ABSTRACT
Immunoadsorption can selectively remove pathogenic antibodies and has recently achieved good results in neuroimmune diseases. The type and titer of pathogenic antibodies play an important role in the clinical symptoms and severity of patients with autoimmune encephalitis. First-line immunotherapy for autoimmune encephalitis includes steroids, intravenous immunoglobulin, plasma exchange or immunoadsorption. Immunoadsorption selectively and rapidly eliminates autoantibodies and can be an effective therapeutic option as part of multimodal immunotherapy.
ABSTRACT
Objective:To investigate the effects of hippocampal injection of tyrosine kinase receptor binding protein B3(Ephrin-B3) agonist on spontaneous seizures and the expression of hippocampal secretory glycoprotein (Reelin) and phosphorylated adaptor protein (p-Dab1) in epileptic model rats.Methods:Seventy-eight rats were randomly divided into control group and model group according to body mass matching with 39 rats in each group.The rats in control group were fed normaly, and the rats in model group were established epilepsy model by intraperitoneal injection of lithium chloride pilocarpine. The hippocampal tissues were taken in the acute phase (7 days), quiescent phase (14 days) and chronic phase (60 days) after the successful induction of status epilepticus. The levels of Reelin protein and p-Dab1 protein in the hippocampal tissues of epileptic model rats and normal rats were detected by immunohistochemistry and Western blot.And thirteen rats were randomly selected at each time point. Another 48 rats were randomly divided into normal Fc-control group, normal EphB3-Fc group, epilepsy Fc-control group and epilepsy EphB3-Fc group, with 12 rats in each group. Rats in the first two groups were fed normally, and those in the latter two groups were established epileptic model. Seven days after modeling, all rats were injected into bilateral hippocampus with EphB3-Fc (Ephrin-B3 agonist) and FC control (control agent of Ephrin-B3 agonist) according to the grouping, once a day for 7 days. After administration, the changes of behavior and EEG were observed within two weeks. At the same time, the expression of Reelin protein and p-Dab1 protein were detected by immunohistochemistry and Western blot. SPSS 21.0 was used for statistical analysis, One-way ANOVA was used for multi group comparison, and Tukey's test was used for pairwise comparison.Results:The results of immunohistochemistry and Western blot showed that compared with the control group, the levels of Reelin and p-Dab1 protein in hippocampus of model group decreased significantly at 7, 14 and 60 days after epilepsy (all P<0.01). The results of immunohistochemistry showed that compared with epilepsy Fc-control group, the levels of p-Dab1 ((0.41±0.04), (0.58±0.06), P<0.05) in epilepsy EphB3-Fc group increased significantly.Western blot result showed that the level of p-Dab1 in epilepsy EphB3-Fc group increased compared with that of epilepsy Fc-control group (1.34±0.04), (2.26±0.10), P<0.01). Compared with epilepsy Fc-control group, epilepsy EphB3-Fc group showed less average seizure duration ((39.00±1.79)s, (26.50±1.87)s; t=23.21, P<0.01), less frequencies ((2.00±0.89), (0.50±0.55); t=2.32, P<0.01) and less latent period ((6.33±1.37)day, (12.50±1.87)day; t=2.52, P<0.01) in spontaneous recurrent seizures. Compared with epilepsy Fc-control group, epilepsy EphB3-Fc group showed lower average amplitude ((37.30±1.21)μV, (29.00±1.41)μV; t=25.14, P<0.01), less average seizure duration ((5.35±0.19)s, (2.35±0.19)s; t=3.13, P<0.01). Conclusion:Ephrin-B3 alleviated spontaneous recurrent seizures by upregulating Reelin and p-Dab1 in temporal lobe epilepsy rat.
ABSTRACT
Objective:To investigate the characteristics of magnetic resonance myelography (MRM) and its application in the treatment of spontaneous intracranial hypotension (SIH).Methods:The clinical data, MRM characteristics, and treatment of 15 patients with SIH who underwent MRM examination in the First Affiliated Hospital of Zhengzhou University from August 2014 to August 2019 were retrospectively analyzed. According to treatment methods, nine patients were divided into conservative treatment group and six patients were divided into combined epidural blood patch treatment group. The gender, age, time interval from onset to MRM examination, cerebrospinal fluid pressure and MRM characteristics between the two groups were compared. SPSS 20.0 software was used for statistical description, and independent sample t-test was applied to compare the differences between groups. Results:All of the 15 cases reported orthostatic headache. Their cerebrospinal fluid pressure was (29.67±19.77, range 0-55) mmH 2O (1 mmH 2O=0.009 8 kPa), and onset-MRM interval was (33.07±24.22, range 7-90) days. The MRM characteristics were observed, including all 15 cases with periradicular leaks, four cases with anterior epidural fluid collections, six cases with posterior epidural fluid collections, and eight cases with high cervical (C 1-2 to C 2-3) retrospinal cerebrospinal fluid collections. There were 2 to 32 leak sites with an average of (10.20±7.87) sites. Among the 153 leak sites, 58(37.9%) sites were located at cervical vertebra, 77(50.3%) sites at thoracic vertebra, 18(11.8%) sites at lumbar vertebra, and 61(39.9%) sites at either the cervicothoracic junction (C 7-T 1 to T 1-2) or the upper thoracic region (T 2-3to T 6-7). Five patients responded well to one-time targeted autologous epidural blood patch on the basis of the location of the cerebrospinal fluid leakage. Besides, one patient improved with targeted epidural blood patch twice. There were no statistically significant differences in gender, age, onset-MRM interval, cerebrospinal fluid pressure, number and location of leak sites between the conservative treatment group and combined treatment group. Conclusions:The periradicular leaks of cerebrospinal fluid at cervical vertebra and thoracic vertebra are the most common feature of MRM in patients with SIH. MRM can identify the existence and location of cerebrospinal fluid leakage, assist in the diagnosis of SIH, and guide targeted epidural blood patch.
ABSTRACT
Objective To investigate the characteristics of intestinal microflora in patients with neuromyelitis optica spectrum disorders (NMOSDs) and related clinical significance.Methods The data about basic clinical features,fecal specimens as well as cerebrospinal fluid samples of 28 patients with NMOSDs,15 patients with multiple sclerosis (MS) and 16 healthy controls admitted to the Department of Neurology,the First Affiliated Hospital of Zhengzhou University from July 2017 to January 2019 were collected.The differences about intestinal microbial characteristics and inflammatory index levels in each group were analyzed.The relevance between the diversity of intestinal microbiota and inflammatory index was explored.Results Compared with healthy controls,the intestinal microfloras of patients with NMOSDs and MS respectively were structurally disordered.The levels of the microbial diversity (chao 1 index) were significantly decreased in patients with NMOSDs compared with healthy controls,while their inflammation indexes,including IL-6,IL-10 and transforming growth factor (TGF)-α,in cerebrospinal fluid were significantly increased ((12.9±4.6) pg/ml vs (2.6±1.8) pg/ml,t=4.197,P=0.001;(3.4±2.1) pg/ml vs (0.9±0.2)pg/ml,t=2.265,P=0.037;(21.4± 12.7) ng/ml vs (13.7±7.8) ng/ml,t=3.702,P=0.004).Compared with control group,the relative abundance of butyrivibrio,prevotella and anaerostipes was decreased significantly in NMOSDs group (6.8％±3.5％ vs 13.0％±4.7％,t=4.941,P＜0.001;3.9％±2.2％ vs 6.9％±3.3％,t=3.282,P=0.003;5.1％±2.5％ vs 7.3％±3.0％,t=2.641,P=0.012),while the relative abundance of ackermania was increased obviously (7.0％±3.1％ vs 4.4％±2.8％,t=2.802,P=0.008);Besides,the quantitative Streptococcus thermophilus and butyrivibrio reduced in MS group (3.4％±2.4％ vs 5.5％±2.1％,t=2.784,P=0.009;7.9％±5.4％ vs 13.0％±4.7％,t=2.501,P=0.018).In the comparison between subgroups,the relative abundance of bacteroides of aquaporin (AQP) 4-IgG-positive patients was lower than that of AQP4-IgG-negative patients (23.1％±8.9％ vs 32.6％± 10.4％,t=2.572,P=0.016),while the former subgroup had the higher level of the relative abundance of bifidobacterium (3.4％± 1.6％ vs 1.7％± 1.4％,t=2.977,P=0.006).Moreover,there was a significant relevance between the diversity of intestinal microflora and the level of inflammatory factor IL-6 in cerebrospinal fluid (r=-0.548,P=0.003).Conclusions The intestinal microflora structural disorder and diversity reduction exist in patients with NMOSDs.Moreover,there is a significant correlation between the intestinal microflora and the level of inflammatory factors in NMOSDs,which can be used as an important means of clinical auxiliary examination.
ABSTRACT
Objective:To analyze risk factors for deep vein thrombosis(DVT)in patients with severe cerebral infarction and to find early and sensitive indicators for the prediction and intervention of DVT.Methods:A total of 226 patients with severe cerebral infarction aged 62.5±12.9 years in our department from January 2017 to May 2020 were enrolled.Clinical data, biochemical examinations and color Doppler ultrasound results were collected.Risk factors for DVT were analyzed.The receiver operating characteristic curve(ROC)was used to determine the cut-off value, area under the curve, sensitivity and specificity.Results:Age, reaction(R)time of blood coagulation factors on thromboelastography(TEG)and fibrinogen degradation products(FDP)were risk factors for DVT with no adjustment of the overall effect of time on coagulation mechanisms.According to time stratified analysis, decreased R time( OR=0.58, 95% CI: 0.40-0.84)and increased FDP( OR=1.17, 95% CI: 1.02-1.33)within 3 days of onset were risk factors for DVT, and the cut-off values were 5.35 min and 0.39 mg/L, respectively; 3 and 7 days after onset, increased D-dimer was a risk factor for DVT( OR=2.73, 95% CI: 1.53-4.86; OR=2.57, 95% CI: 1.32-5.03), and the cut-off values were 0.39 mg/L and 0.76 mg/L, respectively.Excluding the effects of FDP primary and D-Dimer secondary fibrinolysis, risk factors for DVT within 3 days of onset were decreased R time on TEG and increased age, and all risk factors were not statistically significant 3 days and 7 days after onset( P<0.05). Conclusions:The key factors affecting DVT in patients with severe cerebral infarction are different at different stages.Decreased R time within 3 days of onset is a predictive indicator of DVT.FDP and D-dimer can be used to assess thrombosis, but may not be appropriate as predictive indicators.
ABSTRACT
Objective:To explore the incidence and dynamic change of apathy after minor stroke and its influence on the quality of life.Methods:One hundred and six patients with minor stroke(NIHSS≤3) were selected as the research group, one hundred and six cases with healthy physical examination were selected as control group.The apathy evaluation scale, clinician version(AES-C) scale was used to evaluate the degree of apathy after minor stroke, then the patients were divided into minor post-stroke apathy group(mPSA group) and non post-stroke apathy group(NPSA group). At 1, 3, 6, 9 and 12 months after onset, the follow-up visits were carried out and AES-C, modified Barthel index(MBI), modified Rankin scale(mRS) and stroke-specific quality of life scale(SS-QOL) were evaluated.The incidence of minor post-stroke apathy and its dynamic changes over time were analyzed, and the differences of related scales scores between the mPSA group and the NPSA group were compared.Results:The incidence of apathy in research group(35.1%) was higher than that of the control group(7.5%) ( P<0.05). The scores of MRS in the mPSA group at 1 month(1.06±0.86), 3 months(1.18±0.97), 6 months (1.09±0.85), 9 months(1.11±0.71), 12 months(1.11±0.72) after stroke were not significantly different from those in the NPSA group at 1 month(1.00±0.89), 3 months(0.95±0.83), 6 months (0.97±0.87), 9 months (1.00±0.80), 12 months(1.03±0.79) (all P>0.05). The scores of MBI in the mPSA group at 1 month (92.42±5.75), 3 months(91.32±5.81), 6 months (91.71±5.14), 9 months(91.67±4.78), 12 months (91.14±5.01) after stroke were not significantly different from those in the NPSA group at 1 month (91.97±5.79), 3 months(92.42±5.64), 6 months(92.29±5.67), 9 months(92.07±5.46), 12 months(92.12±5.35) (all P>0.05). The scores of SS-QOL in the mPSA group at 1 month (135.09±26.88), 3 months (132.71±24.91), 6 months (134.31±26.63), 9 months(135.89±24.86), 12 months (138.77±27.83) after stroke were lower than those in the NPSA group at 1 month (183.79±24.80), 3 months(183.77±24.18), 6 months (181.80±26.62), 9 months(179.86±28.92), 12 months (179.98±29.13) (all P<0.05). There were no significant differences in the incidence of mPSA at each time point of follow-up( P>0.05). Conclusion:The incidence of apathy after minor stroke is significantly higher than that of the control group, and it remains relatively stable in the first year and seriously affect the quality of patients' life.
ABSTRACT
Objective@#To investigate the characteristics of intestinal microflora in patients with neuromyelitis optica spectrum disorders (NMOSDs) and related clinical significance.@*Methods@#The data about basic clinical features, fecal specimens as well as cerebrospinal fluid samples of 28 patients with NMOSDs, 15 patients with multiple sclerosis (MS) and 16 healthy controls admitted to the Department of Neurology, the First Affiliated Hospital of Zhengzhou University from July 2017 to January 2019 were collected. The differences about intestinal microbial characteristics and inflammatory index levels in each group were analyzed. The relevance between the diversity of intestinal microbiota and inflammatory index was explored.@*Results@#Compared with healthy controls, the intestinal microfloras of patients with NMOSDs and MS respectively were structurally disordered. The levels of the microbial diversity (chao 1 index) were significantly decreased in patients with NMOSDs compared with healthy controls, while their inflammation indexes, including IL-6, IL-10 and transforming growth factor (TGF)-α, in cerebrospinal fluid were significantly increased ((12.9±4.6) pg/ml vs (2.6±1.8) pg/ml, t=4.197, P=0.001; (3.4±2.1) pg/ml vs (0.9±0.2) pg/ml, t=2.265, P=0.037; (21.4±12.7) ng/ml vs (13.7±7.8) ng/ml, t=3.702, P=0.004). Compared with control group, the relative abundance of butyrivibrio, prevotella and anaerostipes was decreased significantly in NMOSDs group (6.8%±3.5% vs 13.0%±4.7%, t=4.941, P<0.001; 3.9%±2.2% vs 6.9%±3.3%, t=3.282, P=0.003; 5.1%±2.5% vs 7.3%±3.0%, t=2.641, P=0.012), while the relative abundance of ackermania was increased obviously (7.0%±3.1% vs 4.4%±2.8%, t=2.802, P=0.008); Besides, the quantitative Streptococcus thermophilus and butyrivibrio reduced in MS group (3.4%±2.4% vs 5.5%±2.1%, t=2.784, P=0.009; 7.9%±5.4% vs 13.0%±4.7%, t=2.501, P=0.018). In the comparison between subgroups, the relative abundance of bacteroides of aquaporin (AQP) 4-IgG-positive patients was lower than that of AQP4-IgG-negative patients (23.1%±8.9% vs 32.6%±10.4%, t=2.572, P=0.016), while the former subgroup had the higher level of the relative abundance of bifidobacterium (3.4%±1.6% vs 1.7%±1.4%, t=2.977, P=0.006). Moreover, there was a significant relevance between the diversity of intestinal microflora and the level of inflammatory factor IL-6 in cerebrospinal fluid (r=-0.548, P=0.003).@*Conclusions@#The intestinal microflora structural disorder and diversity reduction exist in patients with NMOSDs. Moreover, there is a significant correlation between the intestinal microflora and the level of inflammatory factors in NMOSDs, which can be used as an important means of clinical auxiliary examination.
ABSTRACT
To explore the clinical effect of microsurgery in the treatment of the tumor which was diagnosed with the plexiform neurofibroma (PN) of the forearm and palm. Methods From January, 2014 to June, 2017, 6 cases of the PN in the forearm and palm were removed by microsurgery such as neurovascular transplantation, separation and anastomosis under microscope, etc. There were 4 males and 2 females, with an average age of 9.2 (range, 2-18 )years. There was 1 case with PN of the median nerve, ulnar nerve and their branches in the right fore-arm and palm, 2 cases with PN of the median nerve and its branches in the right forearm and palm, 2 cases with PN of the median nerve and its branches in the left forearm and palm, and 1 case with PN of the ulnar nerve and its branches in the left forearm and palm.The postoperative function and feeling of the patients were evaluated by outpa-tient followed-up. Results The pathological results of 6 patients all showed PN, and their incisions healed primari-ly.The patients were followed-up for 6 to 36 months, with an average of 18 months. No obvious scar formation was observed in all incisions. Among them, PN of the palmar of the youngest patient recurred after the operation, and it was resected in a second operation.The remaining 5 patients had no recurrence during follow-up.The 2 point resolu-tion of each fingertip of the affected limb of the patients who had median and ulnar PN was 2-5 mm, with an average of 3.30 mm; the 2 point resolution of the thumb, indicator, middle and ring fingers of the affected limbs of the patients who had median PN was 2-5 mm, with an average of 2.95 mm; the 2 point resolution of the ring and little fingers of the affected limbs of the patients who had ulnar PN was 3-4 mm, with an average of 3.50 mm.According to the related evalu-ation criteria made by the American Orthopedic Foot and Ankle Surgery Society (AOFAS), the results of the forearm and hand functions were excellent in 5 cases, good in 1 case. Conclusion The application of microsurgical techniques in the treatment of PN in the forearm and palm can be effective separation of tumor and nerve fibers, effectively protect the branches of the median nerve and ulnar nerve and their blood circulation, prevent recurrence and reduce nerve damage after operation.
ABSTRACT
Objective: To investigate the effects of levels of D-dimer and N-terminal pro-brain natriuretic peptide [NT-pro BNP] on the prognosis of patients with acute cerebral infarction
Methods: One hundred and twenty-four patients with acute cerebral infarction who were admitted to the hospital between July 2014 and July 2016 were selected as the observation group; 100 normal people who had health examination in the center of physical examination of our hospital were selected as the control group. The levels of D-dimer and NT-pro BNP of the two groups were observed; the correlation between the levels of plasma NT-pro BNP and D-dimer and area of cerebral infarction, complications and death condition of the observation group was investigated
Results: The levels of D-dimer and NT-pro BNP of the observation group were much higher than those of the control group, and the difference was statistically significant [P<0.05]. The levels of D-dimer and NT-pro BNP of the observation group were significantly higher than those of the control group, and the difference had statistical significance [P<0.05]. The levels of plasma NT-pro BNP and D-dimer of the patients with disturbance of consciousness and high blood pressure were apparently higher than those with no disturbance of consciousness and normal blood pressure, and there was a statistically significant difference [P<0.05]. The patients were followed up for half a year. The levels of D-dimer and NT-pro BNP of the dead patients were much higher than those of the survived patients on admission
Conclusion: The levels of plasma NT-pro BNP and D-dimer can reflect the disease condition and prognosis of patients with acute cerebral infarction. Higher levels of NT-pro BNP and D-dimer indicates poorer prognosis. This work can provide a guidance for the clinical treatment of acute cerebral infarction
ABSTRACT
To investigate the protective role and possible mechanisms of Nrf2 gene in cerebral trauma in mice. The types Nrf2[-/-] and Nrf2[+/+] mice were confirmed by PCR, and the model of closed head injury was established. The severity of injury and the effect of the injury on neurological status were assessed by Neurological Severity Score [NSS] and fatality rate, and the activated conditions of microglia and astrocyte around the injured area were observed by immunohistochemical method. Compared with Nrf2[+/+] mice, the nerve dysfunction of the Nrf2[-/-] mice was obviously more severe [P<0.01]. On the first day after injury, the activation of microglia around the injured area increased significantly in Nrf2 [-/-] mice, the difference was more significant on the third day, and there was still statistical difference until the 7th day [P<0.05]. Moreover, On the days 1, 3, 7 after injury, the activation of astrocyte around the injured area also increased in Nrf2[-/-] mice, however, there was statistical difference only on the 3[rd] day [P<0.05]. Nrf2 gene knockout can aggravate the nerve dysfunction after cerebral trauma, and this effect is achieved, at least partly, possibly via the effect of Nrf2 on glial activation
ABSTRACT
Objective To investigate the changes of learning and memory function ,vascular endothelial growth factor (VEGF) and heme oxygenase‐1(HO‐1) expression in cerebral cortex and hippocampus of chronic ischemic vascular dementia rats . Methods Thirty‐six healthy SD rats were divided into the control group ,sham operation group and model group ,12 cases in each group .The chronic ischemic vascular dementia rat model was established by the permanent bilateral carotid artery occlusion The sham operation group received the same treatment to the model group except without bilateral carotid artery occlusion .The learning and memory abilities were tested by the Morris water maze experiment and climbing rope strength experiment at 1 ,4 ,8 ,12 weeks respectively .The expressions of VEGF and HO‐1 in rat cerebral cortex and hippocampus was determined by immunohistochemical SP technique .Results The escape latency time at 8 ,12 weeks in the model group was longer than that in the sham operation group and control group ,and the number of crossing the platform was less than that in the sham operation group and control group ,the differences were statistically significant (P0 .05) .The positive expression of HO‐1 and VEGF protein contents in the control group and sham operation group was less than that in the model group with sta‐tistical difference(P<0 .05) .Conclusion Chronic cerebral hypoperfusion has a permanent damage to the learning and memory abil‐ities in rats ,while has no influence on the motor function .VEGF and HO‐1 may play a protective role in chronic cerebral ischemia .
ABSTRACT
Objective:To evaluate the influence of bone marrow stem cells ( BMSCs ) in the serological indicators of hepatolenticular degeneration combined liver fibrosis.Methods:60 cases were randomly divided into 3 groups: penicillamine group, BMSCs group and BMSCs+penicillamine group.BMSCs(2 ml)were injected into vein with normal saline(100 ml) every 10 days ( 3 times for a period of treatment).Liver tissue pathology biopsy was inspected and TBIL, ALT, ALB, CHE, PDGF-BB, TGF-β1, IL-6 and TNF-αwere detected at 0,4 ,8 and 12 weeks.Results: The level of serological indicators about liver functions were reduced in every group, while the changes in BMSCs+penicillamine group were especially obvious ( P<0.05 ).Conclusion: Penicillamine combined with BMSCs was effective in the improvement of liver functions of hepatolenticular degeneration combined liver fibrosis.
ABSTRACT
BACKGROUND:The microRNAs are involved in regulation of stem cel proliferation, differentiation and aging. To study the effect of Let-7c, a member of Let-7, on the neural differentiation of bone marrow mesenchymal stem cels provides new ideas for stem cel therapy. OBJECTIVE: To investigate the role of Let-7c in the neural differentiation of bone marrow mesenchymal stem cels. METHODS: The lentiviral vectors of Let-7c-up and Let-7c-inhibition were constructed and transfected into rat bone marrow mesenchymal stem cels. Optimal multiplicity of infection was screened. The cels were divided into non-transfected group, negative control group (transfected with empty virus), transfected enhancement group (transfected with LV-rno-Let-7c-up), transfected inhibition group (transfected with LV-rno-Let-7c-5p-inhibition). Bone marrow mesenchymal stem cels were treated with fasudil as an inducer for triggering the cels to differentiate into neurons. The fluorescence expressed by transfected cels was observed under inverted fluorescence microscope. The expression of neuron-specific markers, neuron-specific enolase and microtubule-associated protein 2, were measured by immunocytochemical method. The mRNA expression of microtubule-associated protein 2 was detected by RT-PCR. The cel viability was determined by MTT method. RESULTS AND CONCLUSION:Under the inverted fluorescence microscope, the cels were successfuly transfected with LV-rno-Let-7c-up and LV-rno-Let-7c-5p-inhibition. Fasudil induced bone marrow mesenchymal stem cels to differentiate into neurons. The transfection efficiency and expression levels of neuron-specific enolase and microtubule-associated protein 2 in the transfected enhancement group were significantly higher than those in the negative control group (P < 0.05), while in the transfected inhibition group, they were lower than those in the negative control group (P < 0.05). These findings indicate that the differentiation percentage of bone marrow mesenchymal stem cels is increased by fasudil after transfection with LV-rno-Let-7c-up, and Let-7c may promote the differentiation of bone marrow mesenchymal stem cels into neurons.
ABSTRACT
Bone marrow mesenchymal stem cells (BMSCs),which can be isolated from organs and tissues,are cell populations with high degree of plasticity,similar to hematopoietic stem cells in bone marrow,and can be in vitro cultured,induced and amplified.BMSCs are increasingly used in gene therapy,cell therapy and tissue engineering.BMSCs have been currently studied in a number of autologous transplantations,while not all BMSCs are suitable for autologous transplantation.BMSCs exhibit biological aging gradually when cultured in vitro.Biological aging can be divided into age-induced senescence and long-term passage induced senescence.Aging BMSCs demonstrate changes in biological behaviour which reduces the success rate of autologous transplantation.In this review,biological aging BMSCs are discussed in order to provide help for the transplantation of BMSCs.
ABSTRACT
BACKGROUND:There is no clear understanding about the effect of let-7f and interleukin-6 (IL-6) on the proliferation of bone marrow mesenchymal stem cels and their relationship. OBJECTIVE: To explore the effects of expression levels of let-7f and IL-6 on the proliferation of bone marrow mesenchymal stem cels and their relationship. METHODS:(1) LV-rno-let-7f-up and LV-rno-let-7f-down were constructed and transfected into bone marrow mesenchymal stem cels of Sprague-Dawley rats, respectively. Then, there were four groups in the study: transfection upregulation group transfected with LV-rno-let-7f-up), transfection inhibition group (transfected with LV-rno-let-7f-down), negative control group (transfected with FU-RNAi-NC-LV), and untransfected group. The expression level of let-7f in each group was detected by qRT-PCR. The proliferation ability of cels and expression levels of IL-6 when let-7f expression was at different levels were detected by MTT, flow cytometry and ELISA. The expression of Cyclin D1 at mRNA and protein levels was detected by qRT-PCR and western blot, respectively. (2) To predict the potential target gene of let-7f, the wild-type/mutant IL-6 3’UTR reporter gene vectors were constructed, and cotransfected with let-7f/let-7f inhibitor respectively into the 293T cels to measure the luciferase. RESULTS AND CONCLUSION: Compared with the negative control group, the proliferative and cloning capacities of cels in the transfection upregulation group were higher; the number of cels was significantly decreased at G1 stage and increased at S stage, and the apoptotic cels were reduced in number (P 0.05). Luciferase activity of cels transfected with wide-type IL-6 3’UTR and let-7f was significantly reduced (P < 0.05). These findings indicate that up-regulation of let-7f can promote the proliferative and cloning capacities of bone marrow mesenchymal stem cels and reduce cel apoptosis, but downrelation of let-7f exhibits an inhibitory effect. Overexpression of IL-6 can suppress the proliferation of bone marrow mesenchymal stem cels, which is considered to be a target gene of let-7f, and let-7f may suppress the expression of IL-6 to promote the cel proliferation.
ABSTRACT
Objective To evaluate the effect of bone marrow stem cells (BMSCs) transplantation in the treatment of hepatolenticular degeneration of liver fibrosis. Methods Sixty cases with confirmed hepatolenticular degeneration of liver fibrosis were randomly divided into 3 groups: penicillamine group [40 mg/(kg·d)], BMSCs group and BMSCs + penicillamine group. Autologous BMSCs (2 mL) were injected into vein with normal saline (100 mL). Liver tissue pathology biopsy was inspected and the changes in HA, PCⅢ, LN, CⅣ, TIMP-1 and MMP-1 were observed at 0, 4th, 8th and 12th week during the therapeutic process. Results The level of serum fibrotic markers were reduced in every group , while the changes in BMSCs + penicillamine group were especially obvious (P < 0.05). Conclusion Penicillamine combined with BMSCs was effective in the therapy of hepatolenticular degeneration of liver fibrosis.
ABSTRACT
BACKGROUND:MicroRNA plays an important role in the process of growth and aging of living body. To know the role of let-7d in inducing bone marrow mesenchymal stem celldifferentiation into neurons can promote the stem celltransplantation. OBJECTIVE:To investigate the role of let-7d in inducing bone marrow mesenchymal stem celldifferentiation into neurons. METHODS:(1) The lentiviral vector of let-7d was constructed and transfected into rat bone marrow mesenchymal stem cells. The cells were divided into non-transfected group, negative control group (transfected with FU-RNAi-NC-LV), transfected enhancement group (transfected with let-7d-LV), transfected inhibition group ( transfected with let-7d-inhibition-LV). (2) Rat bone marrow mesenchymal stem cells were treated with fasudil as an inducer for triggering the cells to differentiate into neurons. The expression of neuron-specific markers, neuron-specific enolase and microtubule-associated protein 2, were measured by immunocytochemical method. The mRNA expression of microtubule-associated protein 2 was detected by RT-PCR. The viability of bone marrow mesenchymal stem cells was determined by MTT method. RESULTS AND CONCLUSION:Under inverted fluorescence microscope, the cells were successful y transfected with let-7d. Fasudil induced bone marrow mesenchymal stem cells to differentiate into neurons. The transfection efficiency and expression levels of neuron-specific enolase and microtubule-associated protein 2 in transfected enhancement group were higher than those in the negative control group (P<0.05);while in the inhibition group, they were lower than those in the negative control group (P<0.05). These findings indicate that let-7d can promote the differentiation of bone marrow mesenchymal stem cells into neurons induced by fasudil, and by control ing the expression of let-7d we can influence the differentiation efficiency from bone marrow mesenchymal stem cells to neurons.
ABSTRACT
Objective To investigate cognitive impairment mechanism by studying dorsolateral prefrontal cortex connectivity in patients with primary insomnia.Methods Forty patients with primary insomnia and 50 healthy subjects from the Department of Neurology,People's Hospital of Zhengzhou University during the period April 2011 through April 2013 were included.The World Health OrganizationUniversity of California Los Angeles Auditory Verbal Learning Test (WHO-UCLA AVLT) and the digital pin test were applied to evaluate the subjects' word study ability and vigilance.Resting state functional magnetic resonance imaging was used to observe the connectivity of dorsolateral prefrontal cortex.Results The Pittsburgh Sleep Quality Index (2.00 (1.00,3.00)) and the Hamilton Anxiety Scale scores (13.00 (11.25,15.75)) of primary insomnia patients were significantly higher than that of healthy controls (11.00(9.00,13.00),1.00 (0,2.00),Z=-5.517,Z=-5.525,P＜0.01).Digital pin test efficiency (60.03％ ± 13.95％ vs 66.32％ ± 13.73％,t =2.142,P＜0.05) and WHO-UCLA word learning (10.11 ± 2.29 vs 11.95 ± 2.42,t =-3.493,P ＜ 0.01) of primary insomnia patients were significantly lower than that of healthy controls.Compared to the healthy controls,the right dorsolateral prefrontal cortex of primary insomnia patients exhibited decreased functional connectivity of the right prefrontal lobe (-2.610 3 ± 0.172 6,t =-3.504,P ＜ 0.05).The left dorsolateral prefrontal cortex of primary insomnia patients exhibited increased functional connectivity of the bilateral insular lobes and right prefrontal lobe (2.8204±0.326 5,2.371 7 ±0.106 6,2.492 6 ±0.052 8,t =4.032,t =3.340,t =3.037,P ＜0.05).Conclusions The ability of WHO-UCLA word study and the digital pin test efficiency have been shown to decline in patients with primary insomnia.The possible mechanism of cognitive impairment may be the abnormal dorsolateral prefrontal cortex connectivity in patients with primary insomnia.
ABSTRACT
Objective To observe the survival and migration characteristics after intracarotid transplantation of bone marrow stem cells(BMSCs) and its effect on learning-memory abilities across the blood-brain barrier(BBB) in the vascular dementia(VD) rats .Methods Bone mononuclear cells(BMNCs) were isolated from bone marrow in vitro by standard Ficoll-Hypaque technique , then cells were enriched and expanded by using bone marrow adherent culture .72 Wistar rats were meanly divided into control group ,model group and treatment group .The VD rat model was established by modified pulsinellis 4-vessel occlusion(4 VO) .The treatment group received intracarotid infusion of 0 .5 mL 1 .2 × 107/mL BMSCs which were labeled with BrdU in vitro after opera-tion .Their survival ,migration and the learning-memory abilities were observed at 4th and 8th week .Results BMSCs transplanted by intracarotid transplantation survived and had been found throughout the brain tissue .They major migrated and localized in the is-chemic zone of injury such as hippocampus and cerebral cortex .Compared with the control group ,active avoidance response(AAR) ratio in the model group(42 .1 ± 4 .5) ,group(43 .6 ± 3 .6)showed significantly decrease compared with the control group (90 .0 ± 4 .3) ,(92 .5 ± 5 .0)(P<0 .01) ,and the treatment group(69 .2 ± 4 .7) ,(70 .8 ± 4 .7)was significant higher than the model group(P<0 .01) .Conclusion Intracarotid transplantation of BMSCs could enter the VD rats cerebra parenchyma via BBB ,migrate into the damaged brain tissue to gather and survive .Learning-memory abilities can be improved significantly by transplanted BMSCs .
ABSTRACT
@#Objective To observe the effect of chronic cerebral hypoperfusion on abilities of learning and memory and astrocytes in old rats. Methods 50 Wistar rats were randomly divided into the sham group and model group with 25 animals in each group. All animals were assessed with Morris water maze to test the changes of abilities of learning and memory. The expressions of glial fibrillary acidic protein (GFAP) in the frontal lobe and hippocampus were observed immunohistochemically. Results Compared with the sham group, the scores of Morris water maze decreased in the model group, while the astrocytes marked by GFAP proliferated and enlarged significantly. Conclusion Proliferation and morphological changes of astrocytes are involved in pathological mechanism of chronic cerebral hypoperfusion, which might be associated with the decrease of ability of learning and memory.