Cardiovascular autonomic neuropathy(CAN)is a debilitating condition that mainly occurs in long-standing type 2 diabetes patients but can manifest earlier,even before diabetes is diagnosed.CAN is a microvascular compli...Cardiovascular autonomic neuropathy(CAN)is a debilitating condition that mainly occurs in long-standing type 2 diabetes patients but can manifest earlier,even before diabetes is diagnosed.CAN is a microvascular complication that results from lesions of the sympathetic and parasympathetic nerve fibers,which innervate the heart and blood vessels and promote alterations in cardiovascular autonomic control.The entire mechanism is still not elucidated,but several aspects of the pathophysiology of CAN have already been described,such as the production of advanced glycation end products,reactive oxygen species,nuclear factor kappa B,and pro-inflammatory cytokines.This microvascular complication is an important risk factor for silent myocardial ischemia,chronic kidney disease,myocardial dysfunction,major cardiovascular events,cardiac arrhythmias,and sudden death.It has also been suggested that,compared to other traditional cardiovascular risk factors,CAN progression may have a greater impact on cardiovascular disease development.However,CAN might be subclinical for several years,and a late diagnosis increases the mortality risk.The duration of the transition period from the subclinical to clinical stage remains unknown,but the progression of CAN is associated with a poor prognosis.Several tests can be used for CAN diagnosis,such as heart rate variability(HRV),cardiovascular autonomic reflex tests,and myocardial scintigraphy.Currently,it has already been described that CAN could be detected even during the subclinical stage through a reduction in HRV,which is a non-invasive test with a lower operating cost.Therefore,considering that diabetes mellitus is a global epidemic and that diabetic neuropathy is the most common chronic complication of diabetes,the early identification and treatment of CAN could be a key point to mitigate the morbidity and mortality associated with this long-lasting condition.展开更多
Heart failure(HF)is a complex clinical syndrome characterized by the activation of at least several neurohumoral pathways that have a common role in maintaining cardiac output and adequate perfusion pressure of target...Heart failure(HF)is a complex clinical syndrome characterized by the activation of at least several neurohumoral pathways that have a common role in maintaining cardiac output and adequate perfusion pressure of target organs and tissues.The sympathetic nervous system(SNS)is upregulated in HF as evident in dysfunctional baroreceptor and chemoreceptor reflexes,circulating and neuronal catecholamine spillover,attenuated parasympathetic response,and augmented sympathetic outflow to the heart,kidneys and skeletal muscles.When these sympathoexcitatory effects on the cardiovascular system are sustained chronically they initiate the vicious circle of HF progression and become associated with cardiomyocyte apoptosis,maladaptive ventricular and vascular remodeling,arrhythmogenesis,and poor prognosis in patients with HF.These detrimental effects of SNS activity on outcomes in HF warrant adequate diagnostic and treatment modalities.Therefore,this review summarizes basic physiological concepts about the interaction of SNS with the cardiovascular system and highlights key pathophysiological mechanisms of SNS derangement in HF.Finally,special emphasis in this review is placed on the integrative and up-to-date overview of diagnostic modalities such as SNS imaging methods and novel laboratory biomarkers that could aid in the assessment of the degree of SNS activation and provide reliable prognostic information among patients with HF.展开更多
Background:Renal sympathetic nerves are involved in the reflective activation of the sympathetic nervous system in circulatory control.Catheter-based renal denervation (RDN) ameliorated treatment-resistant hypertensio...Background:Renal sympathetic nerves are involved in the reflective activation of the sympathetic nervous system in circulatory control.Catheter-based renal denervation (RDN) ameliorated treatment-resistant hypertension safely,but 10％-20％ of treated patients are nonresponders to radiofrequency denervation.The purpose of this study was to investigate the safety and efficiency of cryoablation for sympathetic denervation in a swine model and to explore a new way of RDN.Methods:Seven swines randomly assigned to two groups:Renal cryoablation (CR) group and control group.The control group underwent renal angiogram only.The CR group underwent renal angiogram plus bilateral renal cryoablation.Renal angiograms via femoral were performed before denervation,after denervation and prior to the sacrifice to access the diameter of renal arterial and the pressure of aorta abdominalis.Euthanasia of the swine was performed on 28-day to access norepinephrine (NE) changes of the renal cortex and the changes of renal nerves.Results:Cryoablation did not induce severe complications at any time point.There was no significant change in diameter of renal artery.CR reduced systolic blood pressure (BP) from 145.50 ± 9.95 mmHg at baseline to 119.00 ± 14.09 mmHg.There was a slight but insignificant decrease in diastolic BP.The main nerve changes at 28-day consisted of necrosis with perineurial fibrosis at the site of CR exposure in conjunction with the nerve vacuolation.Compared with the control group,renal tissue NE of CR group decreased by 89.85％.Conclusions:Percutaneous catheter-based cryoablation of the renal artery is safe.CR could effectively reduce NE storing in the renal cortex,and the efficiency could be maintained 28-day at least.展开更多
Characteristic findings in patients with cirrhosis are vasodilatation with low overall systemic vascular resistance, high arterial compliance, increased cardiac output, secondary activation of counter-regulatory syste...Characteristic findings in patients with cirrhosis are vasodilatation with low overall systemic vascular resistance, high arterial compliance, increased cardiac output, secondary activation of counter-regulatory systems （renin-angiotensin-aldosterone system, sympathetic nervous system, release of vasopressin）, and resistance to vasopressors. The vasodilatory state is mediated through adrenomedullin, calcitonin generelated peptide, nitric oxide, and other vasodilators, and is most pronounced in the splanchnic area. This constitutes an effective （although relative） counterbalance to increased arterial blood pressure. This review considers the alterations in systemic hemodynamics in patients with cirrhosis in relation to essential hypertension and arterial hypertension of the renal origin. Subjects with arterial hypertension （essential, secondary） may become normotensive during the development of cirrhosis, and arterial hypertension is rarely manifested in patients with cirrhosis, even in cases with renovascular disease and high circulating renin activity. There is much dispute as to the understanding of homoeostatic regulation in cirrhotic patients with manifest arterial hypertension. This most likely includes the combination of vasodilatation and vasoconstriction in parallel.展开更多
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and its prevalence is rising. NAFLD is closely associated with metabolic syndrome, with both conditions sharing common clinical chara...Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and its prevalence is rising. NAFLD is closely associated with metabolic syndrome, with both conditions sharing common clinical characteristics such as obesity, insulin resistance, type 2 diabetes mellitus, hypertension, and hypertriglyceridemia. Several observational studies have evaluated the relationship between NAFLD and hypertension, with the overall evidence suggesting a bidirectional relationship. It is hypothesized that activation of the sympathetic nervous and renin-angiotensin systems, observed in NAFLD with or without insulin resistance promotes the development of hypertension. In patients with hypertension, activation of these systems can lead to hepatic fibrosis and progressive inflammation through increased oxidative stress and activation of hepatic stellate cells and Kupffer cells. The present review examines the pathophysiologic and clinical evidence supporting the bidirectional association between NAFLD and hypertension.展开更多
Stroke-induced immunosuppression is a process that leads to peripheral suppression of the immune system after a stroke and belongs to the central nervous system injury-induced immunosuppressive syndrome.Stroke-induced...Stroke-induced immunosuppression is a process that leads to peripheral suppression of the immune system after a stroke and belongs to the central nervous system injury-induced immunosuppressive syndrome.Stroke-induced immunosuppression leads to increased susceptibility to post-stroke infections,such as urinary tract infections and stroke-associated pneumonia,worsening prognosis.Molecular chaperones are a large class of proteins that are able to maintain proteostasis by directing the folding of nascent polypeptide chains,refolding misfolded proteins,and targeting misfolded proteins for degradation.Various molecular chaperones have been shown to play roles in stroke-induced immunosuppression by modulating the activity of other molecular chaperones,cochaperones,and their associated pathways.This review summarizes the role of molecular chaperones in stroke-induced immunosuppression and discusses new approaches to restore host immune defense after stroke.展开更多
Heart failure(HF)is a clinical syndrome that results from a structural or functional cardiac disorder that reduces the ability of the ventricle of the heart to fill with,or eject,blood.It is a multifaceted clinical co...Heart failure(HF)is a clinical syndrome that results from a structural or functional cardiac disorder that reduces the ability of the ventricle of the heart to fill with,or eject,blood.It is a multifaceted clinical condition that affects up to 2%of the population in the developed world,and is linked to significant morbidity and mortality;it is therefore considered a major concern for public health.Regarding the mechanism of HF,three neurohumoral factors-the reninangiotensin-aldosterone system,the sympathetic nervous system,and natriuretic peptides—are related to the pathology of chronic HF(CHF),and the targets of treatment.Angiotensin receptor blocker and neprilysin inhibitor(angiotensinreceptor neprilysin inhibitor),namely sacubitril/valsartan(SAC/VAL),has been introduced as a treatment for CHF.SAC/VAL is an efficacious,safe,and costeffective therapy that improves quality of life and longevity in patients with HF with reduced ejection fraction(HFrEF),and reduces hospital admissions.An inhospital initiation strategy offers a potential new avenue to improve the clinical uptake of SAC/VAL.In the last five years,SAC/VAL has been established as a cornerstone component of comprehensive disease-modifying medical therapy in the management of chronic HFrEF.On the other hand,further work,with carefully designed and controlled preclinical studies,is necessary for understanding the molecular mechanisms,effects,and confirmation of issues such as long-term safety in both human and animal models.展开更多
Background It has been argued that the benefits of reducing sodium loading may be offset by increased activation of the renin-angiotensin-aldosterone system （RAAS） and sympathetic nervous system. This study aimed to...Background It has been argued that the benefits of reducing sodium loading may be offset by increased activation of the renin-angiotensin-aldosterone system （RAAS） and sympathetic nervous system. This study aimed to investigate the long-term effects of an increase in dialysis sodium removal on circulating RAAS and sympathetic system in hypertensive hemodialysis （HD） patients with ＂normal＂ post-HD volume status. Methods Thirty hypertensive HD patients were enrolled in this pilot trial. After one month period of dialysis with standard dialysate sodium of 138 mmol/L, the patients were followed up for a four months period with dialysate sodium set at 136 retool/L, without changes in instructions regarding dietary sodium control. During the period of study, the dry weight was adjusted monthly under the guidance of bioimpedance spectroscopy to maintain post-HD volume status in a steady state; 44-hour ambulatory blood pressure, plasma renin, angiotensin II （Ang II）, aldosterone, and norepinephrine （NE） were measured. Results After four months of HD with low dialysate sodium of 136 mmol/L, 44-hour systolic and diastolic blood pressures （BPs） were significantly lower （-10 and -6 mmHg）, in the absence of changes in antihypertensive medications. No significant changes were observed in plasma renin, Ang II, aldosterone, and NE concentrations. The post-HD volume parameters were kept constant. Conclusion Mildly increasing dialysis sodium removal over 4 months can significantly improve BP control and does not activate circulating RAAS and sympathetic nervous system in hypertensive HD patients. Chin Med J 2014;127 （14）： 2628-2631展开更多
Experimental autoimmune prostatitis(EAP)-induced persistent inflammatory immune response can significantly upregulate the expression of N-methyl-D-aspartic acid(NMDA)receptors in the paraventricular nucleus(PVN).Howev...Experimental autoimmune prostatitis(EAP)-induced persistent inflammatory immune response can significantly upregulate the expression of N-methyl-D-aspartic acid(NMDA)receptors in the paraventricular nucleus(PVN).However,the mechanism has not yet been elucidated.Herein,we screened out the target prostate-derived inflammation cytokines(PDICs)by comparing the inflammatory cytokine levels in peripheral blood and cerebrospinal fluid(CSF)between EAP rats and their controls.After identifying the target PDIC,qualified males in initial copulatory behavior testing(CBT)were subjected to implanting tubes onto bilateral PVN.Next,they were randomly divided into four subgroups(EAP-1,EAP-2,Control-1,and Control-2).After 1-week recovery,EAP-1 rats were microinjected with the target PDIC inhibitor,Control-1 rats were microinjected with the target PDIC,while the EAP-2 and Control-2 subgroups were only treated with the same amount of artificial CSF(aCSF).Results showed that only interleukin-1β(IL-1β)had significantly increased mRNA-expression in the prostate of EAP rats compared to the controls(P<0.001)and significantly higher protein concentrations in both the serum(P=0.001)and CSF(P<0.001)of the EAP groups compared to the Control groups.Therefore,IL-1βwas identified as the target PDIC which crosses the blood-brain barrier,thereby influencing the central nervous system.Moreover,the EAP-1 subgroup displayed a gradually prolonged ejaculation latency(EL)in the last three CBTs(all P<0.01)and a significantly lower expression of NMDA NR1 subunit in the PVN(P=0.043)compared to the respective control groups after a 10-day central administration of IL-1βinhibitors.However,the Control-1 subgroup showed a gradually shortened EL(P<0.01)and a significantly higher NR1 expression(P=0.004)after homochronous IL-1βadministration.Therefore,we identified IL-1βas the primary PDIC which shortens EL in EAP rats.However,further studies should be conducted to elucidate the specific molecular mechanisms through which IL-1βupregulates NMDA expression.展开更多
Cancer is a systemic disease. In order to fully understand it, we must take a holistic view on how cancer interacts with its host. The brain monitors and responds to natural and aberrant signals arriving from the peri...Cancer is a systemic disease. In order to fully understand it, we must take a holistic view on how cancer interacts with its host. The brain monitors and responds to natural and aberrant signals arriving from the periphery, particularly those of metabolic or immune origin. As has been well described, a hallmark of cancer is marked disruption of metabolic and inflammatory processes. Depending on the salience and timing of these inputs, the brain responds via neural and humoral routes to alter whole-body physiology. These responses have consequences for tumor growth and metastasis, directly influencing patient quality of life and subsequent mortality. Additionally, environmental inputs such as light, diet, and stress, can promote inappropriate neural activity that benefits cancer. Here, I discuss evidence for brain-tumor interactions, with special emphasis on subcortical neuromodulator neural populations, and potential ways of harnessing this cross-talk as a novel approach for cancer treatment.展开更多
Despite repeated attempts to develop a unifying hypothesis that explains the clinical syndrome of heart failure(HF),no single conceptual paradigm for HF has withstood the test of time. The last model that has been dev...Despite repeated attempts to develop a unifying hypothesis that explains the clinical syndrome of heart failure(HF),no single conceptual paradigm for HF has withstood the test of time. The last model that has been developed,the neurohormonal model,has the great virtue of highlighting the role of the heart as an endocrine organ,as well as to shed some light on the key role on HF progression of neurohormones and peripheral organs and tissues beyond the heart itself. However,while survival in clinical trials based on neurohormonal antagonist drugs has improved,HF currently remains a lethal condition. At the borders of the neurohormonal model of HF,a partially unexplored path trough the maze of HF pathophysiology is represented by the feedback systems. There are several evidences,from both animal studies and humans reports,that the deregulation of baro-,ergo- and chemo-reflexes in HF patients elicits autonomic imbalance associated with parasympathetic withdrawal and increased adrenergic drive to the heart,thus fundamentally contributing to the evolution of the disease. Hence,on top of guidelinerecommended medical therapy,mainly based on neurohormonal antagonisms,all visceral feedbacks have been recently considered in HF patients as additional potential therapeutic targets.展开更多
OCT is a powerful tool for detection of physiological functions of micro organs underneath the human skin surface, besides the clinical application to ophthalmology, as recently demonstrated by the authors’ group. In...OCT is a powerful tool for detection of physiological functions of micro organs underneath the human skin surface, besides the clinical application to ophthalmology, as recently demonstrated by the authors’ group. In particular, dynamics of peripheral vessels can be observed clearly in the time-sequential OCT images. Among the vascular system, only the small artery has two physiological functions both for the elastic artery and for muscle-controlled one. It, therefore, is important for dynamic analysis of blood flow and circulation. In the time-sequential OCT images obtained with 25 frames/sec, it is found that the small artery makes a sharp response to sound stress for contraction and expansion while it continues pulsation in synchronization with the heartbeats. This result indicates that the small artery exhibits clearly the two physiological functions for blood flow and circulation. In response to sound stress, blood flow is controlled effectively by thickness change of the tunica media which consists of five to six layers of smooth muscles. It is thus found that the thickness of the tunica media changes remarkably in response to external stress, which shows the activity of the sympathetic nerve. The dynamic analysis of the small artery presented here will allow us not only to understand the mechanism of blood flow control and also to detect abnormal physiological functions in the whole vascular system.展开更多
The sympathetic nervous system regulates cardiac output,blood pressure(BP)and volume,electrolyte balance,and the composition of body fluids.The afferent nervous signals to the brain are regulated by mechano-sensitive
BACKGROUND The sympathetic nervous system makes medium and large peripheral arteries smaller to slow the blood flowing through them.AIM To observe brachial artery sympathetic innervation.METHODS We developed a neuroph...BACKGROUND The sympathetic nervous system makes medium and large peripheral arteries smaller to slow the blood flowing through them.AIM To observe brachial artery sympathetic innervation.METHODS We developed a neurophysiological autonomous test that measured the effects of peripheral sympathetic fibres on peripheral arteries.Our specific objective was to find the sympathetic innervation of the brachial artery.To accomplish this purpose,the brachial artery baseline diameter and flow rate were measured in the right arm of the patients.Afterwards,electrical stimulus was applied to the medial nerve for 5 s.Through electrical sympathetic activation,the vessel diameter and overall flow rate will decrease.After 7 d,a similar experiment was repeated using the ulnar nerve.RESULTS The differences in diameter and flow rate of the brachial artery in response to median and ulnar nerve activation were compared.In the total group,no significant difference in diameter was seen between medial and ulnar nerve stimulation(P=0.648).The difference in absolute slowdown of flow rate between median nerve stimulation and ulnar nerve stimulation was not statistically significant for the entire group(P=0.733).CONCLUSION As a target organ,the brachial artery receives an equal amount of sympathetic innervation from the median and the ulnar nerves.展开更多
The sympathetic nervous system is activated in the setting of heart failure(HF)to compensate for hemodynamic instability.However,acute sympathetic surge or sustained high neuronal firing rates activatesβ-adrenergic r...The sympathetic nervous system is activated in the setting of heart failure(HF)to compensate for hemodynamic instability.However,acute sympathetic surge or sustained high neuronal firing rates activatesβ-adrenergic receptor(βAR)signaling contributing to myocardial remodeling,dysfunction and electrical instability.Thus,sympathoβAR activation is regarded as a hallmark of HF and forms pathophysiological basis forβ-blocking therapy.Building upon earlier research findings,studies conducted in the recent decades have significantly advanced our understanding on the sympatho-adrenergic mechanism in HF,which forms the focus of this article.This review notes recent research progress regarding the roles of cardiacβ2AR orα1AR in the failing heart,significance ofβ1AR-autoantibodies,andβAR signaling through G-protein independent signaling pathways.Sympatho-βAR regulation of immune cells or fibroblasts is specifically discussed.On the neuronal aspects,knowledge is assembled on the remodeling of sympathetic nerves of the failing heart,regulation by presynapticα2AR of NE release,and findings on device-based neuromodulation of the sympathetic nervous system.The review ends with highlighting areas where significant knowledge gaps exist but hold promise for new breakthroughs.展开更多
文摘Cardiovascular autonomic neuropathy(CAN)is a debilitating condition that mainly occurs in long-standing type 2 diabetes patients but can manifest earlier,even before diabetes is diagnosed.CAN is a microvascular complication that results from lesions of the sympathetic and parasympathetic nerve fibers,which innervate the heart and blood vessels and promote alterations in cardiovascular autonomic control.The entire mechanism is still not elucidated,but several aspects of the pathophysiology of CAN have already been described,such as the production of advanced glycation end products,reactive oxygen species,nuclear factor kappa B,and pro-inflammatory cytokines.This microvascular complication is an important risk factor for silent myocardial ischemia,chronic kidney disease,myocardial dysfunction,major cardiovascular events,cardiac arrhythmias,and sudden death.It has also been suggested that,compared to other traditional cardiovascular risk factors,CAN progression may have a greater impact on cardiovascular disease development.However,CAN might be subclinical for several years,and a late diagnosis increases the mortality risk.The duration of the transition period from the subclinical to clinical stage remains unknown,but the progression of CAN is associated with a poor prognosis.Several tests can be used for CAN diagnosis,such as heart rate variability(HRV),cardiovascular autonomic reflex tests,and myocardial scintigraphy.Currently,it has already been described that CAN could be detected even during the subclinical stage through a reduction in HRV,which is a non-invasive test with a lower operating cost.Therefore,considering that diabetes mellitus is a global epidemic and that diabetic neuropathy is the most common chronic complication of diabetes,the early identification and treatment of CAN could be a key point to mitigate the morbidity and mortality associated with this long-lasting condition.
文摘Heart failure(HF)is a complex clinical syndrome characterized by the activation of at least several neurohumoral pathways that have a common role in maintaining cardiac output and adequate perfusion pressure of target organs and tissues.The sympathetic nervous system(SNS)is upregulated in HF as evident in dysfunctional baroreceptor and chemoreceptor reflexes,circulating and neuronal catecholamine spillover,attenuated parasympathetic response,and augmented sympathetic outflow to the heart,kidneys and skeletal muscles.When these sympathoexcitatory effects on the cardiovascular system are sustained chronically they initiate the vicious circle of HF progression and become associated with cardiomyocyte apoptosis,maladaptive ventricular and vascular remodeling,arrhythmogenesis,and poor prognosis in patients with HF.These detrimental effects of SNS activity on outcomes in HF warrant adequate diagnostic and treatment modalities.Therefore,this review summarizes basic physiological concepts about the interaction of SNS with the cardiovascular system and highlights key pathophysiological mechanisms of SNS derangement in HF.Finally,special emphasis in this review is placed on the integrative and up-to-date overview of diagnostic modalities such as SNS imaging methods and novel laboratory biomarkers that could aid in the assessment of the degree of SNS activation and provide reliable prognostic information among patients with HF.
基金grants from National Natural Science Foundation of China，the National Basic Research Program of China (No.2011CB503905) from the Ministry of Science and Technology of China
文摘Background:Renal sympathetic nerves are involved in the reflective activation of the sympathetic nervous system in circulatory control.Catheter-based renal denervation (RDN) ameliorated treatment-resistant hypertension safely,but 10％-20％ of treated patients are nonresponders to radiofrequency denervation.The purpose of this study was to investigate the safety and efficiency of cryoablation for sympathetic denervation in a swine model and to explore a new way of RDN.Methods:Seven swines randomly assigned to two groups:Renal cryoablation (CR) group and control group.The control group underwent renal angiogram only.The CR group underwent renal angiogram plus bilateral renal cryoablation.Renal angiograms via femoral were performed before denervation,after denervation and prior to the sacrifice to access the diameter of renal arterial and the pressure of aorta abdominalis.Euthanasia of the swine was performed on 28-day to access norepinephrine (NE) changes of the renal cortex and the changes of renal nerves.Results:Cryoablation did not induce severe complications at any time point.There was no significant change in diameter of renal artery.CR reduced systolic blood pressure (BP) from 145.50 ± 9.95 mmHg at baseline to 119.00 ± 14.09 mmHg.There was a slight but insignificant decrease in diastolic BP.The main nerve changes at 28-day consisted of necrosis with perineurial fibrosis at the site of CR exposure in conjunction with the nerve vacuolation.Compared with the control group,renal tissue NE of CR group decreased by 89.85％.Conclusions:Percutaneous catheter-based cryoablation of the renal artery is safe.CR could effectively reduce NE storing in the renal cortex,and the efficiency could be maintained 28-day at least.
文摘Characteristic findings in patients with cirrhosis are vasodilatation with low overall systemic vascular resistance, high arterial compliance, increased cardiac output, secondary activation of counter-regulatory systems （renin-angiotensin-aldosterone system, sympathetic nervous system, release of vasopressin）, and resistance to vasopressors. The vasodilatory state is mediated through adrenomedullin, calcitonin generelated peptide, nitric oxide, and other vasodilators, and is most pronounced in the splanchnic area. This constitutes an effective （although relative） counterbalance to increased arterial blood pressure. This review considers the alterations in systemic hemodynamics in patients with cirrhosis in relation to essential hypertension and arterial hypertension of the renal origin. Subjects with arterial hypertension （essential, secondary） may become normotensive during the development of cirrhosis, and arterial hypertension is rarely manifested in patients with cirrhosis, even in cases with renovascular disease and high circulating renin activity. There is much dispute as to the understanding of homoeostatic regulation in cirrhotic patients with manifest arterial hypertension. This most likely includes the combination of vasodilatation and vasoconstriction in parallel.
文摘Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and its prevalence is rising. NAFLD is closely associated with metabolic syndrome, with both conditions sharing common clinical characteristics such as obesity, insulin resistance, type 2 diabetes mellitus, hypertension, and hypertriglyceridemia. Several observational studies have evaluated the relationship between NAFLD and hypertension, with the overall evidence suggesting a bidirectional relationship. It is hypothesized that activation of the sympathetic nervous and renin-angiotensin systems, observed in NAFLD with or without insulin resistance promotes the development of hypertension. In patients with hypertension, activation of these systems can lead to hepatic fibrosis and progressive inflammation through increased oxidative stress and activation of hepatic stellate cells and Kupffer cells. The present review examines the pathophysiologic and clinical evidence supporting the bidirectional association between NAFLD and hypertension.
基金the National Natural Science Foundation of China,Nos.82172147(to YL),81571880(to YL),81373147(to YL),30901555(to JZ),30972870(to YL)the Natural Science Foundation of Hunan Province,Nos.2021JJ30900,2016JJ2157(both to YL)。
文摘Stroke-induced immunosuppression is a process that leads to peripheral suppression of the immune system after a stroke and belongs to the central nervous system injury-induced immunosuppressive syndrome.Stroke-induced immunosuppression leads to increased susceptibility to post-stroke infections,such as urinary tract infections and stroke-associated pneumonia,worsening prognosis.Molecular chaperones are a large class of proteins that are able to maintain proteostasis by directing the folding of nascent polypeptide chains,refolding misfolded proteins,and targeting misfolded proteins for degradation.Various molecular chaperones have been shown to play roles in stroke-induced immunosuppression by modulating the activity of other molecular chaperones,cochaperones,and their associated pathways.This review summarizes the role of molecular chaperones in stroke-induced immunosuppression and discusses new approaches to restore host immune defense after stroke.
文摘Heart failure(HF)is a clinical syndrome that results from a structural or functional cardiac disorder that reduces the ability of the ventricle of the heart to fill with,or eject,blood.It is a multifaceted clinical condition that affects up to 2%of the population in the developed world,and is linked to significant morbidity and mortality;it is therefore considered a major concern for public health.Regarding the mechanism of HF,three neurohumoral factors-the reninangiotensin-aldosterone system,the sympathetic nervous system,and natriuretic peptides—are related to the pathology of chronic HF(CHF),and the targets of treatment.Angiotensin receptor blocker and neprilysin inhibitor(angiotensinreceptor neprilysin inhibitor),namely sacubitril/valsartan(SAC/VAL),has been introduced as a treatment for CHF.SAC/VAL is an efficacious,safe,and costeffective therapy that improves quality of life and longevity in patients with HF with reduced ejection fraction(HFrEF),and reduces hospital admissions.An inhospital initiation strategy offers a potential new avenue to improve the clinical uptake of SAC/VAL.In the last five years,SAC/VAL has been established as a cornerstone component of comprehensive disease-modifying medical therapy in the management of chronic HFrEF.On the other hand,further work,with carefully designed and controlled preclinical studies,is necessary for understanding the molecular mechanisms,effects,and confirmation of issues such as long-term safety in both human and animal models.
文摘Background It has been argued that the benefits of reducing sodium loading may be offset by increased activation of the renin-angiotensin-aldosterone system （RAAS） and sympathetic nervous system. This study aimed to investigate the long-term effects of an increase in dialysis sodium removal on circulating RAAS and sympathetic system in hypertensive hemodialysis （HD） patients with ＂normal＂ post-HD volume status. Methods Thirty hypertensive HD patients were enrolled in this pilot trial. After one month period of dialysis with standard dialysate sodium of 138 mmol/L, the patients were followed up for a four months period with dialysate sodium set at 136 retool/L, without changes in instructions regarding dietary sodium control. During the period of study, the dry weight was adjusted monthly under the guidance of bioimpedance spectroscopy to maintain post-HD volume status in a steady state; 44-hour ambulatory blood pressure, plasma renin, angiotensin II （Ang II）, aldosterone, and norepinephrine （NE） were measured. Results After four months of HD with low dialysate sodium of 136 mmol/L, 44-hour systolic and diastolic blood pressures （BPs） were significantly lower （-10 and -6 mmHg）, in the absence of changes in antihypertensive medications. No significant changes were observed in plasma renin, Ang II, aldosterone, and NE concentrations. The post-HD volume parameters were kept constant. Conclusion Mildly increasing dialysis sodium removal over 4 months can significantly improve BP control and does not activate circulating RAAS and sympathetic nervous system in hypertensive HD patients. Chin Med J 2014;127 （14）： 2628-2631
基金This work was supported by the National Natural Science Foundation of China(Grant No.81501245 and No.81971377)Fellowship of China Postdoctoral Science Foundation(Grant No.2020M671393)Jiangsu Province Postdoctoral Research Support Project(Grant No.2020Z134).
文摘Experimental autoimmune prostatitis(EAP)-induced persistent inflammatory immune response can significantly upregulate the expression of N-methyl-D-aspartic acid(NMDA)receptors in the paraventricular nucleus(PVN).However,the mechanism has not yet been elucidated.Herein,we screened out the target prostate-derived inflammation cytokines(PDICs)by comparing the inflammatory cytokine levels in peripheral blood and cerebrospinal fluid(CSF)between EAP rats and their controls.After identifying the target PDIC,qualified males in initial copulatory behavior testing(CBT)were subjected to implanting tubes onto bilateral PVN.Next,they were randomly divided into four subgroups(EAP-1,EAP-2,Control-1,and Control-2).After 1-week recovery,EAP-1 rats were microinjected with the target PDIC inhibitor,Control-1 rats were microinjected with the target PDIC,while the EAP-2 and Control-2 subgroups were only treated with the same amount of artificial CSF(aCSF).Results showed that only interleukin-1β(IL-1β)had significantly increased mRNA-expression in the prostate of EAP rats compared to the controls(P<0.001)and significantly higher protein concentrations in both the serum(P=0.001)and CSF(P<0.001)of the EAP groups compared to the Control groups.Therefore,IL-1βwas identified as the target PDIC which crosses the blood-brain barrier,thereby influencing the central nervous system.Moreover,the EAP-1 subgroup displayed a gradually prolonged ejaculation latency(EL)in the last three CBTs(all P<0.01)and a significantly lower expression of NMDA NR1 subunit in the PVN(P=0.043)compared to the respective control groups after a 10-day central administration of IL-1βinhibitors.However,the Control-1 subgroup showed a gradually shortened EL(P<0.01)and a significantly higher NR1 expression(P=0.004)after homochronous IL-1βadministration.Therefore,we identified IL-1βas the primary PDIC which shortens EL in EAP rats.However,further studies should be conducted to elucidate the specific molecular mechanisms through which IL-1βupregulates NMDA expression.
基金This study was supported by NIMH BRAIN Initiative (F32 MH115431)
文摘Cancer is a systemic disease. In order to fully understand it, we must take a holistic view on how cancer interacts with its host. The brain monitors and responds to natural and aberrant signals arriving from the periphery, particularly those of metabolic or immune origin. As has been well described, a hallmark of cancer is marked disruption of metabolic and inflammatory processes. Depending on the salience and timing of these inputs, the brain responds via neural and humoral routes to alter whole-body physiology. These responses have consequences for tumor growth and metastasis, directly influencing patient quality of life and subsequent mortality. Additionally, environmental inputs such as light, diet, and stress, can promote inappropriate neural activity that benefits cancer. Here, I discuss evidence for brain-tumor interactions, with special emphasis on subcortical neuromodulator neural populations, and potential ways of harnessing this cross-talk as a novel approach for cancer treatment.
文摘Despite repeated attempts to develop a unifying hypothesis that explains the clinical syndrome of heart failure(HF),no single conceptual paradigm for HF has withstood the test of time. The last model that has been developed,the neurohormonal model,has the great virtue of highlighting the role of the heart as an endocrine organ,as well as to shed some light on the key role on HF progression of neurohormones and peripheral organs and tissues beyond the heart itself. However,while survival in clinical trials based on neurohormonal antagonist drugs has improved,HF currently remains a lethal condition. At the borders of the neurohormonal model of HF,a partially unexplored path trough the maze of HF pathophysiology is represented by the feedback systems. There are several evidences,from both animal studies and humans reports,that the deregulation of baro-,ergo- and chemo-reflexes in HF patients elicits autonomic imbalance associated with parasympathetic withdrawal and increased adrenergic drive to the heart,thus fundamentally contributing to the evolution of the disease. Hence,on top of guidelinerecommended medical therapy,mainly based on neurohormonal antagonisms,all visceral feedbacks have been recently considered in HF patients as additional potential therapeutic targets.
文摘OCT is a powerful tool for detection of physiological functions of micro organs underneath the human skin surface, besides the clinical application to ophthalmology, as recently demonstrated by the authors’ group. In particular, dynamics of peripheral vessels can be observed clearly in the time-sequential OCT images. Among the vascular system, only the small artery has two physiological functions both for the elastic artery and for muscle-controlled one. It, therefore, is important for dynamic analysis of blood flow and circulation. In the time-sequential OCT images obtained with 25 frames/sec, it is found that the small artery makes a sharp response to sound stress for contraction and expansion while it continues pulsation in synchronization with the heartbeats. This result indicates that the small artery exhibits clearly the two physiological functions for blood flow and circulation. In response to sound stress, blood flow is controlled effectively by thickness change of the tunica media which consists of five to six layers of smooth muscles. It is thus found that the thickness of the tunica media changes remarkably in response to external stress, which shows the activity of the sympathetic nerve. The dynamic analysis of the small artery presented here will allow us not only to understand the mechanism of blood flow control and also to detect abnormal physiological functions in the whole vascular system.
文摘The sympathetic nervous system regulates cardiac output,blood pressure(BP)and volume,electrolyte balance,and the composition of body fluids.The afferent nervous signals to the brain are regulated by mechano-sensitive
文摘BACKGROUND The sympathetic nervous system makes medium and large peripheral arteries smaller to slow the blood flowing through them.AIM To observe brachial artery sympathetic innervation.METHODS We developed a neurophysiological autonomous test that measured the effects of peripheral sympathetic fibres on peripheral arteries.Our specific objective was to find the sympathetic innervation of the brachial artery.To accomplish this purpose,the brachial artery baseline diameter and flow rate were measured in the right arm of the patients.Afterwards,electrical stimulus was applied to the medial nerve for 5 s.Through electrical sympathetic activation,the vessel diameter and overall flow rate will decrease.After 7 d,a similar experiment was repeated using the ulnar nerve.RESULTS The differences in diameter and flow rate of the brachial artery in response to median and ulnar nerve activation were compared.In the total group,no significant difference in diameter was seen between medial and ulnar nerve stimulation(P=0.648).The difference in absolute slowdown of flow rate between median nerve stimulation and ulnar nerve stimulation was not statistically significant for the entire group(P=0.733).CONCLUSION As a target organ,the brachial artery receives an equal amount of sympathetic innervation from the median and the ulnar nerves.
基金funded by competitive fellowship or project grants from the National Health and Medical Research Council of Australia(236884,1032687,1043026,1081710)National Heart Foundation of Australia(G03M1126,G10M5126)the National Science Foundation of China(81870223,81870300).
文摘The sympathetic nervous system is activated in the setting of heart failure(HF)to compensate for hemodynamic instability.However,acute sympathetic surge or sustained high neuronal firing rates activatesβ-adrenergic receptor(βAR)signaling contributing to myocardial remodeling,dysfunction and electrical instability.Thus,sympathoβAR activation is regarded as a hallmark of HF and forms pathophysiological basis forβ-blocking therapy.Building upon earlier research findings,studies conducted in the recent decades have significantly advanced our understanding on the sympatho-adrenergic mechanism in HF,which forms the focus of this article.This review notes recent research progress regarding the roles of cardiacβ2AR orα1AR in the failing heart,significance ofβ1AR-autoantibodies,andβAR signaling through G-protein independent signaling pathways.Sympatho-βAR regulation of immune cells or fibroblasts is specifically discussed.On the neuronal aspects,knowledge is assembled on the remodeling of sympathetic nerves of the failing heart,regulation by presynapticα2AR of NE release,and findings on device-based neuromodulation of the sympathetic nervous system.The review ends with highlighting areas where significant knowledge gaps exist but hold promise for new breakthroughs.
