p-AMPK and LKB1,while decreasing the p-TORC2 levels in skeletal muscles and adipose tissues.Moreover,the expression of PEPCK and G6Pase was significantly down-regulated after the treatment with berberine compared to the model group.It was suggested that the mechanism by which berberine inhibited peripheral tissue gluconeogenesis may be attributed to the activation of the LKB1-AMPK-TORC2 signaling pathway.
基金the National Natural Science Foundation of China (No. 81372892,81621062, 81520108009)111 Project of MOE China (B14038)+1 种基金the Open Foundation (SKLOD201601, SKLOD2016OF01) from the State Key Laboratory of Oral Disease Sichuan University and for the financial supportSichuan Province Science and Technology Innovation Team Program (JCPT 2011–9)
文摘Proteases are important molecules that are involved in many physiological and pathological processes of the human body,such as growth,apoptosis and metastasis cancer cells.They are potential targets in cancer diagnosis and biotherapy.In this study,we analyzed the salivary protease spectrum of patients with oral squamous cell carcinoma (OSCC),oral benign masses and chronic periodontitis,as well as that of health,using human protease array kits,enzyme-linked immunosorbent assay,western blot and immunofluorescence.The salivary protease spectrum was found to be associated with oral diseases.For example,the saliva of patients with OSCC contained increased numbers of proteases than those of other oral diseases and health.The levels of matrix metalloproteinase (MMP)-1,MMP-2,MMP-10,MMP-12,A disintegrin and metalloprotease (ADAM)9,A disintegrin and metalloprotease with thrombospondin type 13 motifs (ADAMST13),cathepsin V and kallikrein 5 in the saliva of patients with OSCC were significantly increased compared with those of other groups.Taking MMP-1,cathepsin V,kallikrein 5 and ADAM9 as biomarkers of OSCC,cutoff values were199,11.34,9.29 and 202.55 pg·mL?1,respectively.From the area under the curve,sensitivity and specificity,the combination of cathepsin V/kallikrein5/ADAM9 was an optimal biomarker for diagnosing OSCC.Thus,analysis of the salivary protease spectrum may be an innovative and cost-efficient approach to evaluating the health status of the oral cavity.Specifically,increases in cathepsin V,kallikrein 5 and ADAM9 may be useful biomarkers in the screening and diagnosis of OSCC.
基金supported by the National Natural Science Foundation of China (60932003)the National High Technology Research and Development Program of China (863 Program)(2007AA01Z452+2 种基金 2009AA01Z118)Shanghai Municipal Natural Science Foundation (09ZR1414900)The National Undergraduate Innovative Test Program(091024812)
文摘Due to their characteristics of dynamic topology, wireless channels and limited resources, mobile ad hoc networks are particularly vulnerable to a denial of service (DoS) attacks launched by intruders. The effects of flooding attacks in network simulation 2 (NS2) and measured performance parameters are investigated, including packet loss ratio, average delay, throughput and average number of hops under different numbers of attack nodes, flooding frequency, network bandwidth and network size. Simulation results show that with the increase of the flooding frequency and the number of attack nodes, network performance sharply drops. But when the frequency of flooding attacks or the number of attack nodes is greater than a certain value, performance degradation tends to a stable value.
文摘Background: Helicobacter species are best known for their roles in the pathology of gastritis;however, several Helicobacter species also colonize the intestine, and less is known about effects of Helicobacter on the development of intestinal inflammation. To evaluate contributions of Helicobacter in inflammatory bowel disease, we investigated whether and how pre-existing intestinal colonization would affect disease severity and biomarkers of inflammation in experimental IBD. Materials and Methods: Mice were infected with H. muridarum 2 weeks prior to induction of colitis mediated by 3% dextran sulfate (DSS). Disease activity index, stool blood and consistency, colon length, myeloperoxidase, histopathology, blood and lymphatic vessels, and numbers of dilated mucosal crypts were measured in control, DSS-only, H. muridarum-infected, and H. muridarum-infected + DSS mice. Results: Prior to DSS challenge, H. muridarum-infected mice showed little distal gut injury by several indices of colon inflammation with decreased blood vessel density in the submucosa, and lower lymphatic density in the mucosa and submucosa. However, after DSS colitis, H. muridarum-infected mice exhibited significantly greater disease. Weight change, stool bleeding, diarrhea, and angiogenesis were all increased in H. muridarum-infected mice in DSS colitis compared to DSS controls. Conclusions: Our data show that Helicobacter colonization of the intestine, unlike that of the stomach, lowers basal gut inflammatory scores, but increases disease activity and inflammation in an acute colitis model. Intestinal Helicobacter infection may therefore represent a significant sub-clinical factor which predisposes the gut to inflammatory injury.