Objective: To observe the effects of Xuezhikang (red yeast rice) on blood lipids, blood rheology, and expression of P65 and tissue factor, and to explore the anti-atherosclerosis effect and related mechanisms of Xuezh...Objective: To observe the effects of Xuezhikang (red yeast rice) on blood lipids, blood rheology, and expression of P65 and tissue factor, and to explore the anti-atherosclerosis effect and related mechanisms of Xuezhikang (red yeast rice). Methods: 32 Wistar rats were randomly divided into normal control group, Xuezhikang treatment group, lovastatin treatment group and atherosclerosis model group (8 in each group). Blood lipids, blood rheology, malondialdehyde (MDA), total antioxidant capacity (T-AOC), and expression of aortic tissue factor (TF) and P65 were measured in each group. Results:(1) Both Xuezhikang and lovastatin could reduce blood lipid levels, but there was no significant difference between the two groups;(2) Both Xuezhikang and lovastatin can improve the hemorheology of atherosclerotic rats, but the difference between the two groups is not significant;(3) Compared with lovastatin, Xuezhikang inhibited the expression of TF and P65 in aorta of rats with atherosclerosis;(4) Compared with lovastatin, the Xuezhikang group had lower MDA levels and higher T-AOC. Conclusion: Xuezhikang can improve blood lipid levels and hemorheology in rats with atherosclerosis. Compared with lovastatin, Xuezhikang has stronger effects on inhibiting oxidative stress and down-regulating the expression of tissue factor and P65.展开更多
The connective tissue growth factor (CTGF) expression in cultured corneal fibroblasts and its effect on corneal fibroblasts proliferation in vitro were examined. Total RNA was extracted from early passaged rabbit corn...The connective tissue growth factor (CTGF) expression in cultured corneal fibroblasts and its effect on corneal fibroblasts proliferation in vitro were examined. Total RNA was extracted from early passaged rabbit corneal fibroblasts by guanidine isothiocyanate one-step method and mRNA was reversely transcripted into complementary DNA (cDNA). Specific CTGF primers were used in the PCR reaction and the products were analyzed by electrophoresis to determine the expression of mRNA for CTGF against DNA marker. House-keeping gene GAPDH was used as control. Different concentrations of CTGF (0.5, 5, 50, 500, 5 000, 50 000 ng/ml) were added into the third passaged corneal fibroblast culture system, and its effect on corneal fibroblast proliferation was measured by MTT method. The results showed that compared with a GAPDH 450 bp band, CTGF RT-PCR product showed a specific 120 bp band as expected. CTGF produced a dose-dependent increase in the proliferation of corneal fibroblasts but it inhibited fibroblast proliferation at higher concentrations (5 000 and 50 000 ng/ml). It was concluded that proliferating corneal fibroblasts produce CTGF and CTGF helps to promote corneal fibroblast proliferation. The results indicated that CTGF might be involved in the corneal wound healing after photorefractive keratectomy in which corneal fibroblasts are activated to proliferate and secrete growth factors that in turn promote corneal fibroblast proliferation.展开更多
Tissue factor（TF）, the cell surface receptor and requisite cofactor for the inactive serine protease factor VⅡa（VⅡa）, binds VⅡa and its zymogen factor VⅡ with picomolar affinity on the cell surface. The TF：V...Tissue factor（TF）, the cell surface receptor and requisite cofactor for the inactive serine protease factor VⅡa（VⅡa）, binds VⅡa and its zymogen factor VⅡ with picomolar affinity on the cell surface. The TF：VⅡa complex proteolytically converts downstream zymogen factors X and IX to their active protease states in the cascade responsible for thrombogenesis and hemostasis. The TF pathway also produces cellular signaling through protease activated receptors. Here we present a crystal structure of the completely intact surface domain of TF in complex with VⅡa that reveals a significant conformational difference as compared to free TF. A long loop of residue 78~91 of the tissue factor（named Ω loop here） was found to have well-ordered conformation, whereas this loop in free TF has an expanded conformation and is largely disordered. This loop adopts a tight conformation consisting of five β turns in the TF：VⅡa complex. The Ω loop is located at the interface of the proteins of the complex, has a few interactions with VⅡa, and is possible to accommodate the sequence variations of TF in different mammalian species.展开更多
Breast cancer is a leading cause of cancer death in women, worldwide. Fortunately, breast cancer is relatively chemosensitive, with recent advances leading to the development of effective therapeutic strategies, signi...Breast cancer is a leading cause of cancer death in women, worldwide. Fortunately, breast cancer is relatively chemosensitive, with recent advances leading to the development of effective therapeutic strategies, significantly increasing disease cure rate. However, disease recurrence and treatment of cases lacking therapeutic molecular targets, such as epidermal growth factor receptor 2 and hormone receptors, referred to as triple-negative breast cancers, still pose major hurdles in the treatment of breast cancer. Thus, novel therapeutic approaches to treat aggressive breast cancers are essential. Blood coagulation factor VII(fV II) is produced in the liver and secreted into the blood stream. Tissue factor(TF), the cellular receptor for fV II, is an integral membrane protein that plays key roles in the extrinsic coagulation cascade. TF is overexpressed in breast cancer tissues. The TF-fV II complex may be formed in the absence of injury, because f VII potentially exists in the tissue fluid within cancer tissues. The active form of this complex(TF-fV IIa) may stimulate the expression of numerous malignant phenotypes in breast cancer cells. Thus, the TF-fV II pathway is a potentially attractive target for breast cancer treatment. To date, a number of studies investigating the mecha-nisms by which TF-fV II signaling contributes to breast cancer progression, have been conducted. In this review, we summarize the mechanisms controlling TF and fV II synthesis and regulation in breast cancer cells. Our current understanding of the TF-fV II pathway as a mediator of breast cancer progression will be also described. Finally, we will discuss how this knowledge can be applied to the design of future therapeutic strategies.展开更多
Gal alpha(1, 3) Gal (gal epitope) is a carbohydrate epitope and synthesized in large amount by alpha(1, 3) galactosyltransferase [alpha(1, 3) GT] enzyme on the cells of lower mammalian animals such as pigs and mice. H...Gal alpha(1, 3) Gal (gal epitope) is a carbohydrate epitope and synthesized in large amount by alpha(1, 3) galactosyltransferase [alpha(1, 3) GT] enzyme on the cells of lower mammalian animals such as pigs and mice. Human has no gal epitope due to the inactivation of alpha(1, 3) GT gene but produces a large amount of antibodies (anti-Gal) which recognize Gal alpha(1, 3) Gal structures specifically. In this study, a replication-deficient recombinant adenoviral vector Ad5sGT containing pig alpha(1, 3) GT cDNA was constructed and characterized. Adenoviral vector-mediated transfer of pig alpha(1, 3) GT gene into human tumor cells such as malignant melanoma A375, stomach cancer SGC-7901, and lung cancer SPC-A-1 was reported for the first time. Results showed that Gal epitope did not increase the sensitivity of human tumor cells to human complement-mediated lysis, although human complement activation and the binding of human IgG and IgM natural antibodies to human tumor cells were enhanced significantly after Ad5sGT transduction. Appearance of gal epitope on the human tumor cells changed the expression of cell surface carbohydrates reacting with Ulex europaeus I (UEA I) lectins, Vicia villosa agglutinin (VVA), Arachis hypogaea agglutinin (PNA), and Glycine max agglutinin (SBA) to different degrees. In addition, no effect of gal epitope on the growth in vitro of human tumor cells was observed in MTT assay.展开更多
AIM: To help clarifying the possibility of connective-tissue diseases in men with penile or testicular prostheses. METHODS: Eight patients underwent inflatable penile prostheses and 15, testicular prostheses consented...AIM: To help clarifying the possibility of connective-tissue diseases in men with penile or testicular prostheses. METHODS: Eight patients underwent inflatable penile prostheses and 15, testicular prostheses consented to the study. Their medical records were reviewed and a follow-up interview and physical and serological examinations were performed. RESULTS: In patients with penile prostheses, there was no abnormal antinuclear antibody (ANA) or IgM elevation. The serum levels of the rheumatoid factor (RF), C4, IgA and IgG were abnormal in one patient, and the levels of erythrocyte sedimentation rate (ESR) and C3, abnormal in two. Four had elevated IgE. In patients with testicular prostheses, there was no abnormal RF, ANA or IgM. The serum levels of ESR and IgA were abnormal in two, and three had abnormal C4, ten abnormal C3, and eleven decreased IgG. All had increased IgE. Men with penile prostheses had higher serum levels of IgG and IgM than those with testicular prostheses (P=0.001, P=0.016, respectively). The rates of abnormal values of IgE and IgG were higher in men with testicular prostheses than in men with penile prostheses (P=0.008, P=0.009, respectively). Physical examination was normal in all patients and nobody had documented symptoms pertinent to connective-tissue diseases. CONCLUSION: Our findings suggest that the risk of connective-tissue diseases is not higher in patients wearing prostheses as the ANA is negative and there is no apparent manifestation suggestive of connective-tissue diseases.展开更多
Objective:To determine the effect of Salvianolic acid B (Sal B) on glucose and lipid metabolism in mice with high-fat diet (HFD)-induced obesity,and to investigate the underlying mechanisms by measuring the expression...Objective:To determine the effect of Salvianolic acid B (Sal B) on glucose and lipid metabolism in mice with high-fat diet (HFD)-induced obesity,and to investigate the underlying mechanisms by measuring the expression levels of key adipogenic transcription factors.Methods:Six-week-old C57BL/6J male mice were fed for 12 weeks with a HFD to induce obesity or a standard diet to serve as normal controls.A mean body weight increase of more than 20% after these 12 weeks was used as the criteria for obesity.HFD-fed obese mice then received a supplement of Sal B (100 mg/kg body weight/day),metformin (75 mg/kg body weight/day) or water (an equivalent volume;served as model controls) by oral gavage for an additional 8 weeks,and the normal controls received water (an equivalent volume) by oral gavage for the same period.Results:Sal B significantly reduced body weight gain (P <.05) without influencing food intake in HFD-fed obese mice relative to model controls.Sal B also reduced the body fat mass of the obese mice relative to model controls in a time-dependent manner (P <.05).Sal B significantly decreased the serum concentrations of low-density lipoprotein cholesterol,total cholesterol,triglyceride and free fatty acids by 25.5%,20.2%,20.6% and 13.4%,respectively,and increased the concentration of high-density lipoprotein cholesterol by 50.1% relative to model controls.In addition,Sal B significantly lowered fasting glucose concentrations and improved insulin sensitivity relative to model controls (P <.05).Sal B acted by ameliorating the histopathological changes in both brown and white adipose tissues of obese mice.Moreover,in brown adipose tissue,Sal B up-regulated the mRNA and protein expression of PPARγ and c/EBPα,and the protein expression of PPARα and SREBP-1 (P <.05).In white adipose tissue,Sal B down-regulated the mRNA expression of PPARγ and c/EBPα,and decreased the protein expression of PPARγ and SREBP-1(P <.05).Conclusjons:The results suggest that Sal B can reduce body weight gain and regulate glucose and lipid metabolism in mice with diet-induced obesity by regulating adipogenic transcription factors in their adipose tissues.展开更多
文摘Objective: To observe the effects of Xuezhikang (red yeast rice) on blood lipids, blood rheology, and expression of P65 and tissue factor, and to explore the anti-atherosclerosis effect and related mechanisms of Xuezhikang (red yeast rice). Methods: 32 Wistar rats were randomly divided into normal control group, Xuezhikang treatment group, lovastatin treatment group and atherosclerosis model group (8 in each group). Blood lipids, blood rheology, malondialdehyde (MDA), total antioxidant capacity (T-AOC), and expression of aortic tissue factor (TF) and P65 were measured in each group. Results:(1) Both Xuezhikang and lovastatin could reduce blood lipid levels, but there was no significant difference between the two groups;(2) Both Xuezhikang and lovastatin can improve the hemorheology of atherosclerotic rats, but the difference between the two groups is not significant;(3) Compared with lovastatin, Xuezhikang inhibited the expression of TF and P65 in aorta of rats with atherosclerosis;(4) Compared with lovastatin, the Xuezhikang group had lower MDA levels and higher T-AOC. Conclusion: Xuezhikang can improve blood lipid levels and hemorheology in rats with atherosclerosis. Compared with lovastatin, Xuezhikang has stronger effects on inhibiting oxidative stress and down-regulating the expression of tissue factor and P65.
文摘The connective tissue growth factor (CTGF) expression in cultured corneal fibroblasts and its effect on corneal fibroblasts proliferation in vitro were examined. Total RNA was extracted from early passaged rabbit corneal fibroblasts by guanidine isothiocyanate one-step method and mRNA was reversely transcripted into complementary DNA (cDNA). Specific CTGF primers were used in the PCR reaction and the products were analyzed by electrophoresis to determine the expression of mRNA for CTGF against DNA marker. House-keeping gene GAPDH was used as control. Different concentrations of CTGF (0.5, 5, 50, 500, 5 000, 50 000 ng/ml) were added into the third passaged corneal fibroblast culture system, and its effect on corneal fibroblast proliferation was measured by MTT method. The results showed that compared with a GAPDH 450 bp band, CTGF RT-PCR product showed a specific 120 bp band as expected. CTGF produced a dose-dependent increase in the proliferation of corneal fibroblasts but it inhibited fibroblast proliferation at higher concentrations (5 000 and 50 000 ng/ml). It was concluded that proliferating corneal fibroblasts produce CTGF and CTGF helps to promote corneal fibroblast proliferation. The results indicated that CTGF might be involved in the corneal wound healing after photorefractive keratectomy in which corneal fibroblasts are activated to proliferate and secrete growth factors that in turn promote corneal fibroblast proliferation.
基金financially supported by grants from National Natural Science Foundation of China(31370737,31400637,31570745,31670739)Ministry of Science and Technology(2017YFE0103200)
文摘Tissue factor（TF）, the cell surface receptor and requisite cofactor for the inactive serine protease factor VⅡa（VⅡa）, binds VⅡa and its zymogen factor VⅡ with picomolar affinity on the cell surface. The TF：VⅡa complex proteolytically converts downstream zymogen factors X and IX to their active protease states in the cascade responsible for thrombogenesis and hemostasis. The TF pathway also produces cellular signaling through protease activated receptors. Here we present a crystal structure of the completely intact surface domain of TF in complex with VⅡa that reveals a significant conformational difference as compared to free TF. A long loop of residue 78~91 of the tissue factor（named Ω loop here） was found to have well-ordered conformation, whereas this loop in free TF has an expanded conformation and is largely disordered. This loop adopts a tight conformation consisting of five β turns in the TF：VⅡa complex. The Ω loop is located at the interface of the proteins of the complex, has a few interactions with VⅡa, and is possible to accommodate the sequence variations of TF in different mammalian species.
文摘Breast cancer is a leading cause of cancer death in women, worldwide. Fortunately, breast cancer is relatively chemosensitive, with recent advances leading to the development of effective therapeutic strategies, significantly increasing disease cure rate. However, disease recurrence and treatment of cases lacking therapeutic molecular targets, such as epidermal growth factor receptor 2 and hormone receptors, referred to as triple-negative breast cancers, still pose major hurdles in the treatment of breast cancer. Thus, novel therapeutic approaches to treat aggressive breast cancers are essential. Blood coagulation factor VII(fV II) is produced in the liver and secreted into the blood stream. Tissue factor(TF), the cellular receptor for fV II, is an integral membrane protein that plays key roles in the extrinsic coagulation cascade. TF is overexpressed in breast cancer tissues. The TF-fV II complex may be formed in the absence of injury, because f VII potentially exists in the tissue fluid within cancer tissues. The active form of this complex(TF-fV IIa) may stimulate the expression of numerous malignant phenotypes in breast cancer cells. Thus, the TF-fV II pathway is a potentially attractive target for breast cancer treatment. To date, a number of studies investigating the mecha-nisms by which TF-fV II signaling contributes to breast cancer progression, have been conducted. In this review, we summarize the mechanisms controlling TF and fV II synthesis and regulation in breast cancer cells. Our current understanding of the TF-fV II pathway as a mediator of breast cancer progression will be also described. Finally, we will discuss how this knowledge can be applied to the design of future therapeutic strategies.
基金National..973" project, the Special Funds for Major State Bacsic Reseaxch of China (G1999053905) and NationalNatural Science Fou
文摘Gal alpha(1, 3) Gal (gal epitope) is a carbohydrate epitope and synthesized in large amount by alpha(1, 3) galactosyltransferase [alpha(1, 3) GT] enzyme on the cells of lower mammalian animals such as pigs and mice. Human has no gal epitope due to the inactivation of alpha(1, 3) GT gene but produces a large amount of antibodies (anti-Gal) which recognize Gal alpha(1, 3) Gal structures specifically. In this study, a replication-deficient recombinant adenoviral vector Ad5sGT containing pig alpha(1, 3) GT cDNA was constructed and characterized. Adenoviral vector-mediated transfer of pig alpha(1, 3) GT gene into human tumor cells such as malignant melanoma A375, stomach cancer SGC-7901, and lung cancer SPC-A-1 was reported for the first time. Results showed that Gal epitope did not increase the sensitivity of human tumor cells to human complement-mediated lysis, although human complement activation and the binding of human IgG and IgM natural antibodies to human tumor cells were enhanced significantly after Ad5sGT transduction. Appearance of gal epitope on the human tumor cells changed the expression of cell surface carbohydrates reacting with Ulex europaeus I (UEA I) lectins, Vicia villosa agglutinin (VVA), Arachis hypogaea agglutinin (PNA), and Glycine max agglutinin (SBA) to different degrees. In addition, no effect of gal epitope on the growth in vitro of human tumor cells was observed in MTT assay.
文摘AIM: To help clarifying the possibility of connective-tissue diseases in men with penile or testicular prostheses. METHODS: Eight patients underwent inflatable penile prostheses and 15, testicular prostheses consented to the study. Their medical records were reviewed and a follow-up interview and physical and serological examinations were performed. RESULTS: In patients with penile prostheses, there was no abnormal antinuclear antibody (ANA) or IgM elevation. The serum levels of the rheumatoid factor (RF), C4, IgA and IgG were abnormal in one patient, and the levels of erythrocyte sedimentation rate (ESR) and C3, abnormal in two. Four had elevated IgE. In patients with testicular prostheses, there was no abnormal RF, ANA or IgM. The serum levels of ESR and IgA were abnormal in two, and three had abnormal C4, ten abnormal C3, and eleven decreased IgG. All had increased IgE. Men with penile prostheses had higher serum levels of IgG and IgM than those with testicular prostheses (P=0.001, P=0.016, respectively). The rates of abnormal values of IgE and IgG were higher in men with testicular prostheses than in men with penile prostheses (P=0.008, P=0.009, respectively). Physical examination was normal in all patients and nobody had documented symptoms pertinent to connective-tissue diseases. CONCLUSION: Our findings suggest that the risk of connective-tissue diseases is not higher in patients wearing prostheses as the ANA is negative and there is no apparent manifestation suggestive of connective-tissue diseases.
基金This study is supported by grants from the National Natural Science Foundation of China(81274041 and 81503540)the International Cooperation Projects of MOE(2011DFA30920)+1 种基金a Co-construction Project of Beijing Board of Education(0101216-14)a Research Project of the Beijing University of Chinese Medicine(2014-X-003).
文摘Objective:To determine the effect of Salvianolic acid B (Sal B) on glucose and lipid metabolism in mice with high-fat diet (HFD)-induced obesity,and to investigate the underlying mechanisms by measuring the expression levels of key adipogenic transcription factors.Methods:Six-week-old C57BL/6J male mice were fed for 12 weeks with a HFD to induce obesity or a standard diet to serve as normal controls.A mean body weight increase of more than 20% after these 12 weeks was used as the criteria for obesity.HFD-fed obese mice then received a supplement of Sal B (100 mg/kg body weight/day),metformin (75 mg/kg body weight/day) or water (an equivalent volume;served as model controls) by oral gavage for an additional 8 weeks,and the normal controls received water (an equivalent volume) by oral gavage for the same period.Results:Sal B significantly reduced body weight gain (P <.05) without influencing food intake in HFD-fed obese mice relative to model controls.Sal B also reduced the body fat mass of the obese mice relative to model controls in a time-dependent manner (P <.05).Sal B significantly decreased the serum concentrations of low-density lipoprotein cholesterol,total cholesterol,triglyceride and free fatty acids by 25.5%,20.2%,20.6% and 13.4%,respectively,and increased the concentration of high-density lipoprotein cholesterol by 50.1% relative to model controls.In addition,Sal B significantly lowered fasting glucose concentrations and improved insulin sensitivity relative to model controls (P <.05).Sal B acted by ameliorating the histopathological changes in both brown and white adipose tissues of obese mice.Moreover,in brown adipose tissue,Sal B up-regulated the mRNA and protein expression of PPARγ and c/EBPα,and the protein expression of PPARα and SREBP-1 (P <.05).In white adipose tissue,Sal B down-regulated the mRNA expression of PPARγ and c/EBPα,and decreased the protein expression of PPARγ and SREBP-1(P <.05).Conclusjons:The results suggest that Sal B can reduce body weight gain and regulate glucose and lipid metabolism in mice with diet-induced obesity by regulating adipogenic transcription factors in their adipose tissues.
