Spinal cord injury(SCI)is a debilitating condition characterized by damage to the spinal cord resulting in loss of function,mobility,and sensation with no U.S.Food and Drug Administration-approved cure.Enolase,a multi...Spinal cord injury(SCI)is a debilitating condition characterized by damage to the spinal cord resulting in loss of function,mobility,and sensation with no U.S.Food and Drug Administration-approved cure.Enolase,a multifunctional glycolytic enzyme upregulated after SCI,promotes pro-and anti-inflammatory events and regulates functional recovery in SCI.Enolase is normally expressed in the cytosol,but the expression is upregulated at the cell surface following cellular injury,promoting glial cell activation and signal transduction pathway activation.SCI-induced microglia activation triggers pro-inflammatory mediators at the injury site,activating other immune cells and metabolic events,i.e.,Rho-associated kinase,contributing to the neuroinflammation found in SCI.Enolase surface expression also activates cathepsin X,resulting in cleavage of the C-terminal end of neuron-specific enolase(NSE)and non-neuronal enolase(NNE).Fully functional enolase is necessary as NSE/NNE C-terminal proteins activate many neurotrophic processes,i.e.,the plasminogen activation system,phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B,and mitogen-activated protein kinase/extracellular signal-regulated kinase.Studies here suggest an enolase inhibitor,ENOblock,attenuates the activation of Rho-associated kinase,which may decrease glial cell activation and promote functional recovery following SCI.Also,ENOblock inhibits cathepsin X,which may help prevent the cleavage of the neurotrophic C-terminal protein allowing full plasminogen activation and phosphatidylinositol-4,5-bisphosphate 3-kinase/mitogen-activated protein kinase activity.The combined NSE/cathepsin X inhibition may serve as a potential therapeutic strategy for preventing neuroinflammation/degeneration and promoting neural cell regeneration and recovery following SCI.The role of cell membrane-expressed enolase and associated metabolic events should be investigated to determine if the same strategies can be applied to other neurodegenerative diseases.Hence,this review discusses the importance of enolase activation and inhibition as a potential therapeutic target following SCI to promote neuronal survival and regeneration.展开更多
Spinal cord injuries affect nearly five to ten individuals per million every year. Spinal cord injury causes damage to the nerves, muscles, and the tissue surrounding the spinal cord. Depending on the severity, spinal...Spinal cord injuries affect nearly five to ten individuals per million every year. Spinal cord injury causes damage to the nerves, muscles, and the tissue surrounding the spinal cord. Depending on the severity, spinal injuries are linked to degeneration of axons and myelin, resulting in neuronal impairment and skeletal muscle weakness and atrophy. The protection of neurons and promotion of myelin regeneration during spinal cord injury is important for recovery of function following spinal cord injury. Current treatments have little to no effect on spinal cord injury and neurogenic muscle loss. Clemastine, an Food and Drug Administration-approved antihistamine drug, reduces inflammation, protects cells, promotes remyelination, and preserves myelin integrity. Recent clinical evidence suggests that clemastine can decrease the loss of axons after spinal cord injury, stimulating the differentiation of oligodendrocyte progenitor cells into mature oligodendrocytes that are capable of myelination. While clemastine can aid not only in the remyelination and preservation of myelin sheath integrity, it also protects neurons. However, its role in neurogenic muscle loss remains unclear. This review discusses the pathophysiology of spinal cord injury, and the role of clemastine in the protection of neurons, myelin, and axons as well as attenuation of skeletal muscle loss following spinal cord injury.展开更多
BACKGROUND The presence of two distinct hepatitis B virus(HBV)Pol RT polymorphisms,rt269L and rt269I,could contribute to the unique clinical or virological phenotype of HBV genotype C2.Therefore,a simple and sensitive...BACKGROUND The presence of two distinct hepatitis B virus(HBV)Pol RT polymorphisms,rt269L and rt269I,could contribute to the unique clinical or virological phenotype of HBV genotype C2.Therefore,a simple and sensitive method capable of identifying both types in chronic hepatitis B(CHB)patients infected with genotype C2 should be developed.AIM To develop a novel simple and sensitive locked nucleic acid(LNA)-real timepolymerase chain reaction(RT-PCR)method capable of identifying two rt269 types in CHB genotype C2 patients.METHODS We designed proper primer and probe sets for LNA-RT-PCR for the separation of rt269 types.Using synthesized DNAs of the wild type and variant forms,melting temperature analysis,detection sensitivity,and endpoint genotyping for LNA-RT-PCR were performed.The developed LNA-RT-PCR method was applied to a total of 94 CHB patients of genotype C2 for the identification of two rt269 polymorphisms,and these results were compared with those obtained by a direct sequencing protocol.RESULTS The LNA-RT-PCR method could identify two rt269L and rt269I polymorphisms of three genotypes,two rt269L types[‘L1’(WT)and‘L2’]and one rt269I type(‘I’)in single(63 samples,72.4%)or mixed forms(24 samples,27.6%)in 87(92.6%sensitivity)of 94 samples from Korean CHB patients.When the results were compared with those obtained by the direct sequencing protocol,the LNA-RT-PCR method showed the same results in all but one of 87 positive detected samples(98.9%specificity).CONCLUSION The newly developed LNA-RT-PCR method could identify two rt269 polymorphisms,rt269L and rt269I,in CHB patients with genotype C2 infections.This method could be effectively used for the understanding of disease progression in genotype C2 endemic areas.展开更多
It is known that the pathogenicity of Plasmodium induces the breakdown of haemoglobin, which leads to the induction of oxidative stress. This study aimed to identify the possible effects of oxidative stress and antiox...It is known that the pathogenicity of Plasmodium induces the breakdown of haemoglobin, which leads to the induction of oxidative stress. This study aimed to identify the possible effects of oxidative stress and antioxidant defence systems in symptomatic and asymptomatic Plasmodium falciparum malaria infection in children (1 - 15 years old) in the Mount Cameroon vicinity. This cross-sectional study involved blood samples collected from 473 children and examined for malaria parasitaemia. Full blood counts were performed using an automated haemoanalyser. Serum oxidative stress status (malondialdehyde (MDA), nitric oxide (NO), reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and vitamin C (Vit C)) were each determined by colorimetric enzymatic assays. The prevalence of malaria parasite infection was 32.1% among the participants. Out of that, 62.5% of patients with parasitaemia were symptomatic. Anaemia prevalence increased significantly with parasite density. MDA levels were significantly higher in patients with malaria symptoms than in those without symptoms. A significant and positive correlation was detected between MDA (r = 0.831, P < 0.05), NO (r = 0.779, P < 0.05), and malaria parasite density while, a significant and negative relationship occurred between parasite density and GSH (r = ?0.763, P < 0.05) and Vit C (r = ?0.826, P < 0.05) levels, SOD (r = ?0.621, P < 0.05) and CAT (r = ?0.817, P < 0.05) activities. The SOD activity and GSH level significantly decreased (P < 0.05) with an increase in the MDA levels. These findings showed that MDA and nitric oxide levels increased both in malaria participants with or without symptoms. A similar decrease in the antioxidant defence system was observed in both symptomatic and asymptomatic patients. Therefore, there is a need to develop public health policies that encourage routine diagnosis and treatment of malaria in seemingly healthy people (asymptomatic cases), and this will play an essential role in controlling malaria in tropical countries.展开更多
Human papillomavirus (HPV) is classified into high-risk HPV (HR-HPV) and HPV (LR-HPV) according to their oncogenic potential. These viruses can be found in the cervix, vagina, vulva, anus and in the ENT sphere. HPV EN...Human papillomavirus (HPV) is classified into high-risk HPV (HR-HPV) and HPV (LR-HPV) according to their oncogenic potential. These viruses can be found in the cervix, vagina, vulva, anus and in the ENT sphere. HPV ENT infections can lead to benign or malignant tumors in which we could find both LR-HPV and HR-HPV genotypes. The objective of this study was to investigate the genotypes of HR-HPV and LR-HPV in archived tissue samples derived from both benign and malignant tumors of the ear, nose, and throat (ENT) in Ouagadougou, Burkina Faso. One hundred and twenty formalin-fixed, paraffin-embedded archived tissues of the ENT sphere from 26 benign tumors and 94 malignant tumors were included. The tissues were first deparaffinized with xylem. The extracted DNA was used to test for high-risk and low-risk HPV by Real-Time Multiplex PCR. HPV DNA was found in 57.7% (15/26) of benign tumors and 43.61% (41/94) of malignant tumors. The prevalence of HPV infection was 46.67% (56/120) in all tumors combined. The most common HPV genotypes found were HPV 11 (34.28%), HPV 6 (30%), HPV56 (14.28%) and HPV 33 (8.57%). There were 21.43% (12/56) cases of genotypes co-infections with 10 cases of double infection and 2 cases of triple infection. Both low-risk and high-risk HPV are found in ENT tumors with relatively high HPV prevalence.展开更多
Introduction: Genetic polymorphisms of some Glutathione S-Transferase (GST) which encode the enzyme responsible for the biotransformation of drugs and xenobiotics, have been associated with the risk of several patholo...Introduction: Genetic polymorphisms of some Glutathione S-Transferase (GST) which encode the enzyme responsible for the biotransformation of drugs and xenobiotics, have been associated with the risk of several pathologies that can progress to cancer such as Hepatitis B. This study aims to characterize the impact of the rs1695 polymorphism of GSTP1 gene among people with chronic Hepatitis B infection in Burkina Faso. Methods: rs1695 polymorphisms of GSTP1 gene genotyping was performed for 50 people infected with chronic Hepatitis B virus and 124 healthy people with the PCR-RFLP method. Conventional PCR was used for DNA amplification and Alw26I enzyme was used for enzymatic digestion. Results: The results show that the frequencies of AA, AG and GG genotypes are respectively 31.00%, 36.80% and 32.20% in general the study population with a mutation rate of 50.57%. However, the incidence of the AA, AG and GG genotypes are respectively 30.64%, 38.71% and 30.64% among people with chronic Hepatitis B virus infection and 32.00%, 32.00% and 36.00% among healthy people. In cases, the frequencies of the A and G alleles are 48.00% and 52.00% respectively, and in controls 50.00% each. No statistical difference was found by comparing genotypic and allelic frequencies between cases and controls (p > 0.05). Conclusion: Our study allowed us to determine the rate of GSTP1 rs1695 genotypes in the study population, cases and controls. From our analyses, GSTP1 rs1695 is not associated to chronic Hepatitis B virus infection in Ouagadougou.展开更多
Diabetes is one of the deadliest diseases.Due to its effects on the lives of people,it has attracted a lot of attention recently.The causes of the various forms of diabetes,including type 1 and type 2,were discussed a...Diabetes is one of the deadliest diseases.Due to its effects on the lives of people,it has attracted a lot of attention recently.The causes of the various forms of diabetes,including type 1 and type 2,were discussed along with how they affect those who have the disease.Younger people are more prone to type 1 diabetes than older people,who are more likely to develop type 2.The treatment options and strategies for the two forms of diabetes were also discussed in addition to how the disease affects the quality of life of people.Among several factors that were explained,it has been shown that people from low and middle-income countries are more prone to having diabetes.Additionally,the condition is more likely to affect some races more than others.It is associated with obesity.According to statistics,those who are poor are more severely affected by the disease.The progression of the disease over time has been associated with an increase in disability and mortality.展开更多
Helicobacter pylori(H. pylori) is an extremely common, yet underappreciated, pathogen that is able to alter host physiology and subvert the host immune response, allowing it to persist for the life of the host. H. pyl...Helicobacter pylori(H. pylori) is an extremely common, yet underappreciated, pathogen that is able to alter host physiology and subvert the host immune response, allowing it to persist for the life of the host. H. pylori is the primary cause of peptic ulcers and gastric cancer. In the United States, the annual cost associated with peptic ulcer disease is estimated to be $6 billion and gastric cancer kills over 700000 people per year globally. The prevalence of H. pylori infection remains high(> 50%) in much of the world, although the infection rates are dropping in some developed nations. The drop in H. pylori prevalence could be a double-edged sword, reducing the incidence of gastric diseases while increasing the risk of allergies and esophageal diseases. The list of diseases potentially caused by H. pylori continues to grow; however, mechanistic explanations of how H. pylori could contribute to extragastric diseases lag far behind clinical studies. A number of host factors and H. pylori virulence factors act in concert to determine which individuals are at the highest risk of disease. These include bacterial cytotoxins and polymorphisms in host genes responsible for directing the immune response. This review discusses the latest advances in H. pylori pathogenesis, diagnosis, and treatment. Up-todate information on correlations between H. pylori and extragastric diseases is also provided.展开更多
Nonalcoholic fatty liver disease (NAFLD) is highly prevalent and can result in nonalcoholic steatohepatitis (NASH) and progressive liver disease including cirrhosis and hepatocellular carcinoma. A growing body of lite...Nonalcoholic fatty liver disease (NAFLD) is highly prevalent and can result in nonalcoholic steatohepatitis (NASH) and progressive liver disease including cirrhosis and hepatocellular carcinoma. A growing body of literature implicates the peroxisome proliferators-activated receptors (PPARs) in the pathogenesis and treatment of NAFLD. These nuclear hormone receptors impact on hepatic triglyceride accumulation and insulin resistance. The aim of this review is to describe the data linking PPARα and PPARγ to NAFLD/NASH and to discuss the use of PPAR ligands for the treatment of NASH.展开更多
AIM: To analyze the serum levels and prognostic significance of vascular endothelial growth factor (VEGF) -A,-C,and -D,and their receptors,VEGFR-1 and -2 in gastric adenocarcinomas. METHODS: The serum levels of VEGF f...AIM: To analyze the serum levels and prognostic significance of vascular endothelial growth factor (VEGF) -A,-C,and -D,and their receptors,VEGFR-1 and -2 in gastric adenocarcinomas. METHODS: The serum levels of VEGF family members were measured in 76 control subjects and 76 patients with gastric adenocarcinoma using an enzyme-linked immunosorbent assay (ELISA). These measurements were correlated with clinco-pathological features and survival rates. RESULTS: The serum levels of VEGF-A and its receptor,VEGFR-1,were signifi cantly higher in patients with gastric cancer than in healthy donors (t = 2.3,P = 0.02 and t = 4.2,P < 0.0001,respectively). In contrast,the serum levels of VEGF-D were signif icantly higher in control subjects than in patients (t = 2.9,P = 0.004). There was no significant difference in serum levels of VEGF-C and VEGFR-2 between patients and controls. VEGF-C was associated with advanced tumor stage and presence of metastasis. VEGFR-1 was associated with metastasis,advanced overall stage,tumor differentiation and survival. VEGFR-2 levels were associated with poor tumor differentiation. There was no significant prognostic value for any of the VEGF family members or their receptors except for VEGFR-1 where high levels were associated with a poor overall survival. CONCLUSION: Serum VEGF levels vary significantly in the same cohort of patients with variable clinico-pathological features and prognostic values. The simultaneous measurement of VEGF receptors levels in sera may overcome the limitations of a single biomarker assay.展开更多
This review describes the woodchuck and the woodchuck hepatitis virus (WHV) as an animal model for pathogenesis and therapy of chronic hepatitis B virus (HBV) infection and disease in humans. The establishment of wood...This review describes the woodchuck and the woodchuck hepatitis virus (WHV) as an animal model for pathogenesis and therapy of chronic hepatitis B virus (HBV) infection and disease in humans. The establishment of woodchuck breeding colonies, and use of laboratory-reared woodchucks infected with defined WHV inocula, have enhanced our understanding of the virology and immunology of HBV infection and disease pathogenesis, including major sequelae like chronic hepatitis and hepatocellular carcinoma. The role of persistent WHV infection and of viral load on the natural history of infection and disease progression has been firmly established along the way. More recently, the model has shed new light on the role of host immune responses in these natural processes, and on how the immune system of the chronic carrier can be manipulated therapeutically to reduce or delay serious disease sequelae through induction of the recovery phenotype. The woodchuck is an outbred species and is not well defined immunologically due to a limitation of available host markers. However, the recent development of several key host response assays for woodchucks provides experimental opportunities for further mechanistic studies of outcome predictors in neonatal- and adult-acquired infections. Understanding the virological and immunological mechanisms responsible for resolution of self-limited infection, andfor the onset and maintenance of chronic infection, will greatly facilitate the development of successful strategies for the therapeutic eradication of established chronic HBV infection. Likewise, the results of drug efficacy and toxicity studies in the chronic carrier woodchucks are predictive for responses of patients chronically infected with HBV. Therefore, chronic WHV carrier woodchucks provide a well-characterized mammalian model for preclinical evaluation of the safety and efficacy of drug candidates, experimental therapeutic vaccines, and immunomodulators for the treatment and prevention of HBV disease sequelae.展开更多
This review summarizes the current state of knowledge regarding the role of endothelial dysfunction in the pathogenesis of early and delayed intestinal radiation toxicity and discusses various endothelial-oriented int...This review summarizes the current state of knowledge regarding the role of endothelial dysfunction in the pathogenesis of early and delayed intestinal radiation toxicity and discusses various endothelial-oriented interventions aimed at reducing the risk of radiation enteropathy. Studies published in the biomedical literature during the past four decades and cited in PubMed, as well as clinical and laboratory data from our own research program are reviewed. The risk of injury to normal tissues limits the cancer cure rates that can be achieved with radiation therapy. During treatment of abdominal and pelvic tumors, the intestine is frequently a major dose-limiting factor. Microvascular injury is a prominent feature of both early (inflammatory), as well as delayed (fibroproliferative) radiation injuries in the intestine and in many other normal tissues. Evidence from our and other laboratories suggests that endothelial dysfunction, notably a deficiency of endothelial thrombomodulin, plays a key role in the pathogenesis of these radiation responses. Deficient levels of thrombomodulin cause loss of vascular thromboresistance, excessive activation of cellular thrombin receptors by thrombin, and insufficient activation of protein C, a plasma protein with anticoagulant, anti-inflammatory, and cytoprotective properties. These changes are presumed to be critically involved in many aspects of early intestinal radiation toxicity and may sustain the fi broproliferative processes that lead to delayed intestinal dysfunction, fi brosis, and clinical complications. In conclusion, injury of vascular endothelium is important in the pathogenesis of the intestinal radiation response. Endothelial-oriented interventions are appealing strategies to prevent or treat normal tissue toxicity associated with radiation treatment of cancer.展开更多
AIM: To investigate the effect of synbiotics, i.e. probiotics and prebiotics mixture, on the gut microbial ecology and digestive enzyme activities in rats. METHODS: Forty-eight SD rats weighing about 280 g were used i...AIM: To investigate the effect of synbiotics, i.e. probiotics and prebiotics mixture, on the gut microbial ecology and digestive enzyme activities in rats. METHODS: Forty-eight SD rats weighing about 280 g were used in this study. Rats were divided into three groups according to the contents of probiotics and prebiotics mixture in the feed as control, low and high dose groups. The duration of the experiment was 8 wk. RESULTS: Compared with the control group, thefecal Lactobacillus and Bifidobacterium counts were significantly increased and the fecal Coliform organism counts were markedly reduced in the low and high dose groups. Concerning the digestive enzyme activity of jejunum, only lactase activity increased in low dose group. However, significant increase of lipase, lactase, sucrase, and isomaltase activities were observed in high dose group.CONCLUSION: Intake of low and high dosages of probiotics and prebiotics mixture significantly improved the ecosystem of the intestinal tract by increasing the probiotics population and digestive enzyme activities in rats.展开更多
The clinical course of infections with the hepatitis B virus(HBV)substantially varies between individuals,as a consequence of a complex interplay between viral,host,environmental and other factors.Due to the high gene...The clinical course of infections with the hepatitis B virus(HBV)substantially varies between individuals,as a consequence of a complex interplay between viral,host,environmental and other factors.Due to the high genetic variability of HBV,the virus can be categorized into different HBV genotypes and subgenotypes,which considerably differ with respect to geographical distribution,transmission routes,disease progression,responses to antiviral therapy or vaccination,and clinical outcome measures such as cirrhosis or hepatocellular carcinoma.However,HBV(sub)genotyping has caused some controversies in the past due to misclassifications and incorrect interpretations of different genotyping methods.Thus,an accurate,holistic and dynamic classification system is essential.In this review article,we aimed at highlighting potential pitfalls in genetic and phylogenetic analyses of HBV and suggest novel terms for HBV classification.Analyzing fulllength genome sequences when classifying genotypes and subgenotypes is the foremost prerequisite of this classification system.Careful attention must be paid to all aspects of phylogenetic analysis,such as bootstrapping values and meeting the necessary thresholds for(sub)genotyping.Quasi-subgenotype refers to subgenotypes that were incorrectly suggested to be novel.As many of these strains were misclassified due to genetic differences resulting from recombination,we propose the term"recombino-subgenotype".Moreover,immigration is an important confounding facet of global HBV distribution and substantially changes the geographic pattern of HBV(sub)genotypes.We therefore suggest the term"immigro-subgenotype"to distinguish exotic(sub)genotypes from native ones.We are strongly convinced that applying these two proposed terms in HBV classification will help harmonize this rapidly progressing field and allow for improved prophylaxis,diagnosis and treatment.展开更多
Trans-trans farnesol (tt-farnesol) is a bioactive sesquiterpene alcohol commonly found in propolis (a beehive product) and citrus fruits, which disrupts the ability of Streptococcus mutans (S. mutans) to form virulent...Trans-trans farnesol (tt-farnesol) is a bioactive sesquiterpene alcohol commonly found in propolis (a beehive product) and citrus fruits, which disrupts the ability of Streptococcus mutans (S. mutans) to form virulent biofilms. In this study, we investigated whether tt-farnesol affects cell-membrane function, acid production and/or acid tolerance by planktonic cells and biofilms of S. mutans UA159. Furthermore, the influence of the agent on S. mutans gene expression and ability to form biofilms in the presence of other oral bacteria (Streptococcus oralis (S. oralis) 35037 and Actinomyces naeslundii (A. naeslundii) 12104) was also examined. In general, tt-farnesol (1 mmol·L-1) significantly increased the membrane proton permeability and reduced glycolytic activity of S. mutans in the planktonic state and in biofilms (P<0.05). Moreover, topical applications of 1 mmol·L-1 tt-farnesol twice daily (1 min exposure/treatment) reduced biomass accumulation and prevented ecological shifts towards S. mutans dominance within mixed-species biofilms after introduction of 1% sucrose. S. oralis (a non-cariogenic organism) became the major species after treatments with tt-farnesol, whereas vehicle-treated biofilms contained mostly S. mutans (>90% of total bacterial population). However, the agent did not affect significantly the expression of S. mutans genes involved in acidogenicity, acid tolerance or polysaccharide synthesis in the treated biofilms. Our data indicate that tt-farnesol may affect the competitiveness of S. mutans in a mixed-species environment by primarily disrupting the membrane function and physiology of this bacterium. This naturally occurring terpenoid could be a potentially useful adjunctive agent to the current anti-biofilm/anti-caries chemotherapeutic strategies.展开更多
AIM:To investigate Toll-like receptor(TLR)signaling regulators in microscopic and ulcerative colitis patients.METHODS:Total RNA and microRNA were isolated from fresh frozen colonic biopsies of non-inflamed controls an...AIM:To investigate Toll-like receptor(TLR)signaling regulators in microscopic and ulcerative colitis patients.METHODS:Total RNA and microRNA were isolated from fresh frozen colonic biopsies of non-inflamed controls and patients with active or in-remission collagenous colitis(CC),lymphocytic colitis(LC),or ulcerative colitis(UC).We compared expressions of interleukin-1receptor-associated kinase(IRAK)-2,IRAK-M,interleukin(IL)-37,microRNA(miR)-146a,miR-155,and miR-21 using quantitative real time reverse transcription polymerase chain reaction.RESULTS:IRAK-M expression was increased in LC patients with active disease in histopathological remission(LC-HR;P=0.02)and UC patients(P=0.01),but no differences in IRAK-2 expression were detected compared to controls.miR-146a,-155 and-21 expressions were increased in LC-HR(P=0.04,0.07,and 0.004)and UC(P=0.02,0.04 and 0.03)patients.miR-146a and miR-21 expressions were significantly enhanced in UC patients compared to UC remission(UC-R;P=0.01and 0.04).Likewise,active CC patients showed significantly increased expression of miR-155(P=0.003)and miR-21(P=0.006).IL-37 expression was decreased in both CC(P=0.03)and LC(P=0.04)patients with a similar trend in UC patients but not statistically significant,whilst it was increased in UC-R patients compared to controls(P=0.02)and active UC(P=0.001).CONCLUSION:The identification of differentially expressed miRNAs,IL-37,and IRAK-M suggests different pathophysiologic mechanisms in various disease stages in LC,CC,and UC.展开更多
蛋氨酸 adenosyltransferase II (地席 II ) 是在细胞的新陈代谢的关键酶并且从 L 蛋氨酸和 ATP 催化 S-adenosylmethionine (一样) 的形成。正常休息 T 淋巴细胞举办最小的地席 II 活动，而白血病的房间显著地显示出的激活的增殖的 T ...蛋氨酸 adenosyltransferase II (地席 II ) 是在细胞的新陈代谢的关键酶并且从 L 蛋氨酸和 ATP 催化 S-adenosylmethionine (一样) 的形成。正常休息 T 淋巴细胞举办最小的地席 II 活动，而白血病的房间显著地显示出的激活的增殖的 T 淋巴细胞和转变 T 提高了地席 II 活动。这个工作被执行在白血病的 T 房间的幸存检验地席 II 活动和一样的生合成的角色。在一样的层次的地席 II 和结果的减少的抑制提高了 FasL mRNA 和蛋白质的表示，并且导致了圆盘(导致发信号的建筑群的死亡) 有 FADD (联系船边交货的死亡域) 和 procaspase-8 招募的形成，以及 caspase-8 激活的伴随物增加和在 c 扭动的减少铺平。开始船边交货的发信号由地席 II 抑制导致了被观察经由出价劈开连接到 mitochondrial 小径并且最终在这些房间导致增加的 caspase-3 激活和 DNA 破碎。而且，堵住地席 2A mRNA 表示，它编码地席 II 的催化子单元，用一条小介入的 RNA 途径提高了 FasL 表示和房间死亡，验证在 T 白血病的房间的幸存的地席 II 活动的必要性质。展开更多
To investigate the distribution of the genes of two major metallo-β-lactamases (MBL; i.e., IMP and VIM) and class 1 integrons (intI) in the clinical imipenem-resistant Pseudomonas aeruginosa, a total of 65 isolates,f...To investigate the distribution of the genes of two major metallo-β-lactamases (MBL; i.e., IMP and VIM) and class 1 integrons (intI) in the clinical imipenem-resistant Pseudomonas aeruginosa, a total of 65 isolates,from a university hospital in Sichuan between December 2004 and April 2005 were screened for MBL genes by PCR using primers specific for blaIMP-1, blaVIM and blaVIM-2 genes. The MBL-positive isolates were further assessed for class 1 integrons by PCR using specific primers. The nucleotide sequences of several PCR products were also determined. The results revealed that the blaVIM gene was found in 81.5% (53/65) of all isolates,blaVIM-2 gene was found in only 1 isolate and the intI gene was observed in 45.3% (24/53) of blaVIM-positive isolates. One isolate carried simultaneously both blaIMP-1 and intI genes, and to the best of our knowledge this is the first report of such isolate in southwest China. These observations highlight that the genes for VIM β-lactamase and class 1 integrons were predominantly present among the imipenem-resistant P. aeruginosa tested, confirming the current widespread threat of imipenem-resistant, integron-borne P. aeruginosa.展开更多
基金supported in part by funding from the Veterans Administration,Nos.1IOBX001262(to NLB)1I01 BX004269(to NLB and AH)+2 种基金South Carolina State Spinal Cord Injury Research Fund,No.SCIRF#2018 I-01(to AH)funding from the National Institutes of Health,No.1R21NS118393-01(to NLB and AH)Research Scientist Career Award from the Department of Veterans Affairs,No.1K6BX 005964(to NLB).
文摘Spinal cord injury(SCI)is a debilitating condition characterized by damage to the spinal cord resulting in loss of function,mobility,and sensation with no U.S.Food and Drug Administration-approved cure.Enolase,a multifunctional glycolytic enzyme upregulated after SCI,promotes pro-and anti-inflammatory events and regulates functional recovery in SCI.Enolase is normally expressed in the cytosol,but the expression is upregulated at the cell surface following cellular injury,promoting glial cell activation and signal transduction pathway activation.SCI-induced microglia activation triggers pro-inflammatory mediators at the injury site,activating other immune cells and metabolic events,i.e.,Rho-associated kinase,contributing to the neuroinflammation found in SCI.Enolase surface expression also activates cathepsin X,resulting in cleavage of the C-terminal end of neuron-specific enolase(NSE)and non-neuronal enolase(NNE).Fully functional enolase is necessary as NSE/NNE C-terminal proteins activate many neurotrophic processes,i.e.,the plasminogen activation system,phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B,and mitogen-activated protein kinase/extracellular signal-regulated kinase.Studies here suggest an enolase inhibitor,ENOblock,attenuates the activation of Rho-associated kinase,which may decrease glial cell activation and promote functional recovery following SCI.Also,ENOblock inhibits cathepsin X,which may help prevent the cleavage of the neurotrophic C-terminal protein allowing full plasminogen activation and phosphatidylinositol-4,5-bisphosphate 3-kinase/mitogen-activated protein kinase activity.The combined NSE/cathepsin X inhibition may serve as a potential therapeutic strategy for preventing neuroinflammation/degeneration and promoting neural cell regeneration and recovery following SCI.The role of cell membrane-expressed enolase and associated metabolic events should be investigated to determine if the same strategies can be applied to other neurodegenerative diseases.Hence,this review discusses the importance of enolase activation and inhibition as a potential therapeutic target following SCI to promote neuronal survival and regeneration.
基金supported in part by funding from the Veterans Administration (1IOBX001262, 1I01 BX004269)South Carolina State Spinal Cord Injury Research Fund (SCIRF-2015P-01, SCIRF-2015P-04, SCIRF-2015-I-01, SCIRF#2016 I-03, and SCIRF#2018 I-01)(to AH)+1 种基金supported in part by funding from the National Institutes of Health (1R21NS118393-01)(to AH)a Research Career Scientist award (#IK6BX005964) from the Department of veterans Affairs。
文摘Spinal cord injuries affect nearly five to ten individuals per million every year. Spinal cord injury causes damage to the nerves, muscles, and the tissue surrounding the spinal cord. Depending on the severity, spinal injuries are linked to degeneration of axons and myelin, resulting in neuronal impairment and skeletal muscle weakness and atrophy. The protection of neurons and promotion of myelin regeneration during spinal cord injury is important for recovery of function following spinal cord injury. Current treatments have little to no effect on spinal cord injury and neurogenic muscle loss. Clemastine, an Food and Drug Administration-approved antihistamine drug, reduces inflammation, protects cells, promotes remyelination, and preserves myelin integrity. Recent clinical evidence suggests that clemastine can decrease the loss of axons after spinal cord injury, stimulating the differentiation of oligodendrocyte progenitor cells into mature oligodendrocytes that are capable of myelination. While clemastine can aid not only in the remyelination and preservation of myelin sheath integrity, it also protects neurons. However, its role in neurogenic muscle loss remains unclear. This review discusses the pathophysiology of spinal cord injury, and the role of clemastine in the protection of neurons, myelin, and axons as well as attenuation of skeletal muscle loss following spinal cord injury.
基金Supported by the National Research Foundation of Korea,No.2022R1A2B5B01001421the Korea Health Technology R&D Project through the Korea Health Industry Development Institute,the Ministry of Health&Welfare,Republic of Korea,No.HI22C0476.
文摘BACKGROUND The presence of two distinct hepatitis B virus(HBV)Pol RT polymorphisms,rt269L and rt269I,could contribute to the unique clinical or virological phenotype of HBV genotype C2.Therefore,a simple and sensitive method capable of identifying both types in chronic hepatitis B(CHB)patients infected with genotype C2 should be developed.AIM To develop a novel simple and sensitive locked nucleic acid(LNA)-real timepolymerase chain reaction(RT-PCR)method capable of identifying two rt269 types in CHB genotype C2 patients.METHODS We designed proper primer and probe sets for LNA-RT-PCR for the separation of rt269 types.Using synthesized DNAs of the wild type and variant forms,melting temperature analysis,detection sensitivity,and endpoint genotyping for LNA-RT-PCR were performed.The developed LNA-RT-PCR method was applied to a total of 94 CHB patients of genotype C2 for the identification of two rt269 polymorphisms,and these results were compared with those obtained by a direct sequencing protocol.RESULTS The LNA-RT-PCR method could identify two rt269L and rt269I polymorphisms of three genotypes,two rt269L types[‘L1’(WT)and‘L2’]and one rt269I type(‘I’)in single(63 samples,72.4%)or mixed forms(24 samples,27.6%)in 87(92.6%sensitivity)of 94 samples from Korean CHB patients.When the results were compared with those obtained by the direct sequencing protocol,the LNA-RT-PCR method showed the same results in all but one of 87 positive detected samples(98.9%specificity).CONCLUSION The newly developed LNA-RT-PCR method could identify two rt269 polymorphisms,rt269L and rt269I,in CHB patients with genotype C2 infections.This method could be effectively used for the understanding of disease progression in genotype C2 endemic areas.
文摘It is known that the pathogenicity of Plasmodium induces the breakdown of haemoglobin, which leads to the induction of oxidative stress. This study aimed to identify the possible effects of oxidative stress and antioxidant defence systems in symptomatic and asymptomatic Plasmodium falciparum malaria infection in children (1 - 15 years old) in the Mount Cameroon vicinity. This cross-sectional study involved blood samples collected from 473 children and examined for malaria parasitaemia. Full blood counts were performed using an automated haemoanalyser. Serum oxidative stress status (malondialdehyde (MDA), nitric oxide (NO), reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and vitamin C (Vit C)) were each determined by colorimetric enzymatic assays. The prevalence of malaria parasite infection was 32.1% among the participants. Out of that, 62.5% of patients with parasitaemia were symptomatic. Anaemia prevalence increased significantly with parasite density. MDA levels were significantly higher in patients with malaria symptoms than in those without symptoms. A significant and positive correlation was detected between MDA (r = 0.831, P < 0.05), NO (r = 0.779, P < 0.05), and malaria parasite density while, a significant and negative relationship occurred between parasite density and GSH (r = ?0.763, P < 0.05) and Vit C (r = ?0.826, P < 0.05) levels, SOD (r = ?0.621, P < 0.05) and CAT (r = ?0.817, P < 0.05) activities. The SOD activity and GSH level significantly decreased (P < 0.05) with an increase in the MDA levels. These findings showed that MDA and nitric oxide levels increased both in malaria participants with or without symptoms. A similar decrease in the antioxidant defence system was observed in both symptomatic and asymptomatic patients. Therefore, there is a need to develop public health policies that encourage routine diagnosis and treatment of malaria in seemingly healthy people (asymptomatic cases), and this will play an essential role in controlling malaria in tropical countries.
文摘Human papillomavirus (HPV) is classified into high-risk HPV (HR-HPV) and HPV (LR-HPV) according to their oncogenic potential. These viruses can be found in the cervix, vagina, vulva, anus and in the ENT sphere. HPV ENT infections can lead to benign or malignant tumors in which we could find both LR-HPV and HR-HPV genotypes. The objective of this study was to investigate the genotypes of HR-HPV and LR-HPV in archived tissue samples derived from both benign and malignant tumors of the ear, nose, and throat (ENT) in Ouagadougou, Burkina Faso. One hundred and twenty formalin-fixed, paraffin-embedded archived tissues of the ENT sphere from 26 benign tumors and 94 malignant tumors were included. The tissues were first deparaffinized with xylem. The extracted DNA was used to test for high-risk and low-risk HPV by Real-Time Multiplex PCR. HPV DNA was found in 57.7% (15/26) of benign tumors and 43.61% (41/94) of malignant tumors. The prevalence of HPV infection was 46.67% (56/120) in all tumors combined. The most common HPV genotypes found were HPV 11 (34.28%), HPV 6 (30%), HPV56 (14.28%) and HPV 33 (8.57%). There were 21.43% (12/56) cases of genotypes co-infections with 10 cases of double infection and 2 cases of triple infection. Both low-risk and high-risk HPV are found in ENT tumors with relatively high HPV prevalence.
文摘Introduction: Genetic polymorphisms of some Glutathione S-Transferase (GST) which encode the enzyme responsible for the biotransformation of drugs and xenobiotics, have been associated with the risk of several pathologies that can progress to cancer such as Hepatitis B. This study aims to characterize the impact of the rs1695 polymorphism of GSTP1 gene among people with chronic Hepatitis B infection in Burkina Faso. Methods: rs1695 polymorphisms of GSTP1 gene genotyping was performed for 50 people infected with chronic Hepatitis B virus and 124 healthy people with the PCR-RFLP method. Conventional PCR was used for DNA amplification and Alw26I enzyme was used for enzymatic digestion. Results: The results show that the frequencies of AA, AG and GG genotypes are respectively 31.00%, 36.80% and 32.20% in general the study population with a mutation rate of 50.57%. However, the incidence of the AA, AG and GG genotypes are respectively 30.64%, 38.71% and 30.64% among people with chronic Hepatitis B virus infection and 32.00%, 32.00% and 36.00% among healthy people. In cases, the frequencies of the A and G alleles are 48.00% and 52.00% respectively, and in controls 50.00% each. No statistical difference was found by comparing genotypic and allelic frequencies between cases and controls (p > 0.05). Conclusion: Our study allowed us to determine the rate of GSTP1 rs1695 genotypes in the study population, cases and controls. From our analyses, GSTP1 rs1695 is not associated to chronic Hepatitis B virus infection in Ouagadougou.
文摘Diabetes is one of the deadliest diseases.Due to its effects on the lives of people,it has attracted a lot of attention recently.The causes of the various forms of diabetes,including type 1 and type 2,were discussed along with how they affect those who have the disease.Younger people are more prone to type 1 diabetes than older people,who are more likely to develop type 2.The treatment options and strategies for the two forms of diabetes were also discussed in addition to how the disease affects the quality of life of people.Among several factors that were explained,it has been shown that people from low and middle-income countries are more prone to having diabetes.Additionally,the condition is more likely to affect some races more than others.It is associated with obesity.According to statistics,those who are poor are more severely affected by the disease.The progression of the disease over time has been associated with an increase in disability and mortality.
文摘Helicobacter pylori(H. pylori) is an extremely common, yet underappreciated, pathogen that is able to alter host physiology and subvert the host immune response, allowing it to persist for the life of the host. H. pylori is the primary cause of peptic ulcers and gastric cancer. In the United States, the annual cost associated with peptic ulcer disease is estimated to be $6 billion and gastric cancer kills over 700000 people per year globally. The prevalence of H. pylori infection remains high(> 50%) in much of the world, although the infection rates are dropping in some developed nations. The drop in H. pylori prevalence could be a double-edged sword, reducing the incidence of gastric diseases while increasing the risk of allergies and esophageal diseases. The list of diseases potentially caused by H. pylori continues to grow; however, mechanistic explanations of how H. pylori could contribute to extragastric diseases lag far behind clinical studies. A number of host factors and H. pylori virulence factors act in concert to determine which individuals are at the highest risk of disease. These include bacterial cytotoxins and polymorphisms in host genes responsible for directing the immune response. This review discusses the latest advances in H. pylori pathogenesis, diagnosis, and treatment. Up-todate information on correlations between H. pylori and extragastric diseases is also provided.
文摘Nonalcoholic fatty liver disease (NAFLD) is highly prevalent and can result in nonalcoholic steatohepatitis (NASH) and progressive liver disease including cirrhosis and hepatocellular carcinoma. A growing body of literature implicates the peroxisome proliferators-activated receptors (PPARs) in the pathogenesis and treatment of NAFLD. These nuclear hormone receptors impact on hepatic triglyceride accumulation and insulin resistance. The aim of this review is to describe the data linking PPARα and PPARγ to NAFLD/NASH and to discuss the use of PPAR ligands for the treatment of NASH.
基金a grant from Sultan Qaboos University Research Fund
文摘AIM: To analyze the serum levels and prognostic significance of vascular endothelial growth factor (VEGF) -A,-C,and -D,and their receptors,VEGFR-1 and -2 in gastric adenocarcinomas. METHODS: The serum levels of VEGF family members were measured in 76 control subjects and 76 patients with gastric adenocarcinoma using an enzyme-linked immunosorbent assay (ELISA). These measurements were correlated with clinco-pathological features and survival rates. RESULTS: The serum levels of VEGF-A and its receptor,VEGFR-1,were signifi cantly higher in patients with gastric cancer than in healthy donors (t = 2.3,P = 0.02 and t = 4.2,P < 0.0001,respectively). In contrast,the serum levels of VEGF-D were signif icantly higher in control subjects than in patients (t = 2.9,P = 0.004). There was no significant difference in serum levels of VEGF-C and VEGFR-2 between patients and controls. VEGF-C was associated with advanced tumor stage and presence of metastasis. VEGFR-1 was associated with metastasis,advanced overall stage,tumor differentiation and survival. VEGFR-2 levels were associated with poor tumor differentiation. There was no significant prognostic value for any of the VEGF family members or their receptors except for VEGFR-1 where high levels were associated with a poor overall survival. CONCLUSION: Serum VEGF levels vary significantly in the same cohort of patients with variable clinico-pathological features and prognostic values. The simultaneous measurement of VEGF receptors levels in sera may overcome the limitations of a single biomarker assay.
基金Supported by contract N01-AI-05399 to the College of Veterinary Medicine, Cornell University from the National Institute of Allergy and Infectious Diseases. PC and SM also have been supported by contract N01-AI-95390 to the Georgetown University Medical Center, Georgetown University from the National Institute of Allergy and Infectious Diseases
文摘This review describes the woodchuck and the woodchuck hepatitis virus (WHV) as an animal model for pathogenesis and therapy of chronic hepatitis B virus (HBV) infection and disease in humans. The establishment of woodchuck breeding colonies, and use of laboratory-reared woodchucks infected with defined WHV inocula, have enhanced our understanding of the virology and immunology of HBV infection and disease pathogenesis, including major sequelae like chronic hepatitis and hepatocellular carcinoma. The role of persistent WHV infection and of viral load on the natural history of infection and disease progression has been firmly established along the way. More recently, the model has shed new light on the role of host immune responses in these natural processes, and on how the immune system of the chronic carrier can be manipulated therapeutically to reduce or delay serious disease sequelae through induction of the recovery phenotype. The woodchuck is an outbred species and is not well defined immunologically due to a limitation of available host markers. However, the recent development of several key host response assays for woodchucks provides experimental opportunities for further mechanistic studies of outcome predictors in neonatal- and adult-acquired infections. Understanding the virological and immunological mechanisms responsible for resolution of self-limited infection, andfor the onset and maintenance of chronic infection, will greatly facilitate the development of successful strategies for the therapeutic eradication of established chronic HBV infection. Likewise, the results of drug efficacy and toxicity studies in the chronic carrier woodchucks are predictive for responses of patients chronically infected with HBV. Therefore, chronic WHV carrier woodchucks provide a well-characterized mammalian model for preclinical evaluation of the safety and efficacy of drug candidates, experimental therapeutic vaccines, and immunomodulators for the treatment and prevention of HBV disease sequelae.
基金National Institutes of Health, Grant CA83719US Department of Veterans Affairs
文摘This review summarizes the current state of knowledge regarding the role of endothelial dysfunction in the pathogenesis of early and delayed intestinal radiation toxicity and discusses various endothelial-oriented interventions aimed at reducing the risk of radiation enteropathy. Studies published in the biomedical literature during the past four decades and cited in PubMed, as well as clinical and laboratory data from our own research program are reviewed. The risk of injury to normal tissues limits the cancer cure rates that can be achieved with radiation therapy. During treatment of abdominal and pelvic tumors, the intestine is frequently a major dose-limiting factor. Microvascular injury is a prominent feature of both early (inflammatory), as well as delayed (fibroproliferative) radiation injuries in the intestine and in many other normal tissues. Evidence from our and other laboratories suggests that endothelial dysfunction, notably a deficiency of endothelial thrombomodulin, plays a key role in the pathogenesis of these radiation responses. Deficient levels of thrombomodulin cause loss of vascular thromboresistance, excessive activation of cellular thrombin receptors by thrombin, and insufficient activation of protein C, a plasma protein with anticoagulant, anti-inflammatory, and cytoprotective properties. These changes are presumed to be critically involved in many aspects of early intestinal radiation toxicity and may sustain the fi broproliferative processes that lead to delayed intestinal dysfunction, fi brosis, and clinical complications. In conclusion, injury of vascular endothelium is important in the pathogenesis of the intestinal radiation response. Endothelial-oriented interventions are appealing strategies to prevent or treat normal tissue toxicity associated with radiation treatment of cancer.
基金Supported by Viva Life Science/Westar Nutrition, Costa Mesa,CA, United States
文摘AIM: To investigate the effect of synbiotics, i.e. probiotics and prebiotics mixture, on the gut microbial ecology and digestive enzyme activities in rats. METHODS: Forty-eight SD rats weighing about 280 g were used in this study. Rats were divided into three groups according to the contents of probiotics and prebiotics mixture in the feed as control, low and high dose groups. The duration of the experiment was 8 wk. RESULTS: Compared with the control group, thefecal Lactobacillus and Bifidobacterium counts were significantly increased and the fecal Coliform organism counts were markedly reduced in the low and high dose groups. Concerning the digestive enzyme activity of jejunum, only lactase activity increased in low dose group. However, significant increase of lipase, lactase, sucrase, and isomaltase activities were observed in high dose group.CONCLUSION: Intake of low and high dosages of probiotics and prebiotics mixture significantly improved the ecosystem of the intestinal tract by increasing the probiotics population and digestive enzyme activities in rats.
基金Supported by Mahmoud Reza Pourkarim is supported by a postdoctoral grant from the''Fonds voor Wetenschappelijk Onderzoek Vlaanderen''
文摘The clinical course of infections with the hepatitis B virus(HBV)substantially varies between individuals,as a consequence of a complex interplay between viral,host,environmental and other factors.Due to the high genetic variability of HBV,the virus can be categorized into different HBV genotypes and subgenotypes,which considerably differ with respect to geographical distribution,transmission routes,disease progression,responses to antiviral therapy or vaccination,and clinical outcome measures such as cirrhosis or hepatocellular carcinoma.However,HBV(sub)genotyping has caused some controversies in the past due to misclassifications and incorrect interpretations of different genotyping methods.Thus,an accurate,holistic and dynamic classification system is essential.In this review article,we aimed at highlighting potential pitfalls in genetic and phylogenetic analyses of HBV and suggest novel terms for HBV classification.Analyzing fulllength genome sequences when classifying genotypes and subgenotypes is the foremost prerequisite of this classification system.Careful attention must be paid to all aspects of phylogenetic analysis,such as bootstrapping values and meeting the necessary thresholds for(sub)genotyping.Quasi-subgenotype refers to subgenotypes that were incorrectly suggested to be novel.As many of these strains were misclassified due to genetic differences resulting from recombination,we propose the term"recombino-subgenotype".Moreover,immigration is an important confounding facet of global HBV distribution and substantially changes the geographic pattern of HBV(sub)genotypes.We therefore suggest the term"immigro-subgenotype"to distinguish exotic(sub)genotypes from native ones.We are strongly convinced that applying these two proposed terms in HBV classification will help harmonize this rapidly progressing field and allow for improved prophylaxis,diagnosis and treatment.
基金supported by IADR/GSK Innovation in Oral Care Award, USPHS Research grant 1R01DE 018023 from the National Institute of Dental and Craniofacial Research (National Institutes of Health)Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (2009-0071090)
文摘Trans-trans farnesol (tt-farnesol) is a bioactive sesquiterpene alcohol commonly found in propolis (a beehive product) and citrus fruits, which disrupts the ability of Streptococcus mutans (S. mutans) to form virulent biofilms. In this study, we investigated whether tt-farnesol affects cell-membrane function, acid production and/or acid tolerance by planktonic cells and biofilms of S. mutans UA159. Furthermore, the influence of the agent on S. mutans gene expression and ability to form biofilms in the presence of other oral bacteria (Streptococcus oralis (S. oralis) 35037 and Actinomyces naeslundii (A. naeslundii) 12104) was also examined. In general, tt-farnesol (1 mmol·L-1) significantly increased the membrane proton permeability and reduced glycolytic activity of S. mutans in the planktonic state and in biofilms (P<0.05). Moreover, topical applications of 1 mmol·L-1 tt-farnesol twice daily (1 min exposure/treatment) reduced biomass accumulation and prevented ecological shifts towards S. mutans dominance within mixed-species biofilms after introduction of 1% sucrose. S. oralis (a non-cariogenic organism) became the major species after treatments with tt-farnesol, whereas vehicle-treated biofilms contained mostly S. mutans (>90% of total bacterial population). However, the agent did not affect significantly the expression of S. mutans genes involved in acidogenicity, acid tolerance or polysaccharide synthesis in the treated biofilms. Our data indicate that tt-farnesol may affect the competitiveness of S. mutans in a mixed-species environment by primarily disrupting the membrane function and physiology of this bacterium. This naturally occurring terpenoid could be a potentially useful adjunctive agent to the current anti-biofilm/anti-caries chemotherapeutic strategies.
基金Research Committee of Orebro County CouncilSezin Gunaltay's salary is covered by a grant from Orebro University
文摘AIM:To investigate Toll-like receptor(TLR)signaling regulators in microscopic and ulcerative colitis patients.METHODS:Total RNA and microRNA were isolated from fresh frozen colonic biopsies of non-inflamed controls and patients with active or in-remission collagenous colitis(CC),lymphocytic colitis(LC),or ulcerative colitis(UC).We compared expressions of interleukin-1receptor-associated kinase(IRAK)-2,IRAK-M,interleukin(IL)-37,microRNA(miR)-146a,miR-155,and miR-21 using quantitative real time reverse transcription polymerase chain reaction.RESULTS:IRAK-M expression was increased in LC patients with active disease in histopathological remission(LC-HR;P=0.02)and UC patients(P=0.01),but no differences in IRAK-2 expression were detected compared to controls.miR-146a,-155 and-21 expressions were increased in LC-HR(P=0.04,0.07,and 0.004)and UC(P=0.02,0.04 and 0.03)patients.miR-146a and miR-21 expressions were significantly enhanced in UC patients compared to UC remission(UC-R;P=0.01and 0.04).Likewise,active CC patients showed significantly increased expression of miR-155(P=0.003)and miR-21(P=0.006).IL-37 expression was decreased in both CC(P=0.03)and LC(P=0.04)patients with a similar trend in UC patients but not statistically significant,whilst it was increased in UC-R patients compared to controls(P=0.02)and active UC(P=0.001).CONCLUSION:The identification of differentially expressed miRNAs,IL-37,and IRAK-M suggests different pathophysiologic mechanisms in various disease stages in LC,CC,and UC.
基金Acknowledgments The authors wish to thank Landon Pastushok, Michelle Hanna and other members from the Xiao laboratory for helpful discussion. This work was supported by the Canadian Institutes of Health Research operating grants MOP-38104 and MOP-53240 to W Xiao, and the National Natural Science Foundation of China（Grant no. 30560132） to F Xu.
文摘蛋氨酸 adenosyltransferase II (地席 II ) 是在细胞的新陈代谢的关键酶并且从 L 蛋氨酸和 ATP 催化 S-adenosylmethionine (一样) 的形成。正常休息 T 淋巴细胞举办最小的地席 II 活动，而白血病的房间显著地显示出的激活的增殖的 T 淋巴细胞和转变 T 提高了地席 II 活动。这个工作被执行在白血病的 T 房间的幸存检验地席 II 活动和一样的生合成的角色。在一样的层次的地席 II 和结果的减少的抑制提高了 FasL mRNA 和蛋白质的表示，并且导致了圆盘(导致发信号的建筑群的死亡) 有 FADD (联系船边交货的死亡域) 和 procaspase-8 招募的形成，以及 caspase-8 激活的伴随物增加和在 c 扭动的减少铺平。开始船边交货的发信号由地席 II 抑制导致了被观察经由出价劈开连接到 mitochondrial 小径并且最终在这些房间导致增加的 caspase-3 激活和 DNA 破碎。而且，堵住地席 2A mRNA 表示，它编码地席 II 的催化子单元，用一条小介入的 RNA 途径提高了 FasL 表示和房间死亡，验证在 T 白血病的房间的幸存的地席 II 活动的必要性质。
基金a grant from National Natu-ral Science Foundation of China (No. 30370079)
文摘To investigate the distribution of the genes of two major metallo-β-lactamases (MBL; i.e., IMP and VIM) and class 1 integrons (intI) in the clinical imipenem-resistant Pseudomonas aeruginosa, a total of 65 isolates,from a university hospital in Sichuan between December 2004 and April 2005 were screened for MBL genes by PCR using primers specific for blaIMP-1, blaVIM and blaVIM-2 genes. The MBL-positive isolates were further assessed for class 1 integrons by PCR using specific primers. The nucleotide sequences of several PCR products were also determined. The results revealed that the blaVIM gene was found in 81.5% (53/65) of all isolates,blaVIM-2 gene was found in only 1 isolate and the intI gene was observed in 45.3% (24/53) of blaVIM-positive isolates. One isolate carried simultaneously both blaIMP-1 and intI genes, and to the best of our knowledge this is the first report of such isolate in southwest China. These observations highlight that the genes for VIM β-lactamase and class 1 integrons were predominantly present among the imipenem-resistant P. aeruginosa tested, confirming the current widespread threat of imipenem-resistant, integron-borne P. aeruginosa.
