BACKGROUND Preoperative supplementation with immunonutrients, including arginine and n-3 fatty acids, has been shown in a number of systematic reviews to reduce infectious complications in patients who have undergone ...BACKGROUND Preoperative supplementation with immunonutrients, including arginine and n-3 fatty acids, has been shown in a number of systematic reviews to reduce infectious complications in patients who have undergone gastrointestinal surgery. Limited information, however, is available on the benefits of nutritional supplementation enriched with arginine and n-3 fatty acids in patients undergoing liver resection.AIM To evaluate the effects of preoperative nutritional supplementation enriched with arginine and n-3 fatty acids on inflammatory and immunologic markers and clinical outcome in patients undergoing liver resection.METHODS Thirty-four patients undergoing liver resection were randomized to either five days of preoperative Impact? [1020 kcal/d, immunonutrition(IMN) group], or standard care [no supplementation, standard care(STD) group]. Nutritional status was measured at study entry by subjective global assessment(SGA).Functional assessments(grip strength, fatigue and performance status) were carried out at study entry, on the day prior to surgery, and on postoperative day(POD) 7 and 30. Inflammatory and immune markers were measured at study entry, on the day prior to surgery, and POD 1, 3, 5, 7, 10 and 30. Postoperative complications were recorded prospectively until POD30.RESULTS A total of 32 patients(17 IMN and 15 STD) were analysed. All except four patients were SGA class A. The plasma ratio of(eicosapentaenoic acid plus docosahexaenoic acid) to arachidonic acid was higher in IMN patients on the day prior to surgery and POD 1, 3, 5 and 7(P < 0.05). Plasma interleukin(IL)-6 concentrations were elevated in the IMN group(P = 0.017 for POD7). No treatment effect was detected for functional measures, immune response(white cell count and total lymphocytes) or markers of inflammation(C-reactive protein,tumour necrosis factor-α, IL-8, IL-10). There were 10 patients with infectious complications in the IMN group and 4 in the STD group(P = 0.087). Median hospital stay was 9(range 4–49) d in the IMN group and 8(3-34) d in the STD group(P = 0.476).CONCLUSION In well-nourished patients undergoing elective liver resection, this study failed to show any benefit of preoperative immunonutrition.展开更多
The factors that determine fibrosis progression or normal tissue repair are largely unknown.We previously demonstrated that autophagy inhibition-mediated epithelial-mesenchymal transition(EMT)in human alveolar epithel...The factors that determine fibrosis progression or normal tissue repair are largely unknown.We previously demonstrated that autophagy inhibition-mediated epithelial-mesenchymal transition(EMT)in human alveolar epithelial type Il(ATIl)cells augments local myofibroblast differentiation in pulmonary fibrosis by paracrine signaling.Here,we report that liver kinase B1(LKB1)inactivation in ATIl cells inhibits autophagy and induces EMT as a conse-quence.In IPF lungs,this is caused by the down-regulation of CAB39L,a key subunit within the LKB1 complex.3D co-cultures of ATIl cells and MRC5 lung fibroblasts coupled with RNA sequencing(RNA-seq)confirmed that paracrine signaling between LKB1-depleted ATIl cells and fibroblasts augmented myofibroblast differentiation.Together,these data suggest that reduced autophagy caused by LKB1 inhibition can induce EMT in ATIl cells and contribute to fibrosis via aberrant epithelial-fibroblast crosstalk.展开更多
Progressive lung fibrosis is characterized by dysregulated extracellular matrix(ECM)homeostasis.Understand-ing of disease pathogenesis remains limited and has prevented the development of effective treatments.While an...Progressive lung fibrosis is characterized by dysregulated extracellular matrix(ECM)homeostasis.Understand-ing of disease pathogenesis remains limited and has prevented the development of effective treatments.While an abnormal wound-healing response is strongly implicated in lung fibrosis initiation,factors that determine why fi-brosis progresses rather than regular tissue repair occur are not fully explained.Within human lung fibrosis,there is evidence of altered epithelial and mesenchymal populations as well as cells undergoing epithelial-mesenchymal transition(EMT),a dynamic and reversible biological process by which epithelial cells lose their cell polarity and down-regulate cadherin-mediated cell-cell adhesion to gain migratory properties.This review will focus on the role of EMT and dysregulated epithelial-mesenchymal crosstalk in progressive lung fibrosis.展开更多
Dear Editor,The pandemic of COVID-19,a disease caused by severe acute respiratory syndrome coronavirus 2(SARS-Co V-2;previously known as 2019-n Co V),has placed an enormous burden on health authorities in 213 countrie...Dear Editor,The pandemic of COVID-19,a disease caused by severe acute respiratory syndrome coronavirus 2(SARS-Co V-2;previously known as 2019-n Co V),has placed an enormous burden on health authorities in 213 countries and territories.At the time of writing,over 26 million cases have been recorded across the world,with more than 870 k associated deaths(www.worldometers.info/coronavirus/).World Bank warns COVID-19 pandemic risks dramatic rise in poverty,with the majority of economies expecting to suffer from falling levels of GDP in 2020.展开更多
基金Australasian Society for Parenteral and Enteral Nutrition Research Grant and A+Trust Small Project Grant,No.5576
文摘BACKGROUND Preoperative supplementation with immunonutrients, including arginine and n-3 fatty acids, has been shown in a number of systematic reviews to reduce infectious complications in patients who have undergone gastrointestinal surgery. Limited information, however, is available on the benefits of nutritional supplementation enriched with arginine and n-3 fatty acids in patients undergoing liver resection.AIM To evaluate the effects of preoperative nutritional supplementation enriched with arginine and n-3 fatty acids on inflammatory and immunologic markers and clinical outcome in patients undergoing liver resection.METHODS Thirty-four patients undergoing liver resection were randomized to either five days of preoperative Impact? [1020 kcal/d, immunonutrition(IMN) group], or standard care [no supplementation, standard care(STD) group]. Nutritional status was measured at study entry by subjective global assessment(SGA).Functional assessments(grip strength, fatigue and performance status) were carried out at study entry, on the day prior to surgery, and on postoperative day(POD) 7 and 30. Inflammatory and immune markers were measured at study entry, on the day prior to surgery, and POD 1, 3, 5, 7, 10 and 30. Postoperative complications were recorded prospectively until POD30.RESULTS A total of 32 patients(17 IMN and 15 STD) were analysed. All except four patients were SGA class A. The plasma ratio of(eicosapentaenoic acid plus docosahexaenoic acid) to arachidonic acid was higher in IMN patients on the day prior to surgery and POD 1, 3, 5 and 7(P < 0.05). Plasma interleukin(IL)-6 concentrations were elevated in the IMN group(P = 0.017 for POD7). No treatment effect was detected for functional measures, immune response(white cell count and total lymphocytes) or markers of inflammation(C-reactive protein,tumour necrosis factor-α, IL-8, IL-10). There were 10 patients with infectious complications in the IMN group and 4 in the STD group(P = 0.087). Median hospital stay was 9(range 4–49) d in the IMN group and 8(3-34) d in the STD group(P = 0.476).CONCLUSION In well-nourished patients undergoing elective liver resection, this study failed to show any benefit of preoperative immunonutrition.
基金supported by the UK Medical Research Council(MR/S025480/1)the UK Academy of Medical Sciences/the Wellcome Trust Springboard Award(SBF002/1038)+2 种基金AAIR Charity.ZX and LY were supported by China Scholarship Council.YZ was supported by an Institute for Life Sciences PhD Studentship.JD was supported by the Francis Crick Institute which receives its core funding from Cancer Research UK(FC001070)the UK Medical Research Council(FC001070)the Wellcome Trust(FC001070).
文摘The factors that determine fibrosis progression or normal tissue repair are largely unknown.We previously demonstrated that autophagy inhibition-mediated epithelial-mesenchymal transition(EMT)in human alveolar epithelial type Il(ATIl)cells augments local myofibroblast differentiation in pulmonary fibrosis by paracrine signaling.Here,we report that liver kinase B1(LKB1)inactivation in ATIl cells inhibits autophagy and induces EMT as a conse-quence.In IPF lungs,this is caused by the down-regulation of CAB39L,a key subunit within the LKB1 complex.3D co-cultures of ATIl cells and MRC5 lung fibroblasts coupled with RNA sequencing(RNA-seq)confirmed that paracrine signaling between LKB1-depleted ATIl cells and fibroblasts augmented myofibroblast differentiation.Together,these data suggest that reduced autophagy caused by LKB1 inhibition can induce EMT in ATIl cells and contribute to fibrosis via aberrant epithelial-fibroblast crosstalk.
基金supported by the UK Medical Research Council(MR/S025480/1)the UK Academy of Medical Sciences/the Well-come Trust Springboard Award[SBF002\1038]LY and ZX were sup-ported by the China Scholarship Council.
文摘Progressive lung fibrosis is characterized by dysregulated extracellular matrix(ECM)homeostasis.Understand-ing of disease pathogenesis remains limited and has prevented the development of effective treatments.While an abnormal wound-healing response is strongly implicated in lung fibrosis initiation,factors that determine why fi-brosis progresses rather than regular tissue repair occur are not fully explained.Within human lung fibrosis,there is evidence of altered epithelial and mesenchymal populations as well as cells undergoing epithelial-mesenchymal transition(EMT),a dynamic and reversible biological process by which epithelial cells lose their cell polarity and down-regulate cadherin-mediated cell-cell adhesion to gain migratory properties.This review will focus on the role of EMT and dysregulated epithelial-mesenchymal crosstalk in progressive lung fibrosis.
基金funded by Medical Research Council(UK)[MR/S025480/1]a Key Project of Science and Technology on COVID-19 of Hubei Province[No.2020FCA002]supported by an Institute for Life Sciences(University of Southampton)PhD Studentship。
文摘Dear Editor,The pandemic of COVID-19,a disease caused by severe acute respiratory syndrome coronavirus 2(SARS-Co V-2;previously known as 2019-n Co V),has placed an enormous burden on health authorities in 213 countries and territories.At the time of writing,over 26 million cases have been recorded across the world,with more than 870 k associated deaths(www.worldometers.info/coronavirus/).World Bank warns COVID-19 pandemic risks dramatic rise in poverty,with the majority of economies expecting to suffer from falling levels of GDP in 2020.
