The hydration lubrication paradigm,whereby hydration layers are both strongly held by the charges they surround,and so can support large pressures without being squeezed out,and at the same time remain very rapidly re...The hydration lubrication paradigm,whereby hydration layers are both strongly held by the charges they surround,and so can support large pressures without being squeezed out,and at the same time remain very rapidly relaxing and so have a fluid response to shear,provides a framework for understanding,controlling,and designing very efficient boundary lubrication systems in aqueous and biological media.This review discusses the properties of confined water,which-unlike organic solvents-retains its fluidity down to molecularly thin films.It then describes lubrication by hydrated ions trapped between charged surfaces,and by other hydrated boundary species including charged and zwitterionic polymer brushes,surfactant monolayers,liposomes,and biological macromolecules implicated in synovial joint lubrication.Finally,challenges and prospects for future development of this new boundary lubrication approach are considered.展开更多
AIM: To determine whether adding vitamin D, a potent immunomodulator, improves the hepatitis C virus (HCV) response to antiviral therapy. METHODS: Seventy-two consecutive patients with chronic HCV genotype 1 were rand...AIM: To determine whether adding vitamin D, a potent immunomodulator, improves the hepatitis C virus (HCV) response to antiviral therapy. METHODS: Seventy-two consecutive patients with chronic HCV genotype 1 were randomized into two groups: the treatment group (n = 36, 50% male, mean age 47 ± 11 years) received Peg-α-2b interferon (1.5 μg/kg per week) plus ribavirin (1000-1200 mg/d) together with vitamin D3 (2000 IU/d, target serum level > 32 ng/mL), and the control group (n = 36, 60% male, mean age 49 ± 7 years) received identical therapy without vitamin D. HCV-RNA was assessed by realtime polymerase chain reaction (sensitivity, 10 IU/mL). The sustained virologic response (SVR) was defined as undetectable HCV-RNA at 24 wk post-treatment. RESULTS: Clinical characteristics were similar in both groups. The treatment group had a higher mean bodymass index (27 ± 4 kg/m2 vs 24 ± 3 kg/m2, P < 0.01), viral load (50% vs 42%, P < 0.01), and fibrosis score (> F2: 42% vs 19%, P < 0.001) than the controls. At week 4, 16 (44%) treated patients and 6 (17%) controls were HCV-RNA negative (P < 0.001). At week 12, 34 (94%) treated patients and 17 (48%) controls were HCV-RNA negative (P < 0.001). At 24 wk post-treatment (SVR), 31 (86%) treated patients and 15 (42%) controls were HCV-RNA negative (P < 0.001). Viral load, advanced fibrosis and vitamin D supplementation were strongly and independently associated with SVR (multivariate analysis). Adverse events were mild and typical of Peg-α-2b/ribavirin. CONCLUSION: Adding vitamin D to conventional Peg-α-2b/ribavirin therapy for treatment-na■ve patients with chronic HCV genotype 1 infection significantly improves the viral response.展开更多
The term non-alcoholic fatty liver disease(NAFLD)was coined in 1980 to characterize a disease similar to alcoholic fatty liver disease that developed in patients without a history of excessive alcohol intake.[1]Morpho...The term non-alcoholic fatty liver disease(NAFLD)was coined in 1980 to characterize a disease similar to alcoholic fatty liver disease that developed in patients without a history of excessive alcohol intake.[1]Morphologically,NAFLD is characterized by excess fatty infiltration of the liver in the absence of known causes of liver disease(eg,alcohol,autoimmune liver disease,viral hepatitis,etc).The clinical manifestations of NAFLD(both hepatic and extrahepatic)depend on the outcome of complex interactions between its primary drivers including poor lifestyle habits and diet,a dysfunctional microbiota,genetic predisposition,and environmental cues that result in metabolic dysfunction and liver disease.However,bringing all patients with their markedly different clinical courses under the NAFLD umbrella belies its complexity and implies a homogeneous disease state that then negatively impacts clinical management and a deeper understanding of pathogenesis.With advances in current knowledge on the spectrum of fatty liver diseases,it is apparent that the fourdecade-old outdated term NAFLD can no longer serve to usefully describe a highly heterogeneous disease.The disease as we understand it today not only impacts patients who consume alcohol and those who do not,but also potentially impacts all patients with any form of liver disease,by acting as a disease modifier.[2]展开更多
Over the past decade,topology has emerged as a major branch in broad areas of physics,from atomic lattices to condensed matter.In particular,topology has received significant attention in photonics because light waves...Over the past decade,topology has emerged as a major branch in broad areas of physics,from atomic lattices to condensed matter.In particular,topology has received significant attention in photonics because light waves can serve as a platform to investigate nontrivial bulk and edge physics with the aid of carefully engineered photonic crystals and metamaterials.Simultaneously,photonics provides enriched physics that arises from spin-1 vectorial electromagnetic fields.Here,we review recent progress in the growing field of topological photonics in three parts.The first part is dedicated to the basics of topological band theory and introduces various two-dimensional topological phases.The second part reviews three-dimensional topological phases and numerous approaches to achieve them in photonics.Last,we present recently emerging fields in topological photonics that have not yet been reviewed.This part includes topological degeneracies in nonzero dimensions,unidirectional Maxwellian spin waves,higher-order photonic topological phases,and stacking of photonic crystals to attain layer pseudospin.In addition to the various approaches for realizing photonic topological phases,we also discuss the interaction between light and topological matter and the efforts towards practical applications of topological photonics.展开更多
AIM:To use microarray-based miRNA profiling of colonic mucosal biopsies from patients with ulcerative colitis (UC), Crohn's disease (CD), and controls in order to identify new potential miRNA biomarkers in inflamm...AIM:To use microarray-based miRNA profiling of colonic mucosal biopsies from patients with ulcerative colitis (UC), Crohn's disease (CD), and controls in order to identify new potential miRNA biomarkers in inflammatory bowel disease. METHODS:Colonic mucosal pinch biopsies from the descending part were obtained endoscopically from patients with active UC or CD, quiescent UC or CD, as well as healthy controls. Total RNA was isolated and miRNA expression assessed using the miRNA microarray Geniom Biochip miRNA Homo sapiens (Febit GmbH, Heidelberg, Germany). Data analysis was carried out by principal component analysis and projection to latent structure-discriminant analysis using the SIMCA-P+12 software package (Umetrics, Umea, Sweden). The microarray data were subsequently validated by quantitative real-time polymerase chain reaction (qPCR) performed on colonic tissue samples from active UC patients (n = 20), patients with quiescent UC (n = 19), and healthy controls (n = 20). The qPCR results were analyzed with Mann-WhitneyU test.In silico prediction analysis were performed to identify potential miRNA target genes and the predicted miRNA targets were then compared with all UC associated susceptibility genes reported in the literature. RESULTS:The colonic mucosal miRNA transcriptome differs significantly between UC and controls, UC and CD, as well as between UC patients with mucosal inflammation and those without. However, no clear differences in the transcriptome of patients with CD and controls were found. The miRNAs with the strongest differential power were identified (miR-20b, miR-99a, miR-203, miR-26b, and miR-98) and found to be upregulated more than a 10-fold in active UC as compared to quiescent UC, CD, and controls. Two miRNAs, miR-125b-1* and let-7e*, were up-regulated more than 5-fold in quiescent UC compared to active UC, CD, and controls. Four of the seven miRNAs (miR-20b, miR-98, miR-125b-1*, and let-7e*) were validated by qPCR and found to be specifically upregulated in patients with UC. Usingin sili展开更多
The pathogenesis of inflammatory bowel disease (IBD) is complex and largely unknown. Until recently, research has focused on the study of protein regulators in inflammation to reveal the cellular and molecular network...The pathogenesis of inflammatory bowel disease (IBD) is complex and largely unknown. Until recently, research has focused on the study of protein regulators in inflammation to reveal the cellular and molecular networks in the pathogenesis of IBD. However, in the last few years, new and promising insights have been generated from studies describing an association between an altered expression of a specific class of non-coding RNAs, called microRNAs (miRs or miRNAs) and IBD. The short (approximately 22 nucleotides), endogenous, single-stranded RNAs are evolutionary conserved inanimals and plants, and regulate specific target mRNAs at the post-transcriptional level. MiRNAs are involved in several biological processes, including development, cell differentiation, proliferation and apoptosis. Furthermore, it is estimated that miRNAs may be responsible for regulating the expression of nearly one-third of the genes in the human genome. Thus, miRNA deregulation often results in an impaired cellular function, and a disturbance of downstream gene regulation and signaling cascades, suggesting their implication in disease etiology. Despite the identification of more than 1900 mature human miRNAs, very little is known about their biological functions and functional targets. Recent studies have identified dysregulated miRNAs in tissue samples of IBD patients and have demonstrated similar differences in circulating miRNAs in the serum of IBD patients. Thus, there is great promise that miRNAs will aid in the early diagnosis of IBD, and in the development of personalized therapies. Here, we provide a short review of the current state-of-the-art of miRNAs in IBD pathogenesis, diagnostics and therapeutics.展开更多
AIM: Standard immunosuppression after organ transplantation stimulates tumor growth. Sirolimus has a strong antiproliferative and a tumor inhibiting effect. The purpose is to assess the effect on tumor growth of the i...AIM: Standard immunosuppression after organ transplantation stimulates tumor growth. Sirolimus has a strong antiproliferative and a tumor inhibiting effect. The purpose is to assess the effect on tumor growth of the immunosuppressive compounds sirolimus and tacrolimus alone and in combination on cells of human hepatocellular carcinoma.METHODS: We used the human cell lines SK-Hep 1 and Hep 3B derived from hepatocellular carcinoma. Proliferation analyses after treatment with sirolimus, tacrolimus, or the combination of both were performed. FACS analyses were done to reveal cell cycle changes and apoptotic cell death. The expression of apoptosis-related proteins was estimated by Western blots.RESULTS: Sirolimus alone or combined with tacrolimus inhibited the growth of both cell lines after 5 d by up to 35% in SK-Hep 1 cells, and by up to 68% in Hep 3B cells at 25 ng/mL. Tacrolimus alone stimulated the growth by 12% after 5 ng/mL and by 25% after 25 ng/mL in Hep 3B cells. We found an increase of apoptotic Hep 3B cells from 6 to 16%, and a G1-arrest in SK-Hep 1 cells with an increase of cells from 61 to 82%, when sirolimus and tacrolimus were combined. Bcl-2 was down-regulated in Hep 3B, but not in SK-Hep 1 cells after combined treatment.CONCLUSION: Sirolimus appears to inhibit the growth of hepatocellular carcinoma cells alone and in combination with tacrolimus. Sirolimus seems to inhibit the growth stimulation of tacrolimus.展开更多
Aerial imagery is regularly used by crop researchers,growers and farmers to monitor crops during the growing season.To extract meaningful information from large-scale aerial images collected from the field,high-throug...Aerial imagery is regularly used by crop researchers,growers and farmers to monitor crops during the growing season.To extract meaningful information from large-scale aerial images collected from the field,high-throughput phenotypic analysis solutions are required,which not only produce high-quality measures of key crop traits,but also support professionals to make prompt and reliable crop management decisions.Here,we report AirSurf,an automated and open-source analytic platform that combines modern computer vision,up-to-date machine learning,and modular software engineering in order to measure yield-related phenotypes from ultra-large aerial imagery.To quantify millions of in-field lettuces acquired by fixed-wing light aircrafts equipped with normalised difference vegetation index(NDVI)sensors,we customised AirSurf by combining computer vision algorithms and a deep-learning classifier trained with over 100,000 labelled lettuce signals.The tailored platform,AirSurf-Lettuce,is capable of scoring and categorising iceberg lettuces with high accuracy(>98%).Furthermore,novel analysis functions have been developed to map lettuce size distribution across the field,based on which associated global positioning system(GPS)tagged harvest regions have been identified to enable growers and farmers to conduct precision agricultural practises in order to improve the actual yield as well as crop marketability before the harvest.展开更多
Portal hypertension(PHT) is defined as a pathological increase in portal venous pressure and frequently accompanies cirrhosis.Portal pressure can be increased by a rise in portal blood flow,an increase in vascular res...Portal hypertension(PHT) is defined as a pathological increase in portal venous pressure and frequently accompanies cirrhosis.Portal pressure can be increased by a rise in portal blood flow,an increase in vascular resistance,or the combination.In cirrhosis,the primary factor leading to PHT is an increase in intra-hepatic resistance to blood flow.Although much of this increase is a mechanical consequence of architectural disturbances,there is a dynamic and reversible component that represents up to a third of the increased vascular resistance in cirrhosis.Many vasoactive substances contribute to the development of PHT.Among these,nitric oxide(NO) is the key mediator that paradoxically regulates the sinusoidal(intra-hepatic) and systemic/splanchnic circulations.NO deficiency in the liver leads to increased intra-hepatic resistance while increased NO in the circulation contributes to the hyperdynamic systemic/splanchnic circulation.NO mediated-angiogenesis also plays a role in splanchnic vasodilation and collateral circulation formation.NO donors reduce PHT in animals models but the key clinical challenge is the development of an NO donor or drug delivery system that selectively targets the liver.展开更多
It is now widely recognized that chronic hepatitis C (CHC)is associated with insulin resistance(IR)and type 2 diabetes,so can be considered a metabolic disease.IR is most strongly associated with hepatitis C virus(HCV...It is now widely recognized that chronic hepatitis C (CHC)is associated with insulin resistance(IR)and type 2 diabetes,so can be considered a metabolic disease.IR is most strongly associated with hepatitis C virus(HCV)genotype 1,in contrast to hepatic steatosis, which is associated with genotype 3 infection.Apart from the well-described complications of diabetes,IR in CHC predicts faster progression to fibrosis and cirrhosis that may culminate in liver failure and hepatocellular carcinoma.More recently,it has been recognized that IR in CHC predicts a poor response to antiviral therapy. The molecular mechanisms for the association between IR and HCV infection are not well defined.This review will elaborate on the clinical associations between CHC and IR and summarize current knowledge regarding the molecular mechanisms that potentially mediate HCV-associated IR.展开更多
Evidence has accumulated to suggest an important role of ethanol and/or its metabolites in the pathogenesis of alcohol-related liver disease. In this review, the fibrogenic effects of ethanol and its metabolites on he...Evidence has accumulated to suggest an important role of ethanol and/or its metabolites in the pathogenesis of alcohol-related liver disease. In this review, the fibrogenic effects of ethanol and its metabolites on hepatic stellate cells (HSCs) are discussed. In brief, ethanol interferes with retinoid metabolism and its signaling, induces the release of fibrogenic cytokines such as transforming growth factor β-1 (TGFβ-1) from HSCs, up-regulates the gene expression of collagen I and enhances type I collagen protein production by HSCs. Ethanol further perpetuates an activated HSC phenotype through extracellular matrix remodeling. The underlying pathophysiologic mechanisms by which ethanol exerts these pro-fibrogenic effects on HSCs are reviewed.展开更多
Helicobacter pylori(H. pylori) is a Gram-negative spiral bacterium that is present in nearly half the world's population. It is the major cause of peptic ulcer disease and a recognized cause of gastric carcinoma. ...Helicobacter pylori(H. pylori) is a Gram-negative spiral bacterium that is present in nearly half the world's population. It is the major cause of peptic ulcer disease and a recognized cause of gastric carcinoma. In addition, it is linked to non-ulcer dyspepsia, vitamin B12 deficiency, iron-deficient anemia and immune thrombocytopenic purpura. These conditions are indications for testing and treatment according to current guidelines. An additional indication according to the guidelines is "anyone with a fear of gastric cancer" which results in nearly every infected person being eligible for eradication treatment. There may be beneficial effects of H. pylori in humans, including protection from gastroesophageal reflux disease and esophageal adenocarcinoma. In addition, universal treatment will be extremely expensive(more than $32 billion in the United States), may expose the patients to adverse effects such as anaphylaxis and Clostridium difficile infection, as well as contributing to antibiotic resistance. There may also be an as yet uncertain effect on the fecal microbiome. There is a need for robust clinical data to assist in decision-making regarding treatment of H. pylori infection.展开更多
Peritoneal dialysis （PD） is associated with a high risk of infection of the peritoneum, subcutaneous tunnel and catheter exit site. Although quality standards demand an infection rate 〈 0.67 episodes/patient/year o...Peritoneal dialysis （PD） is associated with a high risk of infection of the peritoneum, subcutaneous tunnel and catheter exit site. Although quality standards demand an infection rate 〈 0.67 episodes/patient/year on dialy-sis, the reported overall rate of PD associated infection is 0.24-1.66 episodes/patient/year. It is estimated that for every 0.5-per-year increase in peritonitis rate, the risk of death increases by 4% and 18% of the episodes resulted in removal of the PD catheter and 3.5% re-sulted in death. Improved diagnosis, increased aware-ness of causative agents in addition to other measures will facilitate prompt management of PD associated infection and salvage of PD modality. The aims of this review are to determine the magnitude of the infection problem, identify possible risk factors and provide an update on the diagnosis and management of PD as-sociated infection. Gram-positive cocci such as Staphy-lococcus epidermidis , other coagulase negative staphy-lococcoci, and Staphylococcus aureus （S. aureus ） are the most frequent aetiological agents of PD-associated peritonitis worldwide. Empiric antibiotic therapy must cover both gram-positive and gram-negative organ-isms. However, use of systemic vancomycin and cip-rofoxacin administration for example, is a simple and efficient first-line protocol antibiotic therapy for PD peritonitis - success rate of 77%. However, for fungal PD peritonitis, it is now standard practice to remove PD catheters in addition to antifungal treatment for a minimum of 3 wk and subsequent transfer to hemodi-alysis. To prevent PD associated infections, prophylactic antibiotic administration before catheter placement, adequate patient training, exit-site care, and treatment for S. aureus nasal carriage should be employed. Mupi-rocin treatment can reduce the risk of exit site infection by 46% but it cannot decrease the risk of peritonitis due to all organisms.展开更多
文摘The hydration lubrication paradigm,whereby hydration layers are both strongly held by the charges they surround,and so can support large pressures without being squeezed out,and at the same time remain very rapidly relaxing and so have a fluid response to shear,provides a framework for understanding,controlling,and designing very efficient boundary lubrication systems in aqueous and biological media.This review discusses the properties of confined water,which-unlike organic solvents-retains its fluidity down to molecularly thin films.It then describes lubrication by hydrated ions trapped between charged surfaces,and by other hydrated boundary species including charged and zwitterionic polymer brushes,surfactant monolayers,liposomes,and biological macromolecules implicated in synovial joint lubrication.Finally,challenges and prospects for future development of this new boundary lubrication approach are considered.
文摘AIM: To determine whether adding vitamin D, a potent immunomodulator, improves the hepatitis C virus (HCV) response to antiviral therapy. METHODS: Seventy-two consecutive patients with chronic HCV genotype 1 were randomized into two groups: the treatment group (n = 36, 50% male, mean age 47 ± 11 years) received Peg-α-2b interferon (1.5 μg/kg per week) plus ribavirin (1000-1200 mg/d) together with vitamin D3 (2000 IU/d, target serum level > 32 ng/mL), and the control group (n = 36, 60% male, mean age 49 ± 7 years) received identical therapy without vitamin D. HCV-RNA was assessed by realtime polymerase chain reaction (sensitivity, 10 IU/mL). The sustained virologic response (SVR) was defined as undetectable HCV-RNA at 24 wk post-treatment. RESULTS: Clinical characteristics were similar in both groups. The treatment group had a higher mean bodymass index (27 ± 4 kg/m2 vs 24 ± 3 kg/m2, P < 0.01), viral load (50% vs 42%, P < 0.01), and fibrosis score (> F2: 42% vs 19%, P < 0.001) than the controls. At week 4, 16 (44%) treated patients and 6 (17%) controls were HCV-RNA negative (P < 0.001). At week 12, 34 (94%) treated patients and 17 (48%) controls were HCV-RNA negative (P < 0.001). At 24 wk post-treatment (SVR), 31 (86%) treated patients and 15 (42%) controls were HCV-RNA negative (P < 0.001). Viral load, advanced fibrosis and vitamin D supplementation were strongly and independently associated with SVR (multivariate analysis). Adverse events were mild and typical of Peg-α-2b/ribavirin. CONCLUSION: Adding vitamin D to conventional Peg-α-2b/ribavirin therapy for treatment-na■ve patients with chronic HCV genotype 1 infection significantly improves the viral response.
基金the Robert W.Storr Bequest to the Sydney Medical Foundation,University of Sydneya National Health and Medical Research Council of Australia(NHMRC)Program Grant(No.APP1053206 and APP1149976)+2 种基金Project grants(No.APP1107178 and APP1108422)Ming-Hua Zheng is supported by grants from the National Natural Science Foundation of China(No.81500665)High Level Creative Talents from Department of Public Health in Zhejiang Province and Project of New Century 551 Talent Nurturing in Wenzhou.
文摘The term non-alcoholic fatty liver disease(NAFLD)was coined in 1980 to characterize a disease similar to alcoholic fatty liver disease that developed in patients without a history of excessive alcohol intake.[1]Morphologically,NAFLD is characterized by excess fatty infiltration of the liver in the absence of known causes of liver disease(eg,alcohol,autoimmune liver disease,viral hepatitis,etc).The clinical manifestations of NAFLD(both hepatic and extrahepatic)depend on the outcome of complex interactions between its primary drivers including poor lifestyle habits and diet,a dysfunctional microbiota,genetic predisposition,and environmental cues that result in metabolic dysfunction and liver disease.However,bringing all patients with their markedly different clinical courses under the NAFLD umbrella belies its complexity and implies a homogeneous disease state that then negatively impacts clinical management and a deeper understanding of pathogenesis.With advances in current knowledge on the spectrum of fatty liver diseases,it is apparent that the fourdecade-old outdated term NAFLD can no longer serve to usefully describe a highly heterogeneous disease.The disease as we understand it today not only impacts patients who consume alcohol and those who do not,but also potentially impacts all patients with any form of liver disease,by acting as a disease modifier.[2]
基金financially supported by the National Research Foundation(NRF)grants(NRF-2019R1A2C3003129,CAMM-2019M3A6B3030637,NRF-2019R1A5A8080290,NRF-2018M3D1A1058997)funded by the Ministry of Science and ICT(MSIT)of the Korean governmentthe Global Ph.D.fellowship(NRF-2017H1A2A1043204)funded by the Ministry of Education of the Korean government.
文摘Over the past decade,topology has emerged as a major branch in broad areas of physics,from atomic lattices to condensed matter.In particular,topology has received significant attention in photonics because light waves can serve as a platform to investigate nontrivial bulk and edge physics with the aid of carefully engineered photonic crystals and metamaterials.Simultaneously,photonics provides enriched physics that arises from spin-1 vectorial electromagnetic fields.Here,we review recent progress in the growing field of topological photonics in three parts.The first part is dedicated to the basics of topological band theory and introduces various two-dimensional topological phases.The second part reviews three-dimensional topological phases and numerous approaches to achieve them in photonics.Last,we present recently emerging fields in topological photonics that have not yet been reviewed.This part includes topological degeneracies in nonzero dimensions,unidirectional Maxwellian spin waves,higher-order photonic topological phases,and stacking of photonic crystals to attain layer pseudospin.In addition to the various approaches for realizing photonic topological phases,we also discuss the interaction between light and topological matter and the efforts towards practical applications of topological photonics.
基金Supported by Fonden til Lgevidenskabens Fremme (the AP MΦller Foundation)the Family Erichsen Memorial Foundationthe Foundation of Aase and Ejnar Danielsen
文摘AIM:To use microarray-based miRNA profiling of colonic mucosal biopsies from patients with ulcerative colitis (UC), Crohn's disease (CD), and controls in order to identify new potential miRNA biomarkers in inflammatory bowel disease. METHODS:Colonic mucosal pinch biopsies from the descending part were obtained endoscopically from patients with active UC or CD, quiescent UC or CD, as well as healthy controls. Total RNA was isolated and miRNA expression assessed using the miRNA microarray Geniom Biochip miRNA Homo sapiens (Febit GmbH, Heidelberg, Germany). Data analysis was carried out by principal component analysis and projection to latent structure-discriminant analysis using the SIMCA-P+12 software package (Umetrics, Umea, Sweden). The microarray data were subsequently validated by quantitative real-time polymerase chain reaction (qPCR) performed on colonic tissue samples from active UC patients (n = 20), patients with quiescent UC (n = 19), and healthy controls (n = 20). The qPCR results were analyzed with Mann-WhitneyU test.In silico prediction analysis were performed to identify potential miRNA target genes and the predicted miRNA targets were then compared with all UC associated susceptibility genes reported in the literature. RESULTS:The colonic mucosal miRNA transcriptome differs significantly between UC and controls, UC and CD, as well as between UC patients with mucosal inflammation and those without. However, no clear differences in the transcriptome of patients with CD and controls were found. The miRNAs with the strongest differential power were identified (miR-20b, miR-99a, miR-203, miR-26b, and miR-98) and found to be upregulated more than a 10-fold in active UC as compared to quiescent UC, CD, and controls. Two miRNAs, miR-125b-1* and let-7e*, were up-regulated more than 5-fold in quiescent UC compared to active UC, CD, and controls. Four of the seven miRNAs (miR-20b, miR-98, miR-125b-1*, and let-7e*) were validated by qPCR and found to be specifically upregulated in patients with UC. Usingin sili
基金Supported by Grants from Fonden til Lgevidenskabens Fremme(the AP Mller Foundation)the Family Erichsen Memorial Foundation+2 种基金the Lundbeck Foundationthe Axel Muusfeldts Foundationthe Foundation of Aase and Ejnar Danielsen
文摘The pathogenesis of inflammatory bowel disease (IBD) is complex and largely unknown. Until recently, research has focused on the study of protein regulators in inflammation to reveal the cellular and molecular networks in the pathogenesis of IBD. However, in the last few years, new and promising insights have been generated from studies describing an association between an altered expression of a specific class of non-coding RNAs, called microRNAs (miRs or miRNAs) and IBD. The short (approximately 22 nucleotides), endogenous, single-stranded RNAs are evolutionary conserved inanimals and plants, and regulate specific target mRNAs at the post-transcriptional level. MiRNAs are involved in several biological processes, including development, cell differentiation, proliferation and apoptosis. Furthermore, it is estimated that miRNAs may be responsible for regulating the expression of nearly one-third of the genes in the human genome. Thus, miRNA deregulation often results in an impaired cellular function, and a disturbance of downstream gene regulation and signaling cascades, suggesting their implication in disease etiology. Despite the identification of more than 1900 mature human miRNAs, very little is known about their biological functions and functional targets. Recent studies have identified dysregulated miRNAs in tissue samples of IBD patients and have demonstrated similar differences in circulating miRNAs in the serum of IBD patients. Thus, there is great promise that miRNAs will aid in the early diagnosis of IBD, and in the development of personalized therapies. Here, we provide a short review of the current state-of-the-art of miRNAs in IBD pathogenesis, diagnostics and therapeutics.
文摘AIM: Standard immunosuppression after organ transplantation stimulates tumor growth. Sirolimus has a strong antiproliferative and a tumor inhibiting effect. The purpose is to assess the effect on tumor growth of the immunosuppressive compounds sirolimus and tacrolimus alone and in combination on cells of human hepatocellular carcinoma.METHODS: We used the human cell lines SK-Hep 1 and Hep 3B derived from hepatocellular carcinoma. Proliferation analyses after treatment with sirolimus, tacrolimus, or the combination of both were performed. FACS analyses were done to reveal cell cycle changes and apoptotic cell death. The expression of apoptosis-related proteins was estimated by Western blots.RESULTS: Sirolimus alone or combined with tacrolimus inhibited the growth of both cell lines after 5 d by up to 35% in SK-Hep 1 cells, and by up to 68% in Hep 3B cells at 25 ng/mL. Tacrolimus alone stimulated the growth by 12% after 5 ng/mL and by 25% after 25 ng/mL in Hep 3B cells. We found an increase of apoptotic Hep 3B cells from 6 to 16%, and a G1-arrest in SK-Hep 1 cells with an increase of cells from 61 to 82%, when sirolimus and tacrolimus were combined. Bcl-2 was down-regulated in Hep 3B, but not in SK-Hep 1 cells after combined treatment.CONCLUSION: Sirolimus appears to inhibit the growth of hepatocellular carcinoma cells alone and in combination with tacrolimus. Sirolimus seems to inhibit the growth stimulation of tacrolimus.
基金the support of NVIDIA Corporation with the award of the Quadro GPU used for this research.J.Z.was partially funded by UKRI Biotechnology and Biological Sciences Research Council’s(BBSRC)Designing Future Wheat Cross-institute Strategic Programme(BB/P016855/1)to Graham Moore,BBS/E/T/000PR9785 to J.Z.J.B.were partially supported by the Core Strategic Programme Grant(BB/CSP17270/1)at the Earlham Institute+1 种基金A.G.B.and C.A.were also partially supported by G’s Growers’s industrial fund awarded to J.Z.A.B.was partially supported by the Newton UK-China Agri-Tech Network+Grant(GP131JZ1G)awarded to J.Z.
文摘Aerial imagery is regularly used by crop researchers,growers and farmers to monitor crops during the growing season.To extract meaningful information from large-scale aerial images collected from the field,high-throughput phenotypic analysis solutions are required,which not only produce high-quality measures of key crop traits,but also support professionals to make prompt and reliable crop management decisions.Here,we report AirSurf,an automated and open-source analytic platform that combines modern computer vision,up-to-date machine learning,and modular software engineering in order to measure yield-related phenotypes from ultra-large aerial imagery.To quantify millions of in-field lettuces acquired by fixed-wing light aircrafts equipped with normalised difference vegetation index(NDVI)sensors,we customised AirSurf by combining computer vision algorithms and a deep-learning classifier trained with over 100,000 labelled lettuce signals.The tailored platform,AirSurf-Lettuce,is capable of scoring and categorising iceberg lettuces with high accuracy(>98%).Furthermore,novel analysis functions have been developed to map lettuce size distribution across the field,based on which associated global positioning system(GPS)tagged harvest regions have been identified to enable growers and farmers to conduct precision agricultural practises in order to improve the actual yield as well as crop marketability before the harvest.
文摘Portal hypertension(PHT) is defined as a pathological increase in portal venous pressure and frequently accompanies cirrhosis.Portal pressure can be increased by a rise in portal blood flow,an increase in vascular resistance,or the combination.In cirrhosis,the primary factor leading to PHT is an increase in intra-hepatic resistance to blood flow.Although much of this increase is a mechanical consequence of architectural disturbances,there is a dynamic and reversible component that represents up to a third of the increased vascular resistance in cirrhosis.Many vasoactive substances contribute to the development of PHT.Among these,nitric oxide(NO) is the key mediator that paradoxically regulates the sinusoidal(intra-hepatic) and systemic/splanchnic circulations.NO deficiency in the liver leads to increased intra-hepatic resistance while increased NO in the circulation contributes to the hyperdynamic systemic/splanchnic circulation.NO mediated-angiogenesis also plays a role in splanchnic vasodilation and collateral circulation formation.NO donors reduce PHT in animals models but the key clinical challenge is the development of an NO donor or drug delivery system that selectively targets the liver.
基金Supported by Australian National Health and Medical Research Council and the Robert W Storr Bequest to the University of Sydney
文摘It is now widely recognized that chronic hepatitis C (CHC)is associated with insulin resistance(IR)and type 2 diabetes,so can be considered a metabolic disease.IR is most strongly associated with hepatitis C virus(HCV)genotype 1,in contrast to hepatic steatosis, which is associated with genotype 3 infection.Apart from the well-described complications of diabetes,IR in CHC predicts faster progression to fibrosis and cirrhosis that may culminate in liver failure and hepatocellular carcinoma.More recently,it has been recognized that IR in CHC predicts a poor response to antiviral therapy. The molecular mechanisms for the association between IR and HCV infection are not well defined.This review will elaborate on the clinical associations between CHC and IR and summarize current knowledge regarding the molecular mechanisms that potentially mediate HCV-associated IR.
文摘Evidence has accumulated to suggest an important role of ethanol and/or its metabolites in the pathogenesis of alcohol-related liver disease. In this review, the fibrogenic effects of ethanol and its metabolites on hepatic stellate cells (HSCs) are discussed. In brief, ethanol interferes with retinoid metabolism and its signaling, induces the release of fibrogenic cytokines such as transforming growth factor β-1 (TGFβ-1) from HSCs, up-regulates the gene expression of collagen I and enhances type I collagen protein production by HSCs. Ethanol further perpetuates an activated HSC phenotype through extracellular matrix remodeling. The underlying pathophysiologic mechanisms by which ethanol exerts these pro-fibrogenic effects on HSCs are reviewed.
文摘Helicobacter pylori(H. pylori) is a Gram-negative spiral bacterium that is present in nearly half the world's population. It is the major cause of peptic ulcer disease and a recognized cause of gastric carcinoma. In addition, it is linked to non-ulcer dyspepsia, vitamin B12 deficiency, iron-deficient anemia and immune thrombocytopenic purpura. These conditions are indications for testing and treatment according to current guidelines. An additional indication according to the guidelines is "anyone with a fear of gastric cancer" which results in nearly every infected person being eligible for eradication treatment. There may be beneficial effects of H. pylori in humans, including protection from gastroesophageal reflux disease and esophageal adenocarcinoma. In addition, universal treatment will be extremely expensive(more than $32 billion in the United States), may expose the patients to adverse effects such as anaphylaxis and Clostridium difficile infection, as well as contributing to antibiotic resistance. There may also be an as yet uncertain effect on the fecal microbiome. There is a need for robust clinical data to assist in decision-making regarding treatment of H. pylori infection.
文摘Peritoneal dialysis （PD） is associated with a high risk of infection of the peritoneum, subcutaneous tunnel and catheter exit site. Although quality standards demand an infection rate 〈 0.67 episodes/patient/year on dialy-sis, the reported overall rate of PD associated infection is 0.24-1.66 episodes/patient/year. It is estimated that for every 0.5-per-year increase in peritonitis rate, the risk of death increases by 4% and 18% of the episodes resulted in removal of the PD catheter and 3.5% re-sulted in death. Improved diagnosis, increased aware-ness of causative agents in addition to other measures will facilitate prompt management of PD associated infection and salvage of PD modality. The aims of this review are to determine the magnitude of the infection problem, identify possible risk factors and provide an update on the diagnosis and management of PD as-sociated infection. Gram-positive cocci such as Staphy-lococcus epidermidis , other coagulase negative staphy-lococcoci, and Staphylococcus aureus （S. aureus ） are the most frequent aetiological agents of PD-associated peritonitis worldwide. Empiric antibiotic therapy must cover both gram-positive and gram-negative organ-isms. However, use of systemic vancomycin and cip-rofoxacin administration for example, is a simple and efficient first-line protocol antibiotic therapy for PD peritonitis - success rate of 77%. However, for fungal PD peritonitis, it is now standard practice to remove PD catheters in addition to antifungal treatment for a minimum of 3 wk and subsequent transfer to hemodi-alysis. To prevent PD associated infections, prophylactic antibiotic administration before catheter placement, adequate patient training, exit-site care, and treatment for S. aureus nasal carriage should be employed. Mupi-rocin treatment can reduce the risk of exit site infection by 46% but it cannot decrease the risk of peritonitis due to all organisms.
