Lung diseases associated with alveoli,such as acute respiratory distress syndrome,have posed a long-term threat to human health.However,an in vitro model capable of simulating different deformations of the alveoli and...Lung diseases associated with alveoli,such as acute respiratory distress syndrome,have posed a long-term threat to human health.However,an in vitro model capable of simulating different deformations of the alveoli and a suitable material for mimicking basement membrane are currently lacking.Here,we present an innovative biomimetic controllable strain membrane(BCSM)at an air–liquid interface(ALI)to reconstruct alveolar respiration.The BCSM consists of a high-precision three-dimensional printing melt-electrowritten polycaprolactone(PCL)mesh,coated with a hydrogel substrate—to simulate the important functions(such as stiffness,porosity,wettability,and ALI)of alveolar microenvironments,and seeded pulmonary epithelial cells and vascular endothelial cells on either side,respectively.Inspired by papercutting,the BCSM was fabricated in the plane while it operated in three dimensions.A series of the topological structure of the BCSM was designed to control various local-area strain,mimicking alveolar varied deformation.Lopinavir/ritonavir could reduce Lamin A expression under over-stretch condition,which might be effective in preventing ventilator-induced lung injury.The biomimetic lung-unit model with BCSM has broader application prospects in alveoli-related research in the future,such as in drug toxicology and metabolism.展开更多
Acute myocardial infarction （AMI） is the leading cause of death and disability worldwide. Timely reperfusion is the standard of care and results in decreased infarct size, improving patient survival and prognosis. H...Acute myocardial infarction （AMI） is the leading cause of death and disability worldwide. Timely reperfusion is the standard of care and results in decreased infarct size, improving patient survival and prognosis. However, 25% of patients proceed to develop heart failure （HF） after myocardial infarction （MI） and 50% of these will die within five years. Since the size of the infarct is the major predictor of the outcome, including the development of HF, therapies to improve myocardial salvage have great potential. Over the past three decades, a number of stimuli have been discovered that activate endogenous cardioprotective pathways. In ischemic preconditioning （IPC） and ischemic postconditioning, ischemia within the heart initiates the protection. Brief reversible episodes of ischemia in vascular beds remote from the heart can also trigger cardioprotection when applied before, during, or immediately after myocardial ischemia-- known as remote ischemic pre-, per-, and post-conditioning, respectively. Although the mechanism of remote ischemic preconditioning （RIPC） has not yet been fully elucidated, many mechanistic components are shared with IPC. The discovery of RIPC led to research into the use of remote non-ischemic stimuli including nerve stimulation （spinal and vagal）, and electroacupuncture （EA）. We discovered and, with others, have elucidated mechanistic aspects of a non- ischemic phenomenon we termed remote preconditioning of trauma （RPCT）. RPCT operates via neural stimulation of skin sensory nerves and has similarities and differences to nerve stimulation and EA conducted at acupoints. We show herein that RPCT can be mimicked using electrical stimulation of the abdominal midline （EA-like treatment） and that this modality of activating cardioprotection is powerful as both a preconditioning and a postconditioning stimulus （when applied at reperfusion）. Investigations of these cardioprotective phenomena have led to a more integrative understanding of mechanisms related to cardioprotection, and in the last five to ten years, it has become clear that the mechanisms are similar, whether induced by ischemic or non-ischemic stimuli. Taking together much of the data in the literature, we propose that all of these cardioprotective ＂conditioning＂ phenomena represent activation from different entry points of a cardiac conditioning network that converges upon specific mediators and effectors of myocardial cell survival, including NF-KB, Stat3/5, protein kinase C, bradykinin, and the mitoKA^P channel. Nervous system pathways may represent a novel mechanism for initiating conditioning of the heart and other organs. IPC and RIPC have proven difficult to translate clinically, as they have associated risks and cannot be used in some patients. Because of this, the use of neural and nociceptive stimuli is emerging as a potential non-ischemic and non-traumatic means to initiate cardiac conditioning. Clinical relevance is underscored by the demonstration of postconditioning with one of these modalities, supporting the conclusion that the development of pharmaceuticals and electroceuticals for this purpose is an area ripe for clinical development.展开更多
Bone Mineral Density(BMD)is one of the primary markers of bone health.Exercise provides constant mechanical stress to bone,which in turn increases BMD.Gut-bone axis is considered to play an important role in the regu-...Bone Mineral Density(BMD)is one of the primary markers of bone health.Exercise provides constant mechanical stress to bone,which in turn increases BMD.Gut-bone axis is considered to play an important role in the regu-lation of exercise on bone.Also,the metabolites of gut microbiota(GM),especially short-chain fatty acids(SCFAs),are thought to be involved in the progress.In this study,by analyzing serum and GM from humans with low and high BMD,we found that exercise indeed enhanced BMD,and butyrate secreted from GM was involved in the regulation.展开更多
基金sponsored by the National Key Research and Development Program of China(2021YFC2501800)the National Natural Science Foundation of China(No.U1909218)the Science Fund for Creative Research Groups of the National Natural Science Foundation of China(No.T2121004).
文摘Lung diseases associated with alveoli,such as acute respiratory distress syndrome,have posed a long-term threat to human health.However,an in vitro model capable of simulating different deformations of the alveoli and a suitable material for mimicking basement membrane are currently lacking.Here,we present an innovative biomimetic controllable strain membrane(BCSM)at an air–liquid interface(ALI)to reconstruct alveolar respiration.The BCSM consists of a high-precision three-dimensional printing melt-electrowritten polycaprolactone(PCL)mesh,coated with a hydrogel substrate—to simulate the important functions(such as stiffness,porosity,wettability,and ALI)of alveolar microenvironments,and seeded pulmonary epithelial cells and vascular endothelial cells on either side,respectively.Inspired by papercutting,the BCSM was fabricated in the plane while it operated in three dimensions.A series of the topological structure of the BCSM was designed to control various local-area strain,mimicking alveolar varied deformation.Lopinavir/ritonavir could reduce Lamin A expression under over-stretch condition,which might be effective in preventing ventilator-induced lung injury.The biomimetic lung-unit model with BCSM has broader application prospects in alveoli-related research in the future,such as in drug toxicology and metabolism.
基金supported by grants from the National Institutes of Health (NIHR01 HL091478) for W.Keith Jonesthe National Natural Science Foundation of China (81470425) for Xiaoping Ren
文摘Acute myocardial infarction （AMI） is the leading cause of death and disability worldwide. Timely reperfusion is the standard of care and results in decreased infarct size, improving patient survival and prognosis. However, 25% of patients proceed to develop heart failure （HF） after myocardial infarction （MI） and 50% of these will die within five years. Since the size of the infarct is the major predictor of the outcome, including the development of HF, therapies to improve myocardial salvage have great potential. Over the past three decades, a number of stimuli have been discovered that activate endogenous cardioprotective pathways. In ischemic preconditioning （IPC） and ischemic postconditioning, ischemia within the heart initiates the protection. Brief reversible episodes of ischemia in vascular beds remote from the heart can also trigger cardioprotection when applied before, during, or immediately after myocardial ischemia-- known as remote ischemic pre-, per-, and post-conditioning, respectively. Although the mechanism of remote ischemic preconditioning （RIPC） has not yet been fully elucidated, many mechanistic components are shared with IPC. The discovery of RIPC led to research into the use of remote non-ischemic stimuli including nerve stimulation （spinal and vagal）, and electroacupuncture （EA）. We discovered and, with others, have elucidated mechanistic aspects of a non- ischemic phenomenon we termed remote preconditioning of trauma （RPCT）. RPCT operates via neural stimulation of skin sensory nerves and has similarities and differences to nerve stimulation and EA conducted at acupoints. We show herein that RPCT can be mimicked using electrical stimulation of the abdominal midline （EA-like treatment） and that this modality of activating cardioprotection is powerful as both a preconditioning and a postconditioning stimulus （when applied at reperfusion）. Investigations of these cardioprotective phenomena have led to a more integrative understanding of mechanisms related to cardioprotection, and in the last five to ten years, it has become clear that the mechanisms are similar, whether induced by ischemic or non-ischemic stimuli. Taking together much of the data in the literature, we propose that all of these cardioprotective ＂conditioning＂ phenomena represent activation from different entry points of a cardiac conditioning network that converges upon specific mediators and effectors of myocardial cell survival, including NF-KB, Stat3/5, protein kinase C, bradykinin, and the mitoKA^P channel. Nervous system pathways may represent a novel mechanism for initiating conditioning of the heart and other organs. IPC and RIPC have proven difficult to translate clinically, as they have associated risks and cannot be used in some patients. Because of this, the use of neural and nociceptive stimuli is emerging as a potential non-ischemic and non-traumatic means to initiate cardiac conditioning. Clinical relevance is underscored by the demonstration of postconditioning with one of these modalities, supporting the conclusion that the development of pharmaceuticals and electroceuticals for this purpose is an area ripe for clinical development.
基金supported by the Natural Science Foundation of Shanxi Province(2023-JC-YB-186)the National Natural Science Foundation of China(Nos.32471510 and 32371240)the Space Medical Experiment Project of China Manned Space Program(HYZHXM01024).
文摘Bone Mineral Density(BMD)is one of the primary markers of bone health.Exercise provides constant mechanical stress to bone,which in turn increases BMD.Gut-bone axis is considered to play an important role in the regu-lation of exercise on bone.Also,the metabolites of gut microbiota(GM),especially short-chain fatty acids(SCFAs),are thought to be involved in the progress.In this study,by analyzing serum and GM from humans with low and high BMD,we found that exercise indeed enhanced BMD,and butyrate secreted from GM was involved in the regulation.
