To study the effects of Icariin on expression of osteopontin （OPN） mRNA and type Ⅰ collagen in rat osteoblasts in vitro and to explore its possible mechanisms in preventing osteoporosis. OB was isolated from calvar...To study the effects of Icariin on expression of osteopontin （OPN） mRNA and type Ⅰ collagen in rat osteoblasts in vitro and to explore its possible mechanisms in preventing osteoporosis. OB was isolated from calvaria of new-born new-born fetal Sprague-Dawley （SD） rats by means of modified sequential collagenase digestion and incubated in MEM medium and the cell morphology was observed under inverted phase contrast microscope, OB was identified by alkaline phosphatase （ALP） staining. Different concentration （0.1μg/mL, 1.0 μg/mL, 10 μ/mL） of Icariin was added to the OB and incubated. The effect of Icariin on the proliferation and osteogenesis of OB was monitored by MTT analysis. The expression of type l collagen was estimated with immunohistochemistry techniques. The expression levels of mRNA of OPN in the cells in every group were examined by reverse-transcriptase ploymerase chain reaction （RT-PCR）. The expression of OPN mRNA and type Ⅰ collagen was strengthened gradually with the increase of Icariin concentration and peaked with 10 μg/mL Icariin on the 5th day. Icariin could significantly promote the expression of OPN mRNA and type Ⅰ collagen in rat osteoblasts in vitro. The levels of expression of OPN mRNA and type Ⅰ collagen were changed with different concentration of Icariin. Icariin could effectively prevent and treat osteoporosis and promote the bone formation.展开更多
The relationship between NaCl concentration and the phase change behavior of microemulsion of anionic surfactant was characterized by the salinity scan experiments.The wettability of WinsorⅠtype surfactant solution(W...The relationship between NaCl concentration and the phase change behavior of microemulsion of anionic surfactant was characterized by the salinity scan experiments.The wettability of WinsorⅠtype surfactant solution(WⅠsolution)and the effect of NaCL concentration on phase change behavior of WⅠsolution and imbibition in oil-wet porous media were investigated by microfluidic experiments in this study.The WⅠsolution and WinsorⅠtype microemulsion are similar in wetting phase with stronger wettability than other phases.Two main mechanisms of WⅠsolution enhancing imbibitions recovery in oil wet porous media are the wetting phase drive and residual oil solubilization.Under the salinity condition of WinsorⅠtype microemulsion,the NaCl concentration has strong impact on the imbibition mechanism of WⅠsolution,the higher the NaCl concentration,the complex the imbibition process and the higher the imbibition efficiency will be.The NaCl concentration has strong impact on the solubilization ability to oil of the WⅠsolution,the higher the NaCl concentration,the stronger the solubility of the WⅠsolution to residual oil will be.展开更多
AIM： To delineate the mechanisms of renal vasoconstriction in hepatorenal syndrome （HRS）, we investigated the expression of type I inositol 1, 4, 5-triphosphate receptors （IP3R I） of kidney in mice with fulminant...AIM： To delineate the mechanisms of renal vasoconstriction in hepatorenal syndrome （HRS）, we investigated the expression of type I inositol 1, 4, 5-triphosphate receptors （IP3R I） of kidney in mice with fulminant hepatic failure （FHF）. METHODS： FHF was induced by lipopolysaccharide （LPS） in D-galactosamine （GAIN） sensitized BALB/c mice. There were 20 mice in normal saline （NS）-treated group, 20 mice in LPS-treated group, 20 mice in GaIN- treated group, and 60 mice in GalN/LPS-treated group （FHF group）. Liver and kidney tissues were obtained at 2, 6, and 9 h after administration. The liver and kidney specimens were stained with hematoxylin-eosin for studying morphological changes under light microscope. The expression of IP3R I in kidney tissue was tested by immunohistochemistry, Western blot and reverse transcription （RT）-PCR. RESULTS： Kidney tissues were morphologically normal at all time points in all groups. IP3R I proteins were found localized in the plasma region of glomerular mesangial cells （GMC） and vascular smooth muscle cells （VSMC） in kidney by immunohistochemical staining. In kidney of mice with FHF at 6 h and 9 h IP3R I staining was upregulated. Results from Western blot demonstrated consistent and significant increment of IP3R I expression in mice with FHF at 6 h and 9 h （t = 3.16, P 〈 0.05; t = 5.43, P 〈 0.01）. Furthermore, we evaluated IP3R I mRNA expression by RT-PCR and observed marked upregulation of IP3R I mRNA in FHF samples at 2 h, 6 h and 9 h compared to controls （t = 2.97, P 〈 0.05; t = 4.42, P 〈 0.01; t = 3.81, P 〈 0.01）. CONCLUSION： The expression of IP3R I protein increased in GMC and renal VSMC of mice with FHF, possibly caused by up-regulation of IP3R I mRNA.展开更多
N-type Si-based type-Ⅰ clathrates with different Ga content were synthesized by combining the solid-state reaction method,melting method and spark plasma sintering （SPS） method.The effects of Ga composition on high...N-type Si-based type-Ⅰ clathrates with different Ga content were synthesized by combining the solid-state reaction method,melting method and spark plasma sintering （SPS） method.The effects of Ga composition on high temperature thermoelectric transport properties were investigated.The results show that at room temperature,the carrier concentration decreases, while the carrier mobility increases slightly with increasing Ga content.The Seebeck coefficient increases with increasing Ga content. Among all the samples,Ba7.93Ga17.13Si28.72exhibits higher Seebeck coefficient than the others and reaches -135μV·K^-1 at 1000 K.The sample prepared by this method exhibits very high electrical conductivity,and reaches 1.95x 10^5 S·m^-1 for Ba8.01Ga16.61Si28.93 at room temperature.The thermal conductivity of all samples is almost temperature independent in the temperature range of 300-1000 K,indicating the behaviour of a typical metal.The maximum ZT value of 0.75 is obtained at 1000 K for the compound Ba7.93Ga17.13Si28.72.展开更多
Recent studies have shown the potential of artificially synthesized conduits in the repair of peripheral nerve injury. Natural biopolymers have received much attention because of their biocompatibility. To investigate...Recent studies have shown the potential of artificially synthesized conduits in the repair of peripheral nerve injury. Natural biopolymers have received much attention because of their biocompatibility. To investigate the effects of novel electrospun absorbable poly(ε-caprolactone)/type Ⅰ collagen nanofiber conduits(biopolymer nanofiber conduits) on the repair of peripheral nerve injury, we bridged 10-mm-long sciatic nerve defects with electrospun absorbable biopolymer nanofiber conduits, poly(ε-caprolactone) or silicone conduits in Sprague-Dawley rats. Rat neurologica1 function was weekly evaluated using sciatic function index within8 weeks after repair. Eight weeks after repair, sciatic nerve myelin sheaths and axon morphology were observed by osmium tetroxide staining, hematoxylin-eosin staining, and transmission electron microscopy.S-100(Schwann cell marker) and CD4(inflammatory marker) immunoreactivities in sciatic nerve were detected by immunohistochemistry. In rats subjected to repair with electrospun absorbable biopolymer nanofiber conduits, no serious inflammatory reactions were observed in rat hind limbs, the morphology of myelin sheaths in the injured sciatic nerve was close to normal. CD4 immunoreactivity was obviously weaker in rats subjected to repair with electrospun absorbable biopolymer nanofiber conduits than in those subjected to repair with poly(ε-caprolactone) or silicone. Rats subjected to repair with electrospun absorbable biopolymer nanofiber conduits tended to have greater sciatic nerve function recovery than those receiving poly(ε-caprolactone) or silicone repair. These results suggest that electrospun absorbable poly(ε-caprolactone)/type Ⅰ collagen nanofiber conduits have the potential of repairing sciatic nerve defects and exhibit good biocompatibility. All experimental procedures were approved by Institutional Animal Care and Use Committee of Taichung Veteran General Hospital, Taiwan, China(La-1031218) on October 2, 2014.展开更多
The Democratic Republic of the Congo holds important reserves of oil shale which is still under geological status.Herein,the characterization and pyrolysis kinetics of typeⅠkerogen-rich oil shale of the western Centr...The Democratic Republic of the Congo holds important reserves of oil shale which is still under geological status.Herein,the characterization and pyrolysis kinetics of typeⅠkerogen-rich oil shale of the western Central Kongo(CK)were investigated.X-ray diffraction,Fourier-transform infrared spectroscopy and thermal analysis(TG/DTA)showed that CK oil shale exhibits a siliceous mineral matrix with a consistent organic matter rich in aliphatic chains.The pyrolysis behavior of kerogen revealed the presence of a single mass loss between 300 and 550°C,estimated at 12.5%and attributed to the oil production stage.Non-isothermal kinetics was performed by determining the activation energy using the iterative isoconversional model-free methods and exhibits a constant value with E=211.5±4.7 kJ mol.1.The most probable kinetic model describing the kerogen pyrolysis mechanism was obtained using the Coats–Redfern and Arrhenius plot methods.The results showed a unique kinetic triplet confirming the nature of kerogen,predominantly typeⅠand reinforcing the previously reported geochemical characteristics of the CK oil shale.Besides,the calculation of thermodynamic parameters(ΔH~*,ΔS~*andΔG~*)corresponding to the pyrolysis of typeⅠkerogen revealed that the process is non-spontaneous,in agreement with DTA experiments.展开更多
BACKGROUND Neurofibromatosis type Ⅰ(NF1) is the most frequent subtype of neurofibromatosis. Its related tumor-suppressor syndromes are characterized by a predisposition to multiple tumor types and other disorder pres...BACKGROUND Neurofibromatosis type Ⅰ(NF1) is the most frequent subtype of neurofibromatosis. Its related tumor-suppressor syndromes are characterized by a predisposition to multiple tumor types and other disorder presentations. In addition, the incidence of tumors is much higher in patients with neurofibromatosis type Ⅰ. However, there are very few reports at home and abroad on this topic. Here, we present a case of NF1 with spindle cell sarcoma.CASE SUMMARY A 50-year-old male was found to have a right axillary mass for 20 years.Specialist examination found cafe-au-lait spots on many parts of the skin,rounded nodules in the skin, a bulge in the right armpit, touching a lump(10 cm× 6 cm, hard, unclear boundary, poor mobility, local tenderness). The anterior side of the thigh felt weakened on the opposite side;in the right groin a swollen lymph node(hard, clear border, good mobility, local tenderness). According to the results of positron emission tomography/computed tomography, puncture pathology and immunohistochemistry, genetic testing, a diagnosis of NF1 with spindle cell sarcoma was confirmed. According to the genetic testing result, the patient was given a targeted treatment with crizotinib.CONCLUSION Surgery, chemotherapy and radiotherapy are the main treatment methods of NF1. However, with the continuous progress of molecular biology research,molecular targeted therapy may bring benefits for patients.展开更多
In this study, serum concentrations of carboxyterminal propeptide of type Ⅰ collagen(PICP) and carboxyterminal cross-linked telopeptide of type Ⅰ collagen (ICTP), which represent the rates of synthesis and degradati...In this study, serum concentrations of carboxyterminal propeptide of type Ⅰ collagen(PICP) and carboxyterminal cross-linked telopeptide of type Ⅰ collagen (ICTP), which represent the rates of synthesis and degradation of type Ⅰ collagen, were determined by radioimmunoassay in 56 patients with multiple myeloma (MM) and 22 healthy controls. It was discovered that serum concentrations of both PICP and ICTP were higher in MM than those in healthy controls (P<0. 01 ). With the disease progressing and the number of bone lesions increasing,serum concentration of ICTP elevated while serum concentration of PICP showed no significant change. Neither serum PICP nor ICTP concentration was related to M-component classes. Our results indicated that serum ICTP concentration was a good serological marker to reflect severity of bone lesions in MM and elevated serum PICP concentration might be due to compensatory increase in type Ⅰ collagen synthesis. Moreover, we also found that serum ICTP concentrations in MM correlated with serum interleukin-6 (IL-6) activities (r= 0. 610, P< 0. 01),which confirms the effectiveness of IL-6 as an osteoclast activating factor.展开更多
BRAF has been recognized as a promising target for cancer therapy. A number of crystal structures have been published. Molecular docking is one of the most effective techniques in the field of computer-aided drug des...BRAF has been recognized as a promising target for cancer therapy. A number of crystal structures have been published. Molecular docking is one of the most effective techniques in the field of computer-aided drug design（CADD）. Appropriate protein conformation and docking method are essential for the successful virtual screening experiments. One approach considering protein flexibility and multiple docking methods was proposed in this study. Six DFG-in/αC-helix-out crystal structures of BRAF, three docking programs（Glide, GOLD and Ligand Fit） and 12 scoring functions were applied for the best combination by judging from the results of pose prediction and retrospective virtual screening（VS）. The most accurate results（mean RMSD of about 0.6 A） of pose prediction were obtained with two complex structures（PDB： 3 C4 C and 3 SKC） using Glide SP. From the retrospective VS, the most active compounds were identified by using the complex structure of 3 SKC, indicated by a ROC/AUC score of 0.998 and an EF of 20.6 at 5% of the database screen with Glide-SP. On the whole, PDB 3 SKC could achieve a higher rate of correct reproduction, a better enrichment and more diverse compounds. A comparison of 3 SKC and the other X-ray crystal structures led to a rationale for the docking results. PDB 3 SKC could achieve a broad range of sulfonamide substitutions through an expanded hydrophobic pocket formed by a further shift of the αC-helix. Our study emphasized the necessity and significance of protein flexibility and scoring functions in both ligand docking and virtual screening.展开更多
Objective Neurofibromatosis typeⅠ(NF1)is an autosomal dominant disorder which is caused by loss-of-function mutations in neurofibromin 1 gene(NF1).Clinically,NF1 mainly manifests several typical features,such as mult...Objective Neurofibromatosis typeⅠ(NF1)is an autosomal dominant disorder which is caused by loss-of-function mutations in neurofibromin 1 gene(NF1).Clinically,NF1 mainly manifests several typical features,such as multiple neurofibromas and café-au-lait spots,as well as axillary freckling and Lisch nodules in iris.The aim of the current study is to identification a splicing mutation and genotype-phenotype correlation.展开更多
文摘To study the effects of Icariin on expression of osteopontin （OPN） mRNA and type Ⅰ collagen in rat osteoblasts in vitro and to explore its possible mechanisms in preventing osteoporosis. OB was isolated from calvaria of new-born new-born fetal Sprague-Dawley （SD） rats by means of modified sequential collagenase digestion and incubated in MEM medium and the cell morphology was observed under inverted phase contrast microscope, OB was identified by alkaline phosphatase （ALP） staining. Different concentration （0.1μg/mL, 1.0 μg/mL, 10 μ/mL） of Icariin was added to the OB and incubated. The effect of Icariin on the proliferation and osteogenesis of OB was monitored by MTT analysis. The expression of type l collagen was estimated with immunohistochemistry techniques. The expression levels of mRNA of OPN in the cells in every group were examined by reverse-transcriptase ploymerase chain reaction （RT-PCR）. The expression of OPN mRNA and type Ⅰ collagen was strengthened gradually with the increase of Icariin concentration and peaked with 10 μg/mL Icariin on the 5th day. Icariin could significantly promote the expression of OPN mRNA and type Ⅰ collagen in rat osteoblasts in vitro. The levels of expression of OPN mRNA and type Ⅰ collagen were changed with different concentration of Icariin. Icariin could effectively prevent and treat osteoporosis and promote the bone formation.
基金Supported by China National Science and Technology Major Project(2017ZX05009-005-003).
文摘The relationship between NaCl concentration and the phase change behavior of microemulsion of anionic surfactant was characterized by the salinity scan experiments.The wettability of WinsorⅠtype surfactant solution(WⅠsolution)and the effect of NaCL concentration on phase change behavior of WⅠsolution and imbibition in oil-wet porous media were investigated by microfluidic experiments in this study.The WⅠsolution and WinsorⅠtype microemulsion are similar in wetting phase with stronger wettability than other phases.Two main mechanisms of WⅠsolution enhancing imbibitions recovery in oil wet porous media are the wetting phase drive and residual oil solubilization.Under the salinity condition of WinsorⅠtype microemulsion,the NaCl concentration has strong impact on the imbibition mechanism of WⅠsolution,the higher the NaCl concentration,the complex the imbibition process and the higher the imbibition efficiency will be.The NaCl concentration has strong impact on the solubilization ability to oil of the WⅠsolution,the higher the NaCl concentration,the stronger the solubility of the WⅠsolution to residual oil will be.
基金Supported by National Natural Science Foundation of China, No. 30270607
文摘AIM： To delineate the mechanisms of renal vasoconstriction in hepatorenal syndrome （HRS）, we investigated the expression of type I inositol 1, 4, 5-triphosphate receptors （IP3R I） of kidney in mice with fulminant hepatic failure （FHF）. METHODS： FHF was induced by lipopolysaccharide （LPS） in D-galactosamine （GAIN） sensitized BALB/c mice. There were 20 mice in normal saline （NS）-treated group, 20 mice in LPS-treated group, 20 mice in GaIN- treated group, and 60 mice in GalN/LPS-treated group （FHF group）. Liver and kidney tissues were obtained at 2, 6, and 9 h after administration. The liver and kidney specimens were stained with hematoxylin-eosin for studying morphological changes under light microscope. The expression of IP3R I in kidney tissue was tested by immunohistochemistry, Western blot and reverse transcription （RT）-PCR. RESULTS： Kidney tissues were morphologically normal at all time points in all groups. IP3R I proteins were found localized in the plasma region of glomerular mesangial cells （GMC） and vascular smooth muscle cells （VSMC） in kidney by immunohistochemical staining. In kidney of mice with FHF at 6 h and 9 h IP3R I staining was upregulated. Results from Western blot demonstrated consistent and significant increment of IP3R I expression in mice with FHF at 6 h and 9 h （t = 3.16, P 〈 0.05; t = 5.43, P 〈 0.01）. Furthermore, we evaluated IP3R I mRNA expression by RT-PCR and observed marked upregulation of IP3R I mRNA in FHF samples at 2 h, 6 h and 9 h compared to controls （t = 2.97, P 〈 0.05; t = 4.42, P 〈 0.01; t = 3.81, P 〈 0.01）. CONCLUSION： The expression of IP3R I protein increased in GMC and renal VSMC of mice with FHF, possibly caused by up-regulation of IP3R I mRNA.
基金Project supported by the National Basic Research Program of China (Grant Nos 2007CB607501 and 2007CB607503)Yunnan Natural Science Fund (Grant No 2008CD114)
文摘N-type Si-based type-Ⅰ clathrates with different Ga content were synthesized by combining the solid-state reaction method,melting method and spark plasma sintering （SPS） method.The effects of Ga composition on high temperature thermoelectric transport properties were investigated.The results show that at room temperature,the carrier concentration decreases, while the carrier mobility increases slightly with increasing Ga content.The Seebeck coefficient increases with increasing Ga content. Among all the samples,Ba7.93Ga17.13Si28.72exhibits higher Seebeck coefficient than the others and reaches -135μV·K^-1 at 1000 K.The sample prepared by this method exhibits very high electrical conductivity,and reaches 1.95x 10^5 S·m^-1 for Ba8.01Ga16.61Si28.93 at room temperature.The thermal conductivity of all samples is almost temperature independent in the temperature range of 300-1000 K,indicating the behaviour of a typical metal.The maximum ZT value of 0.75 is obtained at 1000 K for the compound Ba7.93Ga17.13Si28.72.
基金supported by grants from the Taichung Veterans General Hospital and Central Taiwan University of Science and Technology,No.TCVGH-CTUST1047701(to CCS and BSL)Taichung Veterans General Hospital,No.TCVGH-1034907C(to CCS),Taiwan,China
文摘Recent studies have shown the potential of artificially synthesized conduits in the repair of peripheral nerve injury. Natural biopolymers have received much attention because of their biocompatibility. To investigate the effects of novel electrospun absorbable poly(ε-caprolactone)/type Ⅰ collagen nanofiber conduits(biopolymer nanofiber conduits) on the repair of peripheral nerve injury, we bridged 10-mm-long sciatic nerve defects with electrospun absorbable biopolymer nanofiber conduits, poly(ε-caprolactone) or silicone conduits in Sprague-Dawley rats. Rat neurologica1 function was weekly evaluated using sciatic function index within8 weeks after repair. Eight weeks after repair, sciatic nerve myelin sheaths and axon morphology were observed by osmium tetroxide staining, hematoxylin-eosin staining, and transmission electron microscopy.S-100(Schwann cell marker) and CD4(inflammatory marker) immunoreactivities in sciatic nerve were detected by immunohistochemistry. In rats subjected to repair with electrospun absorbable biopolymer nanofiber conduits, no serious inflammatory reactions were observed in rat hind limbs, the morphology of myelin sheaths in the injured sciatic nerve was close to normal. CD4 immunoreactivity was obviously weaker in rats subjected to repair with electrospun absorbable biopolymer nanofiber conduits than in those subjected to repair with poly(ε-caprolactone) or silicone. Rats subjected to repair with electrospun absorbable biopolymer nanofiber conduits tended to have greater sciatic nerve function recovery than those receiving poly(ε-caprolactone) or silicone repair. These results suggest that electrospun absorbable poly(ε-caprolactone)/type Ⅰ collagen nanofiber conduits have the potential of repairing sciatic nerve defects and exhibit good biocompatibility. All experimental procedures were approved by Institutional Animal Care and Use Committee of Taichung Veteran General Hospital, Taiwan, China(La-1031218) on October 2, 2014.
基金financially supported by University of Mohammed V-Morocco under the Project No.SCH 04/09 and HassanⅡAcademy of Science and Technology,Morocco.
文摘The Democratic Republic of the Congo holds important reserves of oil shale which is still under geological status.Herein,the characterization and pyrolysis kinetics of typeⅠkerogen-rich oil shale of the western Central Kongo(CK)were investigated.X-ray diffraction,Fourier-transform infrared spectroscopy and thermal analysis(TG/DTA)showed that CK oil shale exhibits a siliceous mineral matrix with a consistent organic matter rich in aliphatic chains.The pyrolysis behavior of kerogen revealed the presence of a single mass loss between 300 and 550°C,estimated at 12.5%and attributed to the oil production stage.Non-isothermal kinetics was performed by determining the activation energy using the iterative isoconversional model-free methods and exhibits a constant value with E=211.5±4.7 kJ mol.1.The most probable kinetic model describing the kerogen pyrolysis mechanism was obtained using the Coats–Redfern and Arrhenius plot methods.The results showed a unique kinetic triplet confirming the nature of kerogen,predominantly typeⅠand reinforcing the previously reported geochemical characteristics of the CK oil shale.Besides,the calculation of thermodynamic parameters(ΔH~*,ΔS~*andΔG~*)corresponding to the pyrolysis of typeⅠkerogen revealed that the process is non-spontaneous,in agreement with DTA experiments.
文摘BACKGROUND Neurofibromatosis type Ⅰ(NF1) is the most frequent subtype of neurofibromatosis. Its related tumor-suppressor syndromes are characterized by a predisposition to multiple tumor types and other disorder presentations. In addition, the incidence of tumors is much higher in patients with neurofibromatosis type Ⅰ. However, there are very few reports at home and abroad on this topic. Here, we present a case of NF1 with spindle cell sarcoma.CASE SUMMARY A 50-year-old male was found to have a right axillary mass for 20 years.Specialist examination found cafe-au-lait spots on many parts of the skin,rounded nodules in the skin, a bulge in the right armpit, touching a lump(10 cm× 6 cm, hard, unclear boundary, poor mobility, local tenderness). The anterior side of the thigh felt weakened on the opposite side;in the right groin a swollen lymph node(hard, clear border, good mobility, local tenderness). According to the results of positron emission tomography/computed tomography, puncture pathology and immunohistochemistry, genetic testing, a diagnosis of NF1 with spindle cell sarcoma was confirmed. According to the genetic testing result, the patient was given a targeted treatment with crizotinib.CONCLUSION Surgery, chemotherapy and radiotherapy are the main treatment methods of NF1. However, with the continuous progress of molecular biology research,molecular targeted therapy may bring benefits for patients.
文摘In this study, serum concentrations of carboxyterminal propeptide of type Ⅰ collagen(PICP) and carboxyterminal cross-linked telopeptide of type Ⅰ collagen (ICTP), which represent the rates of synthesis and degradation of type Ⅰ collagen, were determined by radioimmunoassay in 56 patients with multiple myeloma (MM) and 22 healthy controls. It was discovered that serum concentrations of both PICP and ICTP were higher in MM than those in healthy controls (P<0. 01 ). With the disease progressing and the number of bone lesions increasing,serum concentration of ICTP elevated while serum concentration of PICP showed no significant change. Neither serum PICP nor ICTP concentration was related to M-component classes. Our results indicated that serum ICTP concentration was a good serological marker to reflect severity of bone lesions in MM and elevated serum PICP concentration might be due to compensatory increase in type Ⅰ collagen synthesis. Moreover, we also found that serum ICTP concentrations in MM correlated with serum interleukin-6 (IL-6) activities (r= 0. 610, P< 0. 01),which confirms the effectiveness of IL-6 as an osteoclast activating factor.
基金supported by the National Natural Science Foundation of China(21102181,81302634 and 21572273)
文摘BRAF has been recognized as a promising target for cancer therapy. A number of crystal structures have been published. Molecular docking is one of the most effective techniques in the field of computer-aided drug design（CADD）. Appropriate protein conformation and docking method are essential for the successful virtual screening experiments. One approach considering protein flexibility and multiple docking methods was proposed in this study. Six DFG-in/αC-helix-out crystal structures of BRAF, three docking programs（Glide, GOLD and Ligand Fit） and 12 scoring functions were applied for the best combination by judging from the results of pose prediction and retrospective virtual screening（VS）. The most accurate results（mean RMSD of about 0.6 A） of pose prediction were obtained with two complex structures（PDB： 3 C4 C and 3 SKC） using Glide SP. From the retrospective VS, the most active compounds were identified by using the complex structure of 3 SKC, indicated by a ROC/AUC score of 0.998 and an EF of 20.6 at 5% of the database screen with Glide-SP. On the whole, PDB 3 SKC could achieve a higher rate of correct reproduction, a better enrichment and more diverse compounds. A comparison of 3 SKC and the other X-ray crystal structures led to a rationale for the docking results. PDB 3 SKC could achieve a broad range of sulfonamide substitutions through an expanded hydrophobic pocket formed by a further shift of the αC-helix. Our study emphasized the necessity and significance of protein flexibility and scoring functions in both ligand docking and virtual screening.
文摘Objective Neurofibromatosis typeⅠ(NF1)is an autosomal dominant disorder which is caused by loss-of-function mutations in neurofibromin 1 gene(NF1).Clinically,NF1 mainly manifests several typical features,such as multiple neurofibromas and café-au-lait spots,as well as axillary freckling and Lisch nodules in iris.The aim of the current study is to identification a splicing mutation and genotype-phenotype correlation.
