Stroke is a major cause of death and disability among adults in China,and an efficient rehabilitation strategy has been an urgent demand for post-stroke rehabilitation.The non-invasive brain stimulation(NBS)can modula...Stroke is a major cause of death and disability among adults in China,and an efficient rehabilitation strategy has been an urgent demand for post-stroke rehabilitation.The non-invasive brain stimulation(NBS)can modulate the excitability of the cerebral cortex and provide after-effects apart from immediate effects to regain extremity motor functions,whereas robotic therapy provides high-intensity and long-duration repetitive movements to stimulate the cerebral cortex backward.The combined strategy of the two techniques is widely regarded as a promising application for stroke patients with dyskinesia.Transcranial magnetic stimulation(TMS)and transcranial electrical stimulation(TES)are important methods of NBS.Their recovery principles,stimulation parameters,and clinical applications have been summarized.The combined treatments of rTMS/tDCS and robotic therapy are analyzed and discussed to overcome the application barriers of the two techniques.The future development trend and the key technical problems are expounded for the clinical applications.展开更多
Mild therapeutic hypothermia has been shown to mitigate cerebral ischemia, reduce cerebral edema, and improve the prognosis of patients with cerebral ischemia. Adipose-derived stem cell-based therapy can decrease neur...Mild therapeutic hypothermia has been shown to mitigate cerebral ischemia, reduce cerebral edema, and improve the prognosis of patients with cerebral ischemia. Adipose-derived stem cell-based therapy can decrease neuronal death and infiltration of inflammatory cells, exerting a neuroprotective effect. We hypothesized that the combination of mild therapeutic hypothermia and adipose-derived stem cells would be neuroprotective for treatment of stroke. A rat model of transient middle cerebral artery occlusion was established using the nylon monofilament method. Mild therapeutic hypothermia（33°C） was induced after 2 hours of ischemia. Adipose-derived stem cells were administered through the femoral vein during reperfusion. The severity of neurological dysfunction was measured by a modified Neurological Severity Score Scaling System. The area of the infarct lesion was determined by 2,3,5-triphenyltetrazolium chloride staining. Apoptotic neurons were detected by terminal deoxynucleotidyl transferase-mediated d UTP-biotin nick end labeling（TUNEL） staining. The regeneration of microvessels and changes in the glial scar were detected by immunofluorescence staining. The inflammatory responses after ischemic brain injury were evaluated by in situ staining using markers of inflammatory cells. The expression of inflammatory cytokines was measured by reverse transcription-polymerase chain reaction. Compared with mild therapeutic hypothermia or adipose-derived stem cell treatment alone, their combination substantially improved neurological deficits and decreased infarct size. They synergistically reduced the number of TUNEL-positive cells and glial fibrillary acidic protein expression, increased vascular endothelial growth factor levels, effectively reduced inflammatory cell infiltration and down-regulated the m RNA expression of the proinflammatory cytokines interleukin-1β, tumor necrosis factor-α and interleukin-6. Our findings indicate that combined treatment is a better approach for treating stroke compared with mild therapeutic hypothermia or adipose-derived stem cells alone.展开更多
Glioblastoma multiforme(GBM) is the most common primary malignant brain tumor, and it is associated with poor prognosis. Its characteristics of being highly invasive and undergoing heterogeneous genetic mutation, as w...Glioblastoma multiforme(GBM) is the most common primary malignant brain tumor, and it is associated with poor prognosis. Its characteristics of being highly invasive and undergoing heterogeneous genetic mutation, as well as the presence of the blood–brain barrier(BBB), have reduced the efficacy of GBM treatment. The emergence of a novel therapeutic method, namely, sonodynamic therapy(SDT), provides a promising strategy for eradicating tumors via activated sonosensitizers coupled with low-intensity ultrasound. SDT can provide tumor killing effects for deep-seated tumors, such as brain tumors. However, conventional sonosensitizers cannot effectively reach the tumor region and kill additional tumor cells, especially brain tumor cells. Efforts should be made to develop a method to help therapeutic agents pass through the BBB and accumulate in brain tumors. With the development of novel multifunctional nanosensitizers and newly emerging combination strategies, the killing ability and selectivity of SDT have greatly improved and are accompanied with fewer side effects. In this review, we systematically summarize the findings of previous studies on SDT for GBM, with a focus on recent developments and promising directions for future research.展开更多
Introduction: The use of repeated thermal therapy for improving the symptoms of chronic heart failure (CHF) has been recently demonstrated. Usually, thermal therapy requires an infrared dry sauna. However, it is diffi...Introduction: The use of repeated thermal therapy for improving the symptoms of chronic heart failure (CHF) has been recently demonstrated. Usually, thermal therapy requires an infrared dry sauna. However, it is difficult for small clinics to acquire such an expensive and extensive system. The author assessed the efficacy of its substitution with hot water bottles. Moreover, there are no prior studies demonstrating the efficacy of thermal therapy in hemodialysis patients with chronic heart failure. Methods: The author evaluated plasma brain natriuretic peptide (BNP) levels in 98 hemodialysis patients in a clinic. A total of nine patients whose BNP levels were more than 500 pg/mL agreed to be enrolled in this study and received thermal therapy using hot water bottles. Results: Plasma BNP levels, a potential marker for CHF, tended to decrease (891 ± 448 pg/mL to 680 ± 339 pg/mL), but the difference was not significant (P = 0.0845). The oral temperature changed from 36.44℃± 0.45℃ to 37.04℃ ± 0.48℃ (+0.597℃, P < 0.0001). No side effects were experienced during the therapy. Moreover, most patients had an improvement in their symptoms and the ability to perform activities of daily living. Conclusion: Thermal therapy using hot water bottles is very safe and tends to reduce plasma BNP levels in hemodialysis patients with CHF.展开更多
One hundred patients with focal epilepsy were recruited for the present study and their seizures controlled with antiepileptic drugs. The patients then orally received a capsule of tall gastrodis tuber powder, a tradi...One hundred patients with focal epilepsy were recruited for the present study and their seizures controlled with antiepileptic drugs. The patients then orally received a capsule of tall gastrodis tuber powder, a traditional Chinese drug, and underwent single photon emission computed tomography, long-term electroencephalogram, and CT/MRI. Blood drug levels were monitored throughout the study. Before treatment with tall gastrodis tuber, 35 of the 100 cases had abnormal CT/MRI scans; 79 cases had abnormal single photon emission computed tomography images; 86 cases had abnormal electroencephalogram; and a total of 146 abnormal perfusion foci were observed across the 100 subjects. After treatment, the number of patients with normal single photon emission computed tomography images increased by 12; normal electroencephalogram was observed in an additional 27 cases and the number of patients with epileptiform discharge decreased by 29 （34% of 86）; the total number of abnormal perfusion foci decreased by 52 （36%） and changes in abnormal loci were visible in 65 patients. These changes indicate that the administration of tall gastrodis tuber in combination with antiepileptic drugs repairs abnormal perfusion foci in patients with focal epilepsy Our results demonstrate that traditional Chinese drugs can repair abnormal perfusion foci and, as such, are a promising new pathway in the treatment of focal epilepsy.展开更多
Activation of neuroprotective and particularly later neurorestorative mechanisms after stroke attempts to restore or compensate for lost functions.This potentially opens a wide window for restorative therapies to prom...Activation of neuroprotective and particularly later neurorestorative mechanisms after stroke attempts to restore or compensate for lost functions.This potentially opens a wide window for restorative therapies to promote brain repair and improve long-term functional recovery.Although extensively demonstrated in the preclinical setting,the efficacy of cell-based therapies in stroke patients has been modest at best,if any at all.Translational failure may be due to the ineffective survival and integration of transplanted cells in pro-death stroke microenvironments that are not conducive for the structural reconstruction of damaged brain tissue and repair-related network reorganization.Optimal systemic delivery,timing,cell product,and dose remain open as well.Fortunately,a better understanding of the brain plasticity mechanisms underlying stroke recovery has ushered in a combination approach of cell-based therapy and rehabilitation that is aimed at achieving additive,synergistic,or even maximal beneficial effects.This novel combination therapy is not only targeted at promoting exogenous and endogenous cell survival and augmenting stand-alone restorative mechanisms but also at utilizing rehabilitation to facilitate a graft–host structural and functional integration and plasticity that would effectively remodel stroke tissue and restitute lost functions.This review presents an overview of the combination of cell-based therapy and experimental rehabilitation in stroke models.It also discusses associated shortcomings as well as proposes strategies to address them and help facilitate the advancement of this combination approach.展开更多
Chronic kidney disease(CKD)and hypertension(HTN)are closely associated with an overlapping and intermingled cause and effect relationship.Decline in renal functions are usually associated with a rise in blood pressure...Chronic kidney disease(CKD)and hypertension(HTN)are closely associated with an overlapping and intermingled cause and effect relationship.Decline in renal functions are usually associated with a rise in blood pressure(BP),and prolonged elevations in BP hasten the progression of kidney function decline.Regulation of HTN by normalizing the BP in an individual,thereby slowing the progression of kidney disease and reducing the risk of cardiovascular disease,can be effectively achieved by the anti-hypertensive use of calcium channel blockers(CCBs).Use of dihydropyridine CCBs such as amlodipine(ALM)in patients with CKD is an attractive option not only for controlling BP but also for safely improving patient outcomes.Vast clinical experiences with its use as monotherapy and/or in combination with other anti-hypertensives in varied conditions have demonstrated its superior qualities in effectively managing HTN in patients with CKD with minimal adverse effects.In comparison to other counterparts,ALM displays robust reduction in risk of cardiovascular endpoints,particularly stroke,and in patients with renal impairment.ALM with its longer half-life displays effective BP control over 24-h,thereby reducing the progression of endstage-renal disease.In conclusion,compared to other classes of CCBs,ALM is an attractive choice for effectively managing HTN in CKD patients and improving the overall quality of life.展开更多
Lipogenesis is often highly upregulated in breast cancer brain metastases to adapt to intracranial low lipid microenvironments.Lipase inhibitors hold therapeutic potential but their intra-tumoral distribution is often...Lipogenesis is often highly upregulated in breast cancer brain metastases to adapt to intracranial low lipid microenvironments.Lipase inhibitors hold therapeutic potential but their intra-tumoral distribution is often blocked by the blood-tumor barrier(BTB).BTB activates its Wnt signaling to maintain barrier properties,e.g.,Mfsd2a-mediated BTB low transcytosis.Here,we reported VCAM-1-targeting nano-wogonin(W@V-NPs)as an adjuvant of nano-orlistat(O@V-NPs)to intensify drug delivery and inhibit lipogenesis of brain metastases.W@V-NPs were proven to be able to inactivate BTB Wnt signaling,downregulate BTB Mfsd2a,accelerate BTB vesicular transport,and enhance tumor accumulation of O@V-NPs.With the ability to specifically kill cancer cells in a lipid-deprived environment with IC_(50) at 48 ng/mL,W@V-NPs plus O@V-NPs inhibited the progression of brain metastases with prolonged survival of model mice.The combination did not induce brain edema,cognitive impairment,and systemic toxicity in healthy mice.Targeting Wnt signaling could safely modulate the BTB to improve drug delivery and metabolic therapy against brain metastases.展开更多
Effective treatment of Parkinson’s disease(PD),a prevalent central neurodegenerative disorder particularly affecting the elderly population,still remains a huge challenge.We present here a novel nanomedicine formulat...Effective treatment of Parkinson’s disease(PD),a prevalent central neurodegenerative disorder particularly affecting the elderly population,still remains a huge challenge.We present here a novel nanomedicine formulation based on bioactive hydroxyl-terminated phosphorous dendrimers(termed as AK123)complexed with fibronectin(FN)with anti-inflammatory and antioxidative activities.The created optimized AK123/FN nanocomplexes(NCs)with a size of 223 nm display good colloidal stability in aqueous solution and can be specifically taken up by microglia through FN-mediated targeting.We show that the AK123/FN NCs are able to consume excessive reactive oxygen species,promote microglia M2 polarization and inhibit the nuclear factor-kappa B signaling pathway to downregulate inflammatory factors.With the abundant dendrimer surface hydroxyl terminal groups,the developed NCs are able to cross blood-brain barrier(BBB)to exert targeted therapy of a PD mouse model through the AK123-mediated anti-inflammation for M2 polarization of microglia and FN-mediated antioxidant and anti-inflammatory effects,thus reducing the aggregation ofα-synuclein and restoring the contents of dopamine and tyrosine hydroxylase to normal levels in vivo.The developed dendrimer/FN NCs combine the advantages of BBB-crossing hydroxyl-terminated bioactive per se phosphorus dendrimers and FN,which is expected to be extended for the treatment of different neurodegenerative diseases.展开更多
目的基于脑肠轴理论观察针刺治疗卒中后抑郁的临床疗效。方法选取74例卒中后抑郁患者,根据随机数字表法分为试验组和对照组,每组37例。两组均采用常规西药治疗,对照组采用醒脑开窍针刺法治疗,试验组在对照组基础上联合基于脑肠轴理论取...目的基于脑肠轴理论观察针刺治疗卒中后抑郁的临床疗效。方法选取74例卒中后抑郁患者,根据随机数字表法分为试验组和对照组,每组37例。两组均采用常规西药治疗,对照组采用醒脑开窍针刺法治疗,试验组在对照组基础上联合基于脑肠轴理论取穴的电针治疗。比较两组临床疗效,观察两组治疗前后中医主症积分、汉密顿抑郁量表(Hamilton depression scale,HAMD)评分、美国国立卫生研究院卒中量表(National Institute of Health stroke scale,NIHSS)评分和日常生活能力量表(activity of daily living,ADL)评分的变化,比较两组治疗前后血清胃泌素(gastrin,GAS)、生长抑素(somatostatin,SS)、5-羟色胺(5-hydroxytryptamin,5-HT)和脑源性神经生长因子(brain-derived neuotrophyic factor,BDNF)水平的变化。结果试验组抑郁总有效率和中医证候总有效率均高于对照组(P<0.05)。两组治疗后中医主症积分、HAMD评分和NIHSS评分均较同组治疗前降低(P<0.05),ADL评分较同组治疗前升高(P<0.05);试验组治疗后上述评分均优于对照组(P<0.05)。两组治疗后血清SS水平均降低(P<0.05),血清GAS、5-HT和BDNF水平均升高(P<0.05);且试验组治疗后血清SS水平低于对照组(P<0.05),血清GAS、5-HT和BDNF水平高于对照组(P<0.05)。结论在常规西药治疗基础上,醒脑开窍针刺法联合基于脑肠轴理论取穴的电针治疗可更好地缓解卒中后抑郁患者的临床症状,改善神经功能和日常生活能力,提高临床疗效,这可能与调节血清SS、GAS、5-HT和BDNF水平有关。展开更多
目的观察针刺配合通络益气汤治疗脑小血管病致认知功能障碍的临床疗效及其对患者脑微循环、步态平衡和血清神经元PAS结构域蛋白4(neuronal PAS domain protein 4,NPAS4)、P-选择素(CD62P)表达的影响。方法将98例脑小血管病致认知功能障...目的观察针刺配合通络益气汤治疗脑小血管病致认知功能障碍的临床疗效及其对患者脑微循环、步态平衡和血清神经元PAS结构域蛋白4(neuronal PAS domain protein 4,NPAS4)、P-选择素(CD62P)表达的影响。方法将98例脑小血管病致认知功能障碍患者随机分为治疗组和对照组,每组49例。治疗组采用针刺配合通络益气汤治疗,对照组采用单纯通络益气汤治疗。观察两组治疗前后各项实验室指标[谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)、晚期糖基化终末产物(advanced glycation end products,AGEs)、NPAS4、CD62P、一氧化氮(NO)、亲环素A(cyclophilin A,CyPA)、脂蛋白相关磷脂酶A2(lipoprotein-associated phospholipase A2,Lp-PLA2)、血管性血友病因子(von Willebrand factor,vFW)水平]、脑微循环指标[血脑屏障通透性、血管差压、临界压力(critical pressure,CP)、脑血管动态阻力(dynamic resistance,DR)]及各量表[Berg平衡量表(Berg balance scale,BBS)、Tinetti平衡与步态量表、蒙特利尔认知评估量表(Montreal cognitive assessment,MoCA]评分的变化情况,并比较两组临床疗效。结果两组治疗后GSH-Px、NO水平及CP、各量表评分均较同组治疗前显著上升,AGEs、NPAS4、CD62P、CyPA、Lp-PLA2、vFW水平及血脑屏障通透性、血管差压、DR显著下降,差异均具有统计学意义(P<0.05)。治疗组治疗后GSH-Px、NO水平及CP、各量表评分均明显高于对照组,AGEs、NPAS4、CD62P、CyPA、Lp-PLA2、vFW水平及血脑屏障通透性、血管差压、DR均明显低于对照组,两组比较差异均具有统计学意义(P<0.05)。治疗组总有效率为98.0%,明显高于对照组的87.8%,两组比较差异具有统计学意义(P<0.05)。结论针刺配合通络益气汤治疗脑小血管病致认知功能障碍疗效确切,可减少氧化应激反应及炎症反应,降低NPAS4、CD62P水平,减少血管内皮功能及认知功能损伤,改善血脑屏障通透性、脑微循环及步态平衡。展开更多
基金Supported by National Natural Science Foundation of China(Grant Nos.52375279,52175001)National Key R&D Program of China(Grant No.2018YFB1307004).
文摘Stroke is a major cause of death and disability among adults in China,and an efficient rehabilitation strategy has been an urgent demand for post-stroke rehabilitation.The non-invasive brain stimulation(NBS)can modulate the excitability of the cerebral cortex and provide after-effects apart from immediate effects to regain extremity motor functions,whereas robotic therapy provides high-intensity and long-duration repetitive movements to stimulate the cerebral cortex backward.The combined strategy of the two techniques is widely regarded as a promising application for stroke patients with dyskinesia.Transcranial magnetic stimulation(TMS)and transcranial electrical stimulation(TES)are important methods of NBS.Their recovery principles,stimulation parameters,and clinical applications have been summarized.The combined treatments of rTMS/tDCS and robotic therapy are analyzed and discussed to overcome the application barriers of the two techniques.The future development trend and the key technical problems are expounded for the clinical applications.
基金supported by the National Natural Science Foundation of China,No.81371301
文摘Mild therapeutic hypothermia has been shown to mitigate cerebral ischemia, reduce cerebral edema, and improve the prognosis of patients with cerebral ischemia. Adipose-derived stem cell-based therapy can decrease neuronal death and infiltration of inflammatory cells, exerting a neuroprotective effect. We hypothesized that the combination of mild therapeutic hypothermia and adipose-derived stem cells would be neuroprotective for treatment of stroke. A rat model of transient middle cerebral artery occlusion was established using the nylon monofilament method. Mild therapeutic hypothermia（33°C） was induced after 2 hours of ischemia. Adipose-derived stem cells were administered through the femoral vein during reperfusion. The severity of neurological dysfunction was measured by a modified Neurological Severity Score Scaling System. The area of the infarct lesion was determined by 2,3,5-triphenyltetrazolium chloride staining. Apoptotic neurons were detected by terminal deoxynucleotidyl transferase-mediated d UTP-biotin nick end labeling（TUNEL） staining. The regeneration of microvessels and changes in the glial scar were detected by immunofluorescence staining. The inflammatory responses after ischemic brain injury were evaluated by in situ staining using markers of inflammatory cells. The expression of inflammatory cytokines was measured by reverse transcription-polymerase chain reaction. Compared with mild therapeutic hypothermia or adipose-derived stem cell treatment alone, their combination substantially improved neurological deficits and decreased infarct size. They synergistically reduced the number of TUNEL-positive cells and glial fibrillary acidic protein expression, increased vascular endothelial growth factor levels, effectively reduced inflammatory cell infiltration and down-regulated the m RNA expression of the proinflammatory cytokines interleukin-1β, tumor necrosis factor-α and interleukin-6. Our findings indicate that combined treatment is a better approach for treating stroke compared with mild therapeutic hypothermia or adipose-derived stem cells alone.
基金partially supported by the National Natural Science Foundation of China(81702457)the Clinical Medical University and Hospital Joint Construction of Disciplinary Projects 2021(2021lcxk017)+4 种基金the Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer(2020B121201004)the Outstanding Youths Development Scheme of Nanfang Hospital,Southern Medical University(2021J008)the Basic and Clinical Cooperative Research and Promotion Program of Anhui Medical University(2021xkjT028)the Open Fund of Key Laboratory of Antiinflammatory and Immune Medicine(KFJJ-2021-11)Grants for Scientific Research of BSKY from Anhui Medical University(1406012201)。
文摘Glioblastoma multiforme(GBM) is the most common primary malignant brain tumor, and it is associated with poor prognosis. Its characteristics of being highly invasive and undergoing heterogeneous genetic mutation, as well as the presence of the blood–brain barrier(BBB), have reduced the efficacy of GBM treatment. The emergence of a novel therapeutic method, namely, sonodynamic therapy(SDT), provides a promising strategy for eradicating tumors via activated sonosensitizers coupled with low-intensity ultrasound. SDT can provide tumor killing effects for deep-seated tumors, such as brain tumors. However, conventional sonosensitizers cannot effectively reach the tumor region and kill additional tumor cells, especially brain tumor cells. Efforts should be made to develop a method to help therapeutic agents pass through the BBB and accumulate in brain tumors. With the development of novel multifunctional nanosensitizers and newly emerging combination strategies, the killing ability and selectivity of SDT have greatly improved and are accompanied with fewer side effects. In this review, we systematically summarize the findings of previous studies on SDT for GBM, with a focus on recent developments and promising directions for future research.
文摘Introduction: The use of repeated thermal therapy for improving the symptoms of chronic heart failure (CHF) has been recently demonstrated. Usually, thermal therapy requires an infrared dry sauna. However, it is difficult for small clinics to acquire such an expensive and extensive system. The author assessed the efficacy of its substitution with hot water bottles. Moreover, there are no prior studies demonstrating the efficacy of thermal therapy in hemodialysis patients with chronic heart failure. Methods: The author evaluated plasma brain natriuretic peptide (BNP) levels in 98 hemodialysis patients in a clinic. A total of nine patients whose BNP levels were more than 500 pg/mL agreed to be enrolled in this study and received thermal therapy using hot water bottles. Results: Plasma BNP levels, a potential marker for CHF, tended to decrease (891 ± 448 pg/mL to 680 ± 339 pg/mL), but the difference was not significant (P = 0.0845). The oral temperature changed from 36.44℃± 0.45℃ to 37.04℃ ± 0.48℃ (+0.597℃, P < 0.0001). No side effects were experienced during the therapy. Moreover, most patients had an improvement in their symptoms and the ability to perform activities of daily living. Conclusion: Thermal therapy using hot water bottles is very safe and tends to reduce plasma BNP levels in hemodialysis patients with CHF.
基金funded by the Key Project of Gansu Province, No.2GS054-A43-014-19
文摘One hundred patients with focal epilepsy were recruited for the present study and their seizures controlled with antiepileptic drugs. The patients then orally received a capsule of tall gastrodis tuber powder, a traditional Chinese drug, and underwent single photon emission computed tomography, long-term electroencephalogram, and CT/MRI. Blood drug levels were monitored throughout the study. Before treatment with tall gastrodis tuber, 35 of the 100 cases had abnormal CT/MRI scans; 79 cases had abnormal single photon emission computed tomography images; 86 cases had abnormal electroencephalogram; and a total of 146 abnormal perfusion foci were observed across the 100 subjects. After treatment, the number of patients with normal single photon emission computed tomography images increased by 12; normal electroencephalogram was observed in an additional 27 cases and the number of patients with epileptiform discharge decreased by 29 （34% of 86）; the total number of abnormal perfusion foci decreased by 52 （36%） and changes in abnormal loci were visible in 65 patients. These changes indicate that the administration of tall gastrodis tuber in combination with antiepileptic drugs repairs abnormal perfusion foci in patients with focal epilepsy Our results demonstrate that traditional Chinese drugs can repair abnormal perfusion foci and, as such, are a promising new pathway in the treatment of focal epilepsy.
基金European Commission under the Horizon 2020 program,Grant/Award Number:681044。
文摘Activation of neuroprotective and particularly later neurorestorative mechanisms after stroke attempts to restore or compensate for lost functions.This potentially opens a wide window for restorative therapies to promote brain repair and improve long-term functional recovery.Although extensively demonstrated in the preclinical setting,the efficacy of cell-based therapies in stroke patients has been modest at best,if any at all.Translational failure may be due to the ineffective survival and integration of transplanted cells in pro-death stroke microenvironments that are not conducive for the structural reconstruction of damaged brain tissue and repair-related network reorganization.Optimal systemic delivery,timing,cell product,and dose remain open as well.Fortunately,a better understanding of the brain plasticity mechanisms underlying stroke recovery has ushered in a combination approach of cell-based therapy and rehabilitation that is aimed at achieving additive,synergistic,or even maximal beneficial effects.This novel combination therapy is not only targeted at promoting exogenous and endogenous cell survival and augmenting stand-alone restorative mechanisms but also at utilizing rehabilitation to facilitate a graft–host structural and functional integration and plasticity that would effectively remodel stroke tissue and restitute lost functions.This review presents an overview of the combination of cell-based therapy and experimental rehabilitation in stroke models.It also discusses associated shortcomings as well as proposes strategies to address them and help facilitate the advancement of this combination approach.
文摘Chronic kidney disease(CKD)and hypertension(HTN)are closely associated with an overlapping and intermingled cause and effect relationship.Decline in renal functions are usually associated with a rise in blood pressure(BP),and prolonged elevations in BP hasten the progression of kidney function decline.Regulation of HTN by normalizing the BP in an individual,thereby slowing the progression of kidney disease and reducing the risk of cardiovascular disease,can be effectively achieved by the anti-hypertensive use of calcium channel blockers(CCBs).Use of dihydropyridine CCBs such as amlodipine(ALM)in patients with CKD is an attractive option not only for controlling BP but also for safely improving patient outcomes.Vast clinical experiences with its use as monotherapy and/or in combination with other anti-hypertensives in varied conditions have demonstrated its superior qualities in effectively managing HTN in patients with CKD with minimal adverse effects.In comparison to other counterparts,ALM displays robust reduction in risk of cardiovascular endpoints,particularly stroke,and in patients with renal impairment.ALM with its longer half-life displays effective BP control over 24-h,thereby reducing the progression of endstage-renal disease.In conclusion,compared to other classes of CCBs,ALM is an attractive choice for effectively managing HTN in CKD patients and improving the overall quality of life.
基金supported by the National Natural Science Foundation of China(32171381 and 81973254)the National Innovation of Science and Technology-2030(Program of Brain Science and Brain-Inspired Intelligence Technology)grant(2021ZD0204004,China)+1 种基金Jiangsu Key Laboratory of Neuropsychiatric Diseases Research Major Program(No.ZZ2101,China)the Priority Academic Program Development of the Jiangsu Higher Education Institutes(PAPD),Suzhou International Joint Laboratory for Diagnosis and Treatment of Brain Diseases,and the Suzhou Science and Technology Development Project(No.SJC2022021,China).
文摘Lipogenesis is often highly upregulated in breast cancer brain metastases to adapt to intracranial low lipid microenvironments.Lipase inhibitors hold therapeutic potential but their intra-tumoral distribution is often blocked by the blood-tumor barrier(BTB).BTB activates its Wnt signaling to maintain barrier properties,e.g.,Mfsd2a-mediated BTB low transcytosis.Here,we reported VCAM-1-targeting nano-wogonin(W@V-NPs)as an adjuvant of nano-orlistat(O@V-NPs)to intensify drug delivery and inhibit lipogenesis of brain metastases.W@V-NPs were proven to be able to inactivate BTB Wnt signaling,downregulate BTB Mfsd2a,accelerate BTB vesicular transport,and enhance tumor accumulation of O@V-NPs.With the ability to specifically kill cancer cells in a lipid-deprived environment with IC_(50) at 48 ng/mL,W@V-NPs plus O@V-NPs inhibited the progression of brain metastases with prolonged survival of model mice.The combination did not induce brain edema,cognitive impairment,and systemic toxicity in healthy mice.Targeting Wnt signaling could safely modulate the BTB to improve drug delivery and metabolic therapy against brain metastases.
基金supported by the National Natural Science Foundation of China(52350710203 and U23A2096)the Science and Technology Commission of Shanghai Municipality(21490711500,23WZ2503300,23520712500 and 20DZ2254900)+2 种基金the National Key R&D Program(2022YFE0196900)the Shanghai Education Commission through the leading talent program.S.M.and X.S.also acknowledge the support by the Fundaçao para a Ciencia e a Tecnologia(FCT)with Portuguese Government funds through the CQM Base Fund-UIDB/00674/2020(DOI:10.54499/UIDB/00674/2020)Programmatic Fund-UIDP/00674/2020(DOI:10.54499/UIDP/00674/2020).
文摘Effective treatment of Parkinson’s disease(PD),a prevalent central neurodegenerative disorder particularly affecting the elderly population,still remains a huge challenge.We present here a novel nanomedicine formulation based on bioactive hydroxyl-terminated phosphorous dendrimers(termed as AK123)complexed with fibronectin(FN)with anti-inflammatory and antioxidative activities.The created optimized AK123/FN nanocomplexes(NCs)with a size of 223 nm display good colloidal stability in aqueous solution and can be specifically taken up by microglia through FN-mediated targeting.We show that the AK123/FN NCs are able to consume excessive reactive oxygen species,promote microglia M2 polarization and inhibit the nuclear factor-kappa B signaling pathway to downregulate inflammatory factors.With the abundant dendrimer surface hydroxyl terminal groups,the developed NCs are able to cross blood-brain barrier(BBB)to exert targeted therapy of a PD mouse model through the AK123-mediated anti-inflammation for M2 polarization of microglia and FN-mediated antioxidant and anti-inflammatory effects,thus reducing the aggregation ofα-synuclein and restoring the contents of dopamine and tyrosine hydroxylase to normal levels in vivo.The developed dendrimer/FN NCs combine the advantages of BBB-crossing hydroxyl-terminated bioactive per se phosphorus dendrimers and FN,which is expected to be extended for the treatment of different neurodegenerative diseases.
文摘目的基于脑肠轴理论观察针刺治疗卒中后抑郁的临床疗效。方法选取74例卒中后抑郁患者,根据随机数字表法分为试验组和对照组,每组37例。两组均采用常规西药治疗,对照组采用醒脑开窍针刺法治疗,试验组在对照组基础上联合基于脑肠轴理论取穴的电针治疗。比较两组临床疗效,观察两组治疗前后中医主症积分、汉密顿抑郁量表(Hamilton depression scale,HAMD)评分、美国国立卫生研究院卒中量表(National Institute of Health stroke scale,NIHSS)评分和日常生活能力量表(activity of daily living,ADL)评分的变化,比较两组治疗前后血清胃泌素(gastrin,GAS)、生长抑素(somatostatin,SS)、5-羟色胺(5-hydroxytryptamin,5-HT)和脑源性神经生长因子(brain-derived neuotrophyic factor,BDNF)水平的变化。结果试验组抑郁总有效率和中医证候总有效率均高于对照组(P<0.05)。两组治疗后中医主症积分、HAMD评分和NIHSS评分均较同组治疗前降低(P<0.05),ADL评分较同组治疗前升高(P<0.05);试验组治疗后上述评分均优于对照组(P<0.05)。两组治疗后血清SS水平均降低(P<0.05),血清GAS、5-HT和BDNF水平均升高(P<0.05);且试验组治疗后血清SS水平低于对照组(P<0.05),血清GAS、5-HT和BDNF水平高于对照组(P<0.05)。结论在常规西药治疗基础上,醒脑开窍针刺法联合基于脑肠轴理论取穴的电针治疗可更好地缓解卒中后抑郁患者的临床症状,改善神经功能和日常生活能力,提高临床疗效,这可能与调节血清SS、GAS、5-HT和BDNF水平有关。
