ABSTRACT
AIM: To investigate t h e impacts of theaflavins (TFs) on neuronal apoptosis and blood-brain barrier (BBB) by regulating the calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2)/5 '-adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. METHODS: Ninety rats were randomly separated into sham operation group, model group, low-dose TFs group (20 mg/kg TFs), high-dose TFs group (40 mg/kg TFs), and high-dose TFs + STO-609 group (40 mg/kg TFs + 10 ΜL CaMKK2 inhibitor-STO-609), positive control group (2 mg/kg nimodipine injection), with 15 rats in each group. A rat model of intracerebral hemorrhage was induced by collagenase type VII. The behavior of rats and the water content of brain tissue were detected; the serum of rats was isolated, and the levels of inflammatory factors-vascular cell adhesion molecule-1 (VCAM-1), tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule-1 (ICAM-1) were detected; brain tissue around the hematoma was collected to detect neuronal apoptosis, BBB permeability parameter-EB level, and expressions of p-CaMKK2/CaMKK2, p-AMPK/AMPK and apoptosis-related protein Bax. RESULTS: Compared with the sham operation group, the mNSS score, ICAM-1, TNF-α, VCAM-1, brain tissue water content, apoptosis rate, EB level and Bax protein expression in the model group were all increased, both pCaMKK2/CaMKK2 and p-AMPK/AMPK were decreased (P < 0.05); compared with the model group, the mNSS score, ICAM-1, TNF-α, VCAM-1, brain water content, apoptosis rate, EB level and Bax expression in the low- and high-dose TFs groups and the positive control group were all lower than those in the model group, both pCaMKK2/CaMKK2 and p-AMPK/AMPK were increased (P < 0.05); compared with the high-dose TFs group, the mNSS score, ICAM-1, TNF-α, VCAM-1, brain tissue water content, apoptosis rate, EB level and Bax expression were all increased in the high dose TFs + STO-609 group, both p-CaMKK2/CaMKK2 and p-AMPK/AMPK were decreased (P < 0.05). CONCLUSION: TFs can reduce neuronal apoptosis, inflammatory response, BBB permeability, and play a protective role in rats with cerebral hemorrhage injury. Its mechanism is related to the activation of CaMKK2/AMPK signaling pathway.
ABSTRACT
Objective:To investigate the regulatory mechanism of long non-coding RNA (lncRNA) NEF on T cell immune function in postmenopausal osteoporosis (PMOP) mice.Methods:Female Balb/c mice were used to construct OVX model ( n=46) and sham control group ( n=16) . Bone marrow mesenchymal stem cells (BM-SCs) from these two groups of mice were cultured. NEF recombinant expression vector (pIRSE2-NEF) was constructed and transfected into BMSCs. RT-qPCR was used to detect NEF and miR-21 levels in BMSCs cells in sham group, OVX group, and pIRSE2-NEF group. Luciferase gene report experiment was used to verify the binding effect of NEF and miR-21. The remaining 40 OVX mice were divided into 4 groups, including OVX group ( n=10) , pIRSE2-NEF injection group (pIRSE2-NEF group, n=10) , pIRSE2-NEF combined with PD-1 inhibitor group (pIRSE2-NEF+ PD-L1-IN-1 group, n=10) , and pIRSE2-NEF combined with miR-21 mimic (mimic) group (pIRSE2-NEF+ mimic group, n=10) . The remaining 10 mice in sham group were used as the control group. ELI-SA was used to detect the levels of IFN-γ, IL-2, IL-4, IL-13 and PD-1/PD-1L in peripheral blood. Flow cytometry was used to detect the shift of serum Treg-Th17 cell subsets. Results:Compared with the Sham group (1.01±0.04, 1.00±0.03) , the expression of NEF in BMSCs of OVX group was down-regulated (0.23±0.01) , and miR-21 was up-regulated (2.96±0.05) ( P<0.05) . Compared with OVX group (1.23±0.15, 5.20±0.31) , NEF in BMSCs cells of Pirse2-nef group was significantly up-regulated (6.83±0.35) ( P<0.05) , while miR-21 was down-regulated (0.29±0.11) ( P<0.05) .NEF has a direct binding base site with miR-21.The levels of IFN-γ (3.25±0.21) , IL-2 (2.44±0.06) and Th17/Treg ratio (3.18±0.65) in peripheral blood of mice in OVX group were significantly higher than those in Sham group (1.03±0.02, 1.00±0.01, 0.86±0.09) (all P<0.05) . The levels of IL-4 (0.45±0.02) , IL-13 (0.43±0.07) , PD-1 (0.24±0.03) and PD-1L (0.51±0.06) were significantly lower than those of Sham group (1.00±0.04, 1.00±0.02, 1.00±0.03, 1.00±0.00) ( P<0.05) ; Compared with OVX, IFN-γ (2.02±0.06) , IL-2 (0.88±0.01) and Th17/Treg ratio (1.43±0.22) in Pirse2-nef group were decreased. The levels of IL-4 (0.87±0.03) , IL-13 (0.84±0.07) , PD-1 (0.79±0.06) and PD-1L (0.77±0.06) were increased (all P<0.05) ; Compared with Pirse2-nef group, IFN-γ (2.89±0.06) , IL-2 (2.07±0.07) and Th17/Treg ratio (2.39±0.38) were increased in Pirse2-nef+ PD-L1-in-1 group. The levels of IL-4 (0.68±0.03) , IL-13 (0.76±0.08) , PD-1 (0.52±0.02) and PD-1L (0.83±0.04) were decreased (all P<0.05) . Moreover, the pIRSE2-NEF+ mimic group had the same adjustment effect as the pIRSE2-NEF+ PD-L1-IN-1 group. Conclusion:lncRNA-NEF improves immune imbalance and PD-1/PD-1L-mediated Treg-Th17 cell balance in postmenopausal osteoporosis mice by sponging miR-21.
ABSTRACT
Objective@#To observe the effect of Zhen′gan Xifeng decoction combined with mirror therapy on the recovery of upper limb function of stroke patients with syndrome of Yin deficiency and wind stirring.@*Methods@#From January 2015 to October 2017, 90 stroke patients with syndrome of Yin deficiency and wind stirring complicated with hemiplegia of upper limbs in Wenzhou Hospital of Traditional Chinese Medicine were randomly divided into the combined treatment group, the mirror treatment group and the control group according to the digital table, with 30 cases in each group.All patients were treated with conventional western medicine, combined with limb function rehabilitation training; on this basis, the combined treatment group was given mirror therapy in conjunction with Zhen′gan Xifeng decoction, the mirror group was given mirror treatment, the control group only received routine treatment.The three groups were treated for 8 weeks.The recovery of upper limb function score(FMA), arm action test score(ARAT), functional independent measurement(FIM) were used to evaluate the curative effect, and the TCM syndrome scores of the patients before and after treatment were compared in the three groups.@*Results@#After treatment, the FMA scores, ARAT scores and FIM scores of the three groups were higher than those before treatment(all P<0.01). The upper limb FMA score[(33.80±7.17)points], ARAT score[(13.57±4.62)points], FIM score[(69.54±19.23)points] in the combined treatment group were significantly higher than those in the mirror group[(25.90±6.47)points, (11.57±3.84)points and (59.89±22.56)points, P=0.001, 0.036, 0.001] and the control group[(21.90±4.87)points, (10.32±3.21)points, (49.80±23.51)points, P=0.001, 0.025, 0.000]. The Ashworth upper limb spasticity score in the combined treatment group[(1.23±0.34) points] was significantly lower than that in the mirror group[(1.91±0.46)points, P=0.048]and the control group[(1.72±0.51)points, P=0.043], compared with before treatment, the scores in the mirror group and the control group had no statistically statistical differences(t=0.58, P=0.290, t=1.21, P=0.079). The effectiveness of the combined treatment group was 24 cases after treatment of TCM syndrome, and 18 cases were effective in the mirror group, and 6 cases were effective in the control group.@*Conclusion@#The combination of Zhen′gan Xifeng decoction and mirror therapy can better improve the upper extremity motor function of the stroke patients with syndrome of Yin deficiency and wind stirring, promote the recovery of the motor function of the affected side and improve the daily living ability of the patients.The improvement of upper limb spasm is more effective, it is worthy of clinical promotion.
ABSTRACT
Objective To observe the effect of Zhen'gan Xifeng decoction combined with mirror therapy on the recovery of upper limb function of stroke patients with syndrome of Yin deficiency and wind stirring.Methods From January 2015 to October 2017,90 stroke patients with syndrome of Yin deficiency and wind stirring complicated with hemiplegia of upper limbs in Wenzhou Hospital of Traditional Chinese Medicine were randomly divided into the combined treatment group,the mirror treatment group and the control group according to the digital table,with 30 cases in each group.All patients were treated with conventional western medicine,combined with limb function rehabilitation training;on this basis,the combined treatment group was given mirror therapy in conjunction with Zhen'gan Xifeng decoction,the mirror group was given mirror treatment,the control group only received routine treatment.The three groups were treated for 8 weeks.The recovery of upper limb function score (FMA),arm action test score (ARAT),functional independent measurement (FIM) were used to evaluate the curative effect,and the TCM syndrome scores of the patients before and after treatment were compared in the three groups.Results After treatment,the FMA scores,ARAT scores and FIM scores of the three groups were higher than those before treatment(all P ＜ 0.01).The upper limbFMA score[(33.80 ± 7.17) points],ARAT score[(13.57 ± 4.62) points],FIM score[(69.54 ±19.23)points] in the combined treatment group were significantly higher than those in the mirror group [(25.90 ±6.47) points,(11.57 ± 3.84) points and (59.89 ± 22.56) points,P =0.001,0.036,0.001] and the control group [(21.90 ± 4.87) points,(10.32 ± 3.21) points,(49.80 ± 23.51) points,P =0.001,0.025,0.000].The Ashworth upper limb spasticity score in the combined treatment group [(1.23 ± 0.34) points] was significantly lower than that in the mirror group[(1.91 ± 0.46) points,P =0.048] and the control group [(1.72 ± 0.51) points,P =0.043],compared with before treatment,the scores in the mirror group and the control group had no statistically statistical differences (t =0.58,P =0.290,t =1.21,P =0.079).The effectiveness of the combined treatment group was 24 cases after treatment of TCM syndrome,and 18 cases were effective in the mirror group,and 6 cases were effective in the control group.Conclusion The combination of Zhen'gan Xifeng decoction and mirror therapy can better improve the upper extremity motor function of the stroke patients with syndrome of Yin deficiency and wind stirring,promote the recovery of the motor function of the affected side and improve the daily living ability of the patients.The improvement of upper limb spasm is more effective,it is worthy of clinical promotion.
ABSTRACT
Objective To investigate the effect of anti-epileptic soup on the levds of interleukin-2 (IL-2) and interleukin-6 (IL-6) in pentylenetetrazol-induced rats and its mechanism.Methods Healthy adult male SD rats were injected intraperitoneally with pentylenetetrazol kindling 35.0mg/kg to induce a rat epilepsy model.After successful construction of the epilepsy model,the rats were divided into four the groups:blank group,model group,anti -epileptic soup group and sodium valproate (VPA) group.All of the treatments were performed three times a day continuously for 28 days.The rats in the anti-epileptic soup group were given 6ml of anti-epileptic soup.The rats in the VPA group were given 400mg/kg of sodium valproate by garage.The rats in blank group and model group received 6ml of normal saline.After treatment,the seizures level was recorded by using the Diehl six point grading scale,and the expression of serum IL-2 and IL-6 were detected by the enzyme linked immunoassay (ELISA).Results The seizure level of the model group was (4.23 ± 0.43),while that of the anti-epileptic group was (3.47 ± 0.39),indicated that the anti-epileptic soup can reduce the seizures level.The expressions of IL-2 (4.18 ± 0.41)pg/mL and IL-6 (350.0 ± 82.5) pg/mL of the model group were higher than those of the blank group [IL-2 (3.20 ± 0.36) pg/mL,IL-6 (260.2 ± 69.0) pg/mL,P ＜ 0.01],while the expressions of IL-2 (3.48 ± 0.44) pg/mL and IL-6 (287.5 ±74.6) pg/mL of the anti-epileptic group were lower compared with the control group (P ＜0.01).No significant difference was found between the anti-epileptic group and VPA group IL-2 (3.35 ± 0.56) pg/mL and IL-6 (253.8 ± 59.8) pg/mL(P ＞ 0.05).Conclusion The anti-epileptic soup is effective for treating epilepsy in rats,the possible mechanism may be related with downregulating the expression of IL-2 and IL-6.
ABSTRACT
Objective To investigate the correlation between clinical presentations and the findings of video fluoroscopic swallowing study (VFSS)in patients with post-stroke dysphagia. Methods A total of 56 consecutive patients with post-stroke dysphagia admitted to Wenzhou Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University from June 2012 to May 2014 were enrolled. Four different kinds of food were selectively used to complete clinical assessment of swallowing function and VFSS respectively. The SPSS 20. 0 statistical software was used to perform univariate and multivariate Logistic regression analyses for all observed indexes of the 2 methods. Results there were significant correlations in the point correspondence relation among the clinical manifestations and VFSS in food residue in the mouth and abnormal closure of lips in the oral phase (95%CI 1. 430-101. 468;P=0. 022);poor soft palate elevation and food residue in the mouth (95%CI 1. 476-102. 033;P=0. 020);graded swallowing and piecemeal deglutition with delayed oral transit (95% CI 2. 616 -182. 897;P = 0. 004);tongue movement disorders,poor soft palate elevation and tongue dyskinesia with poor bolus formation (95%CI 1. 468-50. 795,1. 220-13. 825;P=0. 017,0. 023);food leak from the corner of mouth,dysphagia,bolus falling to the epiglottis from the base of tongue or trachea (95%CI 1. 146-125. 459,1. 657-174. 400;P=0.038,0. 017). The weakened pharyngeal reflex with weak laryngeal elevation in the pharyngeal phase (95%CI 1. 150-92. 815;P =0. 037);dysphagia and delayed swallowing with prolonged triggering of swallowing reflex (95%CI 2. 123-37. 770,1. 233-114. 176;P=0. 003,0. 032);graded swallowing,hard swallowing, choking sensation,and poor laryngeal elevation with prolonged pharyngeal transit (95%CI 1. 619-223. 316,1. 061-31. 445,2. 834 -132. 707;P =0. 019,0. 042,and 0. 003);dysphagia and the opening of cricopharyngeal muscle insufficiency (95%CI 1. 037 -24. 115;P =0. 045);weak laryngeal elevation,foreign body sensation in the throat,and choking after swallowing with food retention or residual in vallecula or pyriform sinus (95%CI 1. 046 -13. 685,1. 116 -87. 741;P =0. 043, 0.040);and coughing during swallowing and eating choking or aspiration (95%CI 0. 010-0. 921,0. 037-0. 826;P=0. 042,0. 028). Conclusion Some clinical manifestations are closely correlated with the swallowing dysfunction revealed by VFSS. With the help of this law,it may more simply and safely determine the degree and type of dysphagia in patients,and provide guidance for patients with dysphagia after stroke who can not accept VFSS in the rehabilitation treatment.
ABSTRACT
Objective The purpose of this investigation was to investigate the neuroprotective effects of rhubarb for ICH,as well as its mechanism.Methods ICH was produced in adult Spargue-Dawley rats by injection of collagenase IV(0.05U/0.5uL).Intraperitoneal injection of rhubarb (70mg/kg) or saline,was started at 3,6 or 12 hours post-ICH respectivdy.Casepase-3 activity.TUNEL and neurological behavior function were performed 24hours after ICH.Results Rhubarb siven at 3 or 6 hours can inhibit casepase-3 activity(P<0.001),reduce TUNEL positive cells(P<0.05) and attenuate apomorphine-induced rotation(P<0.05) at 24 hours after ICH.However,the animals which were treated 12 hours showed no improvement.Conclusion Rhubarb may be a potential drug for ICH patients for its possible effect of inhibiting apoptosis.