Esophageal variceal bleeding(EVB)is one of the most common and severe complications related to portal hypertension(PH).Despite marked advances in its management during the last three decades,EVB is still associated wi...Esophageal variceal bleeding(EVB)is one of the most common and severe complications related to portal hypertension(PH).Despite marked advances in its management during the last three decades,EVB is still associated with significant morbidity and mortality.The risk of first EVB is related to the severity of both PH and liver disease,and to the size and endoscopic appearance of esophageal varices.Indeed,hepatic venous pressure gradient(HVPG)and esophagogastroduodenoscopy(EGD)are currently recognized as the“gold standard”and the diagnostic reference standard for the prediction of EVB,respectively.However,HVPG is an invasive,expensive,and technically complex procedure,not widely available in clinical practice,whereas EGD is mainly limited by its invasive nature.In this scenario,computed tomography(CT)has been recently proposed as a promising modality for the non-invasive prediction of EVB.Although CT is only a diagnostic modality,thus being not capable of supplanting EGD or HVPG in providing therapeutic and physiological data,it could potentially assist liver disease scores,HVPG,and EGD in a more effective prediction of EVB.However,to date,evidence concerning the role of CT in this setting is still lacking.Our review aimed to summarize and discuss the current evidence concerning the role of CT in predicting the risk of EVB.展开更多
Non-variceal upper gastrointestinal bleeding(NVUGIB)is a common gastroenterological emergency associated with significant morbidity and mortality.Gastroenterologists and other involved clinicians are generally assiste...Non-variceal upper gastrointestinal bleeding(NVUGIB)is a common gastroenterological emergency associated with significant morbidity and mortality.Gastroenterologists and other involved clinicians are generally assisted by international guidelines in its management.However,NVUGIB due to peptic ulcer disease only is mainly addressed by current guidelines,with upper gastrointestinal endoscopy being recommended as the gold standard modality for both diagnosis and treatment.Conversely,the management of rare and extraordinary rare causes of NVUGIB is not covered by current guidelines.Given they are frequently lifethreatening conditions,all the involved clinicians,that is emergency physicians,diagnostic and interventional radiologists,surgeons,in addition obviously to gastroenterologists,should be aware of and familiar with their management.Indeed,they typically require a prompt diagnosis and treatment,engaging a dedicated,patient-tailored,multidisciplinary team approach.The aim of our review was to extensively summarize the current evidence with regard to the management of rare and extraordinary rare causes of NVUGIB.展开更多
Exposed endoscopic full-thickness resection(EFTR)without laparoscopic assistance is a minimally invasive natural orifice transluminal endoscopic surgery technique that is emerging as a promising effective and safe alt...Exposed endoscopic full-thickness resection(EFTR)without laparoscopic assistance is a minimally invasive natural orifice transluminal endoscopic surgery technique that is emerging as a promising effective and safe alternative to surgery for the treatment of muscularis propria-originating gastric submucosal tumors.To date,various techniques have been used for the closure of the transmural postEFTR defect,mainly consisting in clip-and endoloop-assisted closure methods.However,the recent advent of dedicated tools capable of providing full-thickness defect suture could further improve the efficacy and safety of the exposed EFTR procedure.The aim of our review was to evaluate the efficacy and safety of the different closure methods adopted in gastric-exposed EFTR without laparoscopic assistance,also considering the recent advent of flexible endoscopic suturing.展开更多
AIM: To present a case series of MRCP-guided endoscopic biliary stent placement, performed entirely without contrast injection. METHODS: Contrast-free endoscopic biliary drainage was attempted in 20 patients with mali...AIM: To present a case series of MRCP-guided endoscopic biliary stent placement, performed entirely without contrast injection. METHODS: Contrast-free endoscopic biliary drainage was attempted in 20 patients with malignant obstruction, unsuitable for resection on the basis of tumor extent or medical illness. MRCP images were used to confirm the diagnosis of tumor, to exclude other biliary diseases and to demonstrate the stenoses as well as dilation of proximal liver segments. The procedure was carried out under conscious sedation. Patients were placed in the left lateral decubitus position. The endoscope was inserted, the papilla identified and cannulated by a papillotome. A guide wire was inserted and guided deeply into the biliary tree, above the stenosis, by fluoroscopy. A papillotomy approximately 1 cm. long was performed and the papillotome was exchanged with a guiding-catheter. A 10 Fr, Amsterdam-type plastic stent, 7 to 15 cm long, was finally inserted over the guide wire/ guiding catheter by a pusher tube system. RESULTS: Successful stent insertion was achieved in all patients. There were no major complications. Successful drainage, with substantial reduction in bilirubin levels, was achieved in all patients. CONCLUSION: This new method of contrast-free endoscopic stenting in malignant biliary obstruction is a safe and effective method of palliation. However, a larger, randomized study comparing this new approach with the standard procedure is needed to confirm the findings of the present study.展开更多
AIM: To evaluate cortisolemia by using conventional electrochemiluminescence immunoassay(ECLIA) method compared to liquid chromatography-tandem mass spectrometry(LC-MS/MS) method in active ulcerative colitis(UC) patie...AIM: To evaluate cortisolemia by using conventional electrochemiluminescence immunoassay(ECLIA) method compared to liquid chromatography-tandem mass spectrometry(LC-MS/MS) method in active ulcerative colitis(UC) patients treated with oral prednisone(PD). METHODS: Twenty patients(12 males) with acute relapse of UC started oral PD at a dose of 40 mg once a day, tapered of 10 mg every 2 wk. When a stable 2-wk daily dose of 30 mg was reached, blood samples for cortisol levels' measurement were drawn in the morning in fasting conditions to determine circulating cortisol by LC-MS/MS and ECLIA assay. RESULTS: Median interquartile range cortisolemia with ECLIA and LC-MS/MS method was 54.1(185.8) nmol/L and 32.1(124.0) nmol/L, respectively(P < 0.001). The within-patient median differences between the two methods was 23.2(40.6) nmol/L, with higher cortisol levels for the ECLIA method. The estimated geomet-ric mean ratio between methods was 1.85(95%CI: 2.39-1.43) considering all data or 1.58(95%CI: 2.30-1.09) considering only data above the limit of quantification(n = 12). The 95%CIs of the geometric mean ratio between methods confirm a statistically significant difference.CONCLUSION: Blood cortisol levels detected with ECLIA method seems to be higher than the ones measured by LC-MS/MS, indicating a possible overestimation of them in patients treated with PD. Therefore, the cortisol suppression in patients under treatment with oral PD should not be measured using ECLIA method.展开更多
BACKGROUND Fistula between the esophagus and bronchial artery is an extremely rare and potentially life-threatening cause of acute upper gastrointestinal bleeding.Here,we report a case of fistula formation between the...BACKGROUND Fistula between the esophagus and bronchial artery is an extremely rare and potentially life-threatening cause of acute upper gastrointestinal bleeding.Here,we report a case of fistula formation between the esophagus and a nonaneurysmal right bronchial artery(RBA).CASE SUMMARY An 80-year-old woman with previous left pneumonectomy and recent placement of an uncovered self-expandable metallic stent for esophageal adenocarcinoma was admitted due to hematemesis.Emergent computed tomography showed indirect signs of fistulization between the esophagus and a nonaneurysmal RBA,in the absence of active bleeding.Endoscopy revealed the esophageal stent correctly placed and a moderate amount of red blood within the stomach,in the absence of active bleeding or tumor ingrowth/overgrowth.After prompt multidisciplinary evaluation,a step-up approach was planned.The bleeding was successfully controlled by esophageal restenting followed by RBA embolization.No signs of rebleeding were observed and the patient was discharged home with stable hemoglobin level on postoperative day 7.CONCLUSION This was a previously unreported case of an esophageal RBA fistula successfully managed by esophageal restenting followed by RBA embolization.展开更多
BACKGROUND Gastric submucosal arterial collaterals(GSAC)secondary to splenic artery occlusion is an extraordinary rare and potentially life-threatening cause of acute upper gastrointestinal bleeding.Here,we report a c...BACKGROUND Gastric submucosal arterial collaterals(GSAC)secondary to splenic artery occlusion is an extraordinary rare and potentially life-threatening cause of acute upper gastrointestinal bleeding.Here,we report a case of massive bleeding from GSAC successfully treated by means of a multidisciplinary minimally invasive approach.CASE SUMMARY A 60-year-old non-cirrhotic gentleman with a history of arterial hypertension was admitted due to hematemesis.Emergent esophagogastroduodenoscopy revealed pulsating and tortuous varicose shaped submucosal vessels in the gastric fundus along with a small erosion overlying one of the vessels.In order to characterize the fundic lesion,pre-operative emergent computed tomography-angiography was performed showing splenic artery thrombosis(SAT)and tortuous arterial structures arising from the left gastric artery and the left gastroepiploic artery in the gastric fundus.GSAC was successfully treated by means of a minimally invasive step-up approach consisting in endoscopic clipping followed by transcatheter arterial embolization(TAE).CONCLUSION This was a previously unreported case of bleeding GSAC secondary to SAT successfully managed by means of a multidisciplinary minimally invasive approach consisting in endoscopic clipping for the luminal bleeding control followed by elective TAE for the definitive treatment.展开更多
Non-variceal upper gastrointestinal bleeding(NVUGIB)is a common gastroenterological emergency associated with significant morbidity and mortality.Upper gastrointestinal endoscopy is currently recommended as the gold s...Non-variceal upper gastrointestinal bleeding(NVUGIB)is a common gastroenterological emergency associated with significant morbidity and mortality.Upper gastrointestinal endoscopy is currently recommended as the gold standard modality for both diagnosis and treatment,with computed tomography traditionally playing a limited role in the diagnosis of acute NVUGIB.Following the introduction of multidetector computed tomography(MDCT),this modality is emerging as a promising tool in the diagnosis of NVUGIB.However,to date,evidence concerning the role of MDCT in the NVUGIB diagnosis is still lacking.The aim of our study was to review the current evidence concerning the role of MDCT in the diagnosis of acute NVUGIB.展开更多
Exposed endoscopic full-thickness resection(EFTR),with or without laparoscopic assistance,is an emergent natural orifice transluminal endoscopic surgery technique with promising safety and efficacy for the management ...Exposed endoscopic full-thickness resection(EFTR),with or without laparoscopic assistance,is an emergent natural orifice transluminal endoscopic surgery technique with promising safety and efficacy for the management of gastrointestinal submucosal tumors(SMTs)arising from the muscularis propria(MP),especially of the gastric wall.To date,evidence concerning duodenal exposed EFTR is lacking,mainly due to both the technical difficulty involved because of the special duodenal anatomy and concerns about safety and effectiveness of transmural wall defect closure.However,given the non-negligible morbidity and mortality associated with duodenal surgery,the recent availability of dedicated endoscopic tools for tissue-approximation capable to realize full-thickness defect closure could help in promoting the adoption of this endosurgical technique among referral centers.The aim of our study was to review the current evidence concerning exposed EFTR with or without laparoscopic assistance for the treatment of MP-arising duodenal SMTs.展开更多
The use of an air jet to clean the products during the manufacturing is usual in an industrial environment. In this paper the problem of the removal, from the inner of the tube, of the waste arising from the cutting o...The use of an air jet to clean the products during the manufacturing is usual in an industrial environment. In this paper the problem of the removal, from the inner of the tube, of the waste arising from the cutting operation by means of an air blowing system is analysed. In order to obtain indications about the real importance of the involved parameters and their effects, a numerical procedure, based on CFD analysis trough the code STAR CCM+, has been settled. The effects of the different parameters were highlighted. The results are congruent with the experience, indicating that the adopted solution is not suitable for the small tubes. Therefore, a different blowing solution is investigated, with the object to improve the cleaning capabilities of the system. The results for the new blowing solution provide a significant improvement of the capability to remove the waste arising from the cutting operation can be expected.展开更多
The dual role of macrophages in the healing process depends on macrophage ability to polarize into phenotypes that can propagate inflammation or exert anti-inflammatory and tissue-remodeling functions.Controlling scaf...The dual role of macrophages in the healing process depends on macrophage ability to polarize into phenotypes that can propagate inflammation or exert anti-inflammatory and tissue-remodeling functions.Controlling scaf-fold geometry has been proposed as a strategy to influence macrophage behavior and favor the positive host response to implants.Here,we fabricated Polycaprolactone(PCL)scaffolds by Melt Electrowriting(MEW)to investigate the ability of scaffold architecture to modulate macrophage polarization.Primary human macrophages unpolarized(M0)or polarized into M1,M2a,and M2c phenotypes were cultured on PCL films and MEW scaffolds with pore geometries(square,triangle,and rhombus grid)characterized by different angles.M0,M2a,and M2c macrophages wrapped along the fibers,while M1 macrophages formed clusters with rounded cells.Cell bridges were formed only for angles up to 90◦.No relevant differences were found among PCL films and 3D scaffolds in terms of surface markers.CD206 and CD163 were highly expressed by M2a and M2c macrophages,with M2a macrophages presenting also high levels of CD86.M1 macrophages expressed moderate levels of all markers.The rhombus architecture promoted an increased release by M2a macrophages of IL10,IL13,and sCD163 compared to PCL films.The proangiogenic factor IL18 was also upregulated by the rhombus configuration in M0 and M2a macrophages compared to PCL films.The interesting findings obtained for the rhombus architecture represent a starting point for the design of scaffolds able to modulate macrophage phenotype,prompting investigations addressed to verify their ability to facilitate the healing process in vivo.展开更多
Physical inactivity is the fourth leading cause of mortality worldwide;regardless of geographic location and income,it is a contributing risk factor to the other three causes.Physical activity is really a drug,a poly-...Physical inactivity is the fourth leading cause of mortality worldwide;regardless of geographic location and income,it is a contributing risk factor to the other three causes.Physical activity is really a drug,a poly-pill;its“regular use”can reduce this risk throughout the activation of a plethora of responses in virtually all the body tissues.The beneficial effects of physi-cal activity on cardiovascular function and hemodynamics are mainly mediated by skeletal muscle,adipose tissue and the immune system via the usage,delivery and distribution of metabolic substrates and improvement in inflammatory status.There is emerging evidence for exercise-dependent changes in bone metabolism as well;with improved bone quality,reduced fracture risk and increased bone endocrine function,the last of which modulates energy metabolism through its effects on pancreatic islet cells,skeletal muscle and adipose tissue.Bone endocrine function relies on the integration of biomechani-cal stimuli and endocrine signals from other organs and tissues.Here I review current concepts about exercise-dependent modulation of bone endocrine function and its beneficial effects on whole-body metabolism.Several molecular mechanisms have been identified that support this exercise-stimulated bone-mediated metabolic effect and,among these,Wnt signaling,fibroblast growth factor-23,bone morphogenic protein-7,osteocalcin,RANK/RANKL/OPG axis,and lipocalin-2 gave the largest evidences.In conclusion,beside the controversies surrounding technical aspects of the exercise,the efficacy of physi-cal activity in preventing/treating metabolic and inflammatory dysfunctions also passes throughout the bone.展开更多
文摘Esophageal variceal bleeding(EVB)is one of the most common and severe complications related to portal hypertension(PH).Despite marked advances in its management during the last three decades,EVB is still associated with significant morbidity and mortality.The risk of first EVB is related to the severity of both PH and liver disease,and to the size and endoscopic appearance of esophageal varices.Indeed,hepatic venous pressure gradient(HVPG)and esophagogastroduodenoscopy(EGD)are currently recognized as the“gold standard”and the diagnostic reference standard for the prediction of EVB,respectively.However,HVPG is an invasive,expensive,and technically complex procedure,not widely available in clinical practice,whereas EGD is mainly limited by its invasive nature.In this scenario,computed tomography(CT)has been recently proposed as a promising modality for the non-invasive prediction of EVB.Although CT is only a diagnostic modality,thus being not capable of supplanting EGD or HVPG in providing therapeutic and physiological data,it could potentially assist liver disease scores,HVPG,and EGD in a more effective prediction of EVB.However,to date,evidence concerning the role of CT in this setting is still lacking.Our review aimed to summarize and discuss the current evidence concerning the role of CT in predicting the risk of EVB.
文摘Non-variceal upper gastrointestinal bleeding(NVUGIB)is a common gastroenterological emergency associated with significant morbidity and mortality.Gastroenterologists and other involved clinicians are generally assisted by international guidelines in its management.However,NVUGIB due to peptic ulcer disease only is mainly addressed by current guidelines,with upper gastrointestinal endoscopy being recommended as the gold standard modality for both diagnosis and treatment.Conversely,the management of rare and extraordinary rare causes of NVUGIB is not covered by current guidelines.Given they are frequently lifethreatening conditions,all the involved clinicians,that is emergency physicians,diagnostic and interventional radiologists,surgeons,in addition obviously to gastroenterologists,should be aware of and familiar with their management.Indeed,they typically require a prompt diagnosis and treatment,engaging a dedicated,patient-tailored,multidisciplinary team approach.The aim of our review was to extensively summarize the current evidence with regard to the management of rare and extraordinary rare causes of NVUGIB.
文摘Exposed endoscopic full-thickness resection(EFTR)without laparoscopic assistance is a minimally invasive natural orifice transluminal endoscopic surgery technique that is emerging as a promising effective and safe alternative to surgery for the treatment of muscularis propria-originating gastric submucosal tumors.To date,various techniques have been used for the closure of the transmural postEFTR defect,mainly consisting in clip-and endoloop-assisted closure methods.However,the recent advent of dedicated tools capable of providing full-thickness defect suture could further improve the efficacy and safety of the exposed EFTR procedure.The aim of our review was to evaluate the efficacy and safety of the different closure methods adopted in gastric-exposed EFTR without laparoscopic assistance,also considering the recent advent of flexible endoscopic suturing.
文摘AIM: To present a case series of MRCP-guided endoscopic biliary stent placement, performed entirely without contrast injection. METHODS: Contrast-free endoscopic biliary drainage was attempted in 20 patients with malignant obstruction, unsuitable for resection on the basis of tumor extent or medical illness. MRCP images were used to confirm the diagnosis of tumor, to exclude other biliary diseases and to demonstrate the stenoses as well as dilation of proximal liver segments. The procedure was carried out under conscious sedation. Patients were placed in the left lateral decubitus position. The endoscope was inserted, the papilla identified and cannulated by a papillotome. A guide wire was inserted and guided deeply into the biliary tree, above the stenosis, by fluoroscopy. A papillotomy approximately 1 cm. long was performed and the papillotome was exchanged with a guiding-catheter. A 10 Fr, Amsterdam-type plastic stent, 7 to 15 cm long, was finally inserted over the guide wire/ guiding catheter by a pusher tube system. RESULTS: Successful stent insertion was achieved in all patients. There were no major complications. Successful drainage, with substantial reduction in bilirubin levels, was achieved in all patients. CONCLUSION: This new method of contrast-free endoscopic stenting in malignant biliary obstruction is a safe and effective method of palliation. However, a larger, randomized study comparing this new approach with the standard procedure is needed to confirm the findings of the present study.
文摘AIM: To evaluate cortisolemia by using conventional electrochemiluminescence immunoassay(ECLIA) method compared to liquid chromatography-tandem mass spectrometry(LC-MS/MS) method in active ulcerative colitis(UC) patients treated with oral prednisone(PD). METHODS: Twenty patients(12 males) with acute relapse of UC started oral PD at a dose of 40 mg once a day, tapered of 10 mg every 2 wk. When a stable 2-wk daily dose of 30 mg was reached, blood samples for cortisol levels' measurement were drawn in the morning in fasting conditions to determine circulating cortisol by LC-MS/MS and ECLIA assay. RESULTS: Median interquartile range cortisolemia with ECLIA and LC-MS/MS method was 54.1(185.8) nmol/L and 32.1(124.0) nmol/L, respectively(P < 0.001). The within-patient median differences between the two methods was 23.2(40.6) nmol/L, with higher cortisol levels for the ECLIA method. The estimated geomet-ric mean ratio between methods was 1.85(95%CI: 2.39-1.43) considering all data or 1.58(95%CI: 2.30-1.09) considering only data above the limit of quantification(n = 12). The 95%CIs of the geometric mean ratio between methods confirm a statistically significant difference.CONCLUSION: Blood cortisol levels detected with ECLIA method seems to be higher than the ones measured by LC-MS/MS, indicating a possible overestimation of them in patients treated with PD. Therefore, the cortisol suppression in patients under treatment with oral PD should not be measured using ECLIA method.
文摘BACKGROUND Fistula between the esophagus and bronchial artery is an extremely rare and potentially life-threatening cause of acute upper gastrointestinal bleeding.Here,we report a case of fistula formation between the esophagus and a nonaneurysmal right bronchial artery(RBA).CASE SUMMARY An 80-year-old woman with previous left pneumonectomy and recent placement of an uncovered self-expandable metallic stent for esophageal adenocarcinoma was admitted due to hematemesis.Emergent computed tomography showed indirect signs of fistulization between the esophagus and a nonaneurysmal RBA,in the absence of active bleeding.Endoscopy revealed the esophageal stent correctly placed and a moderate amount of red blood within the stomach,in the absence of active bleeding or tumor ingrowth/overgrowth.After prompt multidisciplinary evaluation,a step-up approach was planned.The bleeding was successfully controlled by esophageal restenting followed by RBA embolization.No signs of rebleeding were observed and the patient was discharged home with stable hemoglobin level on postoperative day 7.CONCLUSION This was a previously unreported case of an esophageal RBA fistula successfully managed by esophageal restenting followed by RBA embolization.
文摘BACKGROUND Gastric submucosal arterial collaterals(GSAC)secondary to splenic artery occlusion is an extraordinary rare and potentially life-threatening cause of acute upper gastrointestinal bleeding.Here,we report a case of massive bleeding from GSAC successfully treated by means of a multidisciplinary minimally invasive approach.CASE SUMMARY A 60-year-old non-cirrhotic gentleman with a history of arterial hypertension was admitted due to hematemesis.Emergent esophagogastroduodenoscopy revealed pulsating and tortuous varicose shaped submucosal vessels in the gastric fundus along with a small erosion overlying one of the vessels.In order to characterize the fundic lesion,pre-operative emergent computed tomography-angiography was performed showing splenic artery thrombosis(SAT)and tortuous arterial structures arising from the left gastric artery and the left gastroepiploic artery in the gastric fundus.GSAC was successfully treated by means of a minimally invasive step-up approach consisting in endoscopic clipping followed by transcatheter arterial embolization(TAE).CONCLUSION This was a previously unreported case of bleeding GSAC secondary to SAT successfully managed by means of a multidisciplinary minimally invasive approach consisting in endoscopic clipping for the luminal bleeding control followed by elective TAE for the definitive treatment.
文摘Non-variceal upper gastrointestinal bleeding(NVUGIB)is a common gastroenterological emergency associated with significant morbidity and mortality.Upper gastrointestinal endoscopy is currently recommended as the gold standard modality for both diagnosis and treatment,with computed tomography traditionally playing a limited role in the diagnosis of acute NVUGIB.Following the introduction of multidetector computed tomography(MDCT),this modality is emerging as a promising tool in the diagnosis of NVUGIB.However,to date,evidence concerning the role of MDCT in the NVUGIB diagnosis is still lacking.The aim of our study was to review the current evidence concerning the role of MDCT in the diagnosis of acute NVUGIB.
文摘Exposed endoscopic full-thickness resection(EFTR),with or without laparoscopic assistance,is an emergent natural orifice transluminal endoscopic surgery technique with promising safety and efficacy for the management of gastrointestinal submucosal tumors(SMTs)arising from the muscularis propria(MP),especially of the gastric wall.To date,evidence concerning duodenal exposed EFTR is lacking,mainly due to both the technical difficulty involved because of the special duodenal anatomy and concerns about safety and effectiveness of transmural wall defect closure.However,given the non-negligible morbidity and mortality associated with duodenal surgery,the recent availability of dedicated endoscopic tools for tissue-approximation capable to realize full-thickness defect closure could help in promoting the adoption of this endosurgical technique among referral centers.The aim of our study was to review the current evidence concerning exposed EFTR with or without laparoscopic assistance for the treatment of MP-arising duodenal SMTs.
文摘The use of an air jet to clean the products during the manufacturing is usual in an industrial environment. In this paper the problem of the removal, from the inner of the tube, of the waste arising from the cutting operation by means of an air blowing system is analysed. In order to obtain indications about the real importance of the involved parameters and their effects, a numerical procedure, based on CFD analysis trough the code STAR CCM+, has been settled. The effects of the different parameters were highlighted. The results are congruent with the experience, indicating that the adopted solution is not suitable for the small tubes. Therefore, a different blowing solution is investigated, with the object to improve the cleaning capabilities of the system. The results for the new blowing solution provide a significant improvement of the capability to remove the waste arising from the cutting operation can be expected.
基金Italian Ministry of Health(Ricerca Corrente)Interreg NWE BONE Project(NWE497),and the project NeuroBeta with project number 15900 of the VENI research program which is financed by the Dutch Research Council(NWO).
文摘The dual role of macrophages in the healing process depends on macrophage ability to polarize into phenotypes that can propagate inflammation or exert anti-inflammatory and tissue-remodeling functions.Controlling scaf-fold geometry has been proposed as a strategy to influence macrophage behavior and favor the positive host response to implants.Here,we fabricated Polycaprolactone(PCL)scaffolds by Melt Electrowriting(MEW)to investigate the ability of scaffold architecture to modulate macrophage polarization.Primary human macrophages unpolarized(M0)or polarized into M1,M2a,and M2c phenotypes were cultured on PCL films and MEW scaffolds with pore geometries(square,triangle,and rhombus grid)characterized by different angles.M0,M2a,and M2c macrophages wrapped along the fibers,while M1 macrophages formed clusters with rounded cells.Cell bridges were formed only for angles up to 90◦.No relevant differences were found among PCL films and 3D scaffolds in terms of surface markers.CD206 and CD163 were highly expressed by M2a and M2c macrophages,with M2a macrophages presenting also high levels of CD86.M1 macrophages expressed moderate levels of all markers.The rhombus architecture promoted an increased release by M2a macrophages of IL10,IL13,and sCD163 compared to PCL films.The proangiogenic factor IL18 was also upregulated by the rhombus configuration in M0 and M2a macrophages compared to PCL films.The interesting findings obtained for the rhombus architecture represent a starting point for the design of scaffolds able to modulate macrophage phenotype,prompting investigations addressed to verify their ability to facilitate the healing process in vivo.
文摘Physical inactivity is the fourth leading cause of mortality worldwide;regardless of geographic location and income,it is a contributing risk factor to the other three causes.Physical activity is really a drug,a poly-pill;its“regular use”can reduce this risk throughout the activation of a plethora of responses in virtually all the body tissues.The beneficial effects of physi-cal activity on cardiovascular function and hemodynamics are mainly mediated by skeletal muscle,adipose tissue and the immune system via the usage,delivery and distribution of metabolic substrates and improvement in inflammatory status.There is emerging evidence for exercise-dependent changes in bone metabolism as well;with improved bone quality,reduced fracture risk and increased bone endocrine function,the last of which modulates energy metabolism through its effects on pancreatic islet cells,skeletal muscle and adipose tissue.Bone endocrine function relies on the integration of biomechani-cal stimuli and endocrine signals from other organs and tissues.Here I review current concepts about exercise-dependent modulation of bone endocrine function and its beneficial effects on whole-body metabolism.Several molecular mechanisms have been identified that support this exercise-stimulated bone-mediated metabolic effect and,among these,Wnt signaling,fibroblast growth factor-23,bone morphogenic protein-7,osteocalcin,RANK/RANKL/OPG axis,and lipocalin-2 gave the largest evidences.In conclusion,beside the controversies surrounding technical aspects of the exercise,the efficacy of physi-cal activity in preventing/treating metabolic and inflammatory dysfunctions also passes throughout the bone.
