The evidence from recent surveys on chronic pancreatitis carried out around the world shows that alcohol remains the main factor associated with chronic pancreatitis, even if at a frequency lower than that reported pr...The evidence from recent surveys on chronic pancreatitis carried out around the world shows that alcohol remains the main factor associated with chronic pancreatitis, even if at a frequency lower than that reported previously. It has further conf irmed that heavy alcohol consumption and smoking are independent risk factors for chronic pancreatitis. Autoimmune pancreatitis accounts for 2%-4% of all forms of chronic pancreatitis, but this frequency will probably increase over the next few years. The rise in idiopathic chronic pancreatitis, especially in India, represents a black hole in recently published surveys. Despite the progress made so far regarding the possibility of establishing the hereditary forms of chronic pancreatitis and the recognition of autoimmune pancreatitis, it is possible that we are more inaccurate today than in the past in identifying the factors associated with chronic pancreatitis in our patients.展开更多
Aging is a multidimensional process that leads to an increased risk of developing severe diseases, such as cancer and cardiovascular, neurodegenerative, and immunological diseases. Recently, small non-coding RNAs know...Aging is a multidimensional process that leads to an increased risk of developing severe diseases, such as cancer and cardiovascular, neurodegenerative, and immunological diseases. Recently, small non-coding RNAs known as microRNAs （miRNAs） have been shown to regulate gene expression, which contributes to many physiological and pathophysiological processes in humans. Increasing evidence suggests that changes in miRNA expression profiles contribute to cellular senescence, aging and aging-related diseases. However, only a few miRNAs whose functions have been elucidated have been associated with aging and/or aging-related diseases. This article reviews the currently available findings regarding the roles of aging-related miRNAs, with a focus on cardiac and cardiovascular aging.展开更多
T cell activation following alloantigen recognition plays a critical role in the development of the rejection in all solid organ, tissue and cell transplantation. A recombinant molecule, cytotoxic T lymphocyte antigen...T cell activation following alloantigen recognition plays a critical role in the development of the rejection in all solid organ, tissue and cell transplantation. A recombinant molecule, cytotoxic T lymphocyte antigen 4 antibody （CTLA-4Ig）, is known to induce to T-cell into ＂anergy＂ by blocking the costimulatory B7-CD28 interaction. Either systemic or localized administration of CTLA-Ig has been shown to prolong allograft survival and induce donor-specific tolerance in some transplant models. In this study, we characterized the expression and immunosuppressive effectiveness of adenoviral-mediated CTLA-4Ig gene transfer. We demonstrated transduction of the allografts with AdCTLA-4Ig resulted in localized expression, permanent graft survival and stable donor-specific tolerance. In addition, by performing simultaneous dual-organ through a local expression of CTLA-4Ig via adenoviral-mediated transplantation, we targeted on immunosuppression gene transfer into pancreatic allografts.展开更多
Nodular regenerative hyperplasia(NRH)is a rare liver condition characterized by a widespread benign transformation of the hepatic parenchyma into small regenerative nodules.NRH may lead to the development of non-cirrh...Nodular regenerative hyperplasia(NRH)is a rare liver condition characterized by a widespread benign transformation of the hepatic parenchyma into small regenerative nodules.NRH may lead to the development of non-cirrhotic portal hypertension.There are no published systematic population studies on NRH and our current knowledge is limited to case reports and case series.NRH may develop via autoimmune,hematological,infectious,neoplastic,or drug-related causes.The disease is usually asymptomatic,slowly or nonprogressive unless complications of portal hypertension develop.Accurate diagnosis is made by histopathology,which demonstrates diffuse micronodular transformation without fibrous septa.Lack of perinuclear collagen tissue distinguishes NRH from typical regenerative nodules in the cirrhotic liver.While the initial treatment is to address the underlying disease,ultimately the therapy is directed to the management of portal hypertension.The prognosis of NRH depends on both the severity of the underlying illness and the prevention of secondary complications of portal hypertension.In this review we detail the epidemiology,pathogenesis,diagnosis,management,and prognosis of NRH.展开更多
Natural and synthetic glucocorticoids (GCs) are widely employed in a number of inflammatory, autoimmune and neoplastic diseases, and, despite the introduction of novel therapies, remain the first-line treatment for in...Natural and synthetic glucocorticoids (GCs) are widely employed in a number of inflammatory, autoimmune and neoplastic diseases, and, despite the introduction of novel therapies, remain the first-line treatment for inducing remission in moderate to severe active Crohn’s disease and ulcerative colitis. Despite their extensive therapeutic use and the proven effectiveness, considerable clinical evidence of wide inter-individual differences in GC efficacy among patients has been reported, in particular when these agents are used in inflammatory diseases. In recent years, a detailed knowledge of the GC mechanism of action and of the genetic variants affecting GC activity at the molecular level has arisen from several studies. GCs interact with their cytoplasmic receptor, and are able to repress inflammatory gene expression through several distinct mechanisms. The glucocorticoid receptor (GR) is therefore crucial for the effects of these agents: mutations in the GR gene (NR3C1, nuclear receptor subfamily 3, group C, member 1) are the primary cause of a rare, inherited form of GC resistance; in addition, several polymorphisms of this gene have been described and associated with GC response and toxicity.However, the GR is not self-standing in the cell and the receptor-mediated functions are the result of a complex interplay of GR and many other cellular partners. The latter comprise several chaperonins of the large cooperative hetero-oligomeric complex that binds the hormonefree GR in the cytosol, and several factors involved in the transcriptional machinery and chromatin remodeling, that are critical for the hormonal control of target genes transcription in the nucleus. Furthermore, variants in the principal effectors of GCs (e.g. cytokines and their regulators) have also to be taken into account for a comprehensive evaluation of the variability in GC response. Polymorphisms in genes involved in the transport and/or metabolism of these hormones have also been suggested as other possible candidates of interest that could play a role in the observed inter-individual differences in efficacy and toxicity. The best-characterized example is the drug efflux pump P-glycoprotein, a membrane transporter that extrudes GCs from cells, thereby lowering their intracellular concentration. This protein is encoded by the ABCB1/ MDR1 gene; this gene presents different known polymorphic sites that can influence its expression and function. This editorial reviews the current knowledge on this topic and underlines the role of genetics in predicting GC clinical response. The ambitious goal of pharmacogenomic studies is to adapt therapies to a patient’s specific genetic background, thus improving on efficacy and safety rates.展开更多
Objective: To analyze subtypes and quasi-species of isolatedviruses from HIV-1 infected individuals among the populationof Guangdong Province, for understanding the molecularepidemiological dynamics of local HIV-1 iso...Objective: To analyze subtypes and quasi-species of isolatedviruses from HIV-1 infected individuals among the populationof Guangdong Province, for understanding the molecularepidemiological dynamics of local HIV-1 isolates, thus laying afoundation for designing a candidate AIDS vaccine. Methods: By hetero-duplex mobility assay (HMA) andsingle strand conformation poly-morphism (SSCP) analysison amplicons from single-primed polymerase chain reaction(SP-PCR), subtypes and quasi-species of tested HIV-1 isolateswere elucidated, and amplicons were sequenced forconfirmation. Results: Specific amplicons from different subtypes andquasi-species of HIV-1 could be discernible by HMA andSSCP analysis. Conclusion: HIV-1 isolates from different patients might beeither a different subtype or an identical subtype, and HIV-1isolates from an individual were present in a population ofquasi-species.展开更多
The effect of Pentoxifylline (PTX) on type 1 diabetes was investigated by means of the studies on the expressions of cytokine mRNA in pancreas and the Fas-FasL on islet cells of NOD mice. NOD mice were treated with PT...The effect of Pentoxifylline (PTX) on type 1 diabetes was investigated by means of the studies on the expressions of cytokine mRNA in pancreas and the Fas-FasL on islet cells of NOD mice. NOD mice were treated with PTX from 4-6?wk, and then from 8-12?wk. After treatment, it was found that the incidence of diabetes in NOD mice at ages of 30?wk was reduced to 25% in group of mice treated with PTX, in comparison to 73.3% in case of mice injected with PBS, and the degree of insulitis in the PTX treated mice was lower than that of the PBS injected mice. RT-PCR analysis revealed down-regulatory effect on the expressions of IFN-γ and TNF-α mRNA in PTX treated mice, but there was no any effect on the expression of IL-10. As to the expression of Fas, there was marked decrease in the mean cytoplasmic integral optical density (IOD) in PTX treated mice, but there was little difference between PTX and PBS groups in the expression of FasL. These results indicated that PTX could prevent the development of diabetes in NOD mice, which might be related to the regulation of Th1/Th2 imbalance and the decreased expression of Fas in islet cells.展开更多
The essential trace element iron regulates a wide range of biological processes in virtually all living organisms.Because both iron deficiency and iron overload can lead to various pathological conditions,iron homeost...The essential trace element iron regulates a wide range of biological processes in virtually all living organisms.Because both iron deficiency and iron overload can lead to various pathological conditions,iron homeostasis is tightly regulated,and understanding this complex process will help pave the way to developing new therapeutic strategies for inflammatory disease.In recent years,significant progress has been made with respect to elucidating the roles of iron and iron-related genes in the development and maintenance of the immune system.Here,we review the timing and mechanisms by which systemic and cellular iron metabolism are regulated during the inflammatory response and during infectious disease,processes in which both the host and the pathogen compete for iron.We also discuss the evidence and implications that immune cells such as macrophages,T cells,and B cells require sufficient amounts of iron for their proliferation and for mediating their effector functions,in which iron serves as a co-factor in toll-like receptor 4(TLR4)signaling,mitochondrial respiration,posttranslational regulation,and epigenetic modification.In addition,we discuss the therapeutic implications of targeting ferroptosis,iron homeostasis and/or iron metabolism with respect to conferring protection against pathogen infection,controlling inflammation,and improving the efficacy of immunotherapy.展开更多
The human pathogen, group A rotavirus, is the most prevalent cause of acute infantile and pediatric gastroenteritis worldwide, especially in developing countries. There is an urgent demand for safer, more effective an...The human pathogen, group A rotavirus, is the most prevalent cause of acute infantile and pediatric gastroenteritis worldwide, especially in developing countries. There is an urgent demand for safer, more effective and cheaper vaccines against rotavirus infection. Plant-derived antigens may provide an exclusive way to produce economical subunit vaccines. Virus-like particles, constituting viral capsid proteins without viral nucleic acids, are considered a far safer candidate compared with live attenuated viral vaccines. In this study, the rotavirus capsid proteins VP2, VP6 and VP7 were co-expressed in transgenic tobacco plants, and their expression levels, formation of rotavirus-like particles (RV VLPs) and immunogenicity were extensively studied. Quantitative real-time RT-PCR and Western blot analysis revealed that the expression level of vp6 was the highest while vp7 was expressed at the lowest levels. The RV VLPs were purified from transgenic tobacco plants and analyzed by electron microscopy and Western blot. Results indicated that the plant-derived VP2, VP6 and VP7 proteins self-assembled into 2/6 or 2/6/7 RV VLPs with a diameter of 60-80 nm. When orally delivered into mice with cholera toxin as an adjuvant, the total soluble protein extracted from transgenic tobacco plants induced rotavirus-specific antibodies comparable with those of attenuated rotavirus vaccines, while VP 2/6/7 induced higher serum IgG and fecal IgA titers compared with VP 2/6.展开更多
文摘The evidence from recent surveys on chronic pancreatitis carried out around the world shows that alcohol remains the main factor associated with chronic pancreatitis, even if at a frequency lower than that reported previously. It has further conf irmed that heavy alcohol consumption and smoking are independent risk factors for chronic pancreatitis. Autoimmune pancreatitis accounts for 2%-4% of all forms of chronic pancreatitis, but this frequency will probably increase over the next few years. The rise in idiopathic chronic pancreatitis, especially in India, represents a black hole in recently published surveys. Despite the progress made so far regarding the possibility of establishing the hereditary forms of chronic pancreatitis and the recognition of autoimmune pancreatitis, it is possible that we are more inaccurate today than in the past in identifying the factors associated with chronic pancreatitis in our patients.
文摘Aging is a multidimensional process that leads to an increased risk of developing severe diseases, such as cancer and cardiovascular, neurodegenerative, and immunological diseases. Recently, small non-coding RNAs known as microRNAs （miRNAs） have been shown to regulate gene expression, which contributes to many physiological and pathophysiological processes in humans. Increasing evidence suggests that changes in miRNA expression profiles contribute to cellular senescence, aging and aging-related diseases. However, only a few miRNAs whose functions have been elucidated have been associated with aging and/or aging-related diseases. This article reviews the currently available findings regarding the roles of aging-related miRNAs, with a focus on cardiac and cardiovascular aging.
文摘T cell activation following alloantigen recognition plays a critical role in the development of the rejection in all solid organ, tissue and cell transplantation. A recombinant molecule, cytotoxic T lymphocyte antigen 4 antibody （CTLA-4Ig）, is known to induce to T-cell into ＂anergy＂ by blocking the costimulatory B7-CD28 interaction. Either systemic or localized administration of CTLA-Ig has been shown to prolong allograft survival and induce donor-specific tolerance in some transplant models. In this study, we characterized the expression and immunosuppressive effectiveness of adenoviral-mediated CTLA-4Ig gene transfer. We demonstrated transduction of the allografts with AdCTLA-4Ig resulted in localized expression, permanent graft survival and stable donor-specific tolerance. In addition, by performing simultaneous dual-organ through a local expression of CTLA-4Ig via adenoviral-mediated transplantation, we targeted on immunosuppression gene transfer into pancreatic allografts.
文摘Nodular regenerative hyperplasia(NRH)is a rare liver condition characterized by a widespread benign transformation of the hepatic parenchyma into small regenerative nodules.NRH may lead to the development of non-cirrhotic portal hypertension.There are no published systematic population studies on NRH and our current knowledge is limited to case reports and case series.NRH may develop via autoimmune,hematological,infectious,neoplastic,or drug-related causes.The disease is usually asymptomatic,slowly or nonprogressive unless complications of portal hypertension develop.Accurate diagnosis is made by histopathology,which demonstrates diffuse micronodular transformation without fibrous septa.Lack of perinuclear collagen tissue distinguishes NRH from typical regenerative nodules in the cirrhotic liver.While the initial treatment is to address the underlying disease,ultimately the therapy is directed to the management of portal hypertension.The prognosis of NRH depends on both the severity of the underlying illness and the prevention of secondary complications of portal hypertension.In this review we detail the epidemiology,pathogenesis,diagnosis,management,and prognosis of NRH.
文摘Natural and synthetic glucocorticoids (GCs) are widely employed in a number of inflammatory, autoimmune and neoplastic diseases, and, despite the introduction of novel therapies, remain the first-line treatment for inducing remission in moderate to severe active Crohn’s disease and ulcerative colitis. Despite their extensive therapeutic use and the proven effectiveness, considerable clinical evidence of wide inter-individual differences in GC efficacy among patients has been reported, in particular when these agents are used in inflammatory diseases. In recent years, a detailed knowledge of the GC mechanism of action and of the genetic variants affecting GC activity at the molecular level has arisen from several studies. GCs interact with their cytoplasmic receptor, and are able to repress inflammatory gene expression through several distinct mechanisms. The glucocorticoid receptor (GR) is therefore crucial for the effects of these agents: mutations in the GR gene (NR3C1, nuclear receptor subfamily 3, group C, member 1) are the primary cause of a rare, inherited form of GC resistance; in addition, several polymorphisms of this gene have been described and associated with GC response and toxicity.However, the GR is not self-standing in the cell and the receptor-mediated functions are the result of a complex interplay of GR and many other cellular partners. The latter comprise several chaperonins of the large cooperative hetero-oligomeric complex that binds the hormonefree GR in the cytosol, and several factors involved in the transcriptional machinery and chromatin remodeling, that are critical for the hormonal control of target genes transcription in the nucleus. Furthermore, variants in the principal effectors of GCs (e.g. cytokines and their regulators) have also to be taken into account for a comprehensive evaluation of the variability in GC response. Polymorphisms in genes involved in the transport and/or metabolism of these hormones have also been suggested as other possible candidates of interest that could play a role in the observed inter-individual differences in efficacy and toxicity. The best-characterized example is the drug efflux pump P-glycoprotein, a membrane transporter that extrudes GCs from cells, thereby lowering their intracellular concentration. This protein is encoded by the ABCB1/ MDR1 gene; this gene presents different known polymorphic sites that can influence its expression and function. This editorial reviews the current knowledge on this topic and underlines the role of genetics in predicting GC clinical response. The ambitious goal of pharmacogenomic studies is to adapt therapies to a patient’s specific genetic background, thus improving on efficacy and safety rates.
基金Financially supported by Natural Science Foundation of China(No 39870725)Natural Science Foundation of Guangdong(No 980642)Research Foundation of Guangdong Education Bureau(No.20032).
文摘Objective: To analyze subtypes and quasi-species of isolatedviruses from HIV-1 infected individuals among the populationof Guangdong Province, for understanding the molecularepidemiological dynamics of local HIV-1 isolates, thus laying afoundation for designing a candidate AIDS vaccine. Methods: By hetero-duplex mobility assay (HMA) andsingle strand conformation poly-morphism (SSCP) analysison amplicons from single-primed polymerase chain reaction(SP-PCR), subtypes and quasi-species of tested HIV-1 isolateswere elucidated, and amplicons were sequenced forconfirmation. Results: Specific amplicons from different subtypes andquasi-species of HIV-1 could be discernible by HMA andSSCP analysis. Conclusion: HIV-1 isolates from different patients might beeither a different subtype or an identical subtype, and HIV-1isolates from an individual were present in a population ofquasi-species.
文摘The effect of Pentoxifylline (PTX) on type 1 diabetes was investigated by means of the studies on the expressions of cytokine mRNA in pancreas and the Fas-FasL on islet cells of NOD mice. NOD mice were treated with PTX from 4-6?wk, and then from 8-12?wk. After treatment, it was found that the incidence of diabetes in NOD mice at ages of 30?wk was reduced to 25% in group of mice treated with PTX, in comparison to 73.3% in case of mice injected with PBS, and the degree of insulitis in the PTX treated mice was lower than that of the PBS injected mice. RT-PCR analysis revealed down-regulatory effect on the expressions of IFN-γ and TNF-α mRNA in PTX treated mice, but there was no any effect on the expression of IL-10. As to the expression of Fas, there was marked decrease in the mean cytoplasmic integral optical density (IOD) in PTX treated mice, but there was little difference between PTX and PBS groups in the expression of FasL. These results indicated that PTX could prevent the development of diabetes in NOD mice, which might be related to the regulation of Th1/Th2 imbalance and the decreased expression of Fas in islet cells.
基金This work was supported by the National Natural Science Foundation of China(31930057 and 31970689)the National Key Research and Development Program(2018YFA0507802,2018YFA0507801,and 2018YFC2000405).
文摘The essential trace element iron regulates a wide range of biological processes in virtually all living organisms.Because both iron deficiency and iron overload can lead to various pathological conditions,iron homeostasis is tightly regulated,and understanding this complex process will help pave the way to developing new therapeutic strategies for inflammatory disease.In recent years,significant progress has been made with respect to elucidating the roles of iron and iron-related genes in the development and maintenance of the immune system.Here,we review the timing and mechanisms by which systemic and cellular iron metabolism are regulated during the inflammatory response and during infectious disease,processes in which both the host and the pathogen compete for iron.We also discuss the evidence and implications that immune cells such as macrophages,T cells,and B cells require sufficient amounts of iron for their proliferation and for mediating their effector functions,in which iron serves as a co-factor in toll-like receptor 4(TLR4)signaling,mitochondrial respiration,posttranslational regulation,and epigenetic modification.In addition,we discuss the therapeutic implications of targeting ferroptosis,iron homeostasis and/or iron metabolism with respect to conferring protection against pathogen infection,controlling inflammation,and improving the efficacy of immunotherapy.
基金supported by the National High Technology Research and Development Program of China (Grant No. 2007AA100505)
文摘The human pathogen, group A rotavirus, is the most prevalent cause of acute infantile and pediatric gastroenteritis worldwide, especially in developing countries. There is an urgent demand for safer, more effective and cheaper vaccines against rotavirus infection. Plant-derived antigens may provide an exclusive way to produce economical subunit vaccines. Virus-like particles, constituting viral capsid proteins without viral nucleic acids, are considered a far safer candidate compared with live attenuated viral vaccines. In this study, the rotavirus capsid proteins VP2, VP6 and VP7 were co-expressed in transgenic tobacco plants, and their expression levels, formation of rotavirus-like particles (RV VLPs) and immunogenicity were extensively studied. Quantitative real-time RT-PCR and Western blot analysis revealed that the expression level of vp6 was the highest while vp7 was expressed at the lowest levels. The RV VLPs were purified from transgenic tobacco plants and analyzed by electron microscopy and Western blot. Results indicated that the plant-derived VP2, VP6 and VP7 proteins self-assembled into 2/6 or 2/6/7 RV VLPs with a diameter of 60-80 nm. When orally delivered into mice with cholera toxin as an adjuvant, the total soluble protein extracted from transgenic tobacco plants induced rotavirus-specific antibodies comparable with those of attenuated rotavirus vaccines, while VP 2/6/7 induced higher serum IgG and fecal IgA titers compared with VP 2/6.
