The predictive value of serum F-actin on the severity and early neurological deterioration of acute ischemic stroke: Predictive value of F-actin in stroke.

BACKGROUND: F-actin is involved in the progression of ischemic stroke and is associated with the disruption of the blood-brain barrier. In this article, we evaluated serum F-actin as a biomarker in stroke severity and early neurological deterioration (END) in acute ischemic stroke. METHODS: In this study, serum F-actin was measured in consecutively collected 140 AIS patients and 144 healthy controls matched in gender and age by ELISA. Early neurological deterioration (END) was defined as the deterioration of neurological dysfunction within 72 hours of admission, with an increase of ≥ 4 points in the NIHSS score. Severe stroke was defined as a NIHSS score>8 at admission. RESULTS: The serum F-actin level in AIS was significantly higher than healthy controls (p = 0.041). In large-artery atherosclerosis stroke and cardioembolic stroke, serum F-actin were significantly higher than that in small artery occlusion stroke (padjust = 0.019, padjust < 0.001, respectively).F-actin level above the critical value (>1.37 µg/L) was significantly associated with severe stroke (OR, 3.015; 95 %CI, 1.014-8.963; p = 0.047) . In addition, elevated level of F-actin was significantly associated with END (OR, 1.323; 95 % CI, 1.001-1.747, p = 0.049). When the level of F-actin was above the critical value (>2.17 µg/L), its association with END remained significant (OR, 6.303; 95 %CI, 2.160-18.394; p < 0.001) . CONCLUSION: F-actin is an important blood biomarker in the early stage of AIS, and high levels of F-actin are valuable in determining the severity of stroke and predicting early neurological deterioration.

Safety of early antiplatelet therapy for non-cardioembolic mild stroke patients with thrombocytopenia. / åˆå¹¶è¡€å°æ¿å‡å°‘ç—‡çš„éžå¿ƒæºæ€§è½»åž‹è„‘å’ä¸­æ‚£è€ æ—©æœŸæŠ—è¡€å°æ¿æ²»ç–—çš„å®‰å ¨æ€§ç ”ç©¶.

OBJECTIVES: To investigate the safety of early antiplatelet therapy for non-cardioembolic mild stroke patients with thrombocytopenia. METHODS: Data of acute ischemic stroke patients with baseline National Institutes of Health Stroke Scale (NIHSS) score ≤3 and a platelet count <100×109/L were obtained from a multicenter register. Those who required anticoagulation or had other contraindications to antiplatelet therapy were excluded. Short-term safety outcomes were in-hospital bleeding events, while the long-term safety outcome was a 1-year all-cause death. The short-term neurological outcomes were evaluated by modified Rankin scale (mRS) score at discharge. RESULTS: A total of 1868 non-cardioembolic mild stroke patients with thrombocytopenia were enrolled. Multivariate regression analyses showed that mono-antiplatelet therapy significantly increased the proportion of mRS score of 0-1 at discharge (OR=1.657, 95%CI: 1.253-2.192, P<0.01) and did not increase the risk of intracranial hemorrhage (OR=2.359, 95%CI: 0.301-18.503, P>0.05), compared with those without antiplatelet therapy. However, dual-antiplatelet therapy did not bring more neurological benefits (OR=0.923, 95%CI: 0.690-1.234, P>0.05), but increased the risk of gastrointestinal bleeding (OR=2.837, 95%CI: 1.311-6.136, P<0.01) compared with those with mono-antiplatelet therapy. For patients with platelet counts ≤75×109/L and >90×109/L, antiplatelet therapy significantly improved neurological functional outcomes (both P<0.05). For those with platelet counts (>75-90)×109/L, antiplatelet therapy resulted in a significant improvement of 1-year survival (P<0.05). For patients even with concurrent coagulation abnormalities, mono-antiplatelet therapy did not increase the risk of various types of bleeding (all P>0.05) but improved neurological functional outcomes (all P<0.01). There was no significant difference in the occurrence of bleeding events, 1-year all-cause mortality risk, and neurological functional outcomes between aspirin and clopidogrel (all P>0.05). CONCLUSIONS: For non-cardioembolic mild stroke patients with thrombocytopenia, antiplatelet therapy remains a reasonable choice. Mono-antiplatelet therapy has the same efficiency as dual-antiplatelet therapy in neurological outcome improvement with lower risk of gastrointestinal bleeding.

Patients with Parkinson's disease demonstrate deficits in visual-spatial memory in the Chinese Visual Retention Test.

OBJECTIVE: We aimed to explore the existence of visual-spatial memory deficit in patients with Parkinson's disease (PD) without dementia in the Chinese Visual Retention Test, as well as to assess whether their performance is related to age, duration, severity, stage, and dopamine (DA) dose. METHODS: Forty-two patients with PD and 30 healthy controls were included in our study. The Chinese Visual Retention Test was used to evaluate the visual-spatial memory of the subjects. Parameters of the Chinese Visual Retention Test were compared between the two groups. Correlation analysis and multiple linear regression analysis were used to explore the associations of the Chinese Visual Retention Test with age, duration, severity, stage of PD, and DA dose. RESULTS: Three correct scores in the Chinese Visual Retention Test were all significantly lower in the PD group than in the control group. The total error scores, error scores of omissions, deformation, and persistence in the PD group were significantly higher than those in the control group. Correlation analysis showed the total error scores in the Chinese Visual Retention Test was positively correlated with UPDRS III score and H-Y classification. Multiple linear regression analysis showed that the total error scores in the Chinese Visual Retention Test were associated with the UPDRS III score and H-Y classification. CONCLUSION: Patients with PD without dementia had visual-spatial memory deficits in the Chinese Visual Retention Test which may be affected by the severity and clinical stage of PD.

Argatroban in Patients With Acute Ischemic Stroke With Early Neurological Deterioration: A Randomized Clinical Trial.

Importance: The effect of argatroban in patients with acute ischemic stroke (AIS) and early neurological deterioration (END) is unknown. Objective: To assess the efficacy of argatroban for END in AIS. Design, Setting, and Participants: This open-label, blinded-end point, randomized clinical trial was conducted from April 4, 2020, through July 31, 2022. The date of final follow-up was October 31, 2022. This was a multicenter trial. Eligible patients were adults with AIS who experienced END, which was defined as an increase of 2 or more points on the National Institutes of Health Stroke Scale within 48 hours from symptom onset. Patients who withdrew consent, experienced duplicate randomization, or were lost to follow-up were excluded from the study. Interventions: Patients were randomly assigned to the argatroban group and control group within 48 hours of symptom onset. Both groups received standard therapy based on guidelines, including oral mono or dual antiplatelet therapy. The argatroban group received intravenous argatroban for 7 days (continuous infusion at a dose of 60 mg per day for 2 days, followed by 20 mg per day for 5 days) in addition to standard therapy. Main Outcome and Measure: The primary end point was good functional outcome at 90 days, defined as a modified Rankin Scale score of 0 to 3. Results: A total of 628 patients (mean [SD] age, 65 [11.9] years; 400 male [63.7%]) were included in this study (argatroban group, 314 [50%] and control group, 314 [50%]). Of these, 18 withdrew consent, 1 had duplicate randomization, and 8 were lost to follow-up. A total of 601 patients with stroke were included in the intention-to-treat analysis. Finally, 564 patients were included in the per-protocol analysis as 6 participants in the argatroban group and 31 participants in the control group did not follow the complete protocol. The number of patients with good functional outcome at 90 days was 240 (80.5%) in the argatroban group and 222 (73.3%) in the control group (risk difference, 7.2%; 95% CI, 0.6%-14.0%; risk ratio, 1.10; 95% CI, 1.01-1.20; P = .04). The proportion of symptomatic intracranial hemorrhage was 3 of 317 (0.9%) in the argatroban group and 2 of 272 (0.7%) in the control group (P = .78). Conclusions and Relevance: Among patients with AIS with END, treatment with argatroban and antiplatelet therapy resulted in a better functional outcome at 90 days. This trial provided evidence to support the use of argatroban in reducing disability for patients with END. Trial Registration: ClinicalTrials.gov Identifier: NCT04275180.

Hemodynamic changes in progressive cerebral infarction: An observational study based on blood pressure monitoring.

Progressive cerebral infarction (PCI) is a common complication in patients with ischemic stroke that leads to poor prognosis. Blood pressure (BP) can indicate post-stroke hemodynamic changes which play a key role in the development of PCI. The authors aim to investigate the association between BP-derived hemodynamic parameters and PCI. Clinical data and BP recordings were collected from 80 patients with cerebral infarction, including 40 patients with PCI and 40 patients with non-progressive cerebral infarction (NPCI). Hemodynamic parameters were calculated from the BP recordings of the first 7 days after admission, including systolic and diastolic BP, mean arterial pressure, and pulse pressure (PP), with the mean values of each group calculated and compared between daytime and nighttime, and between different days. Hemodynamic parameters and circadian BP rhythm patterns  were compared between PCI and NPCI groups using t-test or non-parametric equivalent for continuous variables, Chi-squared test or Fisher's exact test for categorical variables, Cox proportional hazards regression analysis and binary logistic regression analysis for potential risk factors. In PCI and NPCI groups, significant decrease of daytime systolic BP appeared on the second and sixth days, respectively. Systolic BP and fibrinogen at admission, daytime systolic BP of the first day, nighttime systolic BP of the third day, PP, and the ratio of abnormal BP circadian rhythms were all higher in the PCI group. PCI and NPCI groups were significantly different in BP circadian rhythm pattern. PCI is associated with higher systolic BP, PP and more abnormal circadian rhythms of BP.

Prediction of in-hospital mortality in patients with exertional heatstroke: a 13-year retrospective study.

Hyperactivity of coagulation is common in exertional heatstroke (EHS). Disseminated intravascular coagulation (DIC) is the most severe form of coagulation dysfunction and associated with poor outcome. DIC, temperature and Glasgow coma scale score were identified as independent risk factors for in-hospital mortality by multivariate logistic regression analysis, and we developed a nomogram for predicting in-hospital mortality in a 13-year EHS patient cohort. The nomogram was assessed by calibration curves and bootstrap with 1,000 resamples. The receiver operating characteristic curve was constructed, and the area under the curve (AUC) was compared. Two hundred and ten patients were included. The in-hospital mortality was 9.0%, and the incidence of DIC was 17.6%. The AUC of the nomogram was 0.897 (95% CI 0.848-0.935, p < .0001) and was non-inferior to SOFA and APACHE II scores but superior to SIRS score, which were widely-used score systems of disease severity. The nomogram contributed to the adverse outcome prediction of EHS.

Predictive Value of CT Perfusion in Hemorrhagic Transformation after Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

Background: Existing studies indicate that some computed tomography perfusion (CTP) parameters may predict hemorrhagic transformation (HT) after acute ischemic stroke (AIS), but there is an inconsistency in the conclusions alongside a lack of comprehensive comparison. Objective: To comprehensively evaluate the predictive value of CTP parameters in HT after AIS. Data sources: A systematical literature review of existing studies was conducted up to 1st October 2022 in six mainstream databases that included original data on the CTP parameters of HT and non-HT groups or on the diagnostic performance of relative cerebral blood flow (rCBF), relative permeability-surface area product (rPS), or relative cerebral blood volume (rCBV) in patients with AIS that completed CTP within 24 h of onset. Data Synthesis: Eighteen observational studies were included. HT and non-HT groups had statistically significant differences in CBF, CBV, PS, rCBF, rCBV, and rPS (p < 0.05 for all). The hierarchical summary receiver operating characteristic (HSROC) revealed that rCBF (area under the curve (AUC) = 0.9), rPS (AUC = 0.89), and rCBV (AUC = 0.85) had moderate diagnostic performances in predicting HT. The pooled sensitivity and specificity of rCBF were 0.85 (95% CI, 0.75−0.91) and 0.83 (95% CI, 0.63−0.94), respectively. Conclusions: rCBF, rPS, and rCBV had moderate diagnostic performances in predicting HT, and rCBF had the best pooled sensitivity and specificity.

ß-Actin: An Emerging Biomarker in Ischemic Stroke.

At present, the diagnosis of ischemic stroke mainly depends on neuroimaging technology, but it still has many limitations. Therefore, it is very important to find new biomarkers of ischemic stroke. Recently, ß-actin has attracted extensive attention as a biomarker of a variety of cancers. Although several recent studies have been investigating its role in ischemic stroke and other cerebrovascular diseases, the understanding of this emerging biomarker in neurology is still limited. We examined human and preclinical studies to gain a comprehensive understanding of the literature on the subject. Most relevant literatures focus on preclinical research, and pay more attention to the role of ß-actin in the process of cerebral ischemia, but some recent literatures reported that in human studies, serum ß-actin increased significantly in the early stage of acute cerebral ischemia. This review will investigate the basic biology of ß-actin, pay attention to the potential role of serum ß-actin as an early diagnostic blood biomarker of ischemic stroke, and explore its potential mechanism in ischemic stroke and new strategies for stroke treatment in the future.

Case Report: New Application of a Gufoni Maneuver Variation for Apogeotropic Lateral Semicircular Canal Benign Paroxysmal Positional Vertigo.

Background: Several canalith repositioning procedures (CRPs) such as Gufoni maneuver have been proposed to treat the apogeotropic lateral semicircular canal variant of BPPV (LC-BPPV). The reported success rate varied widely in different studies. Research showed that there was a risk of treatment failure due to insufficient repositioning of the debris. So far, there is insufficient evidence to recommend a preferable CRP for apogeotropic LC-BPPV. Case description: A 49-year-old woman and a 48-year-old man diagnosed with apogeotropic LC-BPPV relapse were treated with original Gufoni maneuver for apogeotropic variant but no satisfactory result was obtained. A variation of Gufoni maneuver originally proposed for the geotropic variant was applied to detach otoconia toward the utricle or the non-ampullary arm. Apogeotropic nystagmus was successfully transformed into the geotropic variant. The subsequent Gufoni maneuver was successful. On a 64-year-old male with untreated apogeotropic LC-BPPV, we performed the Gufoni maneuver variation and observed a change in nystagmus direction. In all the three cases, no relapse of vertigo was reported after 1 month. Conclusion: The new application of Gufoni maneuver variation may improve the treatment of apogeotropic LC-BPPV. Treatment efficacy and patient-specific optimization such as head rotation angle deserve a large-scale validation and further investigation.

Weaning critically ill patients from mechanical ventilation: a protocol from a multicenter retrospective cohort study.

BACKGROUND: Mechanical ventilation (MV) is an important lifesaving method in intensive care unit (ICU). Prolonged MV is associated with ventilator associated pneumonia (VAP) and other complications. However, premature weaning from MV may lead to higher risk of reintubation or mortality. Therefore, timely and safe weaning from MV is important. In addition, identification of the right patient and performing a suitable weaning process is necessary. Although several guidelines about weaning have been reported, compliance with these guidelines is unknown. Therefore, the aim of this study is to explore the variation of weaning in China, associations between initial MV reason and clinical outcomes, and factors associated with weaning strategies using a multicenter cohort. METHODS: This multicenter retrospective cohort study will be conducted at 17 adult ICUs in China, that included patients who were admitted in this 17 ICUs between October 2020 and February 2021. Patients under 18 years of age and patients without the possibility for weaning will be excluded. The questionnaire information will be registered by a specific clinician in each center who has been evaluated and qualified to carry out the study. DISCUSSION: In a previous observational study of weaning in 17 ICUs in China, weaning practices varies nationally. Therefore, a multicenter retrospective cohort study is necessary to be conducted to explore the present weaning methods used in China. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR) (No. ChiCTR2100044634).

Potential risk factors of persistent postural-perceptual dizziness: a pilot study.

BACKGROUND: Persistent postural-perceptual dizziness (PPPD) unifies the main characteristics of chronic subjective dizziness, visual vertigo and related diseases, which is a common chronic disease in neurology. At present, the pathology of PPPD is not fully understood. OBJECTIVE: In this single-center retrospective case series review, we aim to investigate the potential risk factors of PPPD. METHODS: Eighty inpatients diagnosed with PPPD were recruited with 81 apparently healthy controls. Patient-specific clinico-radiological data were collected from both groups. Conditions of hypertension, diabetes, smoking, and drinking were derived from medical history. Blood test results were recorded including total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fibrinogen, vitamin B12, folic acid, total cholesterol, triglyceride, and folate level. The subjects were examined by carotid artery CTA and cranial MRI, and the imaging findings of carotid atherosclerosis (CAS), white matter hyperintensities (WMHs) and lacunar infarction (LI) were recorded. Binary logistic regression analysis was used to investigate the difference between the case and control groups. Significance was defined as p value less than 0.05. RESULTS: The prevalence rate of hypertension in the case group was significantly higher than that in the control group, and the detection rates of CAS, WMHs, and LI in the case group were significantly higher than those in the control group (p < 0.05 for all). CONCLUSION: Hypertension, CAS, WMHs, and LI are associated with PPPD, which may be potential risk factors for its development.

Plasma urate concentrations and possible REM sleep behavior disorder.

OBJECTIVE: To examine how urate concentrations are related to the risk of having possible REM sleep behavior disorder (pRBD) in a community-based cohort. METHODS: The study included 12,923 Chinese adults of the Kailuan Study, free of Parkinson disease (PD) and dementia. Plasma urate concentrations were measured in 2006, 2008, and 2010. Cumulative average urate concentration was used as primary exposure. In 2012, we determined pRBD status using a validated RBD questionnaire-Hong Kong (RBDQ-HK). Logistic regression analysis was performed to estimate the association between urate concentrations during 2006-2010 and odds of having pRBD in 2012 or pRBD case with symptom onset within 1 year. RESULTS: Higher average urate concentrations were associated with a lower odds of pRBD (P-trend <0.001). The adjusted odds ratio (OR), for the highest versus lowest urate quintiles, was 0.43 (95% confidence intervals (CIs) 0.32-0.57). Significant association was consistently observed when we examined the association of a single urate assessment (2006 or 2010) or the rate of change in urate concentrations during 2006-2010 with pRBD (P-trend <0.001 for all). However, restricting to pRBD onset during 2011-2012, we observed a nonsignificant trend between high urate concentration and high odds of pRBD (P-trend = 0.09). INTERPRETATION: Higher average urate concentrations were associated with a lower likelihood of having pRBD, but not new-onset pRBD. Because of its observational study design, the result should be interpreted with caution due to the possibility of residual confounding.

Meta-Analysis of Visual Evoked Potential and Parkinson's Disease.

BACKGROUND: Previous studies suggested that visual evoked potential (VEP) was impaired in patients with Parkinson's disease (PD), but the results were inconsistent. METHODS: We conducted a systematic review and meta-analysis to explore whether the VEP was significantly different between PD patients and healthy controls. Case-control studies of PD were selected through an electronic search of the databases PubMed, Embase, and the Cochrane Central Register of Controlled Trials. We calculated the pooled weighted mean differences (WMDs) and 95% confidence intervals (CIs) between individuals with PD and controls using the random-effects model. RESULTS: Twenty case-control studies which met our inclusion criteria were included in the final meta-analysis. We found that the P100 latency in PD was significantly higher compared with healthy controls (pooled WMD = 6.04, 95% CI: 2.73 to 9.35, P=0.0003, n=20). However, the difference in the mean amplitude of P100 was not significant between the two groups (pooled WMD = 0.64, 95% CI: -0.06 to 1.33, P=0.07) based on 10 studies with the P100 amplitude values available. CONCLUSIONS: The higher P100 latency of VEP was observed in PD patients, relative to healthy controls. Our findings suggest that electrophysiological changes and functional defect in the visual pathway of PD patients are important to our understanding of the pathophysiology of visual involvement in PD.

Downregulation of long non­coding RNA UCA1 enhances the radiosensitivity and inhibits migration via suppression of epithelial­mesenchymal transition in colorectal cancer cells.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and common cause of cancer­related deaths. Radiotherapy has become a routine treatment for CRC. However, radioresistance affects therapeutic efficacy. Long non­coding RNA urothelial carcinoma associated 1 (UCA1) has been demonstrated to be overexpressed in several tumors and predicts a poor prognosis. In the present study, we revealed that lncRNA­UCA1 was overexpressed in colorectal cancer tissue and colon cancer cells when compared to normal tissue and cells. Quantitative real­time PCR revealed that the expression of UCA1 was significantly higher in CRC tissues after chemoradiotherapy. Downregulation of UCA1 enhanced the radiosensitivity of CCL244 cells via inhibition of the colony formation, proliferation and promotion of radiation­induced apoptosis and G2/M arrest. Moreover, downregulation of UCA1 suppressed the epithelial­mesenchymal transition (EMT) in CCL244 cells.

Assessment of sleep quality using cardiopulmonary coupling analysis in patients with Parkinson's disease.

Objectives: To assess the sleep quality of patients with Parkinson's disease (PD) and evaluate the effect of cardiopulmonary coupling (CPC) analysis on sleep quality and its correlation with subjective complaints in patients with PD. Methods: Our study included 42 patients with PD and 30 healthy controls. CPC analysis and the Pittsburgh Sleep Quality Index (PSQI) were used to evaluate the sleep quality of subjects. Results: High-frequency coupling (HFC) and sleep efficiency were significantly lower in the PD than in the control group, whereas very low-frequency coupling (VLFC) and sleep latency were significantly higher in the PD than in the control group. PSQI scores were significantly higher in the PD than in the control group (all p < .05). The PSQI score showed a negative correlation with the HFC ratio in the PD group (r = -.478, p = .001). Factors related to the occurrence of PD with poor sleep quality were the unified Parkinson's disease rating scale (UPDRS) score and nocturia. Conclusions: The sleep quality of patients with PD was generally decreased. CPC analysis can reflect the subjective sleep quality of patients with PD and serve as an effective sleep monitoring tool.

Evoked potential changes in patients with Parkinson's disease.

OBJECTIVE: Patients with Parkinson's disease (PD) may have sensory dysfunction, and it can be more easily demonstrated through electrophysiologic testing. We aimed to explore whether the impairment of brainstem visual and auditory passageway exists in PD patients using visual evoked potential (VEP) and brainstem auditory evoked potential (BAEP) examinations. METHODS: Forty-two PD cases and thirty controls participated in the study. All subjects underwent the VEP and BAEP examinations. The N75, P100, N145 latencies and P100 amplitude of VEP, the latencies of waves I, III, V and the interpeak latencies (IPL) of waves I-III, III-V, I-V were measured. RESULTS: The N75, P100, N145 latencies of VEP, but not the amplitude of P100, were significantly longer in patients with PD than the control group (p < .05). The latencies of wave III and wave V, the IPL of III-V and I-V were all significantly increased compared with control subjects while no significant difference was noted in waves I and I-III IPL. CONCLUSION: Our results found that brainstem visual and auditory passageway may be impaired in PD patients. SIGNIFICANCE: VEP and BAEP can be served as sensitive measurements in helping prognosis and assessment the severity of the disease.

Gelatin Nanostructured Lipid Carriers Incorporating Nerve Growth Factor Inhibit Endoplasmic Reticulum Stress-Induced Apoptosis and Improve Recovery in Spinal Cord Injury.

Clinical translation of growth factor therapies faces multiple challenges; the most significant one is the short half-life of the naked protein. Gelatin nanostructured lipid carriers (GNLs) had previously been used to encapsulate the basic fibroblast growth factor to enhance the functional recovery in hemiparkinsonian rats. In this research, we comparatively study the enhanced therapy between nerve growth factor (NGF) loaded GNLs (NGF-GNLs) and NGF only in spinal cord injury (SCI). The effects of NGF-GNLs and NGF only were tested by the Basso-Beattie-Bresnahan (BBB) locomotion scale, inclined plane test, and footprint analysis. Western blot analysis and immunofluorescent staining were further performed to identify the expression of ER stress-related proteins, neuron-specific marker neuronal nuclei (NeuN), and growth-associated protein 43 (GAP43). Correlated downstream signals Akt/GSK-3ß and ERK1/2 were also analyzed with or without inhibitors. Results showed that NGF-GNLs, compared to NGF only, enhanced the neuroprotection effect in SCI rats. The ER stress-induced apoptosis response proteins CHOP, GRP78 and caspase-12 inhibited by NGF-GNL treatment were more obvious. Meanwhile, NGF-GNLs in the recovery of SCI are related to the inhibition of ER stress-induced cell death via the activation of downstream signals PI3K/Akt/GSK-3ß and ERK1/2.

Intravenously delivered neural stem cells migrate into ischemic brain, differentiate and improve functional recovery after transient ischemic stroke in adult rats.

Stem cell transplantation may provide an alternative therapy to promote functional recovery after various neurological disorders including cerebral infarct. Due to the minimal immunogenicity and neuronal differentiation potential of neural stem cells (NSCs), we tested whether intravenous administration of mice-derived C17.2 NSCs could improve neurological function deficit and cerebral infarction volume after ischemic stroke in rats. Additionally, we evaluated the survival, migration, proliferation, and differentiation capacity of transplanted NSCs in the rat brain. Intravenous infusion of NSCs after middle cerebral artery occlusion (MCAO) showed better performance in neurobiological severity scores after MCAO compared to control. However, the volume of cerebral infarction was not different at 7 days after MCAO compared with control. Transplanted NSCs were detected in the ischemic region but not in the contralateral hemisphere. NSCs differentiated into neurons or astrocytes after MCAO. These data suggest that intravenously transplanted NSCs can migrate, proliferate, and differentiate into neurons and astrocytes in the rat brain with focal ischemia and improve functional recovery.

Adhesion to fibronectin induces p27(Kip1) nuclear accumulation through down-regulation of Jab1 and contributes to cell adhesion-mediated drug resistance (CAM-DR) in RPMI 8,226 cells.

Mounting evidence has been shown that integrin-mediated cellular adhesion confers resistance to chemotherapy of multiple myeloma. The molecular mechanism underlying cell adhesion-mediated drug resistance (CAM-DR) is, however, poorly understood. In this report, we demonstrated that RPMI 8,226 cells accumulated p27(Kip1) in the nucleus when they were adhered to fibronectin (FN). The adhesion-mediated p27(Kip1) nuclear recruitment was regulated via the down-regulation of Jab1, a negative regulator of cell cycle. Overexpression of Jab1 reversed the elevated p27(Kip1) in the nucleus, which needed phosphorylation of p27(Kip1) on Serine 10, whereas inhibition of Jab1 by siRNA further increased the elevated p27(Kip1). Furthermore, we found overexpression of Jab1 did not affect 8,226 cells adhesion to FN, but reversed doxorubicin or mitoxantrone-induced CAM-DR phenotype. In conclusion, our data suggest that Jab1 plays an important role in CAM-DR, which depends on pSer10-p27(Kip1)-mediated subcellular localization of p27(Kip1). The understanding of this novel molecular mechanism may prove valuable in designing new therapeutic approaches for CAM-DR in Multiple myeloma.

Fibroblast growth factor 1attenuates 6-hydroxydopamine-induced neurotoxicity: an in vitro and in vivo investigation in experimental models of parkinson's disease.

Parkinson's disease (PD) is a degenerative disorder of the central nervous system and is characterized by motor system disorders resulting in loss of dopamine producing brain cells. Acidic fibroblast growth factor, also called FGF1, promotes the survival of neurons. The aims of the present study were to confirm FGF1 could protect neurons cultures from 6-hydroxydopamine (6-OHDA) toxicity in vitro and in vivo. Our results demonstrated FGF1 administration improved the motor function recovery, increased the TH-positive neurons survival and up-regulated the levels of neurotransmitters in PD rats. Meanwhile, FGF1 prevents the death of DA neuron at least in part by reducing the levels of α-synuclein and ER stress. The administration of FGF1 activated downstream signals PI3K/Akt and ERK1/2. In conclusion, FGF1 diminished α-synuclein neurotoxicity by down regulating ER stress mediators and the level of apoptosis, and these effects may underlying the activation of the PI3K/Akt and ERK1/2 signal pathway.