We propose a mathematic model of muscle cell membrane based on thin-walled elastic rod theory. A deformation occurs in rodents’ skeletal and cardiac cells during a period of antiorthostatic suspension. We carried out...We propose a mathematic model of muscle cell membrane based on thin-walled elastic rod theory. A deformation occurs in rodents’ skeletal and cardiac cells during a period of antiorthostatic suspension. We carried out a quantitative evaluation of the deformation using this model. The calculations showed the deformation in cardiac cells to be greater than in skeletal ones. This data corresponds to experimental results of cell response that appears intense in cardiomyocytes than in skeletal muscle cells. Moreover, the deformation in skeletal and heart muscle cells has a different direction (stretching vs. compression), corresponding to experimental data of different adaptive response generation pathways in cells because of external mechanical condition changes.展开更多
A bone cell population dynamics model for cor- tical bone remodeling under mechanical stimulus is devel- oped in this paper. The external experiments extracted from the literature which have not been used in the creat...A bone cell population dynamics model for cor- tical bone remodeling under mechanical stimulus is devel- oped in this paper. The external experiments extracted from the literature which have not been used in the creation of the model are used to test the validity of the model. Not only can the model compare reasonably well with these ex- perimental results such as the increase percentage of final values of bone mineral content （BMC） and bone fracture en- ergy （BFE） among different loading schemes （which proves the validity of the model）, but also predict the realtime devel- opment pattern of BMC and BFE, as well as the dynamics of osteoblasts （OBA）, osteoclasts （OCA）, nitric oxide （NO） and prostaglandin E2 （PGE2） for each loading scheme, which can hardly be monitored through experiment. In conclusion, the model is the first of its kind that is able to provide an in- sight into the quantitative mechanism of bone remodeling at cellular level by which bone cells are activated by mechan- ical stimulus in order to start resorption/formation of bone mass. More importantly, this model has laid a solid foun- dation based on which future work such as systemic control theory analysis of bone remodeling under mechanical stimu- lus can be investigated. The to-be identified control mecha- nism will help to develop effective drugs and combined non- pharmacological therapies to combat bone loss pathologies. Also this deeper understanding of how mechanical forces quantitatively interact with skeletal tissue is essential for the generation of bone tissue for tissue replacement purposes in tissue engineering.展开更多
Cell as elastic rod behavior model is proposed to describe its contractile activity. The model takes into account the result of the transduction of external influences, which is resulting in the formation of internal ...Cell as elastic rod behavior model is proposed to describe its contractile activity. The model takes into account the result of the transduction of external influences, which is resulting in the formation of internal deformation, and evaluates the mobility and/or the tension in the muscle cells under the external influence.展开更多
Cell signaling is a very complex network of biochemical reactions triggered by a huge number of stimuli coming from the external medium. The function of any single signaling component depends not only on its own struc...Cell signaling is a very complex network of biochemical reactions triggered by a huge number of stimuli coming from the external medium. The function of any single signaling component depends not only on its own structure but also on its connections with other biomolecules. During prokaryotic-eukaryotic transition, the rearrangement of cell organization in terms of diffusional compartmentalization exerts a deep change in cell signaling functional potentiality. In this review I briefly introduce an intriguing ancient relationship between pathways involved in cell responses to chemical agonists (growth factors, nutrients, hormones) as well as to mechanical forces (stretch, osmotic changes). Some biomolecules (ion channels and enzymes) act as "hubs", thanks to their ability to be directly or indirectly chemically/mechanically co-regulated. In particular calcium signaling machinery and arachidonic acid metabolism are very ancient networks, already present before eukaryotic appearance. A number of molecular "hubs", including phospholipase A2 and some calcium channels, appear tightly interconnected in a cross regulation leading to the cellular response to chemical and mechanical stimulations.展开更多
AIM： To evaluate the effects of omeprazole on gastric mechanosensitivity in humans. METHODS： A double lumen polyvinyl tube with a plas- tic bag was introduced into the stomach of healthy volunteers under fluorograph...AIM： To evaluate the effects of omeprazole on gastric mechanosensitivity in humans. METHODS： A double lumen polyvinyl tube with a plas- tic bag was introduced into the stomach of healthy volunteers under fluorography and connected to a barostat device. Subjects were then positioned so they were sitting comfortably, and the minimal distending pressure （MDP） was determined after a 30-rain adap- tation period. Isobaric distensions were performed in stepwise increments of 2 mmHg （2 min each） starting from the MDR Subjects were instructed to score feel- ings at the end of every step using a graphic rating scale： 0, no perception; 1, weak/vague; 2, weak but significant; 3, moderate/vague; 4, moderate but signifi- cant; 5, severe discomfort; and 6, unbearable pain. Af- ter this first test, subjects received omeprazole （20 mg, after dinner） once daily for 1 wk. A second test was performed on the last day of treatment. RESULTS： No adverse effects were observed. Mean MDP before and after treatment was 6.3 - 0.3 mmHg and 6.2：1：0.5 mmHg, respectively. One subject before and 2 after treatment did not reach a score of 6 at the maximum bag volume of 750 mL. After omeprazole, there was a significant increase in the distension pres- sure required to reach scores of 1 （P = 0.019） and 2 （P = 0.017） as compared to baseline. There were no changes in pressure required to reach the other scores after treatment. Two subjects before and one after omeprazole rated their abdominal feeling 〈 1 at MDP, and mean （±SE） abdominal discomfort scores at MDP were 0.13±0.09 and 0.04±0.04, respectively. Mean scores induced by each MDP ＋ 2, 4, 6, 8, 10, 12, 14, 16, 18 and 20 （mmHg） were 1.1±0.3, 2.0±0.4, 2.9±0.5, 3.3±0.4, 4.6±0.3, 5.2±0.3, 5.5±0.2, 5.5±0.3, 5.7±0.3, and 5.4, respectively. After omepra- zole, abdominal feeling scores for the same incremen- tal pressures over MDP were 0.3±0.1, 0.8±0.1, 2.0±0.4, 2.8±0.4, 3.8±0.4, 4.6±0.4, 4.9±0.3, 5.4±0.4, 5.2±0.6, and 5.0±1.0, respectivel展开更多
To develop durable bone healing strategies through improved control of bone repair,it is of critical importance to understand the mechanisms of bone mechanical integrity when in contact with biomaterials and implants....To develop durable bone healing strategies through improved control of bone repair,it is of critical importance to understand the mechanisms of bone mechanical integrity when in contact with biomaterials and implants.Bone mechanical integrity is defined here as the adaptation of structural properties of remodeled bone in regard to an applied mechanical loading.Accordingly,the authors present why future investigations in bone repair and regeneration should emphasize on the matrix surrounding the osteocytes.Osteocytes are mechanosensitive cells considered as the orchestrators of bone remodeling,which is the biological process involved in bone homeostasis.These bone cells are trapped in an interconnected porous network,the lacunocanalicular network,which is embedded in a bone mineralized extracellular matrix.As a consequence of an applied mechanical loading,the bone deformation results in the deformation of this lacunocanalicular network inducing a shift in interstitial fluid pressure and velocity,thus resulting in osteocyte stimulation.The material environment surrounding each osteocyte,the so called perilacunar and pericellular matrices properties,define its mechanosensitivity.While this mechanical stimulation pathway is well known,the laws used to predict bone remodeling are based on strains developing at a tissue scale,suggesting that these strains are related to the shift in fluid pressure and velocity at the lacunocanalicular scale.While this relationship has been validated through observation in healthy bone,the fluid behavior at the bone-implant interface is more complex.The presence of the implant modifies fluid behavior,so that for the same strain at a tissue scale,the shift in fluid pressure and velocity will be different than in a healthy bone tissue.In that context,new markers for bone mechanical integrity,considering fluid behavior,have to be defined.The viewpoint exposed by the authors indicates that the properties of the pericellular and the perilacunar matrices have to be systematically investigated展开更多
Focal adhesions(FAs) are large,multiprotein complexs that provides linkers between cytoskeleton to the extracellular matrix(ECM).Cells sense and respond to forces through FAs to regulate a broad range of processes,suc...Focal adhesions(FAs) are large,multiprotein complexs that provides linkers between cytoskeleton to the extracellular matrix(ECM).Cells sense and respond to forces through FAs to regulate a broad range of processes,such as cell growth,migration,differentiation展开更多
Clinical trials and animal experimental studies have demonstrated an association of arterial baroreflex impairment with the prognosis and mortality of cardiovascular diseases and diabetes. As a primary part of the art...Clinical trials and animal experimental studies have demonstrated an association of arterial baroreflex impairment with the prognosis and mortality of cardiovascular diseases and diabetes. As a primary part of the arterial baroreflex arc, the pressure sensitivity of arterial baroreceptors is blunted and involved in arterial baroreflex dysfunction in cardiovascular diseases and diabetes.Changes in the arterial vascular walls, mechanosensitive ion channels, and voltage-gated ion channels contribute to the attenuation of arterial baroreceptor sensitivity. Some endogenous substances(such as angiotensin II and superoxide anion) can modulate these morphological and functional alterations through intracellular signaling pathways in impaired arterial baroreceptors. Arterial baroreceptors can be considered as a potential therapeutic target to improve the prognosis of patients with cardiovascular diseases and diabetes.展开更多
文摘We propose a mathematic model of muscle cell membrane based on thin-walled elastic rod theory. A deformation occurs in rodents’ skeletal and cardiac cells during a period of antiorthostatic suspension. We carried out a quantitative evaluation of the deformation using this model. The calculations showed the deformation in cardiac cells to be greater than in skeletal ones. This data corresponds to experimental results of cell response that appears intense in cardiomyocytes than in skeletal muscle cells. Moreover, the deformation in skeletal and heart muscle cells has a different direction (stretching vs. compression), corresponding to experimental data of different adaptive response generation pathways in cells because of external mechanical condition changes.
文摘A bone cell population dynamics model for cor- tical bone remodeling under mechanical stimulus is devel- oped in this paper. The external experiments extracted from the literature which have not been used in the creation of the model are used to test the validity of the model. Not only can the model compare reasonably well with these ex- perimental results such as the increase percentage of final values of bone mineral content （BMC） and bone fracture en- ergy （BFE） among different loading schemes （which proves the validity of the model）, but also predict the realtime devel- opment pattern of BMC and BFE, as well as the dynamics of osteoblasts （OBA）, osteoclasts （OCA）, nitric oxide （NO） and prostaglandin E2 （PGE2） for each loading scheme, which can hardly be monitored through experiment. In conclusion, the model is the first of its kind that is able to provide an in- sight into the quantitative mechanism of bone remodeling at cellular level by which bone cells are activated by mechan- ical stimulus in order to start resorption/formation of bone mass. More importantly, this model has laid a solid foun- dation based on which future work such as systemic control theory analysis of bone remodeling under mechanical stimu- lus can be investigated. The to-be identified control mecha- nism will help to develop effective drugs and combined non- pharmacological therapies to combat bone loss pathologies. Also this deeper understanding of how mechanical forces quantitatively interact with skeletal tissue is essential for the generation of bone tissue for tissue replacement purposes in tissue engineering.
文摘Cell as elastic rod behavior model is proposed to describe its contractile activity. The model takes into account the result of the transduction of external influences, which is resulting in the formation of internal deformation, and evaluates the mobility and/or the tension in the muscle cells under the external influence.
文摘Cell signaling is a very complex network of biochemical reactions triggered by a huge number of stimuli coming from the external medium. The function of any single signaling component depends not only on its own structure but also on its connections with other biomolecules. During prokaryotic-eukaryotic transition, the rearrangement of cell organization in terms of diffusional compartmentalization exerts a deep change in cell signaling functional potentiality. In this review I briefly introduce an intriguing ancient relationship between pathways involved in cell responses to chemical agonists (growth factors, nutrients, hormones) as well as to mechanical forces (stretch, osmotic changes). Some biomolecules (ion channels and enzymes) act as "hubs", thanks to their ability to be directly or indirectly chemically/mechanically co-regulated. In particular calcium signaling machinery and arachidonic acid metabolism are very ancient networks, already present before eukaryotic appearance. A number of molecular "hubs", including phospholipase A2 and some calcium channels, appear tightly interconnected in a cross regulation leading to the cellular response to chemical and mechanical stimulations.
基金Supported by A Grant-in-Aid for Scientific Research from the Aichi Medical University Alumni Association, in part
文摘AIM： To evaluate the effects of omeprazole on gastric mechanosensitivity in humans. METHODS： A double lumen polyvinyl tube with a plas- tic bag was introduced into the stomach of healthy volunteers under fluorography and connected to a barostat device. Subjects were then positioned so they were sitting comfortably, and the minimal distending pressure （MDP） was determined after a 30-rain adap- tation period. Isobaric distensions were performed in stepwise increments of 2 mmHg （2 min each） starting from the MDR Subjects were instructed to score feel- ings at the end of every step using a graphic rating scale： 0, no perception; 1, weak/vague; 2, weak but significant; 3, moderate/vague; 4, moderate but signifi- cant; 5, severe discomfort; and 6, unbearable pain. Af- ter this first test, subjects received omeprazole （20 mg, after dinner） once daily for 1 wk. A second test was performed on the last day of treatment. RESULTS： No adverse effects were observed. Mean MDP before and after treatment was 6.3 - 0.3 mmHg and 6.2：1：0.5 mmHg, respectively. One subject before and 2 after treatment did not reach a score of 6 at the maximum bag volume of 750 mL. After omeprazole, there was a significant increase in the distension pres- sure required to reach scores of 1 （P = 0.019） and 2 （P = 0.017） as compared to baseline. There were no changes in pressure required to reach the other scores after treatment. Two subjects before and one after omeprazole rated their abdominal feeling 〈 1 at MDP, and mean （±SE） abdominal discomfort scores at MDP were 0.13±0.09 and 0.04±0.04, respectively. Mean scores induced by each MDP ＋ 2, 4, 6, 8, 10, 12, 14, 16, 18 and 20 （mmHg） were 1.1±0.3, 2.0±0.4, 2.9±0.5, 3.3±0.4, 4.6±0.3, 5.2±0.3, 5.5±0.2, 5.5±0.3, 5.7±0.3, and 5.4, respectively. After omepra- zole, abdominal feeling scores for the same incremen- tal pressures over MDP were 0.3±0.1, 0.8±0.1, 2.0±0.4, 2.8±0.4, 3.8±0.4, 4.6±0.4, 4.9±0.3, 5.4±0.4, 5.2±0.6, and 5.0±1.0, respectivel
文摘To develop durable bone healing strategies through improved control of bone repair,it is of critical importance to understand the mechanisms of bone mechanical integrity when in contact with biomaterials and implants.Bone mechanical integrity is defined here as the adaptation of structural properties of remodeled bone in regard to an applied mechanical loading.Accordingly,the authors present why future investigations in bone repair and regeneration should emphasize on the matrix surrounding the osteocytes.Osteocytes are mechanosensitive cells considered as the orchestrators of bone remodeling,which is the biological process involved in bone homeostasis.These bone cells are trapped in an interconnected porous network,the lacunocanalicular network,which is embedded in a bone mineralized extracellular matrix.As a consequence of an applied mechanical loading,the bone deformation results in the deformation of this lacunocanalicular network inducing a shift in interstitial fluid pressure and velocity,thus resulting in osteocyte stimulation.The material environment surrounding each osteocyte,the so called perilacunar and pericellular matrices properties,define its mechanosensitivity.While this mechanical stimulation pathway is well known,the laws used to predict bone remodeling are based on strains developing at a tissue scale,suggesting that these strains are related to the shift in fluid pressure and velocity at the lacunocanalicular scale.While this relationship has been validated through observation in healthy bone,the fluid behavior at the bone-implant interface is more complex.The presence of the implant modifies fluid behavior,so that for the same strain at a tissue scale,the shift in fluid pressure and velocity will be different than in a healthy bone tissue.In that context,new markers for bone mechanical integrity,considering fluid behavior,have to be defined.The viewpoint exposed by the authors indicates that the properties of the pericellular and the perilacunar matrices have to be systematically investigated
文摘Focal adhesions(FAs) are large,multiprotein complexs that provides linkers between cytoskeleton to the extracellular matrix(ECM).Cells sense and respond to forces through FAs to regulate a broad range of processes,such as cell growth,migration,differentiation
基金supported by the American Heart Association(0730108N)the National Institute of Health’s National Heart,Lung,and Blood Institute(R01HL-098503 and R01HL-137832),USA
文摘Clinical trials and animal experimental studies have demonstrated an association of arterial baroreflex impairment with the prognosis and mortality of cardiovascular diseases and diabetes. As a primary part of the arterial baroreflex arc, the pressure sensitivity of arterial baroreceptors is blunted and involved in arterial baroreflex dysfunction in cardiovascular diseases and diabetes.Changes in the arterial vascular walls, mechanosensitive ion channels, and voltage-gated ion channels contribute to the attenuation of arterial baroreceptor sensitivity. Some endogenous substances(such as angiotensin II and superoxide anion) can modulate these morphological and functional alterations through intracellular signaling pathways in impaired arterial baroreceptors. Arterial baroreceptors can be considered as a potential therapeutic target to improve the prognosis of patients with cardiovascular diseases and diabetes.
