Bibliographic analysis is still very rarely used in experimental basic study papers.The comprehensive bibliometric analysis of scientific literature on research progress and challenges in stem cell therapy for diabeti...Bibliographic analysis is still very rarely used in experimental basic study papers.The comprehensive bibliometric analysis of scientific literature on research progress and challenges in stem cell therapy for diabetic chronic wounds,which was conducted in the work of Shi et al can be a case study and a source of valuable information for writing reviews and experimental papers in this field.Basic experimental studies on a role of mesenchymal stem cells(MSCs)in wound healing that are published in 2023-2024,such as Zhang et al in 2023,Hu et al in 2023,Wang et al in 2023 are certainly also subjects for applying this powerful tool to analyze current research,challenges and perspectives in this field.This is due to the fact that these studies have addressed a great variety of aspects of the application of MSCs for the treatment of chronic wounds,such as using both the cells themselves and their various products:Sponges,hydrogels,exosomes,and genetic constructions.Such a wide variety of directions in the field of study and biomedical application of MSCs requires a deep understanding of the current state of research in this area,which can be provided by bibliometric analysis.Thus,the use of such elements of bibliographic analysis as publication count by year and analysis of top-10 keywords calculated independently or cited from bibliometric analysis studies can be safely recommended for every basic study manuscripts,primarily for the“Introduction”section,and review.展开更多
Production of proinflammatory cytokines in the central nervous system is a key process in the neuroinflammatory response to trauma,infection,and neurodegenerative diseases(Kumar,2019).These intercellular signaling mol...Production of proinflammatory cytokines in the central nervous system is a key process in the neuroinflammatory response to trauma,infection,and neurodegenerative diseases(Kumar,2019).These intercellular signaling molecules play multiple roles in the immune response in the central nervous system including the orchestration of the sickness response to innate immune perturbations in the brain(Dantzer et al.,2008).展开更多
Norepinephrine plays an important role in motor functional recovery after a brain injury caused by ferrous chloride.Inhibition of norepinephrine release by clonidine is correlated with motor deficits after motor corte...Norepinephrine plays an important role in motor functional recovery after a brain injury caused by ferrous chloride.Inhibition of norepinephrine release by clonidine is correlated with motor deficits after motor cortex injury.The aim of this study was to analyze the role ofα-adrenergic receptors in the restoration of motor deficits in recovering rats after brain damage.The rats were randomly assigned to the sham and injury groups and then treated with the following pharmacological agents at 3 hours before and 8 hours,3 days,and 20 days after ferrous chloride-induced cortical injury:saline,clonidine,efaroxan(a selective antagonist ofα-adrenergic receptors)and clonidine+efaroxan.The sensorimotor score,the immunohistochemical staining forα-adrenergic receptors,and norepinephrine levels were evaluated.Eight hours post-injury,the sensorimotor score and norepinephrine levels in the locus coeruleus of the injured rats decreased,and these effects were maintained 3 days post-injury.However,20 days later,clonidine administration diminished norepinephrine levels in the pons compared with the sham group.This effect was accompanied by sensorimotor deficits.These effects were blocked by efaroxan.In conclusion,an increase inα-adrenergic receptor levels was observed after injury.Clonidine restores motor deficits in rats recovering from cortical injury,an effect that was prevented by efaroxan.The underlying mechanisms involve the stimulation of hypersensitiveα-adrenergic receptors and inhibition of norepinephrine activity in the locus coeruleus.The results of this study suggest thatαreceptor agonists might restore deficits or impede rehabilitation in patients with brain injury,and therefore pharmacological therapies need to be prescribed cautiously to these patients.展开更多
AIM: To determine the role of c-Jun N-terminal kinase (JNK) activity in ethanol-induced apoptosis and the modulation of this signaling cascade by S-Adenosylmethionine (AdoMet). METHODS: Primary hepatocyte cultur...AIM: To determine the role of c-Jun N-terminal kinase (JNK) activity in ethanol-induced apoptosis and the modulation of this signaling cascade by S-Adenosylmethionine (AdoMet). METHODS: Primary hepatocyte cultures were pretreated with 100 IJmol/L SP600125, a selective JNK inhibitor, 1 mL/L DMSO or 4 mmol/L AdoMet and then exposed to 100 mmo/L ethanol. Hepatocyte apoptosis was determined by the TUNEL and DNA ladder assays. JNK activity and its inhibition by SP600125 and AdoMet were determined by Western blot analysis of c-jun phosphorylation and Bid fragmentation. SP600125 and AdoMet effects on the apoptotic signaling pathway were determined by Western blot analysis of cytochrome c release and pro-caspase 3 fragmentation. The AdoMet effect on glutathione levels was measured by EIIman's method and reactive oxygen species (ROS) generation by cell cytometry. RESULTS: The exposure of hepatocytes to ethanol induced JNK activation, c-jun phosphorylation, Bid fragmentation, cytochrome c release and pro-caspase 3 cleavage; these effects were diminished by SP600125, and caused a significant decrease in ethanol-induced apoptosis (P〈 0.05). AdoMet exerted an antioxidant effect maintaining glutathione levels and decreasing ROS generation, without a significant effect on JNK activity, and prevented cytochrome c release and pro-caspase 3 cleavage.CONCLUSION: The JNK signaling cascade is a key component of the proapoptotic signaling pathway induced by ethanol. JNK activation may be independent from ROS generation, since AdoMet which exerted antioxidant properties did not have a significant effect on JNK activity. JNK pathway modulator agents and AdoMet may be components of promising therapies for alcoholic liver disease (ALD) treatment.展开更多
The waterlogging damage is the pit to agriculture in plain and lake region. This damage is related to the groundwater, ancient lakes, soil, land use and negative landforms, the conventional technique is adopted to the...The waterlogging damage is the pit to agriculture in plain and lake region. This damage is related to the groundwater, ancient lakes, soil, land use and negative landforms, the conventional technique is adopted to the study of this damage. In this paper, we suggest a new technical method, the technique is based on DEM, to study this problem. The DEM is developed on the ECLIPSE MV/ 10000 AOS/ VS system, and the estimation model of waterlogging loss is built on the historical data of the test region in Jianghan Plain. and then, the rice waterlogging loss of test region is estimated by them.展开更多
Absence status is the most common form of non-convulsive status epilepticus and is characterized by confusion with varying degrees of memory loss and cognitive impairment. Patients and Method: Three children were sent...Absence status is the most common form of non-convulsive status epilepticus and is characterized by confusion with varying degrees of memory loss and cognitive impairment. Patients and Method: Three children were sent to neurological consultation due to behavioral alterations and a prolonged confused state;they were hospitalized and treated with sodium diphenylhydantoinate (DPH) IV at a dose of 10 mg/Kg. Results: The duration of symptoms varied from 6 months to 10 days. All three patients presented with global mental alterations, showing slowness in response and action. The electroencephalogram showed a pattern of slow, generalized stem and poly-stem-wavelengths of 3 - 4 Hz, which were registered for one hour. After the DPH bolus, the attack spontaneously ended in the 3 patients and upon examination all three presented with amnesia of the events occurring during the attack. In the follow-up, two of the patients did not experience further episodes and they showed normal scholastic achievement. The third patient however, after suffering a 6-month status epilepticus, failed the school year and finished his elementary education until the age of 15, experiencing similar difficulties with his secondary education. Discussion: Non-convulsive status epilepticus is more difficult to diagnose mainly because the manifestations are predominantly psychiatric and can be confused with other diseases or with an overdose of anti- convulsive drugs. A prolonged state of mental confusion, with no other explanation, should alert the attending physician to take an electroencephalogram in order to confirm the diagnosis. In our patients, DPH immediately controlled paroxysmal activity. We can therefore conclude that the problem is not in the treatment, but rather in making the correct diagnosis.展开更多
Prior static studies of three-dimensionally woven carbon/epoxy textile composites show that large interlaminar normal and shear strains occur as a result of layer waviness under static compression loading. This study ...Prior static studies of three-dimensionally woven carbon/epoxy textile composites show that large interlaminar normal and shear strains occur as a result of layer waviness under static compression loading. This study addresses the dynamic response of 3D through-thickness angle interlock textile composites, and how interaction between different layer waviness influences the modal frequencies. The samples have common as-woven textile architecture, but they are cured at varying compaction pressures to achieve varying levels of fiber volume and fiber architecture distortion. Samples produced have varying final cured laminate thickness, which allows observations on the influence of increased fiber volume (generally believed to improve mechanical performance) weighed against the increased fiber distortion (generally believed to decrease mechanical performance). The results obtained from this study show that no added damping was developed in the as-woven identical panels. Furthermore, a linear relation exists between modal frequency and thickness (fiber volume).展开更多
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are usually suitable candidates for the development of drug delivery devices. Sol-gel chemistry represents an easy method to obtain porous silica nanoparticles. Mesoporou...Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are usually suitable candidates for the development of drug delivery devices. Sol-gel chemistry represents an easy method to obtain porous silica nanoparticles. Mesoporous silica nanomaterials have been widely used for drug delivery purposes. In this work we synthesized silica based materials using two molar alkoxide:water ratios 1:4 and 1:8, incorporating paracetamol to develop a nano-sized matrix for controlled release purposes. The samples exhibited different values for surface area, porosity, particle size and distinct punctual defects. Infrared and UV-visible spectroscopic studies were carried out to demonstrate the effect of water concentration and the adequate incorporation of paracetamol molecules. Nitrogen adsorption characterization was realized and the estimated BET surface values were from 532 to 825 m<sup>2</sup>/g. Kinetic analysis of drug release profiles was performed using the hyperbola model. Transmission electron micrographs showed that all the materials formed aggregates of small particles with size between 10 - 60 nm. Mesoporous SiO<sub>2</sub> materials were proved to be a suitable system for controlled release of paracetamol.展开更多
Objective To study the cavernosa hemodynamics in diabetic erectile dysfunction ( ED).Methods 22 diabetic and 35 psychic ED patients were studied by intracavernosum injection of a mixture papaver-ine and phentolamine (...Objective To study the cavernosa hemodynamics in diabetic erectile dysfunction ( ED).Methods 22 diabetic and 35 psychic ED patients were studied by intracavernosum injection of a mixture papaver-ine and phentolamine (30/1mg) to assess the hemodynamics changes of the corpus cavernosum by means of colour duplex ultrasonography. Results The average hemodynamics data of the diabetic ED patients vs that of the psy-chogenic ED patients in terms of peak flow velocity (PFV):20. 06±7.15cm/s vs 35. 82±9. 41cm/s, end diastolic velocity (EDV) : 8. 82±0. 35cm/s vs 5. 51±0. 42cm/s,artery diameter (Ad) : 0. 78±0. 25cm vs 1. 01±0. 42cm, vein diameter ( Vd) : 1.05±0. 32mm vs 1.21±0. 45mm, resistance index(RI) : 0. 72±0. 28 vs 0. 98±0. 31,mean velocity of artery (MV):6. 71±0. 27cm/s vs 10. 31±3. 32cm/s, dorsal deep vein flow(DDVF) : 28. 81±6. 32cm/ s vs 25. 74±0. 58cm/s. Stasticstical differences existed in PFV, Ad,RI and MV(P <0. 01). The arterial wall is thick and rigid in diabetic ED patients. Conclusion Atheroscleorsis and veno-occlusive dysfunction of the corpus cavernosum are essential to the development of diabetic ED.展开更多
The new prevalence data regarding the estimated global number of human immunodeficiency virus positive (HIV+) cases,i.e.,including people who are either aware or unaware of their HIV infection in 2010,lead many to won...The new prevalence data regarding the estimated global number of human immunodeficiency virus positive (HIV+) cases,i.e.,including people who are either aware or unaware of their HIV infection in 2010,lead many to wonder why the increase in incidence has reached today’s unprecedented level and escalated within such a short time.This,in spite of prevention campaigns in countries affected by HIV/acquired immune deficiency syndrome (AIDS) with their urgent messages aimed at preventing HIV transmission by promoting changes in individual’s behavior.This article analyzes the background of the prevention strategies,in particular their political,social and legal concepts in terms of human rights,and reveals traits of human behavior not considered thus far.A radical reappraisal is necessary,at social and legislative levels,as well as options additional to current concepts.When ethical issues come up,they become blamed for outmoded moralistic positions.However,ignoring the reality has led to dire consequences from prioritizing individual human rights over society’s collective need to prevent the spread of HIV.展开更多
With an exception of few reports,the plasma concentration of ouabain and mari-nobufagenin,mostly studied cardiotonic steroids(CTS)assessed by immunoassay techniques,is less than 1 nM.During the last 3 decades,the impl...With an exception of few reports,the plasma concentration of ouabain and mari-nobufagenin,mostly studied cardiotonic steroids(CTS)assessed by immunoassay techniques,is less than 1 nM.During the last 3 decades,the implication of these endogenous CTS in the path-ogenesis of hypertension and other volume-expanded disorders is widely disputed.The threshold for inhibition by CTS of human and rodent a1-Na,K-ATPase is~1 and 1000 nM,respectively,that rules out the functioning of endogenous CTS(ECTS)as natriuretic hormones and regulators of cell adhesion,cell-to-cell communication,gene transcription and transla-tion,which are mediated by dissipation of the transmembrane gradients of monovalent cat-ions.In several types of cells ouabain and marinobufagenin at concentrations corresponding to its plasma level activate Na,K-ATPase,decrease the[Na^(+)]i;/[K^(+)]i;-ratio and increase cell pro-liferation.Possible physiological significance and mechanism of non-canonical Na^(+)/K^(+)-depen-dent and Nai^(+)/Ki^(+)independent cell responses to CTS are discussed.展开更多
基金Supported by Russian Science Foundation,No.23-74-10027.
文摘Bibliographic analysis is still very rarely used in experimental basic study papers.The comprehensive bibliometric analysis of scientific literature on research progress and challenges in stem cell therapy for diabetic chronic wounds,which was conducted in the work of Shi et al can be a case study and a source of valuable information for writing reviews and experimental papers in this field.Basic experimental studies on a role of mesenchymal stem cells(MSCs)in wound healing that are published in 2023-2024,such as Zhang et al in 2023,Hu et al in 2023,Wang et al in 2023 are certainly also subjects for applying this powerful tool to analyze current research,challenges and perspectives in this field.This is due to the fact that these studies have addressed a great variety of aspects of the application of MSCs for the treatment of chronic wounds,such as using both the cells themselves and their various products:Sponges,hydrogels,exosomes,and genetic constructions.Such a wide variety of directions in the field of study and biomedical application of MSCs requires a deep understanding of the current state of research in this area,which can be provided by bibliometric analysis.Thus,the use of such elements of bibliographic analysis as publication count by year and analysis of top-10 keywords calculated independently or cited from bibliometric analysis studies can be safely recommended for every basic study manuscripts,primarily for the“Introduction”section,and review.
基金supported by an American Australian Association Fellowship(to MVB).
文摘Production of proinflammatory cytokines in the central nervous system is a key process in the neuroinflammatory response to trauma,infection,and neurodegenerative diseases(Kumar,2019).These intercellular signaling molecules play multiple roles in the immune response in the central nervous system including the orchestration of the sickness response to innate immune perturbations in the brain(Dantzer et al.,2008).
基金supported by Consejo Nacional de Ciencia y Tecnología(CONACy T)project CB 2016-287614(to RGP and ABN)by Scholarship Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica de la Universidad Nacional Autónoma de México(PAPIIT-UNAM)IA203319 and PAPIIT-UNAM IN216221 to(LERL)。
文摘Norepinephrine plays an important role in motor functional recovery after a brain injury caused by ferrous chloride.Inhibition of norepinephrine release by clonidine is correlated with motor deficits after motor cortex injury.The aim of this study was to analyze the role ofα-adrenergic receptors in the restoration of motor deficits in recovering rats after brain damage.The rats were randomly assigned to the sham and injury groups and then treated with the following pharmacological agents at 3 hours before and 8 hours,3 days,and 20 days after ferrous chloride-induced cortical injury:saline,clonidine,efaroxan(a selective antagonist ofα-adrenergic receptors)and clonidine+efaroxan.The sensorimotor score,the immunohistochemical staining forα-adrenergic receptors,and norepinephrine levels were evaluated.Eight hours post-injury,the sensorimotor score and norepinephrine levels in the locus coeruleus of the injured rats decreased,and these effects were maintained 3 days post-injury.However,20 days later,clonidine administration diminished norepinephrine levels in the pons compared with the sham group.This effect was accompanied by sensorimotor deficits.These effects were blocked by efaroxan.In conclusion,an increase inα-adrenergic receptor levels was observed after injury.Clonidine restores motor deficits in rats recovering from cortical injury,an effect that was prevented by efaroxan.The underlying mechanisms involve the stimulation of hypersensitiveα-adrenergic receptors and inhibition of norepinephrine activity in the locus coeruleus.The results of this study suggest thatαreceptor agonists might restore deficits or impede rehabilitation in patients with brain injury,and therefore pharmacological therapies need to be prescribed cautiously to these patients.
文摘AIM: To determine the role of c-Jun N-terminal kinase (JNK) activity in ethanol-induced apoptosis and the modulation of this signaling cascade by S-Adenosylmethionine (AdoMet). METHODS: Primary hepatocyte cultures were pretreated with 100 IJmol/L SP600125, a selective JNK inhibitor, 1 mL/L DMSO or 4 mmol/L AdoMet and then exposed to 100 mmo/L ethanol. Hepatocyte apoptosis was determined by the TUNEL and DNA ladder assays. JNK activity and its inhibition by SP600125 and AdoMet were determined by Western blot analysis of c-jun phosphorylation and Bid fragmentation. SP600125 and AdoMet effects on the apoptotic signaling pathway were determined by Western blot analysis of cytochrome c release and pro-caspase 3 fragmentation. The AdoMet effect on glutathione levels was measured by EIIman's method and reactive oxygen species (ROS) generation by cell cytometry. RESULTS: The exposure of hepatocytes to ethanol induced JNK activation, c-jun phosphorylation, Bid fragmentation, cytochrome c release and pro-caspase 3 cleavage; these effects were diminished by SP600125, and caused a significant decrease in ethanol-induced apoptosis (P〈 0.05). AdoMet exerted an antioxidant effect maintaining glutathione levels and decreasing ROS generation, without a significant effect on JNK activity, and prevented cytochrome c release and pro-caspase 3 cleavage.CONCLUSION: The JNK signaling cascade is a key component of the proapoptotic signaling pathway induced by ethanol. JNK activation may be independent from ROS generation, since AdoMet which exerted antioxidant properties did not have a significant effect on JNK activity. JNK pathway modulator agents and AdoMet may be components of promising therapies for alcoholic liver disease (ALD) treatment.
文摘The waterlogging damage is the pit to agriculture in plain and lake region. This damage is related to the groundwater, ancient lakes, soil, land use and negative landforms, the conventional technique is adopted to the study of this damage. In this paper, we suggest a new technical method, the technique is based on DEM, to study this problem. The DEM is developed on the ECLIPSE MV/ 10000 AOS/ VS system, and the estimation model of waterlogging loss is built on the historical data of the test region in Jianghan Plain. and then, the rice waterlogging loss of test region is estimated by them.
文摘Absence status is the most common form of non-convulsive status epilepticus and is characterized by confusion with varying degrees of memory loss and cognitive impairment. Patients and Method: Three children were sent to neurological consultation due to behavioral alterations and a prolonged confused state;they were hospitalized and treated with sodium diphenylhydantoinate (DPH) IV at a dose of 10 mg/Kg. Results: The duration of symptoms varied from 6 months to 10 days. All three patients presented with global mental alterations, showing slowness in response and action. The electroencephalogram showed a pattern of slow, generalized stem and poly-stem-wavelengths of 3 - 4 Hz, which were registered for one hour. After the DPH bolus, the attack spontaneously ended in the 3 patients and upon examination all three presented with amnesia of the events occurring during the attack. In the follow-up, two of the patients did not experience further episodes and they showed normal scholastic achievement. The third patient however, after suffering a 6-month status epilepticus, failed the school year and finished his elementary education until the age of 15, experiencing similar difficulties with his secondary education. Discussion: Non-convulsive status epilepticus is more difficult to diagnose mainly because the manifestations are predominantly psychiatric and can be confused with other diseases or with an overdose of anti- convulsive drugs. A prolonged state of mental confusion, with no other explanation, should alert the attending physician to take an electroencephalogram in order to confirm the diagnosis. In our patients, DPH immediately controlled paroxysmal activity. We can therefore conclude that the problem is not in the treatment, but rather in making the correct diagnosis.
文摘Prior static studies of three-dimensionally woven carbon/epoxy textile composites show that large interlaminar normal and shear strains occur as a result of layer waviness under static compression loading. This study addresses the dynamic response of 3D through-thickness angle interlock textile composites, and how interaction between different layer waviness influences the modal frequencies. The samples have common as-woven textile architecture, but they are cured at varying compaction pressures to achieve varying levels of fiber volume and fiber architecture distortion. Samples produced have varying final cured laminate thickness, which allows observations on the influence of increased fiber volume (generally believed to improve mechanical performance) weighed against the increased fiber distortion (generally believed to decrease mechanical performance). The results obtained from this study show that no added damping was developed in the as-woven identical panels. Furthermore, a linear relation exists between modal frequency and thickness (fiber volume).
文摘Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are usually suitable candidates for the development of drug delivery devices. Sol-gel chemistry represents an easy method to obtain porous silica nanoparticles. Mesoporous silica nanomaterials have been widely used for drug delivery purposes. In this work we synthesized silica based materials using two molar alkoxide:water ratios 1:4 and 1:8, incorporating paracetamol to develop a nano-sized matrix for controlled release purposes. The samples exhibited different values for surface area, porosity, particle size and distinct punctual defects. Infrared and UV-visible spectroscopic studies were carried out to demonstrate the effect of water concentration and the adequate incorporation of paracetamol molecules. Nitrogen adsorption characterization was realized and the estimated BET surface values were from 532 to 825 m<sup>2</sup>/g. Kinetic analysis of drug release profiles was performed using the hyperbola model. Transmission electron micrographs showed that all the materials formed aggregates of small particles with size between 10 - 60 nm. Mesoporous SiO<sub>2</sub> materials were proved to be a suitable system for controlled release of paracetamol.
文摘Objective To study the cavernosa hemodynamics in diabetic erectile dysfunction ( ED).Methods 22 diabetic and 35 psychic ED patients were studied by intracavernosum injection of a mixture papaver-ine and phentolamine (30/1mg) to assess the hemodynamics changes of the corpus cavernosum by means of colour duplex ultrasonography. Results The average hemodynamics data of the diabetic ED patients vs that of the psy-chogenic ED patients in terms of peak flow velocity (PFV):20. 06±7.15cm/s vs 35. 82±9. 41cm/s, end diastolic velocity (EDV) : 8. 82±0. 35cm/s vs 5. 51±0. 42cm/s,artery diameter (Ad) : 0. 78±0. 25cm vs 1. 01±0. 42cm, vein diameter ( Vd) : 1.05±0. 32mm vs 1.21±0. 45mm, resistance index(RI) : 0. 72±0. 28 vs 0. 98±0. 31,mean velocity of artery (MV):6. 71±0. 27cm/s vs 10. 31±3. 32cm/s, dorsal deep vein flow(DDVF) : 28. 81±6. 32cm/ s vs 25. 74±0. 58cm/s. Stasticstical differences existed in PFV, Ad,RI and MV(P <0. 01). The arterial wall is thick and rigid in diabetic ED patients. Conclusion Atheroscleorsis and veno-occlusive dysfunction of the corpus cavernosum are essential to the development of diabetic ED.
文摘The new prevalence data regarding the estimated global number of human immunodeficiency virus positive (HIV+) cases,i.e.,including people who are either aware or unaware of their HIV infection in 2010,lead many to wonder why the increase in incidence has reached today’s unprecedented level and escalated within such a short time.This,in spite of prevention campaigns in countries affected by HIV/acquired immune deficiency syndrome (AIDS) with their urgent messages aimed at preventing HIV transmission by promoting changes in individual’s behavior.This article analyzes the background of the prevention strategies,in particular their political,social and legal concepts in terms of human rights,and reveals traits of human behavior not considered thus far.A radical reappraisal is necessary,at social and legislative levels,as well as options additional to current concepts.When ethical issues come up,they become blamed for outmoded moralistic positions.However,ignoring the reality has led to dire consequences from prioritizing individual human rights over society’s collective need to prevent the spread of HIV.
基金supported by grants from the Russian Science Foundation#19-75-10009-E.A.K.the Russian Foundation for Basic Research(#18-04-00063-S.N.O.,#18-34-00308-A.M.T.)+1 种基金the National Institutes of Health Award 1R56HL127395(N.O.D.)National Center For Advancing Translational Sciences of the National Institutes of Health Award UL1TR000430(N.O.D.)。
文摘With an exception of few reports,the plasma concentration of ouabain and mari-nobufagenin,mostly studied cardiotonic steroids(CTS)assessed by immunoassay techniques,is less than 1 nM.During the last 3 decades,the implication of these endogenous CTS in the path-ogenesis of hypertension and other volume-expanded disorders is widely disputed.The threshold for inhibition by CTS of human and rodent a1-Na,K-ATPase is~1 and 1000 nM,respectively,that rules out the functioning of endogenous CTS(ECTS)as natriuretic hormones and regulators of cell adhesion,cell-to-cell communication,gene transcription and transla-tion,which are mediated by dissipation of the transmembrane gradients of monovalent cat-ions.In several types of cells ouabain and marinobufagenin at concentrations corresponding to its plasma level activate Na,K-ATPase,decrease the[Na^(+)]i;/[K^(+)]i;-ratio and increase cell pro-liferation.Possible physiological significance and mechanism of non-canonical Na^(+)/K^(+)-depen-dent and Nai^(+)/Ki^(+)independent cell responses to CTS are discussed.