A recent explosion in the amount of cardiovascular risk has swept across the globe. Primary prevention is the preferred method to lower cardiovascular risk. Lowering the prevalence of obesity is the most urgent matter...A recent explosion in the amount of cardiovascular risk has swept across the globe. Primary prevention is the preferred method to lower cardiovascular risk. Lowering the prevalence of obesity is the most urgent matter, and is pleiotropic since it affects blood pressure, lipid profiles, glucose metabolism, inflammation, and atherothrombotic disease progression. Given the current obstacles, success of primary prevention remains uncertain. At the same time, the consequences of delay and inaction will inevitably be disastrous, and the sense of urgency mounts. Pathological and epidemiological data confirm that atherosclerosis begins in early childhood, and advances seamlessly and inexorably throughout life. Risk factors in childhood are similar to those in adults, and track between stages of life. When indicated, aggressive treatment should begin at the earliest indication, and be continued for many years. For those patients at intermediate risk according to global risk scores, C-reactive protein, coronary artery calcium, and carotid intima-media thickness are available for further stratification. Using statins for primary prevention is recommended by guidelines, is prevalent, but remains under prescribed. Statin drugs are unrivaled, evidence-based, major weapons to lower cardiovascular risk. Even when low density lipoprotein cholesterol targets are attained, over half of patients continue to have disease progression and clinical events. Though clinical evidence is incomplete, altering or raising the blood high density lipoprotein cholesterol level continues to be pursued. The aim of this review is to point out the attention of key aspects of vulnerable plaques regarding their pathogenesis and treatment.展开更多
Alcohol ingestion causes alteration in several cellular mechanisms, and leads to inflammation, apoptosis, immunological response defects, and fibrosis. These phenomena are associated with significant changes in the ep...Alcohol ingestion causes alteration in several cellular mechanisms, and leads to inflammation, apoptosis, immunological response defects, and fibrosis. These phenomena are associated with significant changes in the epigenetic mechanisms, and subsequently, to liver cell memory. The ubiquitin-proteasome pathway is one of the vital pathways in the cell that becomes dysfunctionial as a result of chronic ethanol consumption. Inhibition of the proteasome activity in the nucleus causes changes in the turnover of transcriptional factors, histone modifying enzymes, and therefore, affects epigenetic mechanisms. Alcohol consumption has been associated with an increase in histone acetylation and a decrease in histone methylation, which leads to gene expression changes. DNA and histone modifications that result from ethanol-induced proteasome inhibition are key players in regulating gene expression, especially genes involved in the cell cycle, immunological responses, and metabolism of ethanol. The present review highlights the consequences of ethanol-induced proteasome inhibition in the nucleus of liver cells that are chronically exposed to ethanol.展开更多
On arrival in the Arctic, migrant birds must adjust their physiology and behavior to unpredictable snow cover, weather, food sources and predator pressure. In other words they must be resistant to environmental pertur...On arrival in the Arctic, migrant birds must adjust their physiology and behavior to unpredictable snow cover, weather, food sources and predator pressure. In other words they must be resistant to environmental perturbations (stress) so that they can migrate to their tundra nesting areas and settle on territories as soon as possible. They can then begin breeding as soon as when environmental conditions become favorable. They do this partly by using micro-habitats such as areas where snow depth is low, and patches of tundra that melt out rapidly (especially near willows Salix sp). Ground temperatures increase dramatically within hours after exposure to sun; and invertebrate activity begins simultaneously. Wind speeds are attenuated almost completely within 10 cm of the ground in willows and tussock tundra. The combination of these conditions provides an ideal refuge, especially for passerine migrants in early spring. However, if conditions worsen, the birds can leave. There are adjustments of the adrenocortical responses to stress because arctic conditions in spring are potentially severe, at least compared with wintering grounds to the south. Secretion of corticosterone in response to acute stress is enhanced at arrival in males, accompanied by a decrease in sensitivity to negative feedback and a change in responsiveness of the adrenal cortex cells to adrenocorticotropin. There is also an increase in levels of corticosterone-binding globulin (CBG) so that the actions of corticosterone are buffered according to the severity of environmental conditions. Regulation at the level of genomic receptors, particularly the low affinity glucocorticosteroid-like receptor for corticosterone in brain and liver, may be important; and non-genomic actions of corticosterone may play a major role too. In other words, the hormone-behavior system associated with arrival biology is highly flexible.展开更多
The ribosomal protein S29 also known as RPS29, is not only a component of the 40S subunit of ribosome, but also involved in embryonic development, oncogenesis and other pathologic conditions. However, rare commercial ...The ribosomal protein S29 also known as RPS29, is not only a component of the 40S subunit of ribosome, but also involved in embryonic development, oncogenesis and other pathologic conditions. However, rare commercial antibody against RPS29 restricts the discovery of precise physiological and pathological function of this protein. In this study, the whole RPS29 gene was inserted into plasmid pGEX-6p-1 to express glutathione＇s transferase （GST） fusion proteins in Escherichia eoli （E. coli） strain BL21. High yields of soluble recombinant proteins were obtained. Mice were immunized with the recombinant RPS29 protein. The serum from the immunized mice could specially react with purified recombinant RPS29 proteins and native RPS29 proteins in CCE cells by western blotting, immunofluorescence staining and flow cytometric analysis. Further more the polyclonal antibodies also reacted specifically with human cell strain ECV304, which showed typical cytoplasmatic fluorescence. The polyclonal antibodies we prepared would be an available tool for studying the roles of RPS29 in embryonic development and human diseases.展开更多
Recently, genome wide association studies showed that there is a strong association between abacavir-induced serious, idio- syncratic, adverse drag reactions （ADRs） and human leukocyte antigen-B＊5701 （HLA-B＊5701...Recently, genome wide association studies showed that there is a strong association between abacavir-induced serious, idio- syncratic, adverse drag reactions （ADRs） and human leukocyte antigen-B＊5701 （HLA-B＊5701）. Studies also found that ab- acavir-induced ADRs were seldom observed in patients carrying the HLA-B＊5801 subtype. HLA-B＊5801 of the same sero- type （B17） as B＊5701 differs by only 4 amino acids from B＇5701. It is believed that because of these sequence differences, HLA-B＊5801 cannot bind the specific peptides which are required for HLA-B＊5701 to stimulate the T cell immune response. Thus, the difference in peptide binding profiles between HLA-B＊5701 and B＊5801 is an important clue for exploring the mechanisms of abacavir-induced ADRs. VHSE （principal component score vector of hydrophobic, steric, and electronic prop- erties）, a set of amino acid structural descriptors, was employed to establish QSAR models of peptide-binding affinities of HLA-B＊5701 and B＊5801. Optimal linear SVM （support vector machine） models with high predictive capabilities were ob- tained for both B＊5701 and B＇5801. The R2 （coefficient of determination）, Q2 （cross-validated R：）, and RpRE2 （R2 of test set） of two optimal models were 0,7530, 0.7037, 0.6153 （B＇5701） and 0.6074, 0.5966, 0.5762 （B＊5801）, respectively. For B＇5701 and B＇5801, the mutations in positions 45 （MET-THR） and 46 （ALA-GLU） have little influence on the selection specificity of the P2 position of the bound peptide. However, the mutation in position 97 （VAL-ARG） greatly influences the selection speci- ficity of the P7 position. HLA-B＊5701 prefers the bulky and positively charged amino acids at the P7 position. In contrast, HLA-B＊5801 prefers the non-polar hydrophobic amino acids at the P7 position while positively charged amino acids are un- favored.展开更多
文摘A recent explosion in the amount of cardiovascular risk has swept across the globe. Primary prevention is the preferred method to lower cardiovascular risk. Lowering the prevalence of obesity is the most urgent matter, and is pleiotropic since it affects blood pressure, lipid profiles, glucose metabolism, inflammation, and atherothrombotic disease progression. Given the current obstacles, success of primary prevention remains uncertain. At the same time, the consequences of delay and inaction will inevitably be disastrous, and the sense of urgency mounts. Pathological and epidemiological data confirm that atherosclerosis begins in early childhood, and advances seamlessly and inexorably throughout life. Risk factors in childhood are similar to those in adults, and track between stages of life. When indicated, aggressive treatment should begin at the earliest indication, and be continued for many years. For those patients at intermediate risk according to global risk scores, C-reactive protein, coronary artery calcium, and carotid intima-media thickness are available for further stratification. Using statins for primary prevention is recommended by guidelines, is prevalent, but remains under prescribed. Statin drugs are unrivaled, evidence-based, major weapons to lower cardiovascular risk. Even when low density lipoprotein cholesterol targets are attained, over half of patients continue to have disease progression and clinical events. Though clinical evidence is incomplete, altering or raising the blood high density lipoprotein cholesterol level continues to be pursued. The aim of this review is to point out the attention of key aspects of vulnerable plaques regarding their pathogenesis and treatment.
文摘Alcohol ingestion causes alteration in several cellular mechanisms, and leads to inflammation, apoptosis, immunological response defects, and fibrosis. These phenomena are associated with significant changes in the epigenetic mechanisms, and subsequently, to liver cell memory. The ubiquitin-proteasome pathway is one of the vital pathways in the cell that becomes dysfunctionial as a result of chronic ethanol consumption. Inhibition of the proteasome activity in the nucleus causes changes in the turnover of transcriptional factors, histone modifying enzymes, and therefore, affects epigenetic mechanisms. Alcohol consumption has been associated with an increase in histone acetylation and a decrease in histone methylation, which leads to gene expression changes. DNA and histone modifications that result from ethanol-induced proteasome inhibition are key players in regulating gene expression, especially genes involved in the cell cycle, immunological responses, and metabolism of ethanol. The present review highlights the consequences of ethanol-induced proteasome inhibition in the nucleus of liver cells that are chronically exposed to ethanol.
文摘On arrival in the Arctic, migrant birds must adjust their physiology and behavior to unpredictable snow cover, weather, food sources and predator pressure. In other words they must be resistant to environmental perturbations (stress) so that they can migrate to their tundra nesting areas and settle on territories as soon as possible. They can then begin breeding as soon as when environmental conditions become favorable. They do this partly by using micro-habitats such as areas where snow depth is low, and patches of tundra that melt out rapidly (especially near willows Salix sp). Ground temperatures increase dramatically within hours after exposure to sun; and invertebrate activity begins simultaneously. Wind speeds are attenuated almost completely within 10 cm of the ground in willows and tussock tundra. The combination of these conditions provides an ideal refuge, especially for passerine migrants in early spring. However, if conditions worsen, the birds can leave. There are adjustments of the adrenocortical responses to stress because arctic conditions in spring are potentially severe, at least compared with wintering grounds to the south. Secretion of corticosterone in response to acute stress is enhanced at arrival in males, accompanied by a decrease in sensitivity to negative feedback and a change in responsiveness of the adrenal cortex cells to adrenocorticotropin. There is also an increase in levels of corticosterone-binding globulin (CBG) so that the actions of corticosterone are buffered according to the severity of environmental conditions. Regulation at the level of genomic receptors, particularly the low affinity glucocorticosteroid-like receptor for corticosterone in brain and liver, may be important; and non-genomic actions of corticosterone may play a major role too. In other words, the hormone-behavior system associated with arrival biology is highly flexible.
基金Supported by the National Natural Science Foundation of China(30800983,30700418 and 30972596)the Natural Science Foundation of Chongqing(2008BB5113 and 2009BB5015) the Scientific Research Foundation of Third Military Medical University(2009XHG03 and 2009XYY04)
文摘The ribosomal protein S29 also known as RPS29, is not only a component of the 40S subunit of ribosome, but also involved in embryonic development, oncogenesis and other pathologic conditions. However, rare commercial antibody against RPS29 restricts the discovery of precise physiological and pathological function of this protein. In this study, the whole RPS29 gene was inserted into plasmid pGEX-6p-1 to express glutathione＇s transferase （GST） fusion proteins in Escherichia eoli （E. coli） strain BL21. High yields of soluble recombinant proteins were obtained. Mice were immunized with the recombinant RPS29 protein. The serum from the immunized mice could specially react with purified recombinant RPS29 proteins and native RPS29 proteins in CCE cells by western blotting, immunofluorescence staining and flow cytometric analysis. Further more the polyclonal antibodies also reacted specifically with human cell strain ECV304, which showed typical cytoplasmatic fluorescence. The polyclonal antibodies we prepared would be an available tool for studying the roles of RPS29 in embryonic development and human diseases.
基金supported by the National Natural Science Foundation of China (Grant No. 61073135)Chongqing Natural Science Foundation(Grant No. CSTC, 2009BA5068)
文摘Recently, genome wide association studies showed that there is a strong association between abacavir-induced serious, idio- syncratic, adverse drag reactions （ADRs） and human leukocyte antigen-B＊5701 （HLA-B＊5701）. Studies also found that ab- acavir-induced ADRs were seldom observed in patients carrying the HLA-B＊5801 subtype. HLA-B＊5801 of the same sero- type （B17） as B＊5701 differs by only 4 amino acids from B＇5701. It is believed that because of these sequence differences, HLA-B＊5801 cannot bind the specific peptides which are required for HLA-B＊5701 to stimulate the T cell immune response. Thus, the difference in peptide binding profiles between HLA-B＊5701 and B＊5801 is an important clue for exploring the mechanisms of abacavir-induced ADRs. VHSE （principal component score vector of hydrophobic, steric, and electronic prop- erties）, a set of amino acid structural descriptors, was employed to establish QSAR models of peptide-binding affinities of HLA-B＊5701 and B＊5801. Optimal linear SVM （support vector machine） models with high predictive capabilities were ob- tained for both B＊5701 and B＇5801. The R2 （coefficient of determination）, Q2 （cross-validated R：）, and RpRE2 （R2 of test set） of two optimal models were 0,7530, 0.7037, 0.6153 （B＇5701） and 0.6074, 0.5966, 0.5762 （B＊5801）, respectively. For B＇5701 and B＇5801, the mutations in positions 45 （MET-THR） and 46 （ALA-GLU） have little influence on the selection specificity of the P2 position of the bound peptide. However, the mutation in position 97 （VAL-ARG） greatly influences the selection speci- ficity of the P7 position. HLA-B＊5701 prefers the bulky and positively charged amino acids at the P7 position. In contrast, HLA-B＊5801 prefers the non-polar hydrophobic amino acids at the P7 position while positively charged amino acids are un- favored.
