Changes in lipid metabolism have been implicated in protection against infectious diseases. In the first experiment of this study, we measured clinical lipid parameters in a murine model where the unmethylated cytidin...Changes in lipid metabolism have been implicated in protection against infectious diseases. In the first experiment of this study, we measured clinical lipid parameters in a murine model where the unmethylated cytidine phosphate guanosine (CpG) oligodinucleotide (ODN1826), a Toll-like receptor 9 (TLR9) agonist was administered in combination with D-galactosamine (GalN) that caused relatively liver-specific inflammation and toxicity. In the control mice group injected with phosphate-buffered saline (PBS) (acute psychological stress model associated with blood sampling), the serum triglyceride (TG) levels showed a rapid decrease followed by a rebound at 24 h as we have recently reported. However, such a TG rebound was impaired in the CpG/GalN- and solely CpG-treated groups of mice despite an absence of liver injury based on serum alanine aminotransferase levels in the latter group. Thus, the stress-associated serum TG rebound was abrogated by the injection of a sub-hepatotoxic CpG dose. In the second experiment, we simply measured the hepatic CD36 and SACRB1 (the gene for scavenger receptor B1 (SR-B1)) transcripts after the i.p. administration of PBS, CpG or CpG/GalN. There was a remarkable elevation of hepatic CD36 transcript expression in both the CpG- and CpG/GalN-treated mice at 8 h post-CpG injection whereas the increase in the PBS-treated mice was slower than the former two groups, suggesting that hepatic CD36 transcript expression is more pronounced in the combined stress models than under psychological stress alone. The individual mice data showed that the increase in CD36 expression was accompanied by a reduction in SCARB1 mRNA, showing reciprocal regulation between these two genes. Together with our previously reported findings, these data suggest that, in a murine model combining psychological stress with TLR-triggered hepatic inflammation, the psychological stress facilitates liver uptake of plasma TG (and its components fatty acids), but the subsequent re-esterification and/or release of TG-rich lipoproteins from the liver is impaired due to the concomitant TLR-signaling. We hypothesize that lipid metabolism during acute stress shifts toward an elevated hepatic uptake of lipids due to concomitant TLR signaling, facilitating the clearance of bacterial lipids by the liver.展开更多
Cytidine 5'-monophosphate(5'-CMP)is an essential nucleotide for additives.In this study,enhanced production of 5'-CMP was realized by the transformation of cytidine using co-immobilized di-enzymes,uridine-...Cytidine 5'-monophosphate(5'-CMP)is an essential nucleotide for additives.In this study,enhanced production of 5'-CMP was realized by the transformation of cytidine using co-immobilized di-enzymes,uridine-cytidine kinase(UCK)and acetate kinase(AcK).The immobilization yield of the enzyme had a clear correlation with the surface charges as zeta potential(ξ).Among them,ε-polylysinefunctionalized sepharose(SA-EPL,ξ=9.31 m V)showed high immobilization yield(78.8%),which was4.9-fold than that of nitrilotriacetic acid functionalized sepharose(SA-NTA,ξ=-12.6 m V).The residual activity of affinity co-immobilized enzyme(EPL-Ni/EPL@Ac K-UCK)was higher than 70.6%after recycled 10 times.Thus,this study provides an effective approach for the production of 5'-CMP with the advantages of low adenosine 5'-triphosphate(ATP)consumption,reduced side reactions,and improved reusability by co-immobilized UCK and Ac K on the functionalized Sepharose.展开更多
To study the possible anticancer mechanisms of chelerythrine (CHE), and its interactions with cytidine were investigated by UV–vis spectrophotometric and spectrofluorimetric measurements and by thermodynamic calculat...To study the possible anticancer mechanisms of chelerythrine (CHE), and its interactions with cytidine were investigated by UV–vis spectrophotometric and spectrofluorimetric measurements and by thermodynamic calculations. The binding of CHE to cytidine could be characterized by the hypochromic and bathochromic effects in the absorption bands, and the quenching of fluorescence intensity. The spectral data were fit by linear analysis, yielding a binding constant of 2.49 × 10(4) L mol(?1)at 25 °C of CHE and cytidine, and a van’t Hoff enthalpy of ?20.02 kJ/mol for the exothermic interaction in the standard state. In addition, with and , the interactions should be entropy-driven.展开更多
Rationale: In a previously published trial on spinal acute non-traumatic pain, peripheral neuro- regenerative combination of UTP, CMP and hydroxocobalamin presented unexpected analgesicproperties. Objective: To corrob...Rationale: In a previously published trial on spinal acute non-traumatic pain, peripheral neuro- regenerative combination of UTP, CMP and hydroxocobalamin presented unexpected analgesicproperties. Objective: To corroborate analgesiceffects of UTP, CMP and hydroxocobalamin combination in a self-paired evolutionary model. Methods: Mean VAS scores from pretreatment, V2 (5th treatment day) and V3 (10th treatment day) were plotted and statistically analyzed (ANOVA) for differences. PFQ scores from pretreatment, V2, and V3 were analyzed using the chisquare test. Results: The difference between V3 and pretreatment mean VAS scores was statistically significant (p < 0.0001). The improvement in PFQ scores throughout the study was found to be statistically significant (p < 0.0001). Conclusion: The combination of UTP, CMP and hydroxocobalamin seems to have analgesic properties in mediumterm use. The complex peripheral neu-roregenerative pharmacodynamics of this combination provides a plausible basis for this finding. Further randomized studies are needed to explore this combination for the indication of neuropathic pain due to spinal structure involvement.展开更多
Purpose:To investigate the efficacy of anisodine combined with cytidine-5'-diphosp-bocholine (citicoline) in the treatment of early optic nerve contusion.Methods:A total of 33 subjects eligible for inclusion were ...Purpose:To investigate the efficacy of anisodine combined with cytidine-5'-diphosp-bocholine (citicoline) in the treatment of early optic nerve contusion.Methods:A total of 33 subjects eligible for inclusion were selected from 105 patients clinically diagnosed with optic nerve contusion.These patients were subsequently divided into the control group (n =16) and the intervention group (n =17).In the control group,the participants received therapy consisting of glucocorticoids,mannitol,vasodilators and vitamin B.The patients in the intervention group additionally received anisodine in combination with citicoline.The visual acuity was graded on a scale from 0 to 8.Results:Prior to treatment,.the 25th,50th and 75th percentiles of visual acuity grade were 3,4 and 6.75 for the controls,and 3,4 and 6.5 for the patients in the intervention group (P=0.97).After treatment,the 25th,50th and 75th percentiles of visual acuity grade were 4,6 and 7.75 in the control group,and 7,7 and 8 in the intervention group (P=0.046).A significant difference was observed in both control (P=0.005) and intervention groups(P=0.001) when comparing presenting visual acuity before and after treatment.Conclusion:The combination of anisodine and citicoline with standard steroid and mannitol therapy appears to be effective in the treatment of early optic nerve contusion.展开更多
Objective: To explore the feasibility of transfecting cytidine deaminase (CD) gene into mouse bone marrow cells in order to observe the drug resistance of high dose Ara-C and improve the tolerance of myelosuppressi...Objective: To explore the feasibility of transfecting cytidine deaminase (CD) gene into mouse bone marrow cells in order to observe the drug resistance of high dose Ara-C and improve the tolerance of myelosuppression following combination chemotherapy. Methods: Human cytidine deaminase gene was transfected into mice bone marrow cells by retroviral vector. Resistant colony-forming unit granulocyte-macrophage (CFU-GM) assay was performed after the transfected mice bone marrow cells treated by the Ara-C. DNA was extracted from mice bone marrow cells. The drug resistant gene in mice bone marrow cells after transfection was detected by PCR. Results: Bone marrow cells of the donor mice cultured with the retroviral producer cells showed the drug resistant colonies and resistance to Ara-C, so did accept mice transplanted with the CD gene (CFU-GM of donor mice was 52%, χ^2 = 124.62, P 〈 0.01; accept mice was 54%, χ^2 = 126.26, P 〈 0.01, both compared with the contrast group). The animal survival rate was significantly higher in gene transfected group than that of the control (χ^2= 7.42, P 〈 0.01). CD gene of transfected bone marrow cells was confirmed by PCR. Conclusion: CD gene can be transfected into bone marrow cells of mice efficiently and increase the drug resistance to Ara-C.展开更多
Interaction of dioxouranitm (VI) UO2^2+ ion with Adenosine-5'-triphosphate, Guanosine-5'-triphosphate and 3ytidine-5'-triphosphate were obtained a complexs of Adenosine, Guanosine and Cytidine with uranium UO2^2...Interaction of dioxouranitm (VI) UO2^2+ ion with Adenosine-5'-triphosphate, Guanosine-5'-triphosphate and 3ytidine-5'-triphosphate were obtained a complexs of Adenosine, Guanosine and Cytidine with uranium UO2^2+ ions and X-ray nethod to explore these complexes.展开更多
文摘Changes in lipid metabolism have been implicated in protection against infectious diseases. In the first experiment of this study, we measured clinical lipid parameters in a murine model where the unmethylated cytidine phosphate guanosine (CpG) oligodinucleotide (ODN1826), a Toll-like receptor 9 (TLR9) agonist was administered in combination with D-galactosamine (GalN) that caused relatively liver-specific inflammation and toxicity. In the control mice group injected with phosphate-buffered saline (PBS) (acute psychological stress model associated with blood sampling), the serum triglyceride (TG) levels showed a rapid decrease followed by a rebound at 24 h as we have recently reported. However, such a TG rebound was impaired in the CpG/GalN- and solely CpG-treated groups of mice despite an absence of liver injury based on serum alanine aminotransferase levels in the latter group. Thus, the stress-associated serum TG rebound was abrogated by the injection of a sub-hepatotoxic CpG dose. In the second experiment, we simply measured the hepatic CD36 and SACRB1 (the gene for scavenger receptor B1 (SR-B1)) transcripts after the i.p. administration of PBS, CpG or CpG/GalN. There was a remarkable elevation of hepatic CD36 transcript expression in both the CpG- and CpG/GalN-treated mice at 8 h post-CpG injection whereas the increase in the PBS-treated mice was slower than the former two groups, suggesting that hepatic CD36 transcript expression is more pronounced in the combined stress models than under psychological stress alone. The individual mice data showed that the increase in CD36 expression was accompanied by a reduction in SCARB1 mRNA, showing reciprocal regulation between these two genes. Together with our previously reported findings, these data suggest that, in a murine model combining psychological stress with TLR-triggered hepatic inflammation, the psychological stress facilitates liver uptake of plasma TG (and its components fatty acids), but the subsequent re-esterification and/or release of TG-rich lipoproteins from the liver is impaired due to the concomitant TLR-signaling. We hypothesize that lipid metabolism during acute stress shifts toward an elevated hepatic uptake of lipids due to concomitant TLR signaling, facilitating the clearance of bacterial lipids by the liver.
基金supported by grants from the National Key Research and Development Program of China(2021YFC2102805,2019YFD1101204)the National Natural Science Foundation of China(21878142,21776132)+3 种基金Key Research and Development Plan of Jiangsu Province(BE2020712)Key Research and Development Plan of Jiangsu Province(BE2019001)Jiangsu Natural Science Fund for Distinguished Young Scholars(BK20190035)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)。
文摘Cytidine 5'-monophosphate(5'-CMP)is an essential nucleotide for additives.In this study,enhanced production of 5'-CMP was realized by the transformation of cytidine using co-immobilized di-enzymes,uridine-cytidine kinase(UCK)and acetate kinase(AcK).The immobilization yield of the enzyme had a clear correlation with the surface charges as zeta potential(ξ).Among them,ε-polylysinefunctionalized sepharose(SA-EPL,ξ=9.31 m V)showed high immobilization yield(78.8%),which was4.9-fold than that of nitrilotriacetic acid functionalized sepharose(SA-NTA,ξ=-12.6 m V).The residual activity of affinity co-immobilized enzyme(EPL-Ni/EPL@Ac K-UCK)was higher than 70.6%after recycled 10 times.Thus,this study provides an effective approach for the production of 5'-CMP with the advantages of low adenosine 5'-triphosphate(ATP)consumption,reduced side reactions,and improved reusability by co-immobilized UCK and Ac K on the functionalized Sepharose.
文摘To study the possible anticancer mechanisms of chelerythrine (CHE), and its interactions with cytidine were investigated by UV–vis spectrophotometric and spectrofluorimetric measurements and by thermodynamic calculations. The binding of CHE to cytidine could be characterized by the hypochromic and bathochromic effects in the absorption bands, and the quenching of fluorescence intensity. The spectral data were fit by linear analysis, yielding a binding constant of 2.49 × 10(4) L mol(?1)at 25 °C of CHE and cytidine, and a van’t Hoff enthalpy of ?20.02 kJ/mol for the exothermic interaction in the standard state. In addition, with and , the interactions should be entropy-driven.
文摘Rationale: In a previously published trial on spinal acute non-traumatic pain, peripheral neuro- regenerative combination of UTP, CMP and hydroxocobalamin presented unexpected analgesicproperties. Objective: To corroborate analgesiceffects of UTP, CMP and hydroxocobalamin combination in a self-paired evolutionary model. Methods: Mean VAS scores from pretreatment, V2 (5th treatment day) and V3 (10th treatment day) were plotted and statistically analyzed (ANOVA) for differences. PFQ scores from pretreatment, V2, and V3 were analyzed using the chisquare test. Results: The difference between V3 and pretreatment mean VAS scores was statistically significant (p < 0.0001). The improvement in PFQ scores throughout the study was found to be statistically significant (p < 0.0001). Conclusion: The combination of UTP, CMP and hydroxocobalamin seems to have analgesic properties in mediumterm use. The complex peripheral neu-roregenerative pharmacodynamics of this combination provides a plausible basis for this finding. Further randomized studies are needed to explore this combination for the indication of neuropathic pain due to spinal structure involvement.
文摘Purpose:To investigate the efficacy of anisodine combined with cytidine-5'-diphosp-bocholine (citicoline) in the treatment of early optic nerve contusion.Methods:A total of 33 subjects eligible for inclusion were selected from 105 patients clinically diagnosed with optic nerve contusion.These patients were subsequently divided into the control group (n =16) and the intervention group (n =17).In the control group,the participants received therapy consisting of glucocorticoids,mannitol,vasodilators and vitamin B.The patients in the intervention group additionally received anisodine in combination with citicoline.The visual acuity was graded on a scale from 0 to 8.Results:Prior to treatment,.the 25th,50th and 75th percentiles of visual acuity grade were 3,4 and 6.75 for the controls,and 3,4 and 6.5 for the patients in the intervention group (P=0.97).After treatment,the 25th,50th and 75th percentiles of visual acuity grade were 4,6 and 7.75 in the control group,and 7,7 and 8 in the intervention group (P=0.046).A significant difference was observed in both control (P=0.005) and intervention groups(P=0.001) when comparing presenting visual acuity before and after treatment.Conclusion:The combination of anisodine and citicoline with standard steroid and mannitol therapy appears to be effective in the treatment of early optic nerve contusion.
基金Supported by a grant from the NationaI-Naturl Science Foundation of China (No. 30471678).
文摘Objective: To explore the feasibility of transfecting cytidine deaminase (CD) gene into mouse bone marrow cells in order to observe the drug resistance of high dose Ara-C and improve the tolerance of myelosuppression following combination chemotherapy. Methods: Human cytidine deaminase gene was transfected into mice bone marrow cells by retroviral vector. Resistant colony-forming unit granulocyte-macrophage (CFU-GM) assay was performed after the transfected mice bone marrow cells treated by the Ara-C. DNA was extracted from mice bone marrow cells. The drug resistant gene in mice bone marrow cells after transfection was detected by PCR. Results: Bone marrow cells of the donor mice cultured with the retroviral producer cells showed the drug resistant colonies and resistance to Ara-C, so did accept mice transplanted with the CD gene (CFU-GM of donor mice was 52%, χ^2 = 124.62, P 〈 0.01; accept mice was 54%, χ^2 = 126.26, P 〈 0.01, both compared with the contrast group). The animal survival rate was significantly higher in gene transfected group than that of the control (χ^2= 7.42, P 〈 0.01). CD gene of transfected bone marrow cells was confirmed by PCR. Conclusion: CD gene can be transfected into bone marrow cells of mice efficiently and increase the drug resistance to Ara-C.
文摘Interaction of dioxouranitm (VI) UO2^2+ ion with Adenosine-5'-triphosphate, Guanosine-5'-triphosphate and 3ytidine-5'-triphosphate were obtained a complexs of Adenosine, Guanosine and Cytidine with uranium UO2^2+ ions and X-ray nethod to explore these complexes.