Diffusion weighted magnetic resonance imaging (DWI) is an imaging technique which provides tissue contrast by the measurement of diffusion properties of water molecules within tissues. Diffusion is expressed in an app...Diffusion weighted magnetic resonance imaging (DWI) is an imaging technique which provides tissue contrast by the measurement of diffusion properties of water molecules within tissues. Diffusion is expressed in an apparent diffusion coefficient (ADC), which reflects the diffusion properties unique to each type of tissue. DWI has been originally used in neuroradiology. More recently, DWI has increasingly been used in addition to conventional unenhanced and enhanced magnetic resonance imaging (MRI) in other parts of the body. The reason for this delay was a number of technical problems inherent to the technique, making DWI very sensitive to artifacts, which had to be overcome. With assessment of ADC values, DWI proved to be helpful in characterization of focal liver lesions. However, DWI should always be used in conjunction to conventional MRI since there is considerable overlap between ADC values of benign and malignant lesions. DWI is useful in the detection of hepatocellular carcinoma in the cirrhotic liver and detection of liver metastases in oncological patients. In addition, DWI is a promising tool in the prediction of tumor responsiveness to chemotherapy and the follow-up of oncological patients after treatment, as DWI may be capable of detecting recurrent disease earlier than conventional imaging.This review focuses on the most common applications of DWI in the liver.展开更多
Metagenomic approaches are currently being used to decipher the genome of the microbiota(microbiome),and,in parallel,functional studies are being performed to analyze the effects of the microbiota on the host.Gnotobio...Metagenomic approaches are currently being used to decipher the genome of the microbiota(microbiome),and,in parallel,functional studies are being performed to analyze the effects of the microbiota on the host.Gnotobiological methods are an indispensable tool for studying the consequences of bacterial colonization.Animals used as models of human diseases can be maintained in sterile conditions(isolators used for germ-free rearing)and specifically colonized with defined microbes(including non-cultivable commensal bacteria).The effects of the germ-free state or the effects of colonization on disease initiation and maintenance can be observed in these models.Using this approach we demonstrated direct involvement of components of the microbiota in chronic intestinal inflammation and development of colonic neoplasia(i.e.,using models of human inflammatory bowel disease and colorectal carcinoma).In contrast,a protective effect of microbiota colonization was demonstrated for the development of autoimmune diabetes in non-obese diabetic(NOD)mice.Interestingly,the development of atherosclerosis in germ-free apolipoprotein E(ApoE)-deficient mice fed by a standard low-cholesterol diet is accelerated compared with conventionally reared animals.Mucosal induction of tolerance to allergen Bet v1 was not influenced by the presence or absence of microbiota.Identification of components of the microbiota and elucidation of the molecular mechanisms of their action in inducing pathological changes or exerting beneficial,disease-protective activities could aid in our ability to influence the composition of the microbiota and to find bacterial strains and components(e.g.,probiotics and prebiotics)whose administration may aid in disease prevention and treatment.展开更多
Infection with H pylori leads to a persistent chronic inflammation of the gastric mucosa, thereby increasing the risk of distal gastric adenocarcinoma. Numerous studies have determined a clear correlation between Hpyl...Infection with H pylori leads to a persistent chronic inflammation of the gastric mucosa, thereby increasing the risk of distal gastric adenocarcinoma. Numerous studies have determined a clear correlation between Hpylori infection and the risk of gastric cancer; however, general eradication is not recommended as cancer prophylaxis and time points for treatment remain controversial in different areas of the world. Prevalence rates in Western countries are decreasing, especially in younger people （〈 10%）; and a decline in distal gastric adenocarcinoma has been observed. Risk groups in Western countries still show considerably higher risk of developing cancer, especially in patients infected with cagA^＋ strains and in persons harboring genetic polymorphism of the IL-1B promoter （-511T/T） and the corresponding IL-1 receptor antagonist （IL-1RN^＊2）. Thus, general eradication of all infected persons in Western countries not recommended and is limited to risk groups in order to achieve a risk reduction. In contrast, infection rates and cancer prevalence are still high in East Asian countries. A prevention strategy to treat infected persons may avoid the development of gastric cancer to a large extent and with enormous clinical importance. However, studies in China and Japan indicate that prevention of gastric cancer is effective only in those patients that do not display severe histological changes such as atrophy and intestinal metaplasia. Thus, prophylactic strategies to prevent gastric cancer in high risk populations such as China should therefore especially aim at individuals now at younger age when the histological alterations caused by the bacterial infection was still reversible. In countries with a low prevalence of gastric cancer, risk groups carrying cagA^＋ strains and IL-1 genetic polymorphisms should be identified and treated.展开更多
Iron is an essential element for life on Earth and its shortage, or excess, in the living organism may lead to severe health disorders. Plants serve as the primary source of dietary iron and improving crop iron conten...Iron is an essential element for life on Earth and its shortage, or excess, in the living organism may lead to severe health disorders. Plants serve as the primary source of dietary iron and improving crop iron content is an important step towards a better public health. Our review focuses on the control of iron acquisition in dicotyledonous plants and monocots that apply a reduction-based strategy in order to mobilize and import iron from the rhizosphere. Achieving a balance between shortage and excess of iron requires a tight regulation of the activity of the iron uptake system. A number of studies, ranging from single gene characterization to systems biology analyses, have led to the rapid expansion of our knowledge on iron uptake in recent years. Here, we summarize the novel insights into the regulation of iron ac- quisition and internal mobilization from intracellular stores. We present a detailed view of the main known regulatory networks defined by the Arabidopsis regulators FIT and POPEYE （PYE）. Additionally, we analyze the root and leaf iron- responsive regulatory networks, revealing novel potential gene interactions and reliable iron-deficiency marker genes. We discuss perspectives and open questions with regard to iron sensing and post-translational regulation.展开更多
AIM：To characterize the IFN-response and its modulation by the antiviral compound lamivudine in HBV- transfected HepG2.2.15 cells. METHODS： HepG2.2.15 and HepG2 cells were stimulated with various concentrations of I...AIM：To characterize the IFN-response and its modulation by the antiviral compound lamivudine in HBV- transfected HepG2.2.15 cells. METHODS： HepG2.2.15 and HepG2 cells were stimulated with various concentrations of IFN-α 2a in the presence or absence of lamivudine. Then, total RNA was extracted and analysed by customised cDNA arrays and northern blot for interferon-inducible genes （ISGs）. In addition, cellular proteins were extracted for EMSA and western blot. HBV replication was assessed by southern blot or ELISAs for HBsAg and HBeAg. RESULTS： Two genes （MxA, CigS） with completely abolished and 4 genes （IFITM1, -2, -3, and 6-16） with partially reduced IFN-responses were identified in HepG2.2.15 cells. In 2 genes （IFITM1, 6-16）, the response to IFN-α could be restored by treatment with lamivudine. This effect could not be explained by a direct modulation of the Jak/Stat signalling pathway since EMSA and western blot experiments revealed no suppression of Statl activation and ISGF3 formation after stimulation with IFN-α in HepG2.2.15 compared to HepG2 cells. CONCLUSION： These results are consistent with the assumption that chronic hepatitis B may specifically modulate the cellular response to IFN by a selective blockage of some ISGs. Antiviral treatment with lamivudine may partially restore ISG expressionby reducing HBV gene expression and replication.展开更多
AIM：To analyze the in vitro activity of moxifloxacin and piperacillin/sulbactam against pathogens isolated from patients with acute cholangitis. METHODS： In this prospective study a total of 65 patients with acute c...AIM：To analyze the in vitro activity of moxifloxacin and piperacillin/sulbactam against pathogens isolated from patients with acute cholangitis. METHODS： In this prospective study a total of 65 patients with acute cholangitis due to biliary stone obstruction （n = 7）, benign biliary stricture （n = 16）, and malignant biliary stricture （n = 42） were investigated with regard to spectrum of bacterial infection and antibiotic resistance. Pathogens were isolated from bile cultures in all study patients. In 22 febrile patients, blood cultures were also obtained. In vitro activity of moxifloxacin and piperacillin/ sulbactam was determined by agar diffusion. RESULTS： Thirty-one out of 65 patients had positive bile and/or blood cultures. In 31 patients, 63 isolates with 17 different species were identified. The predominant strains were Enterococcus species （26/63）, Ecoli （13/63） and Klebsiella species （8/63）. A comparable in vitro activity of moxifloxacin and piperacillin/sulbactam was observed for E.coli and Klebsiella species. In contrast, Enterococcus species had higher resistances towards moxifloxacin. Overall bacteria showed antibiotic resistances in vitro of 34.9% for piperacillin/sulbactam and 36.5% for moxifioxacin.CONCLUSION： Enterococcus species, E.co/i and Klebsiella species were the most common bacteria isolated from bile and/or blood from patients with acute cholangitis. Overall, a mixed infection with several species was observed, and bacteria showed a comparable in vitro activity for piperacillin/sulbactam and moxifloxacin.展开更多
Background:Newborn screening for Duchenne muscular dystrophy (DMD) is currently being initiated in Zhejiang Province,China and is under consideration in other countries,including the United States.As China begins to i...Background:Newborn screening for Duchenne muscular dystrophy (DMD) is currently being initiated in Zhejiang Province,China and is under consideration in other countries,including the United States.As China begins to implement DMD newborn screening (DMD-NBS),there is ongoing discussion regarding the steps forward for follow up care of positively identified patients as well as false positive and false negative results.Data sources:Relevant papers related to DMD-NBS,and NBS in China were reviewed in PubMed.Results:The current state of DMD-NBS is discussed,along with the steps needed to effectively screen infants for this disease in China,recommendations for establishment of follow up care in patients with positive and negative screens,and measurement of patient outcomes.Conclusions:Zhejiang Province,China is ready to implement DMD-NBS.Future challenges that exist for this program,and other countries,include the ability to track patients,assist with access to care,and ensure adequate follow-up care according to evidence-based guidelines.In addition,China's large rural population,lack of specialty providers,and difficulty in educating patients regarding the benefits of treatment create challenges that will need to be addressed.展开更多
Colorectal cancer(CRC)is the second most common cancer in Europe and its incidence is steadily increasing.This trend could be reversed through timely secondary prevention(screening).In the last twenty years,CRC screen...Colorectal cancer(CRC)is the second most common cancer in Europe and its incidence is steadily increasing.This trend could be reversed through timely secondary prevention(screening).In the last twenty years,CRC screening programs across Europe have experienced considerable improvements(fecal occult blood testing;transition from opportunistic to population based program settings).The Czech Republic is a typical example of a country with a long history of nationwide CRC screening programs in the face of very high CRC incidence and mortality rates.Each year,approximately 8000 people are diagnosed with CRC and some 4000 die from this malignancy.Twenty years ago,the first pilot studies on CRC screening led to the introduction of the opportunistic Czech National Colorectal Cancer Screening Program in 2000.Originally,this program was based on the guaiac fecal occult blood test(FOBT)offered by general practitioners,followed by colonoscopy in cases of FOBT positivity.The program has continuously evolved,namely with the implementation of immunochemical FOBTs and screening colonoscopy,as well as the involvement of gynecologists.Since the establishment of the Czech CRC Screening Registry in 2006,2405850 FOBTs have been performed and 104565 preventive colonoscopies recorded within the screening program.The overall program expanded to cover 25.0%of the target population by 2011.However,stagnation in the annual number of performed FOBTs lately has led to switching to the option of a population-based program with personal invitation,which is currently being prepared.展开更多
AIM: To investigate the feasibility of separation and cultivation of circulating tumor cells (CTCs) in pancreatic cancer (PaC) using a filtration device.
Plant pathogens deliver effector proteins that alter host processes to create an environment conducive to colonization. Attention has focused on identifying the targets of effectors and how their manipulation facil- i...Plant pathogens deliver effector proteins that alter host processes to create an environment conducive to colonization. Attention has focused on identifying the targets of effectors and how their manipulation facil- itates disease. RXLR effector Pi04089 from the potato blight pathogen Phytophthora infestans accumu- lates in the host nucleus and enhances colonization when transiently expressed in planta. Its nuclear local- ization is required for enhanced P. infestans colonization. Pi04089 interacts in yeast and in planta with a putative potato K-homology （KH） RNA-binding protein, StKRBPI. Co-localization of Pi04089 and StKRBP1, and bimolecular fluorescence complementation between them, indicate they associate at nuclear speckles. StKRBP1 protein levels increased when it was co-expressed with Pi04089. Indeed, such accumu- lation of StKRBP1 was observed also on the first day of leaf colonization by the pathogen. Remarkably, overexpression of StKRBP1 significantly enhances P. infestans infection. Mutation of the nucleotide- binding motif GxxG to GDDG in all three KH domains of StKRBP1 abolishes its interaction with Pi04089, its localization to nuclear speckles, and its increased accumulation when co-expressed with the effector. Moreover, the mutant StKRBP1 protein no longer enhances leaf colonization by P. infestans, implying that nucleotide binding is likely required for this activity. We thus argue that StKRBP1 can be regarded as a sus- ceptibility factor, as its activity is beneficial to the pathogen.展开更多
AIM: To study statements and recommendations on psychosocial issues as presented in international evidence-based guidelines on the management of inflammatory bowel diseases (IBD).
The DELLA protein RGA-LIKE2 （RGL2） is a key transcriptional repressor of gibberellic acid （GA） signaling that regulates seed germination. We identified GATA12, a gene encoding a GATA-type zinc finger transcription...The DELLA protein RGA-LIKE2 （RGL2） is a key transcriptional repressor of gibberellic acid （GA） signaling that regulates seed germination. We identified GATA12, a gene encoding a GATA-type zinc finger transcription factor, as one of the downstream targets of RGL2 in Arabidopsis thaliana. Our data show that freshly harvested （unstratified） seeds of GATA 12 antisense suppression lines have reduced dormancy compared with the wild-type, while ectopic expression lines show enhanced seed dormancy. We show that GATA12 expression is negatively regulated by GA, and its transcript levels decline dramatically under dormancy- breaking conditions such as dry storage and cold stratification of seeds. GATA12 promoter has several GAMYB- and DOF-associated motifs that are known to be GA- and RGL2-responsive, respectively. Chromatin immunoprecipitation assay showed that a protein complex containing RGL2 can bind to GATA12 promoter and thereby regulate its expression. RGL2 lacks a DNA binding domain and requires a transcription factor to induce GATA12 expression. Our data show that this RGL2-containing protein complex includes DNA BINDING1 ZINC FINGER6 （DOF6）, which is a known negative regulator of germination in freshly harvested seeds. We further show that this novel RGL2-DOF6 complex is required for activating GATA12 expression, thus revealing a molecular mechanism to enforce primary seed dormancy.展开更多
The incidence and prevalence of metabolic syndrome(MS) and colorectal cancer(CRC) has been rising in developed countries. The association between these two diseases has been widely studied and reported. Less evidence ...The incidence and prevalence of metabolic syndrome(MS) and colorectal cancer(CRC) has been rising in developed countries. The association between these two diseases has been widely studied and reported. Less evidence is available about the relationship between MS and CRC precancerous lesions(adenomatous polyps, adenomas). The aim of this paper is to present an overview of our scientific understanding of that topic and its implication in clinical practice. One of the principal goals of current CRC secondary prevention efforts is to detect and remove the precancerous lesions in individuals with an average CRC risk to prevent the development of invasive cancer. MS is not currently considered a high-risk CRC factor and is therefore not included in the guidelines of organized screening programs. However, in light of growing scientific evidence, the approach to patients with MS should be changed. Metabolic risk factors for the development of adenomas and cancers are the same- obesity, impaired glucose tolerance, dyslipidemia, hypertension, cardiovascular diseases and diabetes mellitus type 2. Therefore, the key issue in the near future is the development of a simple scoring system, easy to use in clinical practice, which would identify individuals with high metabolic risk of colorectal neoplasia and would be used for individual CRC secondary prevention strategies. Currently, such scoring systems have been published based on Asian(Asia-Pacific Colorectal Screening Score; APCS) and Polish populations.展开更多
Increasing numbers of clinical trials and animal experiments have shown that probiotic bacteria are promising tools for allergy prevention. Here, we analyzed the immunomodulatory properties of three selected lactobaci...Increasing numbers of clinical trials and animal experiments have shown that probiotic bacteria are promising tools for allergy prevention. Here, we analyzed the immunomodulatory properties of three selected lactobacillus strains and the impact of their mixture on allergic sensitization to Bet v I using a gnotobiotic mouse model. We showed that Lactobacillus （L.） rhamnosus LOCK0900, L. rhamnosus LOCK0908 and L. casei LOCK0919 are recognized via Toll-like receptor 2 （TLR2） and nucleotide-binding oligomerization domain-containing protein 2 （NOD2） receptors and stimulate bone marrow-derived dendritic cells to produce cytokines in species- and strain-dependent manners. Colonization of germ-free （GF） mice with a mixture of all three strains （Lmix） improved the intestinal barrier by strengthening the apical junctional complexes of enterocytes and restoring the structures of microfilaments extending into the terminal web. Mice colonized with Lmix and sensitized to the Bet v I allergen showed significantly lower levels of allergen-specific IgE, IgG 1 and IgG2a and an elevated total IgA level in the sera and intestinal lavages as well as an increased transforming growth factor （TGF）-β level compared with the sensitized GF mice. Splenocytes and mesenteric lymph node cells from the Lmix-colonized mice showed the significant upregulation of TGF-β after in vitro stimulation with Bet v 1. Our results show that Lmix colonization improved the gut epithelial barrier and reduced allergic sensitization to Bet v 1. Furthermore, these findings were accompanied by the increased production of circulating and secretory IgA and the regulatory cytokine TGF-β. Thus, this mixture of three lactobacillus strains shows potential for use in the prevention of increased gut permeability and the onset of allergies in humans,展开更多
AIM： Prostaglandin G/H synthase 2 （PTGS2 or COX2） is one of the key factors in the cellular response to inflammation. PTGS2 is expressed in the affected intestinal segments of patients with inflammatory bowel disea...AIM： Prostaglandin G/H synthase 2 （PTGS2 or COX2） is one of the key factors in the cellular response to inflammation. PTGS2 is expressed in the affected intestinal segments of patients with inflammatory bowel diseases （IBD）. In IBD patients, non-steroidal anti-inflammatory drugs, which have been shown to reduce both the production and activity of PTGS2, may activate IBD and aggravate the symptoms. We aimed at examining genetic variants of PTGS2 that may be risk factors for IBD. METHODS： We genotyped 291 individuals diagnosed with IBD and 367 controls from the Dutch population for the five most frequent polymorphisms of the PTG52 gene. Clinical data were collected on all patients. DNA was extracted via normal laboratory methods. Genotyping was carried out using multiplex PCR followed by the Invader Assay and the 5＇ exonuclease assay （TaqMan）. New polymorphism screening was performed by pre-screening with denaturing high-performance liquid chromatography, followed by fluorescent sequencing. RESULTS： Allele 5209G was weakly associated with Crohn＇s disease （odds ratio [OR] 1.63, 95% confidence interval [CI] 1.03-2.57）, and allele 8473T with ulcerativecolitis （OR 1.50, 95%CI 1.00-2.27）. The haplotype including both alleles showed a strong association with IBD （OR 13.15, 95%CI 3.17-116.15）. This haplotype, while rare （-0.3%） in the general population, is found more frequently in patients （3.5%）. CONCLUSION： Our data suggest that this haplotype of PTGS2 contributes to the susceptibility of IBD.展开更多
文摘Diffusion weighted magnetic resonance imaging (DWI) is an imaging technique which provides tissue contrast by the measurement of diffusion properties of water molecules within tissues. Diffusion is expressed in an apparent diffusion coefficient (ADC), which reflects the diffusion properties unique to each type of tissue. DWI has been originally used in neuroradiology. More recently, DWI has increasingly been used in addition to conventional unenhanced and enhanced magnetic resonance imaging (MRI) in other parts of the body. The reason for this delay was a number of technical problems inherent to the technique, making DWI very sensitive to artifacts, which had to be overcome. With assessment of ADC values, DWI proved to be helpful in characterization of focal liver lesions. However, DWI should always be used in conjunction to conventional MRI since there is considerable overlap between ADC values of benign and malignant lesions. DWI is useful in the detection of hepatocellular carcinoma in the cirrhotic liver and detection of liver metastases in oncological patients. In addition, DWI is a promising tool in the prediction of tumor responsiveness to chemotherapy and the follow-up of oncological patients after treatment, as DWI may be capable of detecting recurrent disease earlier than conventional imaging.This review focuses on the most common applications of DWI in the liver.
基金grants from the Czech Science Foundation(nos.303/08/0367,303/09/0449,310/07/014,305/08/0535,310/09/1640 and 310/08/H077)the Grant Agency of the Academy of Sciences of the Czech Republic(nos.IAA500200910,IAA500200710,KJB500200904,IAA500200917 and A500200709)+3 种基金the Ministry of Education,Youth and Sports of the Czech Republic(nos.2B06053,2B06155 and MSM 0021620812)the Ministry of Health of the Czech Republic(nos.NS/9775-4,NS/10054-3 and NS/10340-3)EU Project Marie Curie CT 215553,EU Project IPODD consortium(202020)the Institutional Research Concept AV0Z50200510.
文摘Metagenomic approaches are currently being used to decipher the genome of the microbiota(microbiome),and,in parallel,functional studies are being performed to analyze the effects of the microbiota on the host.Gnotobiological methods are an indispensable tool for studying the consequences of bacterial colonization.Animals used as models of human diseases can be maintained in sterile conditions(isolators used for germ-free rearing)and specifically colonized with defined microbes(including non-cultivable commensal bacteria).The effects of the germ-free state or the effects of colonization on disease initiation and maintenance can be observed in these models.Using this approach we demonstrated direct involvement of components of the microbiota in chronic intestinal inflammation and development of colonic neoplasia(i.e.,using models of human inflammatory bowel disease and colorectal carcinoma).In contrast,a protective effect of microbiota colonization was demonstrated for the development of autoimmune diabetes in non-obese diabetic(NOD)mice.Interestingly,the development of atherosclerosis in germ-free apolipoprotein E(ApoE)-deficient mice fed by a standard low-cholesterol diet is accelerated compared with conventionally reared animals.Mucosal induction of tolerance to allergen Bet v1 was not influenced by the presence or absence of microbiota.Identification of components of the microbiota and elucidation of the molecular mechanisms of their action in inducing pathological changes or exerting beneficial,disease-protective activities could aid in our ability to influence the composition of the microbiota and to find bacterial strains and components(e.g.,probiotics and prebiotics)whose administration may aid in disease prevention and treatment.
基金Supported by Deutsche Forschungsgemeinschaft (DFGGraduiertenkolleg 333: Biology of Human Diseases) and by agrant from the DFG to C.P. (Pr 411/9-1) and the Dr. Else Kr nerFresenius Stiftung
文摘Infection with H pylori leads to a persistent chronic inflammation of the gastric mucosa, thereby increasing the risk of distal gastric adenocarcinoma. Numerous studies have determined a clear correlation between Hpylori infection and the risk of gastric cancer; however, general eradication is not recommended as cancer prophylaxis and time points for treatment remain controversial in different areas of the world. Prevalence rates in Western countries are decreasing, especially in younger people （〈 10%）; and a decline in distal gastric adenocarcinoma has been observed. Risk groups in Western countries still show considerably higher risk of developing cancer, especially in patients infected with cagA^＋ strains and in persons harboring genetic polymorphism of the IL-1B promoter （-511T/T） and the corresponding IL-1 receptor antagonist （IL-1RN^＊2）. Thus, general eradication of all infected persons in Western countries not recommended and is limited to risk groups in order to achieve a risk reduction. In contrast, infection rates and cancer prevalence are still high in East Asian countries. A prevention strategy to treat infected persons may avoid the development of gastric cancer to a large extent and with enormous clinical importance. However, studies in China and Japan indicate that prevention of gastric cancer is effective only in those patients that do not display severe histological changes such as atrophy and intestinal metaplasia. Thus, prophylactic strategies to prevent gastric cancer in high risk populations such as China should therefore especially aim at individuals now at younger age when the histological alterations caused by the bacterial infection was still reversible. In countries with a low prevalence of gastric cancer, risk groups carrying cagA^＋ strains and IL-1 genetic polymorphisms should be identified and treated.
文摘Iron is an essential element for life on Earth and its shortage, or excess, in the living organism may lead to severe health disorders. Plants serve as the primary source of dietary iron and improving crop iron content is an important step towards a better public health. Our review focuses on the control of iron acquisition in dicotyledonous plants and monocots that apply a reduction-based strategy in order to mobilize and import iron from the rhizosphere. Achieving a balance between shortage and excess of iron requires a tight regulation of the activity of the iron uptake system. A number of studies, ranging from single gene characterization to systems biology analyses, have led to the rapid expansion of our knowledge on iron uptake in recent years. Here, we summarize the novel insights into the regulation of iron ac- quisition and internal mobilization from intracellular stores. We present a detailed view of the main known regulatory networks defined by the Arabidopsis regulators FIT and POPEYE （PYE）. Additionally, we analyze the root and leaf iron- responsive regulatory networks, revealing novel potential gene interactions and reliable iron-deficiency marker genes. We discuss perspectives and open questions with regard to iron sensing and post-translational regulation.
基金Supported by grants from the Deutsche Forschungsgemeinschaft (DFG SCHL 377/2-2, LU 669/2-1 and GRK 1045/1)
文摘AIM：To characterize the IFN-response and its modulation by the antiviral compound lamivudine in HBV- transfected HepG2.2.15 cells. METHODS： HepG2.2.15 and HepG2 cells were stimulated with various concentrations of IFN-α 2a in the presence or absence of lamivudine. Then, total RNA was extracted and analysed by customised cDNA arrays and northern blot for interferon-inducible genes （ISGs）. In addition, cellular proteins were extracted for EMSA and western blot. HBV replication was assessed by southern blot or ELISAs for HBsAg and HBeAg. RESULTS： Two genes （MxA, CigS） with completely abolished and 4 genes （IFITM1, -2, -3, and 6-16） with partially reduced IFN-responses were identified in HepG2.2.15 cells. In 2 genes （IFITM1, 6-16）, the response to IFN-α could be restored by treatment with lamivudine. This effect could not be explained by a direct modulation of the Jak/Stat signalling pathway since EMSA and western blot experiments revealed no suppression of Statl activation and ISGF3 formation after stimulation with IFN-α in HepG2.2.15 compared to HepG2 cells. CONCLUSION： These results are consistent with the assumption that chronic hepatitis B may specifically modulate the cellular response to IFN by a selective blockage of some ISGs. Antiviral treatment with lamivudine may partially restore ISG expressionby reducing HBV gene expression and replication.
文摘AIM：To analyze the in vitro activity of moxifloxacin and piperacillin/sulbactam against pathogens isolated from patients with acute cholangitis. METHODS： In this prospective study a total of 65 patients with acute cholangitis due to biliary stone obstruction （n = 7）, benign biliary stricture （n = 16）, and malignant biliary stricture （n = 42） were investigated with regard to spectrum of bacterial infection and antibiotic resistance. Pathogens were isolated from bile cultures in all study patients. In 22 febrile patients, blood cultures were also obtained. In vitro activity of moxifloxacin and piperacillin/ sulbactam was determined by agar diffusion. RESULTS： Thirty-one out of 65 patients had positive bile and/or blood cultures. In 31 patients, 63 isolates with 17 different species were identified. The predominant strains were Enterococcus species （26/63）, Ecoli （13/63） and Klebsiella species （8/63）. A comparable in vitro activity of moxifloxacin and piperacillin/sulbactam was observed for E.coli and Klebsiella species. In contrast, Enterococcus species had higher resistances towards moxifloxacin. Overall bacteria showed antibiotic resistances in vitro of 34.9% for piperacillin/sulbactam and 36.5% for moxifioxacin.CONCLUSION： Enterococcus species, E.co/i and Klebsiella species were the most common bacteria isolated from bile and/or blood from patients with acute cholangitis. Overall, a mixed infection with several species was observed, and bacteria showed a comparable in vitro activity for piperacillin/sulbactam and moxifloxacin.
基金Muscular Dystrophy Association,unrestricted grants from Sarepta and Marathon,PerkinElmer,National High Technology Research and Development Program(863 Program,2015AA020513)Zhejiang Provincial Natural Science Foundation of China(LY16H0900007).
文摘Background:Newborn screening for Duchenne muscular dystrophy (DMD) is currently being initiated in Zhejiang Province,China and is under consideration in other countries,including the United States.As China begins to implement DMD newborn screening (DMD-NBS),there is ongoing discussion regarding the steps forward for follow up care of positively identified patients as well as false positive and false negative results.Data sources:Relevant papers related to DMD-NBS,and NBS in China were reviewed in PubMed.Results:The current state of DMD-NBS is discussed,along with the steps needed to effectively screen infants for this disease in China,recommendations for establishment of follow up care in patients with positive and negative screens,and measurement of patient outcomes.Conclusions:Zhejiang Province,China is ready to implement DMD-NBS.Future challenges that exist for this program,and other countries,include the ability to track patients,assist with access to care,and ensure adequate follow-up care according to evidence-based guidelines.In addition,China's large rural population,lack of specialty providers,and difficulty in educating patients regarding the benefits of treatment create challenges that will need to be addressed.
基金Supported by The Intern Grant Agency of the Czech Ministry of Health(IGA),No.NT 13673-4
文摘Colorectal cancer(CRC)is the second most common cancer in Europe and its incidence is steadily increasing.This trend could be reversed through timely secondary prevention(screening).In the last twenty years,CRC screening programs across Europe have experienced considerable improvements(fecal occult blood testing;transition from opportunistic to population based program settings).The Czech Republic is a typical example of a country with a long history of nationwide CRC screening programs in the face of very high CRC incidence and mortality rates.Each year,approximately 8000 people are diagnosed with CRC and some 4000 die from this malignancy.Twenty years ago,the first pilot studies on CRC screening led to the introduction of the opportunistic Czech National Colorectal Cancer Screening Program in 2000.Originally,this program was based on the guaiac fecal occult blood test(FOBT)offered by general practitioners,followed by colonoscopy in cases of FOBT positivity.The program has continuously evolved,namely with the implementation of immunochemical FOBTs and screening colonoscopy,as well as the involvement of gynecologists.Since the establishment of the Czech CRC Screening Registry in 2006,2405850 FOBTs have been performed and 104565 preventive colonoscopies recorded within the screening program.The overall program expanded to cover 25.0%of the target population by 2011.However,stagnation in the annual number of performed FOBTs lately has led to switching to the option of a population-based program with personal invitation,which is currently being prepared.
基金Supported by Research project"CTC in gastrointestinal cancer"awarded by League Against Cancer Prague,Czech Republic and grant of the Czech Ministry of Health,No.IGA NT14439-3/2013the projects by Ministry of Helath Czech Republic,conceptual development of research organization,University Hospital Motol,Prague Czech Republic,No.000 64203
文摘AIM: To investigate the feasibility of separation and cultivation of circulating tumor cells (CTCs) in pancreatic cancer (PaC) using a filtration device.
文摘Plant pathogens deliver effector proteins that alter host processes to create an environment conducive to colonization. Attention has focused on identifying the targets of effectors and how their manipulation facil- itates disease. RXLR effector Pi04089 from the potato blight pathogen Phytophthora infestans accumu- lates in the host nucleus and enhances colonization when transiently expressed in planta. Its nuclear local- ization is required for enhanced P. infestans colonization. Pi04089 interacts in yeast and in planta with a putative potato K-homology （KH） RNA-binding protein, StKRBPI. Co-localization of Pi04089 and StKRBP1, and bimolecular fluorescence complementation between them, indicate they associate at nuclear speckles. StKRBP1 protein levels increased when it was co-expressed with Pi04089. Indeed, such accumu- lation of StKRBP1 was observed also on the first day of leaf colonization by the pathogen. Remarkably, overexpression of StKRBP1 significantly enhances P. infestans infection. Mutation of the nucleotide- binding motif GxxG to GDDG in all three KH domains of StKRBP1 abolishes its interaction with Pi04089, its localization to nuclear speckles, and its increased accumulation when co-expressed with the effector. Moreover, the mutant StKRBP1 protein no longer enhances leaf colonization by P. infestans, implying that nucleotide binding is likely required for this activity. We thus argue that StKRBP1 can be regarded as a sus- ceptibility factor, as its activity is beneficial to the pathogen.
文摘AIM: To study statements and recommendations on psychosocial issues as presented in international evidence-based guidelines on the management of inflammatory bowel diseases (IBD).
文摘The DELLA protein RGA-LIKE2 （RGL2） is a key transcriptional repressor of gibberellic acid （GA） signaling that regulates seed germination. We identified GATA12, a gene encoding a GATA-type zinc finger transcription factor, as one of the downstream targets of RGL2 in Arabidopsis thaliana. Our data show that freshly harvested （unstratified） seeds of GATA 12 antisense suppression lines have reduced dormancy compared with the wild-type, while ectopic expression lines show enhanced seed dormancy. We show that GATA12 expression is negatively regulated by GA, and its transcript levels decline dramatically under dormancy- breaking conditions such as dry storage and cold stratification of seeds. GATA12 promoter has several GAMYB- and DOF-associated motifs that are known to be GA- and RGL2-responsive, respectively. Chromatin immunoprecipitation assay showed that a protein complex containing RGL2 can bind to GATA12 promoter and thereby regulate its expression. RGL2 lacks a DNA binding domain and requires a transcription factor to induce GATA12 expression. Our data show that this RGL2-containing protein complex includes DNA BINDING1 ZINC FINGER6 （DOF6）, which is a known negative regulator of germination in freshly harvested seeds. We further show that this novel RGL2-DOF6 complex is required for activating GATA12 expression, thus revealing a molecular mechanism to enforce primary seed dormancy.
基金Supported by Intern Grant Agency of the Czech Ministry of Health(IGA)No.NT 13673-4
文摘The incidence and prevalence of metabolic syndrome(MS) and colorectal cancer(CRC) has been rising in developed countries. The association between these two diseases has been widely studied and reported. Less evidence is available about the relationship between MS and CRC precancerous lesions(adenomatous polyps, adenomas). The aim of this paper is to present an overview of our scientific understanding of that topic and its implication in clinical practice. One of the principal goals of current CRC secondary prevention efforts is to detect and remove the precancerous lesions in individuals with an average CRC risk to prevent the development of invasive cancer. MS is not currently considered a high-risk CRC factor and is therefore not included in the guidelines of organized screening programs. However, in light of growing scientific evidence, the approach to patients with MS should be changed. Metabolic risk factors for the development of adenomas and cancers are the same- obesity, impaired glucose tolerance, dyslipidemia, hypertension, cardiovascular diseases and diabetes mellitus type 2. Therefore, the key issue in the near future is the development of a simple scoring system, easy to use in clinical practice, which would identify individuals with high metabolic risk of colorectal neoplasia and would be used for individual CRC secondary prevention strategies. Currently, such scoring systems have been published based on Asian(Asia-Pacific Colorectal Screening Score; APCS) and Polish populations.
基金The excellent technical assistance of J Jarkovska, A Smolova, I Grimova and D Drasnarova is gratefully acknowledged. This research was supported by grant NR12-0101-10/2011 of the Republic of Poland, grants P304/11/1252 and 303/09/0449 of the Czech Science Foundation, grants CZ.3.22/2.1.00/09.01574 and CZ.3.22/2.1.00/ 13.03892, grant SFB F46 from the Austrian Science Fund. and Institutional Research Concept RVO 61388971.
文摘Increasing numbers of clinical trials and animal experiments have shown that probiotic bacteria are promising tools for allergy prevention. Here, we analyzed the immunomodulatory properties of three selected lactobacillus strains and the impact of their mixture on allergic sensitization to Bet v I using a gnotobiotic mouse model. We showed that Lactobacillus （L.） rhamnosus LOCK0900, L. rhamnosus LOCK0908 and L. casei LOCK0919 are recognized via Toll-like receptor 2 （TLR2） and nucleotide-binding oligomerization domain-containing protein 2 （NOD2） receptors and stimulate bone marrow-derived dendritic cells to produce cytokines in species- and strain-dependent manners. Colonization of germ-free （GF） mice with a mixture of all three strains （Lmix） improved the intestinal barrier by strengthening the apical junctional complexes of enterocytes and restoring the structures of microfilaments extending into the terminal web. Mice colonized with Lmix and sensitized to the Bet v I allergen showed significantly lower levels of allergen-specific IgE, IgG 1 and IgG2a and an elevated total IgA level in the sera and intestinal lavages as well as an increased transforming growth factor （TGF）-β level compared with the sensitized GF mice. Splenocytes and mesenteric lymph node cells from the Lmix-colonized mice showed the significant upregulation of TGF-β after in vitro stimulation with Bet v 1. Our results show that Lmix colonization improved the gut epithelial barrier and reduced allergic sensitization to Bet v 1. Furthermore, these findings were accompanied by the increased production of circulating and secretory IgA and the regulatory cytokine TGF-β. Thus, this mixture of three lactobacillus strains shows potential for use in the prevention of increased gut permeability and the onset of allergies in humans,
基金Supported by The Grants from the International Agency for Research on Cancer (Special Training Award to DGC)the French Association for Research on Cancer (grant #7478)the Crohn's and Colitis Foundation of America (to ASP)
文摘AIM： Prostaglandin G/H synthase 2 （PTGS2 or COX2） is one of the key factors in the cellular response to inflammation. PTGS2 is expressed in the affected intestinal segments of patients with inflammatory bowel diseases （IBD）. In IBD patients, non-steroidal anti-inflammatory drugs, which have been shown to reduce both the production and activity of PTGS2, may activate IBD and aggravate the symptoms. We aimed at examining genetic variants of PTGS2 that may be risk factors for IBD. METHODS： We genotyped 291 individuals diagnosed with IBD and 367 controls from the Dutch population for the five most frequent polymorphisms of the PTG52 gene. Clinical data were collected on all patients. DNA was extracted via normal laboratory methods. Genotyping was carried out using multiplex PCR followed by the Invader Assay and the 5＇ exonuclease assay （TaqMan）. New polymorphism screening was performed by pre-screening with denaturing high-performance liquid chromatography, followed by fluorescent sequencing. RESULTS： Allele 5209G was weakly associated with Crohn＇s disease （odds ratio [OR] 1.63, 95% confidence interval [CI] 1.03-2.57）, and allele 8473T with ulcerativecolitis （OR 1.50, 95%CI 1.00-2.27）. The haplotype including both alleles showed a strong association with IBD （OR 13.15, 95%CI 3.17-116.15）. This haplotype, while rare （-0.3%） in the general population, is found more frequently in patients （3.5%）. CONCLUSION： Our data suggest that this haplotype of PTGS2 contributes to the susceptibility of IBD.
