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OBJECTIVE To study the effects and potential mechanism of wogonin （Wog） on airway inflammation in rats with chronic obstructive pulmonary disease （COPD）. METHODS Eighty-four rats were randomly divided into control group， model group， Wog low-dose and high-dose groups （intragastric administration of 50， 100 mg/kg）， aminophylline group （positive control， intragastric administration of 2.3 mg/kg）， recombinant rat receptor-interacting protein kinase 1 [rRIPK1， receptor-interacting protein kinase 1 （RIPK1） activator] group （tail vein injection of 8 µg/kg）， and Wog high-dose+rRIPK1 group （intragastric administration of Wog 100 mg/kg+tail vein injection of rRIPK 8 µg/kg）， with 12 rats in each group. Except for control group， COPD model of other groups was induced by smoking combined with tracheal injection of lipopolysaccharide. Twenty-four hours after successful modeling， the rats were administered once a day for 4 weeks. The changes of peak inspiratory flow （PIF）， peak expiratory flow （PEF） and minute ventilation （MV），forced expiratory volume in one second（FEV1）/forced vital capacity（FVC） were measured after the last medication； the serum levels of interleukin 1β（IL-1β）， IL-6 and tumor necrosis factor-α （TNF-α） were measured by ELISA； the pathological changes of lung tissue in rats were observed； the apoptotic rate of pulmonary epithelial cells was detected. mRNA expressions of RIPK1， RIPK3 and mixed lineage kinase domain-like protein （MLKL）， and protein expressions of RIPK1， RIPK3 and p-MLKL were all detected in lung tissue of rats. RESULTS Compared with control group， PIF， PEF， MV and FEV1/FVC of model group were decreased significantly （P＜0.05）， while the levels of IL-1β， IL-6 and TNF- α were increased significantly （P＜0.05）； there was a large number of inflammatory cells infiltration in the lung tissue and bronchialwall thickening in model group； the apoptotic rate of pulmonary epithelial cells，mRNA expressions of RIPK1， RIPK3 and MLKL， protein expressions of RIPK1， RIPK3 and p-MLKL were increased significantly （P＜0.05）. Compared with model group， above indexes of rats were improved significantly in Wog low-dose and high-dose groups （P＜0.05）， and pathological injuries were alleviated significantly. The corresponding indexes of rats were worsened in rRIPK1 group （P＜0.05）， and pathological damage had further worsened. rRIPK1 significantly attenuated the inhibitory effect of high-dose Wog on airway inflammation and RIPK1/RIPK3/ MLKL pathway in COPD rats （P＜0.05）. CONCLUSIONS Wog may improve airway inflammation in COPD rats by inhibiting RIPK1/RIPK3/MLKL signal pathway.
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ObjectiveTo explore low-frequency repetitive transcranial magnetic stimulation (rTMS) combined with bilateral isokinematic training (BIT) on upper limb motor function and activities of daily living of stroke patients. MethodsFrom September, 2021 to September, 2022, 60 stroke inpatients in Zhejiang Provincial People's Hospital were randomly divided into rTMS group (n = 20), BIT group (n = 20) and combination group (n = 20). All the patients accepted routine rehabilitation, moreover, rTMS group accepted 1 Hz rTMS on healthy side, BIT group accepted BIT, and the combination group accepted the combination of 1 Hz rTMS on healthy side and BIT, for four weeks. They were evaluated with Fugl-Meyer Assessment-Upper Extremities (FMA-UE), Wolf Motor Function Test (WMFT), Carroll Upper Extremities Function Test (UEFT) and modified Barthel Index (MBI) before and after treatment. ResultsThe scores of FMA-UE, WMFT, UEFT and MBI significantly improved in all the groups after treatment (|t| > 5.052, P < 0.001), and improved the most in the combination group (F > 9.834, P < 0.001). ConclusionBoth low-frequency rTMS and BIT can effectively improve upper limb motor function and activities of daily living of stroke patients, and the combination of them is more effective.
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Objective To explore the effect of high-frequency repetitive transcranial magnetic stimulation (rTMS) on activity in the intact motor cortex controlling the suprahyoid muscles and thus on dysphagia after an unilateral stroke.Methods Forty patients suffering dysphagia more than two weeks after a unilateral cerebral stroke were randomly divided into an experimental group and a control group,each of 20.Both groups were given traditional swallowing rehabilitation training,while the experimental group was additionally provided with 5 Hz rTMS for two weeks.Before and after the treatment,all of the patients were characterized using X-ray fluoroscopy,video fluoroscopic swallowing study (VFSS) and surface electromyography,and their swallowing was evaluated using a standardized swallowing assessment (SSA) and a penetration-aspiration scale (PAS).Results After the treatment,significant improvement was observed in both groups in the average swallowing time and in the maximum amplitude of sEMG,as well as the average SSA,PAS and VFSS scores (P＜0.05).The average values in the experimental group were in all cases significantly better than the control group's averages (P＜0.05).Conclusion Applying rTMS at 5 Hz to the motor cortex of the contralateral hemisphere controlling the suprahyoid muscles can effectively improve unilateral-hemisphere dysphagia after stroke.
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Objective Dendritic cells (DCs), helper T cells 17 (Th17) and regulatory T cells (Treg) are closely related to the pathogenesis of chronic obstructive pulmonary disease (COPD). This study aimed to investigate the changes of Th17- and Treg-related cytokines in the bronchoalveolar lavage fluid (BALF) of COPD mice after DC-based adoptive immunotherapy with over-expressed suppressor of cytokine signaling protein 1 (SOCS1) and provide some new ideas for the treatment of COPD. Methods A total of 48 male C57BL/6 mice were randomly divided into 5 groups: healthy control, COPD model control, immature DC (imDC), DC-SOCS1 1×106, and DC-SOCS1 2×106. The healthy controls were exposed to air and fed normally, the COPD model controls injected with normal saline at 0.5 mL/ on the first day of modeling by fumigation, the mice of the imDC group injected via the tail vein with 1 ×106 imDCs, and those of the DC-SOCS1 groups injected with 1 ×106 or 2 ×106 DCs with over expressed SOCS1, all via the tail vein on the 1st and 7th day of modeling. Then the lung tissues were collected from the mice for preparation of paraffin sections and HE staining, and ELISA was employed for determination of the levels of Th17-related IL-17 and IL-23 and Treg-related IL-10 and TGF-β in the BALF of the model mice. Results Compared with the COPD model controls, the mice in the imDC, DC-SOCS1 1×106 and DC-SOCS1 2×106 groups showed significantly decreased levels of IL-17 on the 1st day ([78.87 ± 1.08] vs [46.46 ± 0.77], [34.09 ± 3.98] and [24.12 ± 0.57] pg/mL, P < 0.05) and 7th day after modeling ([78.87 ± 1.08] vs [55.69 ±0.35], [35.65 ± 0.54] and [27.00 ± 0.58] pg/mL, P < 0.05), and IL-23 on the 1st day ([200.62 ± 0.65] vs [150.19 ± 0.53], [121.09 ± 0. 53] and [70.21 ± 0.91] pg/mL, P < 0.05) and 7th day ([200.62 ± 0.65] vs [167.70 ± 1.73], [136.34 ± 0.90] and [99.35 ± 1.83] pg/mL, P < 0.05), but remarkably increased levels of IL-10 on the 1st day ([39.46 ± 3.88] vs [50.74 ± 1.77], [58.71 ± 3.84] and [70.12 ± 2.62] pg/mL, P < 0.05) and 7th day ([39.46 ± 3.88] vs [44.56 ± 2.63], [54.78 ± 1.43] and [63.00 ± 2.57] pg/mL, P < 0.05), TGF-β on the 1st day ([24.98 ± 0.43] vs [36.46 ± 0.98], [42.40 ± 0.62] and [50.55 ± 0.53] pg/mL, P < 0.05) and 7th day ([24.98 ± 0.43] vs [33.27 ± 0.92], [40.12 ± 0.83] and [44.98 ± 0.52] pg/mL, P < 0.05). The contents of IL-17 and IL-23 were markedly lower while those of IL-10 and TGF-β higher in the DC-SOCS1 1×106 than in the imDC group (P < 0.05), and the levels of the former two significantly higher and those of the latter two lower in the DC-SOCS1 2×106 than in the DC-SOCS1 1×106 group (P < 0.05). Conclusion Transfusion of DCs with over-expressed SOCS1 can inhibit the secretion of Th17-related cytokines in COPD, and the effect is better than that of imDCs alone and related to the concentration and time.
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Objective To explore the role of lung dendritic cells (DCs) and Th17/regulatory T cells (Treg) pathway in the pathogenesis of chronic obstructive pulmonary disease(COPD).Methods COPD patients who received lobectomy from Sep.2015 to Mar.2016 in our hospital were enrolled and classified into non-smoking non-COPD group,smoking without COPD group and COPD group.The expression of CD80,chemokine recepter-6 (CCR6),interleukin-17A (IL-17A) and fork-head transcription factor P3 (FoxP3) were detected by immunohistochemistry (IHC) in lung tissue.Mature DCs (mDCs),immature DCs (imDCs),Th17 cells and Treg cells in lung tissue were detected by flow cytometry (FCM) and the correlation between Th17/ Treg cells with lung function was analyzed.Results (1) The expression of CD80 and FoxP3 in COPD group was decreased,while the expression of CCR6 and IL-17A was increased (P＜0.05).(2) The percentage of mDCs and Treg in lung tissue of COPD group was significantly decreased.In contrast,the proportion of imDCs and Th17 cells in COPD group was significantly increased (P＜0.05).(3) The imbalance of Th17/Treg ratio in lung tissue was seen in patients with COPD,suggesting the potential mechanism of Th17 cell-mediated proinflammatory response.(4) The percentage of Th17 cells and Th17/Treg ratio in COPD patients was negatively correlated with forced expiratory volume in the first second (FEV1) as a percentage of predicted value (FEV1％ pred),forced vital capacity(FVC) as a percentage of predicted value (FVC％ pred),FEV1/FVC.On the other hand,the percentage of Treg cells was positively correlated with FEV1％ pred,FVC％ pred,FEV1/FVC.Conclusions The data in this study demonstrate the maturation disorder of dendritic cells in lung tissue of COPD patients.The imbalance of Th17/Treg ratio suggests that Th17 cell-mediated proinflammatory response may be involved in the pathogenesis of COPD.
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BACKGROUND: Repetitive brief and non-lethal cerebral ischemia can produce cumulative neuronal damage and vascular dementia; however, precisely injured patterns and mechanisms are still unclear. Thalamus is an important structure of learning and memory; meanwhile, it is also one of the selectively vulnerable regions of cerebral ischemia.However, there are a few reports about neuronal damage induced by repetitive cerebral ischemia.OBJECTIVE: To investigate the pathological damage and mechanism of neurons induced by repetitive cerebral ischemia in thalamus.DESIGN: Randomized controlled experimental study.SETTING: Department of Neurology, General Hospital of Chengdu Military Area Command of Chinese PLA.MATERIALS: The experiment was carried out at the Animal Central Laboratory of the Third Military Medical University of Chinese PLA from March to December 1999. A total of 72 healthy male Wistar rats were randomly divided into sham operation group, single cerebral ischemic group,repetitive cerebral ischemic group, MK-801 treatment group and saline group.METHODS: Transient global cerebral ischemia models of rats were established with modified Pulsinelli-4 vessel occluing method for single 15-minute ischemia and repetitive three 5-minute ischemia at hourly intervals,followed by 5 hours, 2 days and 4 days of survival. Rats in sham operation group were not treated with burning vertebral artery and clipping common carotid artery. 45Ca autoradiography and light microscopy were used to determine the calcium accumulation and neuronal pathological changes of thalamus following repetitive cerebral ischemia as compared with single cerebral ischemia. The effects of MK-801, a N-methyl-D-aspartate (NMDA)receptor antagonist, were also examined.MAIN OUTCOME MEASURES: Distribution and degree of calcium accumulation and neuronal damage in the thalamus of rats in each group.RESULTS: Sham-operated rats revealed no abnormal calcium accumulation and neuronal damage in the thalamus. At 5 hours following ischemia,slightly abnormal calcium accumulation was found in the partial thalamus of the repeated ischemic group, and the neuronal damage was also relatively severer than that in the single ischemic group (0.98±0.19, 0.60±0.14, P＞ 0.05). At 2 days after ischemia, obviously abnormal calcium accumula tion and neuronal damage were shown in thalamus, and the degree of calcium accumulation and score of neuronal damage in repeated ischemic group were significantly severer than that in single ischemic group (1.62±0.31, 0.88±0.21, P ＜ 0.01). At 4 days, the thalamus calcium accumulation and neuronal damage were further increased, and also that in repeated ischemic group was significantly severer than that in single ischemic group (1.80±0.21, 1.02±0.23, P ＜ 0.01), especially marked calcium accumulation and cumulative damage were shown in the ventral thalamus. MK-801 significantly relieved the abnormal calcium accumulation and neuronal damage in the thalamus in repeated ischemic group, showing significant protection of thalamus neurons as compared with that in saline-treated group (0.20±0.12, 1.80±0.15, P ＜ 0.01).CONCLUSION: Repetitive non-lethal cerebral ischemia results in an intense cumulative damage in the ventral thalamus, and the excitatory amino acid and Ca2+ may play a major role in it.