1.Study of the Post Effect of Electroacupuncture on Blood Flow in the Skins of Related Meridian Points in Rats with Acute Ischemic Myocardial Injury
Yali LIU ; Guozhen ZHAO ; Ping ZHANG ; Bo JI ; Jian DAI ; Yawen LU ; Mingna YAN ; Dan WANG ; Mengwei GUO ; Yingqiu MAO ; Xiaomin SUN ; Hongxin BAI ; Yongsi XU
Shanghai Journal of Acupuncture and Moxibustion 2016;35(6):732-737
Objective To observe over-time changes in rat blood flow in the skins of related meridian points during physiological status, the pathological state of ischemic myocardial injury and low or high frequency electroacupuncture intervention and explore the post effect of different frequency electroacupuncture on related meridian points after treating ischemic myocardial injury. Method Fifty male Wister rats were randomized into five groups: blank control, sham operation, model, low frequency electroacupuncture (meridian point A) and high frequency electroacupuncture (meridian point B), 10 rats each. Blood flow in the skins of bilateral points Neiguan (PC6), Ximen (PC4) and Tianquan (PC2), and non-meridian and non-acupoint control points was measured by laser speckle contrast imaging in every group immediately and at 30 and 60 min after the end of three treatments. Statistical analysis was made. Result Blood flow in the skins of bilateral points Neiguan, Ximen and Tianquan was significantly lower in the blank control group than in the model group (P<0.01,P<0.05). Blood flow in the skin of every acupoint increased in varing degrees after low or high frequency electroacupuncture treatment. Blood flow in bilateral points Neiguan, Ximen and Tianquan regions in meridian point group A was closer to that in the blank control group immediately after treatment. Blood flow in three left-side and three right-side acupoint regions in meridian point group B was closer to that in the blank control group at 30 and 60 min, respectively, after treatment. Conclusion The immediate effect of low frequency electroacupuncture on blood flow in acupoint regions is better than high frequency electroacupuncture during intervention in ischemic myocardial injury. The post effect of high frequency electroacupuncture on blood flow in acupoint regions is better than low frequency electroacupuncture during intervention in ischemic myocardial injury.
2.Predictors of early neurological deterioration in patients with acute ischemic stroke
Mei SUN ; Xiaoxia HOU ; Mengwei LYU ; Yangyang ZHANG ; Hong CHENG
International Journal of Cerebrovascular Diseases 2018;26(9):654-659
Objective To investigate the predictors of early neurological deterioration (END) in patients with acute ischemic stroke (AIS). Methods From January 2015 to April 2018, patients with AIS without receiving thrombolytic therapy and endovascular treatment admitted to the Department of Neurology, the First Affiliated Hospital of Nanjing Medical University were collected retrospectively. END was defined as National Institutes of Health Stroke Scale (NIHSS) score increased by ≥2 within 7 days after onset from baseline. The baseline clinical data, imaging examinations, and laboratory findings were compared in patients of the END group and the non-END group. Multivariate logistic regression analysis was used to determine the independent predictors of END. Results A total of 652 patients with AIS were enrolled,including 437 males (67. 0%). There were 247 patients (37. 9%) in the END group and 405 (62. 1%) in the non-END group. There were significant differences in low-density lipoprotein cholesterol, fasting blood glucose, homocysteine, lipoprotein (a), neutrophil percentage, and NIHSS scores between the 2 groups (all P < 0. 05). There were significant differences in the proportion of severity of stroke, serious lesion of the guilty vessels, watershed infarction, etiologic classification of stroke, Oxfordshire Community Stroke Projects classification, and taking statins before onset between the 2 groups (all P < 0. 05 ). Multivariate logistic regression analysis showed that lipoprotein (a) (odds ratio [OR] 1. 001, 95% confidence interval [CI] 1. 000-1. 002; P = 0. 021), total anterior circulation infarcts (OR 3. 842, 95%CI 1. 383-10. 671; P =0. 003), and partial anterior circulation infarcts (OR 2. 642, 95%CI 1. 486-4. 695; P = 0. 001) were the independent risk factors for END, and prior statin use was an independent protective factor of END (OR 0. 222, 95%CI 0. 072-0. 679; P = 0. 008). Conclusion Lipoprotein (a), total anterior circulation infarcts, and partial anterior circulation infarcts were the independent risk factors for END. Taking statins before onset was an independent protective factor of END.
3.Repair effect and mechanism of neural cell adhesion molecule derived peptide P2 on nerve function injury in ischemic stroke rats
Xiaoyan LAN ; Zhengwu SUN ; Chengyan CHU ; Mengwei ZHAO ; Shen LI
Chinese Journal of Behavioral Medicine and Brain Science 2022;31(11):968-975
Objective:To clarify the neuroprotective effects of neural cell adhesion molecule (NCAM) derived peptide P2 on in vitro cultured neuron and ischemic stroke rat. Methods:Primary cortical neurons were extracted and cultured, and CCK-8 method was used to observe the protective effect of different concentrations of P2 on cortical neurons under oxygen-glucose deprivation (OGD) conditions.The levels of apoptosis-related proteins and extracellular signal regulated kinase 1/2 (Erk1/2) were observed by Western blot. Clean grade male SD rats were selected for animal experiments. The middle cerebral artery occlusion (MCAO) method was used to establish the rat model of cerebral ischemia/reperfusion injury. The rats with successful model were divided into sham operation group, MCAO group and MCAO+ P2 group according to the random number table, with 12 rats in each group. After operation, rats in MCAO+ P2 group were subcutaneously injected with 1 mg/kg P2 once a day until 14 days after operation, and rats in the other two groups were subcutaneously injected with 0.9% sodium chloride solution of the same volume.Beam-walking test was used to evaluate the motor function of rats.Immunofluorescence staining and Western blot were used to detect the in-situ apoptosis of neuronal cells and the expression of Erk1/2 in ischemic penumbra of rat brains, respectively. All statistical analyses were performed using SPSS 22.0.Repeated measurement ANOVA was used to evaluate the beam-walking experimental data, and one-way ANOVA were used to analyze other experimental data among multiple groups.Results:Compared with OGD group, 0.5, 1.0 and 2.0 μmol/L P2 improved the activity of neurons under OGD conditions, of which 1 μmol/L P2 had the best effect ((2.436±0.284), (1.551±0.410), P<0.05). Western blot showed that the protein levels of bax ((76.120±3.232)%, (88.965±5.208)%, P<0.05), cleaved caspase-3 ((76.736±4.306)%, (97.781±8.111)%, P<0.05) and cleaved caspase-9 ((88.833±6.581)%, (104.962±4.788)%, P<0.05) in 1 μmol/L P2 treated group were all lower than those in OGD group, while the protein levels of bcl-2 ((56.146±3.882)%, (43.170±6.945)%, P<0.05) and phosphorylated Erk1/2 ((73.583±8.557)%, (55. 219±4.615)%, P<0.05) in 1 μmol/L P2 treated group were both higher than those in OGD group. Compared with MCAO group, on the 14th day after P2 intervention, the slip ratio of hindlimb of the paralyzed hind limbs of rats was lower ((23.438±11.540)%, (41.733±13.631)%, P<0.05), the apoptosis rate of neurons around the focus was lower ((13.144±6.485)%, (26. 699±6. 402)%, P<0.05), and the level of phosphorylated Erk1/2 protein in the brain tissues around the infarct focus was higher ((74.062±7.458)%, (53.327±7.093)%, P<0.05). Conclusion:Low doses of neural cell adhesion molecule derived peptide P2 exert neuroprotective effects on OGD neurons and ischemic stroke rats. The underlying mechanism may be related to the activation of Erk.
4. Effects and mechanism of dapagliflozin on myocardial injury in type 1 diabetes mice
Xuejiao ZHANG ; Jieting LIU ; Luxin LI ; Peijian CHEN ; Minglu DING ; Mengwei SUN ; Yanhui CHU ; Zhen ZHANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2023;28(3):257-265
AIM: To investigate the effect of dapagliflozin on myocardial injury in type 1 diabetes mice and its mechanism. METHODS: Normal C57BL / 6J male mice were randomly divided into normal control group (Control), diabetes cardiomyopathy group (DCM) and dapagliflozin group (DAPA). The model of diabetes was induced by streptozotocin (STZ) and given maintenance feed. DAPA group was given 10 mg · kg
5. Early transplantation of growth differentiation factor 11-silenced bone marrow stromal cells promotes osteogenesis in necrotic femoral head induced by steroid in rats
Lingchi KONG ; Xingliang SUN ; Rongtai ZUO ; Mengwei WANG ; Junjie GUAN ; Qinglin KANG
Chinese Journal of Orthopaedic Trauma 2019;21(9):802-809
Objective:
To study the effect of growth differentiation factor (GDF) 11-silenced bone marrow stromal cells (BMSCs) on bone regeneration in early steroid-induced osteonecrosis of the femoral head in rats.
Methods:
After GDF11 expression in BMSCs was inhibited by siRNA, the knockdown efficiency and transfection cytotoxicity were detected. The further experiments both in vitro (
6.High-throughput screening of novel TFEB agonists in protecting against acetaminophen-induced liver injury in mice.
Xiaojuan CHAO ; Mengwei NIU ; Shaogui WANG ; Xiaowen MA ; Xiao YANG ; Hua SUN ; Xujia HU ; Hua WANG ; Li ZHANG ; Ruili HUANG ; Menghang XIA ; Andrea BALLABIO ; Hartmut JAESCHKE ; Hong-Min NI ; Wen-Xing DING
Acta Pharmaceutica Sinica B 2024;14(1):190-206
Macroautophagy (referred to as autophagy hereafter) is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and organelles. Previous studies showed that autophagy protects against acetaminophen (APAP)-induced injury (AILI) via selective removal of damaged mitochondria and APAP protein adducts. The lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with autophagosomes. In the present study, we showed that transcription factor EB (TFEB), a master transcription factor for lysosomal biogenesis, was impaired by APAP resulting in decreased lysosomal biogenesis in mouse livers. Genetic loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI, respectively. Mechanistically, overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2 (NRF2) activation to protect against AILI. We also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB agonists. Among these agonists, salinomycin, an anticoccidial and antibacterial agent, activated TFEB and protected against AILI in mice. In conclusion, genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.