Cementum is critical for anchoring the insertion of periodontal ligament fibers to the tooth root. Several aspects of cementogenesis remain unclear, including differences between acellular cementum and cellular cement...Cementum is critical for anchoring the insertion of periodontal ligament fibers to the tooth root. Several aspects of cementogenesis remain unclear, including differences between acellular cementum and cellular cementum, and between cementum and bone. Biomineralization is regulated by the ratio of inorganic phosphate （Pi） to mineral inhibitor pyrophosphate （PPi）, where local Pi and PPi concentrations are controlled by phosphatases including tissue-nonspecific alkaline phosphatase （TNAP） and ectonucleotide pyrophosphatase/phosphodiesterase 1 （NPP1）. The focus of this study was to define the roles of these phosphatases in cementogenesis. TNAP was associated with earliest cementoblasts near forming acellular and cellular cementum. With loss of TNAP in the Alpl null mouse, acellular cementum was inhibited, while cellular cementum production increased, albeit as hypomineralized cementoid. In contrast, NPP1 was detected in cementoblasts after acellular cementum formation, and at low levels around cellular cementum. Loss of NPP1 in the Enppl null mouse increased acellular cementum, with little effect on cellular cementum. Developmental patterns were recapitulated in a mouse model for acellular cementum regeneration, with early TNAP expression and later NPP1 expression. In vitro, cementoblasts expressed Alpl gene/protein early, whereas Enppl gene/protein expression was significantly induced only under mineralization conditions. These patterns were confirmed in human teeth, including widespread TNAP, and NPP1 restricted to cementoblasts lining acellular cementum. These studies suggest that early TNAP expression creates a low PPi environment promoting acellular cementum initiation, while later NPP1 expression increases PPi, restricting acellular cementum apposition. Alterations in PPi have little effect on cellular cementum formation, though matrix mineralization is affected.展开更多
Effect of nitrate and ammonium on the activity of tonoplast pyrophosphatase (V-PPase) was investigated in the roots of tomato ( Lycopersicon esculentum L.). The results showed that the activity of V-PPase was increase...Effect of nitrate and ammonium on the activity of tonoplast pyrophosphatase (V-PPase) was investigated in the roots of tomato ( Lycopersicon esculentum L.). The results showed that the activity of V-PPase was increased by ammonium nutrition, compared with nitrate nutrition. The H+ transport of tonoplast vesicles by V-PPase was also stimulated by ammonium nutrition. The result of Western blot indicated that the protein amount of V-PPase was increased by ammonium nutrition.展开更多
Objective Findings from the previous studies have suggested a relationship between ectonucleotide pyrophosphatase /phosphodiesterase 1 （ENPP‐1） or plasma cell membrane glycoprotein 1 （PC‐1） gene single nucleotid...Objective Findings from the previous studies have suggested a relationship between ectonucleotide pyrophosphatase /phosphodiesterase 1 （ENPP‐1） or plasma cell membrane glycoprotein 1 （PC‐1） gene single nucleotide polymorphism （K121Q, rs1044498） and genetic susceptibility to obesity. However, such relationship is not reproduced by some currently available studies. In this context, the present study is aimed to quantitatively analyze the association of K121Q variant with obesity in all published case‐control studies in European adult populations. Methods Published literature from PubMed, EMBASE, and ISI web of science databases were retrieved. The studies evaluating the association of ENPP1/PC1 gene K121Q polymorphism with obesity were included, in which sufficient data were presented to calculate the odds ratio （OR） with 95% confidence intervals （CIs）. Results Ten case‐control studies meeting the inclusion criteria identified a total of 24,324 subjects including 11,372 obese and 12,952 control subjects. The meta‐analysis results showed a statistically significant association of K121Q with obesity [OR （95%CI）： 1.25 （1.04‐1.52） P=0.021] under a recessive model of inheritance （QQ vs. KK＋KQ） without heterogeneity or publication bias. Conclusions The results from the present study have indicated that ENPP1/PC1 Q121 variant may increase the risk of obesity and that more well‐designed studies based on a larger population will be required to further evaluate the role of ENPP1/PC1 gene K121Q polymorphism in obesity and other related metabolic syndromes.展开更多
AIM: To analyze the host genetics factors influencing the clinical course and the response to antiviral treatment in patients with chronic hepatitis C(CHC).METHODS: We conducted an electronic search on the Pub Med and...AIM: To analyze the host genetics factors influencing the clinical course and the response to antiviral treatment in patients with chronic hepatitis C(CHC).METHODS: We conducted an electronic search on the Pub Med and MEDLINE(2000-2014) databases and Cochrane library(2000-2014). A total of 73 articles were retrieved and their data were extensively evaluated and discussed by the authors and then analyzed in this review article.RESULTS: Several studies associated polymorphisms in the interleukin 28 B gene on chromosome 19(19q13.13) with a spontaneous viral clearance in acute hepatitis C and with the response to pegylated interferon(PegIFN)-based treatment in chronic hepatitis C patients. Other investigations demonstrated that inosine triphosphate pyrophosphatase genetic variants protect hepatitis C virus-genotype-1 CHC patients from ribavirin-induced anemia, and other studies that a polymorphism in the patatin-like phospholipase domain-containing protein 3 was associated with hepatic steatosis in CHC patients. Although not conclusive, some investigations suggested that the vitamin D-associated polymorphisms play an important role in the achievement of sustained virologic response in CHC patients treated with Peg-IFN-based antiviral therapy. Several other polymorphisms have been investigated to ascertain their possible impact on the natural history and on the response to treatment in patients with CHC, but the data are preliminary and warrant confirmation. CONCLUSION: Several genetic polymorphisms seem to influence the clinical course and the response to antiviral treatment in patients with CHC, suggesting individualized follow up and treatment strategies.展开更多
The ultracytochemical effects in the liver of rabbit undergoing high energy shock wave (HESW) were studied with electron microscope. The application of lanthanum as a tracer for ultrastructural study demonstrated that...The ultracytochemical effects in the liver of rabbit undergoing high energy shock wave (HESW) were studied with electron microscope. The application of lanthanum as a tracer for ultrastructural study demonstrated that intracellular lanthanum could be observed, most of which entered the hepatocytes and its mitochondria. The lanthanum granules were also found to deposite in the zone of tight junctions of bile canaliculi, which indicated that the tight junctions had been damaged. The activities of succinate dehydrogenase (SDH) in liver cells, alkaline phosphatase (ALP) and thiamine pyrophosphatase (TPPase) on the wall of bile canaliculi became diminished obviously. Both the activites and localizations of TPPase had changed. Some TPPase from the damaged lysosome like vesicles and Golgi saccules of liver cells discharged into cytoplasm. TPPase reaction production in some bile canaliculi decreased. In the intercellular space of the liver cells and the tight junctions of bile canaliculi TPPase reaction could be seen. Ultrastructurally, the changes commonly seen were hydropic mitochondria and dilatation of rough endoplasmic reticulum. Serologic test demonstrated that there was an abnormal change of SGPT, SGOT and ALP. The results showed that HESW can damage the ultrastructure and function of liver.展开更多
The extracellular contractile injection systems(e CISs)are encoded in the genomes of a large number of bacteria and archaea.We have previously characterized the overall structure of Photorhabdus Virulence Cassette(PVC...The extracellular contractile injection systems(e CISs)are encoded in the genomes of a large number of bacteria and archaea.We have previously characterized the overall structure of Photorhabdus Virulence Cassette(PVC),a typical member of the e CIS family.PVC resembles the contractile tail of bacteriophages and exerts its action by the contraction of outer sheath and injection of inner tube plus central spike.Nevertheless,the biological function of PVC effectors and the mechanism of effector translocation are still lacking.By combining cryo-electron microscopy and functional experiments,here we show that the PVC effectors Pdp1(a new family of widespread d NTP pyrophosphatase effector in e CIS)and Pnf(a deamidase effector)are loaded inside the inner tube lumen in a"Peas in the Pod"mode.Moreover,we observe that Pdp1 and Pnf can be directly injected into J774 A.1 murine macrophage and kill the target cells by disrupting the d NTP pools and actin cytoskeleton formation,respectively.Our results provide direct evidence of how PVC cargoes are loaded and delivered directly into mammalian macrophages.展开更多
Polychemotherapeutic protocols for the treatment of pediatric acute lymphoblastic leukemia(ALL)always include thiopurines.Specific approaches vary in terms of drugs,dosages and combinations.Such therapeutic schemes,in...Polychemotherapeutic protocols for the treatment of pediatric acute lymphoblastic leukemia(ALL)always include thiopurines.Specific approaches vary in terms of drugs,dosages and combinations.Such therapeutic schemes,including risk-adapted intensity,have been extremely successful for children with ALL who have reached an outstanding 5-year survival of greater than 90%in developed countries.Innovative drugs such as the proteasome inhibitor bortezomib and the bi-specific T cell engager blinatumomab are available to further improve therapeutic outcomes.Nevertheless,daily oral thiopurines remain the backbone maintenance or continuation therapy.Pharmacogenetics allows the personalization of thiopurine therapy in pediatric ALL and clinical guidelines to tailor therapy on the basis of genetic variants in TPMT and NUDT15 genes are already available.Other genes of interest,such as ITPA and PACSIN2,have been implicated in interindividual variability in thiopurines efficacy and adverse effects and need additional research to be implemented in clinical protocols.In this review we will discuss current literature and clinical guidelines available to implement pharmacogenetics for tailoring therapy with thiopurines in pediatric ALL.展开更多
基金supported by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) of the National Institutes of Health (NIH) and extramural NIH funding(JLM-DE12889 and AR53102)
文摘Cementum is critical for anchoring the insertion of periodontal ligament fibers to the tooth root. Several aspects of cementogenesis remain unclear, including differences between acellular cementum and cellular cementum, and between cementum and bone. Biomineralization is regulated by the ratio of inorganic phosphate （Pi） to mineral inhibitor pyrophosphate （PPi）, where local Pi and PPi concentrations are controlled by phosphatases including tissue-nonspecific alkaline phosphatase （TNAP） and ectonucleotide pyrophosphatase/phosphodiesterase 1 （NPP1）. The focus of this study was to define the roles of these phosphatases in cementogenesis. TNAP was associated with earliest cementoblasts near forming acellular and cellular cementum. With loss of TNAP in the Alpl null mouse, acellular cementum was inhibited, while cellular cementum production increased, albeit as hypomineralized cementoid. In contrast, NPP1 was detected in cementoblasts after acellular cementum formation, and at low levels around cellular cementum. Loss of NPP1 in the Enppl null mouse increased acellular cementum, with little effect on cellular cementum. Developmental patterns were recapitulated in a mouse model for acellular cementum regeneration, with early TNAP expression and later NPP1 expression. In vitro, cementoblasts expressed Alpl gene/protein early, whereas Enppl gene/protein expression was significantly induced only under mineralization conditions. These patterns were confirmed in human teeth, including widespread TNAP, and NPP1 restricted to cementoblasts lining acellular cementum. These studies suggest that early TNAP expression creates a low PPi environment promoting acellular cementum initiation, while later NPP1 expression increases PPi, restricting acellular cementum apposition. Alterations in PPi have little effect on cellular cementum formation, though matrix mineralization is affected.
文摘Effect of nitrate and ammonium on the activity of tonoplast pyrophosphatase (V-PPase) was investigated in the roots of tomato ( Lycopersicon esculentum L.). The results showed that the activity of V-PPase was increased by ammonium nutrition, compared with nitrate nutrition. The H+ transport of tonoplast vesicles by V-PPase was also stimulated by ammonium nutrition. The result of Western blot indicated that the protein amount of V-PPase was increased by ammonium nutrition.
文摘Objective Findings from the previous studies have suggested a relationship between ectonucleotide pyrophosphatase /phosphodiesterase 1 （ENPP‐1） or plasma cell membrane glycoprotein 1 （PC‐1） gene single nucleotide polymorphism （K121Q, rs1044498） and genetic susceptibility to obesity. However, such relationship is not reproduced by some currently available studies. In this context, the present study is aimed to quantitatively analyze the association of K121Q variant with obesity in all published case‐control studies in European adult populations. Methods Published literature from PubMed, EMBASE, and ISI web of science databases were retrieved. The studies evaluating the association of ENPP1/PC1 gene K121Q polymorphism with obesity were included, in which sufficient data were presented to calculate the odds ratio （OR） with 95% confidence intervals （CIs）. Results Ten case‐control studies meeting the inclusion criteria identified a total of 24,324 subjects including 11,372 obese and 12,952 control subjects. The meta‐analysis results showed a statistically significant association of K121Q with obesity [OR （95%CI）： 1.25 （1.04‐1.52） P=0.021] under a recessive model of inheritance （QQ vs. KK＋KQ） without heterogeneity or publication bias. Conclusions The results from the present study have indicated that ENPP1/PC1 Q121 variant may increase the risk of obesity and that more well‐designed studies based on a larger population will be required to further evaluate the role of ENPP1/PC1 gene K121Q polymorphism in obesity and other related metabolic syndromes.
文摘AIM: To analyze the host genetics factors influencing the clinical course and the response to antiviral treatment in patients with chronic hepatitis C(CHC).METHODS: We conducted an electronic search on the Pub Med and MEDLINE(2000-2014) databases and Cochrane library(2000-2014). A total of 73 articles were retrieved and their data were extensively evaluated and discussed by the authors and then analyzed in this review article.RESULTS: Several studies associated polymorphisms in the interleukin 28 B gene on chromosome 19(19q13.13) with a spontaneous viral clearance in acute hepatitis C and with the response to pegylated interferon(PegIFN)-based treatment in chronic hepatitis C patients. Other investigations demonstrated that inosine triphosphate pyrophosphatase genetic variants protect hepatitis C virus-genotype-1 CHC patients from ribavirin-induced anemia, and other studies that a polymorphism in the patatin-like phospholipase domain-containing protein 3 was associated with hepatic steatosis in CHC patients. Although not conclusive, some investigations suggested that the vitamin D-associated polymorphisms play an important role in the achievement of sustained virologic response in CHC patients treated with Peg-IFN-based antiviral therapy. Several other polymorphisms have been investigated to ascertain their possible impact on the natural history and on the response to treatment in patients with CHC, but the data are preliminary and warrant confirmation. CONCLUSION: Several genetic polymorphisms seem to influence the clinical course and the response to antiviral treatment in patients with CHC, suggesting individualized follow up and treatment strategies.
文摘The ultracytochemical effects in the liver of rabbit undergoing high energy shock wave (HESW) were studied with electron microscope. The application of lanthanum as a tracer for ultrastructural study demonstrated that intracellular lanthanum could be observed, most of which entered the hepatocytes and its mitochondria. The lanthanum granules were also found to deposite in the zone of tight junctions of bile canaliculi, which indicated that the tight junctions had been damaged. The activities of succinate dehydrogenase (SDH) in liver cells, alkaline phosphatase (ALP) and thiamine pyrophosphatase (TPPase) on the wall of bile canaliculi became diminished obviously. Both the activites and localizations of TPPase had changed. Some TPPase from the damaged lysosome like vesicles and Golgi saccules of liver cells discharged into cytoplasm. TPPase reaction production in some bile canaliculi decreased. In the intercellular space of the liver cells and the tight junctions of bile canaliculi TPPase reaction could be seen. Ultrastructurally, the changes commonly seen were hydropic mitochondria and dilatation of rough endoplasmic reticulum. Serologic test demonstrated that there was an abnormal change of SGPT, SGOT and ALP. The results showed that HESW can damage the ultrastructure and function of liver.
基金supported by the National Natural Science Foundation of China(31870108,32070081,32000080,31725007,31630087,and 31922036)the Beijing Natural Science Foundation(5192019)+3 种基金the CAMS Innovation Fund for Medical Sciences(2016-I2M-1013)the Non-profit Central Institute Fund of Chinese Academy of Medical Sciences(2017PT31049,2018PT51009,and 2018PT31012)the National Key Research and Development Program of China(2019YFA0508904)supported by High-performance Computing Platform of Peking University。
文摘The extracellular contractile injection systems(e CISs)are encoded in the genomes of a large number of bacteria and archaea.We have previously characterized the overall structure of Photorhabdus Virulence Cassette(PVC),a typical member of the e CIS family.PVC resembles the contractile tail of bacteriophages and exerts its action by the contraction of outer sheath and injection of inner tube plus central spike.Nevertheless,the biological function of PVC effectors and the mechanism of effector translocation are still lacking.By combining cryo-electron microscopy and functional experiments,here we show that the PVC effectors Pdp1(a new family of widespread d NTP pyrophosphatase effector in e CIS)and Pnf(a deamidase effector)are loaded inside the inner tube lumen in a"Peas in the Pod"mode.Moreover,we observe that Pdp1 and Pnf can be directly injected into J774 A.1 murine macrophage and kill the target cells by disrupting the d NTP pools and actin cytoskeleton formation,respectively.Our results provide direct evidence of how PVC cargoes are loaded and delivered directly into mammalian macrophages.
基金This project is supported by the Italian Ministry of Health(Progetto Ricerca Corrente 5/2012).
文摘Polychemotherapeutic protocols for the treatment of pediatric acute lymphoblastic leukemia(ALL)always include thiopurines.Specific approaches vary in terms of drugs,dosages and combinations.Such therapeutic schemes,including risk-adapted intensity,have been extremely successful for children with ALL who have reached an outstanding 5-year survival of greater than 90%in developed countries.Innovative drugs such as the proteasome inhibitor bortezomib and the bi-specific T cell engager blinatumomab are available to further improve therapeutic outcomes.Nevertheless,daily oral thiopurines remain the backbone maintenance or continuation therapy.Pharmacogenetics allows the personalization of thiopurine therapy in pediatric ALL and clinical guidelines to tailor therapy on the basis of genetic variants in TPMT and NUDT15 genes are already available.Other genes of interest,such as ITPA and PACSIN2,have been implicated in interindividual variability in thiopurines efficacy and adverse effects and need additional research to be implemented in clinical protocols.In this review we will discuss current literature and clinical guidelines available to implement pharmacogenetics for tailoring therapy with thiopurines in pediatric ALL.
