Helicobacter pylori (H. pylori) infection is well known to be associated with the development of precancerous lesions such as chronic atrophic gastritis (AG), or gastric intestinal metaplasia (GIM), and cancer. Variou...Helicobacter pylori (H. pylori) infection is well known to be associated with the development of precancerous lesions such as chronic atrophic gastritis (AG), or gastric intestinal metaplasia (GIM), and cancer. Various molecular alterations are identified not only in gastric cancer (GC) but also in precancerous lesions. H. pylori treatment seems to improve AG and GIM, but still remains controversial. In contrast, many studies, including meta-analysis, show that H. pylori eradication reduces GC. Molecular markers detected by genetic and epigenetic alterations related to carcinogenesis reverse following H. pylori eradication. This indicates that these changes may be an important factor in the identification of high risk patients for cancer development. Patients who underwent endoscopic treatment of GC are at high risk for development of metachronous GC. A randomized controlled trial from Japan concluded that prophylactic eradication of H. pylori after endoscopic resection should be used to prevent the development of metachronous GC, but recent retrospective studies did not show the tendency. Patients with precancerous lesions (molecular alterations) that do not reverse after H. pylori treatment, represent the “point of no return” and may be at high risk for the development of GC. Therefore, earlier H. pylori eradication should be considered for preventing GC development prior to the appearance of precancerous lesions.展开更多
The role of vitamin D as an immune modulator has been emphasized in recent years,and low levels of the hormone were observed in several autoimmune diseases including multiple sclerosis and systemic lupus erythematosus...The role of vitamin D as an immune modulator has been emphasized in recent years,and low levels of the hormone were observed in several autoimmune diseases including multiple sclerosis and systemic lupus erythematosus.Vitamin D mediates its effect though binding to vitamin D receptor(VDR),and activation of VDR-responsive genes.While VDR gene polymorphism was found to associate with autoimmune thyroid diseases(AITDs),few studies examined levels of vitamin D in these patients and those that did yielded conflicting results.We therefore undertook to evaluate the levels of vitamin D in patients with AITDs compared to patients with non-AITDs and healthy controls.Serum vitamin D(25-OH)levels were measured in 50 patients with AITDs,42 patients with non-AITDs and 98 healthy subjects,utilizing the LIAISON chemiluminescence immunoassay(DiaSorin,Saluggia,Italy).VitaminD deficiency was designated at levels lower than 10 ng/ml.Antithyroid antibodies,thyroid functions and demographic parameters were evaluated in all patients.The prevalence of vitamin D deficiency was significantly higher in patients with AITDs compared with healthy individuals(72% versus 30.6%;P<0.001),as well as in patients with Hashimoto’s thyroiditis compared to patients with non-AITDs(79% versus 52%;P<0.05).Vitamin D deficiency also correlated to the presence of antithyroid antibodies(P=0.01)and abnormal thyroid function tests(P=0.059).Significantly low levels of vitamin D were documented in patients with AITDs that were related to the presence of anti thyroid antibodies and abnormal thyroid function tests,suggesting the involvement of vitamin D in the pathogenesis of AITDs and the advisability of supplementation.展开更多
The thymus is a central lymphatic organ that is responsible for many immunological functions,including the production of mature,functional T cells and the induction of self-tolerance.Benign or malignant tumors may ori...The thymus is a central lymphatic organ that is responsible for many immunological functions,including the production of mature,functional T cells and the induction of self-tolerance.Benign or malignant tumors may originate from the thymus gland,with thymoma being the most common and accounting for 50% of anterior mediastinal tumors.Malignancies linked to thymoma include the loss of self-tolerance and the presence of autoimmunity.In this review,we compiled the current scientific evidence detailing the various interactions between thymoma and autoimmune diseases,including myasthenia gravis,systemic lupus erythematosus,inappropriate antidiuretic hormone secretion,pure red cell aplasia,pernicious anemia,pemphigus and autoimmune thyroid diseases.In recent years,several mechanisms have been proposed to explain these interactions.Most are based on the assumption that the‘sick’thymus,like the‘normal’thymus,can generate mature T cells;however,the T cells generated by the sick thymus are impaired and thus may exert cellular autoreactivity.Here,we present several theories that may shed light on the loss of self-tolerance associated with this epithelial tumor of the thymus.展开更多
This review provides information on the definition of constipation, normal continence and defecation and a description of the pathophysiologic mechanisms of constipation. In addition, changes in the anatomy and physio...This review provides information on the definition of constipation, normal continence and defecation and a description of the pathophysiologic mechanisms of constipation. In addition, changes in the anatomy and physiology of the lower gastrointestinal tract associated with aging that may contribute to constipation are described. MEDLINE (1966-2007) and CINAHL (1980-2007) were searched. The following MeSH terms were used: constipation/etiology OR constipation/ physiology OR constipation/physiopathology) AND (age factors OR aged OR older OR 80 and over OR middle age). Constipation is not well defined in the literature. While self-reported constipation increases with age, findings from a limited number of clinical studies that utilized objective measures do not support this association. Dysmotility and pelvic floor dysfunction are important mechanisms associated with constipation. Changes in GI function associated with aging appear to be relatively subtle based on a limited amount of conflicting data. Additional research is warranted on the effects of aging on GI function, as well as on the timing of these changes.展开更多
Bilirubin has traditionally been considered a cytotoxic waste product.However,recent studies have shown bilirubin to have anti-oxidant,anti-inflammatory,vasodilatory,anti-apoptotic and anti-proliferative functions.The...Bilirubin has traditionally been considered a cytotoxic waste product.However,recent studies have shown bilirubin to have anti-oxidant,anti-inflammatory,vasodilatory,anti-apoptotic and anti-proliferative functions.These properties potentially confer bilirubin a new role of protection especially in coronary artery disease(CAD),which is a low grade inflammatory process exacerbated by oxidative stress.In fact,recent literature reports an inverse relationship between serum concentration of bilirubin and the presence of CAD.In this article,we review the current literature exploring the association between levels of bilirubin and risk of CAD.We conclude that current evidence is inconclusive regarding the protective effect of bilirubin on CAD.A causal relationship between low serum bilirubin level and increased risk of CAD is not currently established.展开更多
Indoleamine 2, 3-dioxygenase (IDO) is a rate-limiting enzyme for the tryptophan catabolism. In human and murine cells, IDO inhibits antigen-specific T cell proliferation in vitro and suppresses T cell responses to fet...Indoleamine 2, 3-dioxygenase (IDO) is a rate-limiting enzyme for the tryptophan catabolism. In human and murine cells, IDO inhibits antigen-specific T cell proliferation in vitro and suppresses T cell responses to fetal alloantigens during murine pregnancy. In mice, IDO expression is an inducible feature of specific subsets of dendritic cells (DCs), and is important for T cell regulatory properties. However, the effect of IDO and tryptophan deprivation on DC func- tions remains unknown. We report here that when tryptophan utilization was prevented by a pharmacological inhibitor of IDO, 1-methyl tryptophan (1MT), DC activation induced by pathogenic stimulus lipopolysaccharide (LPS) or inflam- matory cytokine TNF-α was inhibited both phenotypically and functionally. Such an effect was less remarkable when DC was stimulated by a physiological stimulus, CD40 ligand. Tryptophan deprivation during DC activation also regu- lated the expression of CCR5 and CXCR4, as well as DC responsiveness to chemokines. These results suggest that tryptophan usage in the microenvironment is essential for DC maturation, and may also play a role in the regulation of DC migratory behaviors.展开更多
Urokinase-type plasminogen activator receptor(uPAR),is a multifunctional receptor on cell surface,widely present in endothelial cells,fibroblasts,and a variety of malignant cells.Current studies have suggested that uP...Urokinase-type plasminogen activator receptor(uPAR),is a multifunctional receptor on cell surface,widely present in endothelial cells,fibroblasts,and a variety of malignant cells.Current studies have suggested that uPAR overexpressed on synovial tissues or in synovial fluid or plasma in patients with rheumatoid arthritis(RA).However,there are limited researches regarding the role of uPAR on fibroblast-like synoviocytes of rheumatoid arthritis(RA-FLSs)and its underlying mechanisms.Here,our studies show that the expression of uPAR protein was significantly higher in fibroblast-like synoviocytes(FLSs)from RA than those from osteoarthritis or traumatic injury patients.uPAR gene silencing significantly inhibited RA-FLSs cell proliferation,restrained cell transformation from the G0/G1 phase to S phase,aggravated cell apoptosis,interfered with RA-FLSs cell migration and invasion,and reduced activation of the PI3K/Akt signaling pathway,which may be associated withβ1-integrin.Cell supernatants from uPAR gene-silenced RA-FLSs markedly inhibited the migration and tubule formation ability of the HUVECs(a human endothelial cell line).Therefore,we demonstrate that uPAR changes the biological characteristics of RA-FLSs,and affects neoangiogenesis of synovial tissues in patients with RA.All of these may be associated with theβ1-integrin/PI3K/Akt signaling pathway.These results imply that targeting uPAR and its downstream signal pathway may provide therapeutic effects in RA.展开更多
Non-alcoholic fatty liver disease(NAFLD)is the most common liver disease in the United States.While the American Association for the Study of Liver Diseases guidelines define NAFLD as hepatic steatosis detected either...Non-alcoholic fatty liver disease(NAFLD)is the most common liver disease in the United States.While the American Association for the Study of Liver Diseases guidelines define NAFLD as hepatic steatosis detected either on histology or imaging without a secondary cause of abnormal hepatic fat accumulation,no imaging modality is recommended as standard of care for screening or diagnosis.Bedside ultrasound has been evaluated as a non-invasive method of diagnosing NAFLD with the presence of characteristic sonographic findings.Prior studies suggest characteristic sonographic findings for NAFLD include bright hepatic echoes,increased hepatorenal echogenicity,vascular blurring of portal or hepatic vein and subcutaneous tissue thickness.These sonographic characteristics have not been shown to aid bedside clinicians easily identify potential cases of NAFLD.While sonographic findings such as attenuation of image,diffuse echogenicity,uniform heterogeneous liver,thick subcutaneous depth,and enlarged liver filling of the entire field could be identifiedby clinicians from bedside ultrasound.The accessibility,ease of use,and low-side effect profile of ultrasound make bedside ultrasound an appealing imaging modality in the detection of hepatic steatosis.When used with appropriate clinical risk factors and steatosis involves greater than 33%of the liver,ultrasound can reliably diagnose NAFLD.Despite the ability of ultrasound in detecting moderate hepatic steatosis,it cannot replace liver biopsy in staging the degree of fibrosis.The purpose of this review is to examine the diagnostic accuracy,utility,and limitations of ultrasound in the diagnosis of NAFLD and its potential use by clinicians in routine practices.展开更多
The use of medicinal plants in treating illnesses has been reported since ancestral times.In the case of hepatic diseases,several species such as Silybum marianum,Phyllanthus niruri,and Panus giganteus(Berk.)have been...The use of medicinal plants in treating illnesses has been reported since ancestral times.In the case of hepatic diseases,several species such as Silybum marianum,Phyllanthus niruri,and Panus giganteus(Berk.)have been shown to ameliorate hepatic lesions.Silymarin is a natural compound derived from the species Silybum marianum,which is commonly known as Milk thistle.This plant contains at least seven flavoligands and the flavonoid taxifolin.The hepatoprotective and antioxidant activity of silymarin is caused by its ability to inhibit the free radicals that are produced from the metabolism of toxic substances such as ethanol,acetaminophen,and carbon tetrachloride.The generation of free radicals is known to damage cellular membranes and cause lipoperoxidation.Silymarin enhances hepatic glutathione and may contribute to the antioxidant defense of the liver.It has also been shown that silymarin increases protein synthesis in hepatocytes by stimulating RNA polymerase I activity.A previous study on humans reported that silymarin treatment caused a slight increase in the survival of patients with cirrhotic alcoholism compared with untreated controls.展开更多
AIM： To investigate the differences in injury patterns caused by arterial, venous or arteriovenous mesenteric occlusion. METHODS： Male Wistar rats were separated equally into four groups. Occlusion was performed by ...AIM： To investigate the differences in injury patterns caused by arterial, venous or arteriovenous mesenteric occlusion. METHODS： Male Wistar rats were separated equally into four groups. Occlusion was performed by clamping the superior mesenteric artery （A）, the mesenteric vein （V） or both （AV） for 30 min, followed by 60 min of reperfusion. A control group received sham surgery only. Intestinal sections were examined for histological damage and serum tumor necrosis factor-α （TNF-α）, endothelin-1 （ET-1）, P-selectin, antithrombin Ⅲ （AT Ⅲ） and soluble intracellular adhesion molecule-1 （ICAM-1） concentrations were measured. RESULTS： All groups showed significant mucosal injury compared to controls. Furthermore, mucosal injury was significantly more severe in the V and AV groups compared to the A group （3.6 ± 0.55, 3.4 ± 0.55 and 2± 0.71, respectively, P = 0.01）. ICAM-1 was similarly elevated in all groups, with no significant differences between the groups. P-selectin levels were significantly elevated in the V and AV groups but not the A group （1.4 ± 0.5 ng/mL, 2.52 ± 0.9 ng/mL and 0.02± 0.01 ng/mL, respectively, P = 0.01） and ET-1 was significantly elevated in the A and V groups but not the AV group （0.32 ± 0.04 pg/mL, 0.36 ± 0.05 pg/mL and 0.29 ± 0.03 pg/mL, respectively, P = 0.01） compared to sham controls. ATⅢ levels were markedly depleted in the V and AV groups, but not in the A group （29.1 ± 5.2 pg/mL, 31.4 ±21.8 pg/mL and 55.8± 35.6 pg/mL, respectively, P = 0.01）, compared to controls. Serum TNF-α was significantly increased in all groups compared to sham controls （1.32 ± 0.87 ng/mL, 1.79 ± 0.20 ng/mL and 4.4 ± 0.69 ng/mL, for groups A, V and AV, respectively, P = 0.01）, with higher values in the AV group. CONCLUSION： Different patterns of response to ischemia/reperfusion are associated with venous, arterial or arteriovenous occlusion. Venous and arteriovenous occlusion was associated with the most severe alterations展开更多
Fibroblast-like synoviocytes （FLSs） contribute to synovial hyperplasia in rheumatoid arthritis （RA）. Smoothened （Smo） is a key component of sonic hedgehog （Shh） signaling and contributes to tumor cell prolifer...Fibroblast-like synoviocytes （FLSs） contribute to synovial hyperplasia in rheumatoid arthritis （RA）. Smoothened （Smo） is a key component of sonic hedgehog （Shh） signaling and contributes to tumor cell proliferation. The objective of this study was to investigate the role of Smo in RA synoviocyte proliferation. FLSs were isolated from RA synovium. Shh signaling was studied using a Smo antagonist （GDC-0449） and small interfering RNA （siRNA） targeting the Smo gene in FLSs. Cell proliferation was quantified by using kit-8 assay and cell cycle distribution and apoptosis were evaluated by flow cytometry. Cell cycle-related genes and proteins were detected by real-time PCR and western blot. FLSs treated with GDC-0449 or Smo-siRNA showed significantly decreased proliferation compared to controls （P〈0.05）. Incubation with GDC-0449 or transfection with Smo-siRNA resulted in a significant increase of G1 phase cells compared to controls （P 〈 0.05）. Cell cycle arrest was validated by the significant increase in cyclin D1 and E1 mRNA expression, decrease in cyclin-dependent kinase p21 mRNA expression in Smo-siRNA transfected cells （P 〈 0.05）. Protein expression of cyclin D1 was also downregulated after Smo gene knockdown （P 〈0.05）.The results suggest that Shh signaling plays an important role in RA-FLSs proliferation in a Smo-dependent manner and may contribute to synovial hyperplasia. Targeting Shh signaling may help control joint damage in patients with RA.展开更多
Zircon U-Pb thermal ionization mass-spectrometer (TIMS) and secondary ion mass-spectrometer (SIMS) dating, mica and amphibole 40Ar-39Ar dating and mineral Sm-Nd isotopic compositions of Huangzhen low temperature eclog...Zircon U-Pb thermal ionization mass-spectrometer (TIMS) and secondary ion mass-spectrometer (SIMS) dating, mica and amphibole 40Ar-39Ar dating and mineral Sm-Nd isotopic compositions of Huangzhen low temperature eclogite and country granitic gneiss are carried out. The zircon U-Pb weighted average SIMS age is (231.6?9.7) Ma for one eclogite. The mica 40Ar-39Ar isochron age is (232.6?2.1) Ma and the lowest plateau age is (221.7?2.4) Ma from same sample. U-Pb TIMS concordant ages from other eclogite zircons are from (221.3?1.4) Ma to (222.5?2.3) Ma. U-Pb SIMS low intercept age from country granitic gneiss is (221?35) Ma. The retrograde amphibole 40Ar-39Ar isochron age is (205.9?1.0) Ma. Except for mica, which may contain excess 40Ar, all the ages represent peak and retrograde metamorphism of low temperature eclogites. It is indicated that the Huangzhen low temperature eclogites differ from Xiongdian low temperature eclogites of north of the Northern Dabie Terrain in metamorphic ages. Huangzhen low temperature eclogites share one coherent HP-UHP terrain with high temperature eclogites from Southern Dabie Terrain and they may have differences in subduction depth and cooling rates during exhumation.展开更多
Biodiversity is thought to be essential for ecosystem stability, function and long-term sustainability. Since nitrogen is the limiting nutrient for plant growth in many terrestrial ecosystems, reactive nitrogen has th...Biodiversity is thought to be essential for ecosystem stability, function and long-term sustainability. Since nitrogen is the limiting nutrient for plant growth in many terrestrial ecosystems, reactive nitrogen has the potential to reduce the diversity of terrestrial vegetation and associated biota through favouring species adapted to quickly exploiting available nutrients. Although the potential has long been recognised, only recently has enough evidence come together to show beyond reasonable doubt that these changes are already occurring. Linked together, experimental, regional/empirical, and time-series research provide a powerful argument that enhanced deposition of reactive nitrogen across Great Britain, and potentially the rest of Europe, has resulted in a significant and ongoing decline in grassland species richness and diversity.展开更多
基金Supported by Grant,NIDDK,RO1DK63618 to KMD from the National Institutes of Health,Bethesda,MD
文摘Helicobacter pylori (H. pylori) infection is well known to be associated with the development of precancerous lesions such as chronic atrophic gastritis (AG), or gastric intestinal metaplasia (GIM), and cancer. Various molecular alterations are identified not only in gastric cancer (GC) but also in precancerous lesions. H. pylori treatment seems to improve AG and GIM, but still remains controversial. In contrast, many studies, including meta-analysis, show that H. pylori eradication reduces GC. Molecular markers detected by genetic and epigenetic alterations related to carcinogenesis reverse following H. pylori eradication. This indicates that these changes may be an important factor in the identification of high risk patients for cancer development. Patients who underwent endoscopic treatment of GC are at high risk for development of metachronous GC. A randomized controlled trial from Japan concluded that prophylactic eradication of H. pylori after endoscopic resection should be used to prevent the development of metachronous GC, but recent retrospective studies did not show the tendency. Patients with precancerous lesions (molecular alterations) that do not reverse after H. pylori treatment, represent the “point of no return” and may be at high risk for the development of GC. Therefore, earlier H. pylori eradication should be considered for preventing GC development prior to the appearance of precancerous lesions.
文摘The role of vitamin D as an immune modulator has been emphasized in recent years,and low levels of the hormone were observed in several autoimmune diseases including multiple sclerosis and systemic lupus erythematosus.Vitamin D mediates its effect though binding to vitamin D receptor(VDR),and activation of VDR-responsive genes.While VDR gene polymorphism was found to associate with autoimmune thyroid diseases(AITDs),few studies examined levels of vitamin D in these patients and those that did yielded conflicting results.We therefore undertook to evaluate the levels of vitamin D in patients with AITDs compared to patients with non-AITDs and healthy controls.Serum vitamin D(25-OH)levels were measured in 50 patients with AITDs,42 patients with non-AITDs and 98 healthy subjects,utilizing the LIAISON chemiluminescence immunoassay(DiaSorin,Saluggia,Italy).VitaminD deficiency was designated at levels lower than 10 ng/ml.Antithyroid antibodies,thyroid functions and demographic parameters were evaluated in all patients.The prevalence of vitamin D deficiency was significantly higher in patients with AITDs compared with healthy individuals(72% versus 30.6%;P<0.001),as well as in patients with Hashimoto’s thyroiditis compared to patients with non-AITDs(79% versus 52%;P<0.05).Vitamin D deficiency also correlated to the presence of antithyroid antibodies(P=0.01)and abnormal thyroid function tests(P=0.059).Significantly low levels of vitamin D were documented in patients with AITDs that were related to the presence of anti thyroid antibodies and abnormal thyroid function tests,suggesting the involvement of vitamin D in the pathogenesis of AITDs and the advisability of supplementation.
文摘The thymus is a central lymphatic organ that is responsible for many immunological functions,including the production of mature,functional T cells and the induction of self-tolerance.Benign or malignant tumors may originate from the thymus gland,with thymoma being the most common and accounting for 50% of anterior mediastinal tumors.Malignancies linked to thymoma include the loss of self-tolerance and the presence of autoimmunity.In this review,we compiled the current scientific evidence detailing the various interactions between thymoma and autoimmune diseases,including myasthenia gravis,systemic lupus erythematosus,inappropriate antidiuretic hormone secretion,pure red cell aplasia,pernicious anemia,pemphigus and autoimmune thyroid diseases.In recent years,several mechanisms have been proposed to explain these interactions.Most are based on the assumption that the‘sick’thymus,like the‘normal’thymus,can generate mature T cells;however,the T cells generated by the sick thymus are impaired and thus may exert cellular autoreactivity.Here,we present several theories that may shed light on the loss of self-tolerance associated with this epithelial tumor of the thymus.
文摘This review provides information on the definition of constipation, normal continence and defecation and a description of the pathophysiologic mechanisms of constipation. In addition, changes in the anatomy and physiology of the lower gastrointestinal tract associated with aging that may contribute to constipation are described. MEDLINE (1966-2007) and CINAHL (1980-2007) were searched. The following MeSH terms were used: constipation/etiology OR constipation/ physiology OR constipation/physiopathology) AND (age factors OR aged OR older OR 80 and over OR middle age). Constipation is not well defined in the literature. While self-reported constipation increases with age, findings from a limited number of clinical studies that utilized objective measures do not support this association. Dysmotility and pelvic floor dysfunction are important mechanisms associated with constipation. Changes in GI function associated with aging appear to be relatively subtle based on a limited amount of conflicting data. Additional research is warranted on the effects of aging on GI function, as well as on the timing of these changes.
文摘Bilirubin has traditionally been considered a cytotoxic waste product.However,recent studies have shown bilirubin to have anti-oxidant,anti-inflammatory,vasodilatory,anti-apoptotic and anti-proliferative functions.These properties potentially confer bilirubin a new role of protection especially in coronary artery disease(CAD),which is a low grade inflammatory process exacerbated by oxidative stress.In fact,recent literature reports an inverse relationship between serum concentration of bilirubin and the presence of CAD.In this article,we review the current literature exploring the association between levels of bilirubin and risk of CAD.We conclude that current evidence is inconclusive regarding the protective effect of bilirubin on CAD.A causal relationship between low serum bilirubin level and increased risk of CAD is not currently established.
文摘Indoleamine 2, 3-dioxygenase (IDO) is a rate-limiting enzyme for the tryptophan catabolism. In human and murine cells, IDO inhibits antigen-specific T cell proliferation in vitro and suppresses T cell responses to fetal alloantigens during murine pregnancy. In mice, IDO expression is an inducible feature of specific subsets of dendritic cells (DCs), and is important for T cell regulatory properties. However, the effect of IDO and tryptophan deprivation on DC func- tions remains unknown. We report here that when tryptophan utilization was prevented by a pharmacological inhibitor of IDO, 1-methyl tryptophan (1MT), DC activation induced by pathogenic stimulus lipopolysaccharide (LPS) or inflam- matory cytokine TNF-α was inhibited both phenotypically and functionally. Such an effect was less remarkable when DC was stimulated by a physiological stimulus, CD40 ligand. Tryptophan deprivation during DC activation also regu- lated the expression of CCR5 and CXCR4, as well as DC responsiveness to chemokines. These results suggest that tryptophan usage in the microenvironment is essential for DC maturation, and may also play a role in the regulation of DC migratory behaviors.
基金This work was supported in part by the grants from Science and Technology Planning Project of Guangdong Province,China(2012B031800363)Science and Technology Program of Guangzhou,China(Special Project on the Integration of Industry,Education and Research)+2 种基金Developing Program of the Major Research Plan of the National Natural Science Foundation of Guangdong,China(2014A030308005)National Natural Science Foundation of China(81671611)and Major National developing program of the national level in Higher Education of Guangdong,China(Natural Science).
文摘Urokinase-type plasminogen activator receptor(uPAR),is a multifunctional receptor on cell surface,widely present in endothelial cells,fibroblasts,and a variety of malignant cells.Current studies have suggested that uPAR overexpressed on synovial tissues or in synovial fluid or plasma in patients with rheumatoid arthritis(RA).However,there are limited researches regarding the role of uPAR on fibroblast-like synoviocytes of rheumatoid arthritis(RA-FLSs)and its underlying mechanisms.Here,our studies show that the expression of uPAR protein was significantly higher in fibroblast-like synoviocytes(FLSs)from RA than those from osteoarthritis or traumatic injury patients.uPAR gene silencing significantly inhibited RA-FLSs cell proliferation,restrained cell transformation from the G0/G1 phase to S phase,aggravated cell apoptosis,interfered with RA-FLSs cell migration and invasion,and reduced activation of the PI3K/Akt signaling pathway,which may be associated withβ1-integrin.Cell supernatants from uPAR gene-silenced RA-FLSs markedly inhibited the migration and tubule formation ability of the HUVECs(a human endothelial cell line).Therefore,we demonstrate that uPAR changes the biological characteristics of RA-FLSs,and affects neoangiogenesis of synovial tissues in patients with RA.All of these may be associated with theβ1-integrin/PI3K/Akt signaling pathway.These results imply that targeting uPAR and its downstream signal pathway may provide therapeutic effects in RA.
文摘Non-alcoholic fatty liver disease(NAFLD)is the most common liver disease in the United States.While the American Association for the Study of Liver Diseases guidelines define NAFLD as hepatic steatosis detected either on histology or imaging without a secondary cause of abnormal hepatic fat accumulation,no imaging modality is recommended as standard of care for screening or diagnosis.Bedside ultrasound has been evaluated as a non-invasive method of diagnosing NAFLD with the presence of characteristic sonographic findings.Prior studies suggest characteristic sonographic findings for NAFLD include bright hepatic echoes,increased hepatorenal echogenicity,vascular blurring of portal or hepatic vein and subcutaneous tissue thickness.These sonographic characteristics have not been shown to aid bedside clinicians easily identify potential cases of NAFLD.While sonographic findings such as attenuation of image,diffuse echogenicity,uniform heterogeneous liver,thick subcutaneous depth,and enlarged liver filling of the entire field could be identifiedby clinicians from bedside ultrasound.The accessibility,ease of use,and low-side effect profile of ultrasound make bedside ultrasound an appealing imaging modality in the detection of hepatic steatosis.When used with appropriate clinical risk factors and steatosis involves greater than 33%of the liver,ultrasound can reliably diagnose NAFLD.Despite the ability of ultrasound in detecting moderate hepatic steatosis,it cannot replace liver biopsy in staging the degree of fibrosis.The purpose of this review is to examine the diagnostic accuracy,utility,and limitations of ultrasound in the diagnosis of NAFLD and its potential use by clinicians in routine practices.
文摘The use of medicinal plants in treating illnesses has been reported since ancestral times.In the case of hepatic diseases,several species such as Silybum marianum,Phyllanthus niruri,and Panus giganteus(Berk.)have been shown to ameliorate hepatic lesions.Silymarin is a natural compound derived from the species Silybum marianum,which is commonly known as Milk thistle.This plant contains at least seven flavoligands and the flavonoid taxifolin.The hepatoprotective and antioxidant activity of silymarin is caused by its ability to inhibit the free radicals that are produced from the metabolism of toxic substances such as ethanol,acetaminophen,and carbon tetrachloride.The generation of free radicals is known to damage cellular membranes and cause lipoperoxidation.Silymarin enhances hepatic glutathione and may contribute to the antioxidant defense of the liver.It has also been shown that silymarin increases protein synthesis in hepatocytes by stimulating RNA polymerase I activity.A previous study on humans reported that silymarin treatment caused a slight increase in the survival of patients with cirrhotic alcoholism compared with untreated controls.
文摘AIM： To investigate the differences in injury patterns caused by arterial, venous or arteriovenous mesenteric occlusion. METHODS： Male Wistar rats were separated equally into four groups. Occlusion was performed by clamping the superior mesenteric artery （A）, the mesenteric vein （V） or both （AV） for 30 min, followed by 60 min of reperfusion. A control group received sham surgery only. Intestinal sections were examined for histological damage and serum tumor necrosis factor-α （TNF-α）, endothelin-1 （ET-1）, P-selectin, antithrombin Ⅲ （AT Ⅲ） and soluble intracellular adhesion molecule-1 （ICAM-1） concentrations were measured. RESULTS： All groups showed significant mucosal injury compared to controls. Furthermore, mucosal injury was significantly more severe in the V and AV groups compared to the A group （3.6 ± 0.55, 3.4 ± 0.55 and 2± 0.71, respectively, P = 0.01）. ICAM-1 was similarly elevated in all groups, with no significant differences between the groups. P-selectin levels were significantly elevated in the V and AV groups but not the A group （1.4 ± 0.5 ng/mL, 2.52 ± 0.9 ng/mL and 0.02± 0.01 ng/mL, respectively, P = 0.01） and ET-1 was significantly elevated in the A and V groups but not the AV group （0.32 ± 0.04 pg/mL, 0.36 ± 0.05 pg/mL and 0.29 ± 0.03 pg/mL, respectively, P = 0.01） compared to sham controls. ATⅢ levels were markedly depleted in the V and AV groups, but not in the A group （29.1 ± 5.2 pg/mL, 31.4 ±21.8 pg/mL and 55.8± 35.6 pg/mL, respectively, P = 0.01）, compared to controls. Serum TNF-α was significantly increased in all groups compared to sham controls （1.32 ± 0.87 ng/mL, 1.79 ± 0.20 ng/mL and 4.4 ± 0.69 ng/mL, for groups A, V and AV, respectively, P = 0.01）, with higher values in the AV group. CONCLUSION： Different patterns of response to ischemia/reperfusion are associated with venous, arterial or arteriovenous occlusion. Venous and arteriovenous occlusion was associated with the most severe alterations
基金This work was supported in part by grants from the National Natural Science Foundation of China （81072480）, from the Natural Science Foundation of Guangdong Province （$2012020010927）, and from the Science and Technology Program of Guangdong Province （2013B021800076） （Jian-lin Huang） the major projects from Science and Technology Program of Guangzhou City, from the National Natural Science Foundation of Guangdong Province, from the Department of Education of Guangdong Province, and grants from NIH AR059103 and NIH AI084359 （Song Guo Zheng）.
文摘Fibroblast-like synoviocytes （FLSs） contribute to synovial hyperplasia in rheumatoid arthritis （RA）. Smoothened （Smo） is a key component of sonic hedgehog （Shh） signaling and contributes to tumor cell proliferation. The objective of this study was to investigate the role of Smo in RA synoviocyte proliferation. FLSs were isolated from RA synovium. Shh signaling was studied using a Smo antagonist （GDC-0449） and small interfering RNA （siRNA） targeting the Smo gene in FLSs. Cell proliferation was quantified by using kit-8 assay and cell cycle distribution and apoptosis were evaluated by flow cytometry. Cell cycle-related genes and proteins were detected by real-time PCR and western blot. FLSs treated with GDC-0449 or Smo-siRNA showed significantly decreased proliferation compared to controls （P〈0.05）. Incubation with GDC-0449 or transfection with Smo-siRNA resulted in a significant increase of G1 phase cells compared to controls （P 〈 0.05）. Cell cycle arrest was validated by the significant increase in cyclin D1 and E1 mRNA expression, decrease in cyclin-dependent kinase p21 mRNA expression in Smo-siRNA transfected cells （P 〈 0.05）. Protein expression of cyclin D1 was also downregulated after Smo gene knockdown （P 〈0.05）.The results suggest that Shh signaling plays an important role in RA-FLSs proliferation in a Smo-dependent manner and may contribute to synovial hyperplasia. Targeting Shh signaling may help control joint damage in patients with RA.
基金supported by the National Natural Science Foundation of China(Grant Nos.40273028 and 40033010)the State Key Basic Research Project(Grant No.G1999075503).
文摘Zircon U-Pb thermal ionization mass-spectrometer (TIMS) and secondary ion mass-spectrometer (SIMS) dating, mica and amphibole 40Ar-39Ar dating and mineral Sm-Nd isotopic compositions of Huangzhen low temperature eclogite and country granitic gneiss are carried out. The zircon U-Pb weighted average SIMS age is (231.6?9.7) Ma for one eclogite. The mica 40Ar-39Ar isochron age is (232.6?2.1) Ma and the lowest plateau age is (221.7?2.4) Ma from same sample. U-Pb TIMS concordant ages from other eclogite zircons are from (221.3?1.4) Ma to (222.5?2.3) Ma. U-Pb SIMS low intercept age from country granitic gneiss is (221?35) Ma. The retrograde amphibole 40Ar-39Ar isochron age is (205.9?1.0) Ma. Except for mica, which may contain excess 40Ar, all the ages represent peak and retrograde metamorphism of low temperature eclogites. It is indicated that the Huangzhen low temperature eclogites differ from Xiongdian low temperature eclogites of north of the Northern Dabie Terrain in metamorphic ages. Huangzhen low temperature eclogites share one coherent HP-UHP terrain with high temperature eclogites from Southern Dabie Terrain and they may have differences in subduction depth and cooling rates during exhumation.
文摘Biodiversity is thought to be essential for ecosystem stability, function and long-term sustainability. Since nitrogen is the limiting nutrient for plant growth in many terrestrial ecosystems, reactive nitrogen has the potential to reduce the diversity of terrestrial vegetation and associated biota through favouring species adapted to quickly exploiting available nutrients. Although the potential has long been recognised, only recently has enough evidence come together to show beyond reasonable doubt that these changes are already occurring. Linked together, experimental, regional/empirical, and time-series research provide a powerful argument that enhanced deposition of reactive nitrogen across Great Britain, and potentially the rest of Europe, has resulted in a significant and ongoing decline in grassland species richness and diversity.
