The Experts below are selected from a list of 6267 Experts worldwide ranked by ideXlab platform
Heinrich Jasper - One of the best experts on this subject based on the ideXlab platform.
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AWD regulates timed activation of BMP signaling in intestinal stem cells to maintain tissue homeostasis
Nature Communications, 2019Co-Authors: Xiaoyu Tracy Cai, Abu Safyan, Jennifer Gawlik, George Pyrowolakis, Hongjie Li, Heinrich JasperAbstract:Precise control of stem cell (SC) proliferation ensures tissue homeostasis. In the Drosophila Intestine, Injury-induced regeneration involves initial activation of intestinal SC (ISC) proliferation and subsequent return to quiescence. These two phases of the regenerative response are controlled by differential availability of the BMP type I receptor Thickveins (Tkv), yet how its expression is dynamically regulated remains unclear. Here we show that during homeostasis, the E3 ubiquitin ligase Highwire and the ubiquitin-proteasome system maintain low Tkv protein expression. After ISC activation, Tkv is stabilized by proteasome inhibition and undergoes endocytosis due to the induction of the nucleoside diphosphate kinase Abnormal Wing Disc (AWD). Tkv internalization is required for the activation of the Smad protein Mad, and for the return to quiescence after a regenerative episode. Our data provide insight into the mechanisms ensuring tissue homeostasis by dynamic control of somatic stem cell activity.Regeneration after Injury in the Drosophila Intestine involves early activation of intestinal stem cells (ISCs) and subsequent return to quiescence. Here the authors show that return to quiescence by ISCs involves BMP Type I receptor Tkv protein stabilization along with AWD mediated internalization into endocytic vesicles.
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AWD regulates timed activation of BMP signaling in intestinal stem cells to maintain tissue homeostasis.
Nature communications, 2019Co-Authors: Xiaoyu Tracy Cai, Abu Safyan, Jennifer Gawlik, George Pyrowolakis, Heinrich JasperAbstract:Precise control of stem cell (SC) proliferation ensures tissue homeostasis. In the Drosophila Intestine, Injury-induced regeneration involves initial activation of intestinal SC (ISC) proliferation and subsequent return to quiescence. These two phases of the regenerative response are controlled by differential availability of the BMP type I receptor Thickveins (Tkv), yet how its expression is dynamically regulated remains unclear. Here we show that during homeostasis, the E3 ubiquitin ligase Highwire and the ubiquitin-proteasome system maintain low Tkv protein expression. After ISC activation, Tkv is stabilized by proteasome inhibition and undergoes endocytosis due to the induction of the nucleoside diphosphate kinase Abnormal Wing Disc (AWD). Tkv internalization is required for the activation of the Smad protein Mad, and for the return to quiescence after a regenerative episode. Our data provide insight into the mechanisms ensuring tissue homeostasis by dynamic control of somatic stem cell activity.
Christian Wunder - One of the best experts on this subject based on the ideXlab platform.
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effects of crystalloids and colloids on liver and Intestine microcirculation and function in cecal ligation and puncture induced septic rodents
BMC Gastroenterology, 2012Co-Authors: Martin A Schick, Jobst Tobias Isbary, Tanja Nadine Stueber, Juergen Brugger, Jan Stumpner, Nicolas Schlegel, Norbert Roewer, Otto Eichelbroenner, Christian WunderAbstract:Background Septic acute liver and intestinal failure is associated with a high mortality. We therefore investigated the influence of volume resuscitation with different crystalloid or colloid solutions on liver and Intestine Injury and microcirculation in septic rodents.
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Effects of crystalloids and colloids on liver and Intestine microcirculation and function in cecal ligation and puncture induced septic rodents
BMC Gastroenterology, 2012Co-Authors: Martin A Schick, Jobst Tobias Isbary, Tanja Nadine Stueber, Juergen Brugger, Jan Stumpner, Nicolas Schlegel, Norbert Roewer, Otto Eichelbroenner, Christian WunderAbstract:Background Septic acute liver and intestinal failure is associated with a high mortality. We therefore investigated the influence of volume resuscitation with different crystalloid or colloid solutions on liver and Intestine Injury and microcirculation in septic rodents. Methods Sepsis was induced by cecal ligation and puncture (CLP) in 77 male rats. Animals were treated with different crystalloids (NaCl 0.9% (NaCl), Ringer’s acetate (RA)) or colloids (Gelafundin 4% (Gel), 6% HES 130/0.4 (HES)). After 24 h animals were re-anesthetized and intestinal (n = 6/group) and liver microcirculation (n = 6/group) were obtained using intravital microscopy, as well as macrohemodynamic parameters were measured. Blood assays and organs were harvested to determine organ function and Injury. Results HES improved liver microcirculation, cardiac index and DO_2-I, but significantly increased IL-1β, IL-6 and TNF-α levels and resulted in a mortality rate of 33%. Gel infused animals revealed significant reduction of liver and Intestine microcirculation with severe side effects on coagulation (significantly increased PTT and INR, decreased haemoglobin and platelet count). Furthermore Gel showed severe hypoglycemia, acidosis and significantly increased ALT and IL-6 with a lethality of 29%. RA exhibited no derangements in liver microcirculation when compared to sham and HES. RA showed no intestinal microcirculation disturbance compared to sham, but significantly improved the number of intestinal capillaries with flow compared to HES. All RA treated animals survided and showed no severe side effects on coagulation, liver, macrohemodynamic or metabolic state. Conclusions Gelatine 4% revealed devastated hepatic and intestinal microcirculation and severe side effects in CLP induced septic rats, whereas the balanced crystalloid solution showed stabilization of macro- and microhemodynamics with improved survival. HES improved liver microcirculation, but exhibited significantly increased pro-inflammatory cytokine levels. Crystalloid infusion revealed best results in mortality and microcirculation, when compared with colloid infusion.
Zhenhua Zeng - One of the best experts on this subject based on the ideXlab platform.
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Melatonin Attenuates Sepsis-Induced Small-Intestine Injury by Upregulating SIRT3-Mediated Oxidative-Stress Inhibition, Mitochondrial Protection, and Autophagy Induction.
Frontiers in immunology, 2021Co-Authors: Haihong Fang, Zhongqing Chen, Yunyang Han, Qiaobing Huang, Zhenhua ZengAbstract:Melatonin reportedly alleviates sepsis-induced multi-organ Injury by inducing autophagy and activating class III deacetylase Sirtuin family members (SIRT1-7). However, whether melatonin attenuates small-Intestine Injury along with the precise underlying mechanism remain to be elucidated. To investigate this, we employed cecal ligation and puncture (CLP)- or endotoxemia-induced sepsis mouse models and confirmed that melatonin treatment significantly prolonged the survival time of mice and ameliorated multiple-organ Injury (lung/liver/kidney/small Intestine) following sepsis. Melatonin partially protected the intestinal barrier function and restored SIRT1 and SIRT3 activity/protein expression in the small Intestine. Mechanistically, melatonin treatment enhanced NF-κB deacetylation and subsequently reduced the inflammatory response and decreased the TNF-α, IL-6, and IL-10 serum levels; these effects were abolished by SIRT1 inhibition with the selective blocker, Ex527. Correspondingly, melatonin treatment triggered SOD2 deacetylation and increased SOD2 activity and subsequently reduced oxidative stress; this amelioration of oxidative stress by melatonin was blocked by the SIRT3-selective inhibitor, 3-TYP, and was independent of SIRT1. We confirmed this mechanistic effect in a CLP-induced sepsis model of intestinal SIRT3 conditional-knockout mice, and found that melatonin preserved mitochondrial function and induced autophagy of small-Intestine epithelial cells; these effects were dependent on SIRT3 activation. This study has shown, to the best of our knowledge, for the first time that melatonin alleviates sepsis-induced small-Intestine Injury, at least partially, by upregulating SIRT3-mediated oxidative-stress inhibition, mitochondrial-function protection, and autophagy induction.
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Polydatin Alleviates Small Intestine Injury during Hemorrhagic Shock as a SIRT1 Activator
Oxidative medicine and cellular longevity, 2015Co-Authors: Zhenhua Zeng, Zhongqing Chen, Rui Song, Hong Yang, Ke-seng ZhaoAbstract:Objective. To evaluate the role of SIRT1 in small Intestine damage following severe hemorrhagic shock and to investigate whether polydatin (PD) can activate SIRT1 in shock treatment. Research Design and Methods. The severe hemorrhagic shock model was reproduced in Sprague Dawley rats. Main Outcome Measures. Two hours after drug administration, half of the rats were assessed for survival time evaluation and the remainder were used for small intestinal tissue sample collection. Results. Bleeding and swelling appeared in the small Intestine with epithelial apoptosis and gut barrier disturbance during hemorrhagic shock. SIRT1 activity and PGC-1α protein expression of the small Intestine were decreased, which led to an increase in acetylated SOD2 and decreases in the expression and activity of SOD2, resulting in severe oxidative stress. The decreased SIRT1 activity and expression were partially restored in the PD administration group, which showed reduced Intestine Injury and longer survival time. Notably, the effect of PD was abolished after the addition of Ex527, a selective inhibitor of SIRT1. Conclusions. The results collectively suggest a role for the SIRT1-PGC-1α-SOD2 axis in small Intestine Injury following severe hemorrhagic shock and that PD is an effective SIRT1 activator for the shock treatment.
Shuo Zhang - One of the best experts on this subject based on the ideXlab platform.
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Pure Total Flavonoids From Citrus Protect Against Nonsteroidal Anti-inflammatory Drug-Induced Small Intestine Injury by Promoting Autophagy in vivo and in vitro
Frontiers in Pharmacology, 2021Co-Authors: Shanshan Chen, Jianping Jiang, Guanqun Chao, Xiaojie Hong, Haijun Cao, Shuo ZhangAbstract:Small Intestine Injury is an adverse effect of non-steroidal anti-inflammatory drugs (NSAIDs) that urgently needs to be addressed for their safe application. Although pure total flavonoids from citrus (PTFC) have been marketed for the treatment of digestive diseases, their effects on small Intestine Injury and the underlying mechanism of action remain unknown. This study aimed to investigate the potential role of autophagy in the mechanism of NSAID (diclofenac)-induced intestinal Injury in vivo and in vitro and to demonstrate the protective effects of PTFC against NSAID-induced small Intestine disease. The results of qRT-PCR, western blotting, and immunohistochemistry showed that the expression levels of autophagy-related 5 (Atg5), light chain 3 (LC3)-II, and tight junction (TJ) proteins ZO-1, claudin-1, and occludin were decreased in rats with NSAID-induced small Intestine Injury and diclofenac-treated IEC-6 cells compared with the control groups. In the PTFC group, Atg5 and LC3-II expression, TJ protein expression, and the LC3-II/LC3-I ratio increased. Furthermore, the mechanism by which PTFC promotes autophagy in vivo and in vitro was evaluated by western blotting. Expression levels of p-PI3K and p-Akt increased in the Intestine disease-induced rat model group compared with the control, but decreased in the PTFC group. Autophagy of IEC-6 cells was upregulated after treatment with a PI3K inhibitor, and the upregulation was significantly more after PTFC treatment, suggesting PTFC promoted autophagy through the PI3K/Akt signaling pathway. In conclusion, PTFC protected intestinal barrier integrity by promoting autophagy, which demonstrates its potential as a therapeutic candidate for NSAID-induced small Intestine Injury.
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Protective effect of naringin on small Intestine Injury in NSAIDs related enteropathy by regulating ghrelin/GHS-R signaling pathway
Life sciences, 2020Co-Authors: Guanqun Chao, Jian Dai, Shuo ZhangAbstract:Abstract Objective To investigate the mechanism of Ghrelin/GHS-R signaling pathway in small Intestine Injury induced by NSAIDs related enteropathy. To clarify the mechanism network of intestinal mucosal repair with naringin as a new therapeutic method. Methods Naringin was used as the intervention method, observed the damage of small intestinal mucosa and detected the expression of ghrelin, GHS-R, leptin and TNF-α by electron microscopy, HE staining and immunohistochemistry. Results Compared with the control group, the weight of rats in the model group decreased, the thickness of intestinal mucosa became thinner, the structure of intestinal mucosa changed, the expression of ghrelin, GHS-R and leptin decreased, the expression of TNF-α increased. Compared with the model group, the intestinal mucosa of the treatment group was repaired, the expression of ghrelin, GHS-R and leptin was increased, and the expression TNF-α was decreased. Conclusion The mechanism of intestinal mucosal damage in patients with NSAIDs related enteropathy may be related to the decreased expression of ghrelin, GHS-R and leptin, and promotion of TNF-α secretion. Naringin can effectively promote the secretion of ghrelin and leptin, the expression of GSH-R, and inhibit the release of TNF-α, so as to repair intestinal mucosa naringin will become a new method to treat and prevent NSAIDs related intestinal diseases.
Jennifer Gawlik - One of the best experts on this subject based on the ideXlab platform.
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AWD regulates timed activation of BMP signaling in intestinal stem cells to maintain tissue homeostasis
Nature Communications, 2019Co-Authors: Xiaoyu Tracy Cai, Abu Safyan, Jennifer Gawlik, George Pyrowolakis, Hongjie Li, Heinrich JasperAbstract:Precise control of stem cell (SC) proliferation ensures tissue homeostasis. In the Drosophila Intestine, Injury-induced regeneration involves initial activation of intestinal SC (ISC) proliferation and subsequent return to quiescence. These two phases of the regenerative response are controlled by differential availability of the BMP type I receptor Thickveins (Tkv), yet how its expression is dynamically regulated remains unclear. Here we show that during homeostasis, the E3 ubiquitin ligase Highwire and the ubiquitin-proteasome system maintain low Tkv protein expression. After ISC activation, Tkv is stabilized by proteasome inhibition and undergoes endocytosis due to the induction of the nucleoside diphosphate kinase Abnormal Wing Disc (AWD). Tkv internalization is required for the activation of the Smad protein Mad, and for the return to quiescence after a regenerative episode. Our data provide insight into the mechanisms ensuring tissue homeostasis by dynamic control of somatic stem cell activity.Regeneration after Injury in the Drosophila Intestine involves early activation of intestinal stem cells (ISCs) and subsequent return to quiescence. Here the authors show that return to quiescence by ISCs involves BMP Type I receptor Tkv protein stabilization along with AWD mediated internalization into endocytic vesicles.
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AWD regulates timed activation of BMP signaling in intestinal stem cells to maintain tissue homeostasis.
Nature communications, 2019Co-Authors: Xiaoyu Tracy Cai, Abu Safyan, Jennifer Gawlik, George Pyrowolakis, Heinrich JasperAbstract:Precise control of stem cell (SC) proliferation ensures tissue homeostasis. In the Drosophila Intestine, Injury-induced regeneration involves initial activation of intestinal SC (ISC) proliferation and subsequent return to quiescence. These two phases of the regenerative response are controlled by differential availability of the BMP type I receptor Thickveins (Tkv), yet how its expression is dynamically regulated remains unclear. Here we show that during homeostasis, the E3 ubiquitin ligase Highwire and the ubiquitin-proteasome system maintain low Tkv protein expression. After ISC activation, Tkv is stabilized by proteasome inhibition and undergoes endocytosis due to the induction of the nucleoside diphosphate kinase Abnormal Wing Disc (AWD). Tkv internalization is required for the activation of the Smad protein Mad, and for the return to quiescence after a regenerative episode. Our data provide insight into the mechanisms ensuring tissue homeostasis by dynamic control of somatic stem cell activity.
