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BACKGROUND: Although traditional therapies, including drugs and surgery, cannot repair the damaged myocardial tissue, the mortality rate of myocardial infarction remains high. Stem cells provide the possibility to solve this problem due to their self-renewal and multi-directional differentiation potential. OBJECTIVE: To analyze the research progress of stem cell therapy for myocardial infarction in recent ten years by bibliometric analysis. METHODS: The related articles on stem cells and myocardial infarction published in SCI-E and SSCI from January 1, 2012 to December 1, 2022 in the Web of Science database were searched. EXCEL, CiteSpace and VOSviewer software were used to make statistical and visualization analyses of the data such as the number of publications, authors, institutions, journals, countries and keywords. RESULTS AND CONCLUSION: A total of 3 210 core articles were published, and the total number increased year by year. hausenloy,derek j. is the author with the largest number of publications, China is the country with the largest number of publications, and the Fourth Military Medical University is the institution with the largest number of publications. The research hotspots in this field are changing from cell experiments and animal experiments to clinical trials. In the past ten years, research in this field has been highly popular and still has great development prospects. It is necessary to promote international and interagency exchange and learning, and further explore the role of stem cells in the treatment of myocardial infarction. [ABSTRACT FROM AUTHOR]

BACKGROUND: Ischemic stroke is a serious threat to human health. After ischemia and hypoxia, astrocyte expresses lipocalin-2 in large amounts to aggravate brain injury, but the specific mechanism is not clear. Hydroxysafflor yellow A has anti-ischemia, anti-oxidation, anti-thrombosis and anti-inflammatory effects. However, whether hydroxysafflor yellow A affects the expression of lipocalin-2 in astrocytes after cerebral ischemia and hypoxia and its mechanism are not clear. OBJECTIVE: To investigate the effect and mechanism of hydroxysafflor yellow A on the expression of lipocalin-2 in astrocytes after cerebral ischemia and reperfusion. METHODS: (1) Thirty adult SD rats were randomly divided into three groups: sham operation group, middle cerebral artery occlusion and reperfusion group, and hydroxysafflor yellow A group. The middle cerebral artery occlusion and reperfusion model was established in the latter two groups, and hydroxysafflor yellow A group was intraperitoneally injected with 12 mg/kg hydroxysafflor yellow A after reperfusion. Longa score was used to evaluate the degree of neurological impairment. Infarct volume was determined by TTC staining. JAK2/STAT3 pathway and lipocalin-2 expression were detected by western blot assay and immunofluorescence. Levels of interleukin 1β, interleukin 6 and tumor necrosis factor α were detected by ELISA. (2) Astrocytes were divided into four groups: Normal group, glucose-oxygen deprivation group, hydroxysafflor yellow A group and AG490 group. In the latter three groups, glucose-oxygen deprivation and glucose-oxygen recovery models were established. Astrocytes were treated with 75 μmol/L hydroxysafflor yellow A and 10 μmol/L tyrosine phosphorylation inhibitor AG490 for 8 hours during glucose-oxygen deprivation, respectively. The mechanism of hydroxysafflor yellow A on lipocalin-2 was further verified. RESULTS AND CONCLUSION: (1) Compared with the sham operation group, cerebral infarction was significantly increased in the middle cerebral artery occlusion and reperfusion group, accompanied by aggravated neurological impairment (P < 0.01). Hydroxysafflor yellow A treatment could reduce cerebral infarction volume and improve neurological function (P < 0.01). (2) The expressions of p-JAK2, p-STAT3 and lipocalin-2 in the middle cerebral artery occlusion and reperfusion group were higher than those in the sham operation group (P < 0.01). Hydroxysafflor yellow A treatment reduced the expressions of JAK2, STAT3 and lipocalin-2 (P < 0.01). (3) The expression levels of interleukin 1β, interleukin-6 and tumor necrosis factor α in the middle cerebral artery occlusion and reperfusion group were higher than those in the sham operation group (P < 0.01). Hydroxysafflor yellow A inhibited the expressions of interleukin 1β, interleukin-6 and tumor necrosis factor α (P < 0.01). (4) In vitro, the expressions of p-JAK2, p-STAT3 and lipocalin-2 in the glucose-oxygen deprivation group were significantly higher than those in the normal group (P < 0.01). After adding AG490, the phosphorylation of JAK2 and STAT3 decreased, and the expression of lipocalin-2 was inhibited (P < 0.01). The results suggest that hydroxysafflor yellow A may inhibit the expression of lipocalin-2 in astrocytes after ischemia and hypoxia by regulating the JAK2/STAT3 signaling pathway, thereby reducing brain injury. [ABSTRACT FROM AUTHOR]

报道 1例在山东省济宁市第一人民医院内分泌科新诊断的 2型糖尿病（T2DM）合并肥 胖、严重高脂血症患者，使用利拉鲁肽治疗的诊疗过程。患者为一中年男性，有糖尿病家族史，有口 干、多饮症状。初诊时，糖化血红蛋白高达11.3%，合并严重高脂血症。给予患者坚持糖尿病饮食、运 动控制治疗基础上应用利拉鲁肽2个月，血糖、血脂、体重、内脏脂肪均得到有效的控制。 [ABSTRACT FROM AUTHOR]

Objective To explore the relationship between Chongqing residents' characteristics and fit-ness behavior and the influencing factors of fitness behavior. A and to seek effective ways to motivate residents fitness behavior and so as to help residents form good exercise habits and improve the development of physical and mental health. Methods Residents aged 18-065 in Chongqing were selected as research objects. A 15-items questionnaire was carefully designed,involving the gender, age marital status, children's situation, education background occupation status, frequency of physical exercise, sports activities and other key indicators of the interviewees. In the process of analysis, the basic situation of residents' fitness was illustrated intuitively with the help of charts, and the influencing factors of residents' project selection were analyzed by logistic regression model. Results The residents in Chongqing mostly spent 30.--60 minutes (41. 48% ) on fitness, with purposes of fitness was to be body build (63. 57%) and keep fit (42. 50%). The amount of fitness expenditure was generally not high. Participants in different projects were obviously differentiated in terms of gender, fitness period, fitness frequency. fitness purpose, weekly fitness duration. etc. and the life status of each project was different. For example participants of the big-ball project were mostly male aged between 21 and 35 .and the fitness time was more than 60 minutes each time. Conclusion Participants of different fitness projects have obvious differences in gender,age. fitness frequency, fitness purpose, fitness period. fitness duration and other factors that combine personal basic situation, life status and fitness needs. Different sports are suitable for different life status, such as running, gym exercises and ball sports are still the most favorite sports activities among men and women, and ball sports are especially popular among boys. Mainly with the individual alone exercise and friends exercise together. [ABSTRACT FROM AUTHOR]

Objective: To explore the feasibility of BAG -1 and MCM2 as effective predictors for neoadjuvant chemotherapy (NACT) of cervical cancer. Methods: Clinical data of 90 patients of cervical cancer treated with preoperative platinum -based NACT and surgery were collected in Gansu Provincial Cancer Hospital from January 2015 to June 2018. Immunohistochemical methods were used to detect the expression of BAG-1 and MCM2 proteins in normal cervical tissues and cervical biopsy tissues of the same cervical cancer patients before NACT and after NACT. The expression differences between normal cervical tissues and cervical cancer tissues, cervical cancer tissues before and after NACT was compared, and the correlation of the 2 proteins with the clinical efficacy of NACT was analyzed. Results: The high expression rates of BAG-1 and MCM2 in pre-NACT cervical cancer tissues were 67.8% (61/90) and 81.1% (73/90), respectively, which was higher than 11.7% (7/60) and 6.7% (4/60) of normal cervical tissues. There was a significant difference between the two groups ( X² 2=45.736 and 76.909 both P=0.000). The high expression rates of BAG-1 and MCM2 in cervical cancer tissues after NACT were 70.0% (63/ 90) and 78.9% (71/90), respectively. There was no significant difference between before and after NACT ( X² 2=0.104 and 0.139, both P＞0.05). After NACT, 59 of 90 cases of cervical cancer were effective (65.6%), while 31 of 90 cases were invalid (34.4%). There was no correlation of the efficacy of NACT with age, pathological type, differentiation degree, tumor maximum diameter and FIGO stage (both P＞0.05). The high expression rate of BAG-1 in the chemotherapy-effective group was lower than that ineffective group, and there was a significant difference between the two groups (54.2% vs. 93.5%, X² 2=12.636, P=0.000). However, there was no significant difference of MCM2 high expression rate between the effective group and the ineffective group X²79.7% vs. 83.9%, X² 2 =0.235, P=0.628. Conclusions: Detection of BAG -1 expression may be a reference indicator for predicting the chemotherapy efficacy of platinum-based NACT regimens for cervical cancer [ABSTRACT FROM AUTHOR]

Objective To establish a mathematical diagnostic model of Alzheimer's disease (AD) and mild cognitive impairment (MCI) with a higher accuracy. Methods Taking the four selected indexes as input variables, 391 samples were randomly divided into the training set and the testing set. Generalized regression neural network (GRNN) was used for parameter training and simulation diagnosis in the training set and the testing set respectively, and the diagnosis effects were compared with those of BP neural network (BPNN), ra-dial basis function neural network (RBFNN) and perceptron neural network (PNN). Results The diagnostic accuracy rate of GRNN for the three groups of people was significantly higher than that of BPNN, RBFNN and PNN, the differences were statistically significant (P <0. 05). When the optimal smoothing factor of GRNN was 1. 5, the diagnostic accuracy rate of 391 samples reached 75. 7%. Conclusion The GRNN model has good diagnostic effect on AD and MCI, which can be used as an auxiliary means of clinical diagnosis. [ABSTRACT FROM AUTHOR]

BACKGROUND: Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system mediated by T cells. The Toll-like receptors (TLRs)/myeloid differentiation factor 88 (MyD88)/nuclear factor kappa-B (NF-κB) signaling pathway plays an important role in the development of the disease. Exploring the specific mechanism of the signaling pathway is essential for further treatment of the disease and improving the prognosis of patients. OBJECTIVE: To review the TLRs/MyD88/NF-κB signaling pathway and its role in multiple sclerosis/experimental autoimmune encephalomyelitis models, which provides new ideas and strategies for the treatment of multiple sclerosis by inhibiting the TLRs/MyD88/NF-κB signaling pathway. METHODS: The literature related to the topic from January 2002 to December 2022 was searched in CNKI, WanFang and PubMed databases. A total of 61 articles were finally included for analysis. RESULTS AND CONCLUSION: The TLRs/MyD88/NF-κB signaling pathway is an important pathway that triggers a pro-inflammatory immune response. The TLRs/ MyD88/NF-κB signaling pathway plays an important role in the development of multiple sclerosis by regulating the antigen presentation of dendritic cells, destroying the integrity of the blood-brain barrier, and promoting the activation of T cells, B cells and microglia. By targeting TLRs, MyD88 and NF-κB molecules, inhibiting the activation or signal transduction of TLRs, MyD88 and NF-κB, and reducing the secretion of pro-inflammatory factors, multiple sclerosis can be treated. Animal studies have shown that active ingredients of traditional Chinese medicines, such as flavonoids and glycosides, and traditional Chinese medicine compound formulas, such as Buyang Huanwu Tang, can also treat experimental autoimmune encephalomyelitis by regulating the TLRs/MyD88/NF-κB signaling pathway, which points to the direction of searching for medicines targeting the TLRs/MyD88/NF-κB signaling pathway for the treatment of multiple sclerosis. [ABSTRACT FROM AUTHOR]

BACKGROUND: Ischemic stroke is a highly prevalent disease associated with apoptosis. Neuronal death occurs after cerebral ischemia, including necrosis and apoptosis. The ischemic core region is dominated by necrosis, while delayed neuronal death in the penumbra is dominated by apoptosis. The penumbra has become a target for the treatment of ischemic stroke. This bibliometric analysis was used to identify the characteristics, hotspots, and frontiers of global scientific output related to apoptosis in ischemic stroke over the past 5 years. OBJECTIVE: To analyze the role of apoptosis and its mechanisms in the pathological process of ischemic stroke through a bibliometric approach. METHODS: A total of 927 relevant literature records from 2018 to 2022 were retrieved from Science Citation Index Expanded (SCI-Expanded) and Social Science Citation Index Expanded (SSCI-Expanded) of the Web of Science Core Collection. Research trends and hotspots of apoptosis in ischemic stroke were visualized using Citespace, VOSviewer and Bibliometrix. RESULTS AND CONCLUSION: From 2018 to 2020, the number of papers on the role of apoptosis in ischemic stroke showed an upward trend, but in 2020, the number of papers began to reduce. China had the largest number of publications, and the United States ranked the second. Capital Medical University and BRAIN RESEARCH BULLETIN were the institutions and journals with the most articles, respectively. In recent years, the two keywords “expression” and “oxidative stress” have appeared more frequently. The bibliometric study showed that in the past 5 years, most of the studies focused on basic research, in which research on the role of apoptosis in ischemic stroke has gradually decreased in the last 3 years, showing a downward trend. On the contrary, nerve regeneration has gradually become a research hotspot, especially the regulation of neurotrophic factors under the influence of different mechanisms, and the research on angiogenesis and glial cell repair is on the rise. At the same time, apoptosis in nerve regeneration is a potential point of discovery. [ABSTRACT FROM AUTHOR]

BACKGROUND: Vascular regeneration, as one of the crucial repair processes after its onset, necessitates visual analysis between the two. OBJECTIVE: To analyze the literature on ischemic stroke and vascular regeneration in the past decade using bibliometrics and sort out the current status, hotspots, and future research trends in this field. METHODS: We used a bibliometric approach to search the Web of Science database for literature on ischemic stroke and vascular regeneration published between January 2011 and May 2023. The obtained data were systematically analyzed using the VOSviewer visualization software to identify the number of articles, countries, keywords, institutions, authors, citations, and trends. RESULTS AND CONCLUSION: We searched and selected 1 484 articles and found that the relationship between ischemic stroke and vascular regeneration has emerged as a research hotspot in the cerebrovascular field, with the number of published articles continuing to rise. Most of these articles were authored by institutions from China and the United States. Shanghai Jiao Tong University was the most cited institution. The most influential author was Hermann DM, whose article had been cited 1 003 times. The current hot research topics in the field include extracellular vesicles, microRNAs and mesenchymal stem cells, which are being studied for their correlations with relevant diseases. To conclude, the bibliometric analysis provides a visual analysis of ischemic stroke and vascular regeneration, which is found to be an emerging focus as well as a valuable reference for future trends and highlights in ischemic stroke and vascular regeneration. [ABSTRACT FROM AUTHOR]

BACKGROUND: In the initial stage of multiple sclerosis, central immune cells activate and release a large number of inflammatory factors, causing white matter demyelination and even involving gray matter neurons. The equilibrium of differentiation between different subsets of CD4+ T cells plays an important role in the progression of experimental autoimmune encephalomyelitis. The previous results of the research group showed that the active ingredient astragalus glycoprotein in astragalus can regulate the immune response in experimental autoimmune encephalomyelitis mice, and whether it has a regulatory effect on the differentiation of T cell subsets has not been determined. OBJECTIVE: To explore the therapeutic effects and immune regulatory mechanisms of astragaloside IV on experimental autoimmune encephalomyelitis mice. METHODS: Female C57BL/6 mice were divided into the normal control group, experimental autoimmune encephalomyelitis disease model group, and astragaloside IV treatment group (n=8 per group). Myelin oligodendrocyte glycoprotein peptides 35-55 were used for experimental autoimmune encephalomyelitis model induction in the last two groups. On day 10 to 28 after immunization, the astragaloside IV treatment group was treated with 40 mg/kg per day astragaloside IV intragastrically. Body weight and clinical scores of mice in each group were recorded from the immunization day to the 28th day. On the 28th day after immunization, the mouse spinal cord was taken and made into frozen sections for hematoxylin-eosin staining and Lux fast blue staining to observe pathological changes in the spinal cord. Percentage of splenic T cell subsets was detected using flow cytometry. Western blot assay was used to determine the protein expression of interferon-γ, interleukin-17 and interleukin-6 in the spinal cord. Levels of interferon-γ, interleukin-17, interleukin-6 and interleukin-4 in supernatants of cultured splenocytes were determined by ELISA. RESULTS AND CONCLUSION: (1) Compared with the experimental autoimmune encephalomyelitis disease model group, astragaloside IV could reduce the degree of weight loss in experimental autoimmune encephalomyelitis mice (P < 0.05), ameliorate clinical symptoms (P < 0.05), inhibit the infiltration of inflammatory cells and alleviate myelin loss (P < 0.01, P < 0.05). (2) Compared with the experimental autoimmune encephalomyelitis disease model group, astragaloside IV could inhibit the proportion of CD4+ T cell subsets expressing interferon-γ (P < 0.001) and interleukin-17 (P < 0.001), but increase percentages of CD4+ interleukin-10+ (P < 0.001) and CD4+ transforming growth factor-β+ (P < 0.01) T cell subsets. (3) Astragaloside IV could inhibit the expression of interferon-γ (P < 0.05, P < 0.01), interleukin-17 (P < 0.05, P < 0.05), and interleukin-6 (P < 0.05, P < 0.05) in the spinal cord and spleen, and up-regulate the expression of interleukin-4 (P < 0.01) in spleen. (4) These findings confirm that astragaloside IV alleviates clinical symptoms in experimental autoimmune encephalomyelitis mice, which may be related to regulating the splenic T cell subsets, therefore, inhibiting the infiltration of inflammatory cells into the center and reducing the demyelination. [ABSTRACT FROM AUTHOR]

BACKGROUND: Cerebral ischemic stroke is one of the main fatal and disabling diseases in the clinic, but only a few patients benefit from vascular recanalization in time, so it is urgent to explore new and effective therapy. As one of the critical pathological changes of ischemic stroke, the glial scar formed mainly by astrocytes is one major cause that hinders axonal regeneration and neurological recovery at the late stage of stroke. OBJECTIVE: To elucidate the pathological process and crucial signal regulatory mechanism of astrocytes in the formation of glial scar after ischemic stroke, as well as the potential therapeutic targets, to provide a theoretical reference for intervening astrocytic scar formation against ischemic stroke effectively, and novel strategies for promoting post-stroke rehabilitation. METHODS: The relevant articles published in CNKI, PubMed and Web of Science databases from 2010 to 2022 were retrieved. The search terms were “Ischemic stroke, Brain ischemi*, Cerebral ischemi*, Astrocyt*, Astroglia*, Glial scar, Gliosis, Astrogliosis” in Chinese and English. Finally, 78 articles were included after screening and summarized. RESULTS AND CONCLUSION: (1) Astrocytes play an important role in the maintenance of central nervous system homeostasis. After ischemic stroke, astrocytes change from a resting state to an active state. According to the different severities of cerebral ischemic injury, astrocyte activation changes dynamically from swelling and proliferation to glial scar formation. (2) Mature astrocytes are stimulated to restart the cell cycle, then proliferate and migrate to lesions, which is the main source of the glial scar. Neural stem cells in the subventricular zone, neuron-glial antigen 2 precursor cells and ependymal precursor cells in the brain parenchyma can also differentiate into astrocytes. Endothelin-1, aquaporin 4, ciliary neurotrophic factor and connexins are involved in this process. In addition, chondroitin sulfate proteoglycan, as the main component of the extracellular matrix, forms the dense glial scar barrier with proliferated astrocytes, which hinders the polarization and extension of axons. (3) Activation or inhibition of crucial signal molecules involved in astrocyte activation, proliferation, migration and pro-inflammation functions regulate the glial scar formation. Transforming growth factor beta 1/Smad and Janus kinase/signal transducer and activator of transcription 3 are classical pathways related to astrogliosis, while receptor-interacting protein 1 kinase and glycogen synthase kinase 3β are significant molecules regulating the inflammatory response. However, there are relatively few studies on Smad ubiquitination regulatory factor 2 and Interleukin-17 and their downstream signaling pathways in glial scar formation, which are worthy of further exploration. (4) Drugs targeting astrogliosis-related signaling pathways, cell proliferation regulatory proteins and inflammatory factors effectively inhibit the formation of glial scar after cerebral ischemic stroke. Among them, the role of commonly used clinical drugs such as melatonin and valproic acid in regulating glial scar formation has been verified, which makes it possible to use drugs that inhibit glial scar formation to promote the recovery of neurological function in patients with stroke. (5) Considering the protective effects of glial scar in the acute phase, how to choose the appropriate intervention chance of drugs to maintain the protective effect of the glial scar while promoting nerve regeneration and repair in the local microenvironment is the direction of future efforts. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of Hydroxyfasudil(HF)on oxidative stress in experimental autoimmune encephalomyelitis (EAE)mice and its probable mechanisms. Methods: BV2 cells were randomly separated into normal control group, LPS group and LPS+HF group. After pretreatment with HF for 2 h, LPS was given to stimulate for 24 h, and the cell supernatant was collected. Sixteen C57BL/6 mice were randomly separated into EAE group and HF group. Mice in HF group were intraperitoneally injected with HF]40 mg/(kg·d)] from day 3 after immunization, and mice in EAE group were injected with the same amount of normal saline. From the day of immunization, clinical scores of mice were observed every two days. Scavenging effect of different concentrations of HF on free radicals was tested by DPPH and ABTS. Changes in cell viability of BV2 cells under the intervention of different concentrations of HF were detected by MTT. Inflammation and demyelination of spinal cords were detected by HE and LFB staining. Contents of RNS, ROS, MDA, SOD, CAT and GSH-Px in cell supernatant and mice spinal cords were detected by ELISA, expressions of Nrf2 and HO-1 were detected by immunofluorescence staining and Western blot. Results: HF had hardly scavenging effect on DPPH and ABTS free radicals in concentration range of 3.75~60 μg/ml, and no changes in BV2 cells viability were observed when the concentration of HF was in 0~15 μg/ml. HF inhibited clinical scores of EAE mice, improved inflammation and demyelination of spinal cords, reduced oxidation products ROS, RNS and MDA, increased antioxidant enzymes SOD, CAT and GSH-Px, and increased expressions of Nrf2 and HO-1 in spinal cords of mice. Conclusion: HF inhibited clinical symptoms of EAE mice and reduced central nervous system inflammatory infiltration and demyelination, which might be related to activation of Nrf2/HO-1 signaling pathway by HF to inhibit oxidative stress in EAE mice. [ABSTRACT FROM AUTHOR]

AIM: To investigate the effect of astragaloside IV （AST IV） on cognition and pathology in Alzheimer disease （AD） mouse model, and to explore its underlying possible mechanism. METHODS: The APP/PS1 transgenic mice were randomly classified into AD+AST IV and AD groups, and C57BL/6 wild-type （WT） mice were used as control group（ WT group）. The mice were treated by intragastric administration for 2 months. Morris water maze and Ymaze tests were performed to evaluate the spatial cognitive function of the mice. Nissl staining was used to detect the number and morphology of neurons, while immunofluorescence staining was used to detect neuronal nuclear antigen （NeuN） and amyloid β-protein （Aβ） levels. The expression levels of neurite outgrowth inhibitor A （NogoA）, Nogo-66 receptor （NgR）, p75 neurotrophin receptor （p75NTR）, leucine rich repeat and immunoglobin-like domain-containing protein-1 （LINGO-1）, cyclic adenosine monophosphate （cAMP）, and protein kinase A （PKA） in the whole brain were detected by Western blot. RESULTS: Treatment with AST IV significantly improved cognitive function in APP/PS1 mice, and enhanced learning, memory and exploration abilities. Compared with WT mice, APP/PS1 mice exhibited increased Aβ deposition in the cerebral cortex and hippocampus （P<0. 01）, significant loss of Nissl bodies （P<0. 05 or P<0. 01）, and decreased number of neurons （P<0. 05）. However, AST IV treatment significantly reduced Aβ deposition （P<0. 05） and the loss of Nissl bodies（ P<0. 05）, and increased the number of neurons（ P<0. 05）. Compared with WT mice, the expression levels of NogoA, NgR, p75NTR and LINGO-1 in the whole brain tissue of APP/PS1 mice were significantly increased （P<0. 05 or P<0. 01）, whereas those of cAMP and PKA were significantly decreased （P<0. 05 or P<0. 01）. However, AST IV treatment significantly inhibited the expression of NogoA, NgR, p75NTR and LINGO-1 （P<0. 05 or P<0. 01）, and increased the expression of cAMP and PKA（ P<0. 05）. CONCLUSION: Treatment with AST IV reduced Aβ deposition and neuronal damage in the brains of APP/PS1 mice by inhibiting the expression of NogoA and NgR/p75NTR/LINGO-1 receptor complex and up-regulating the cAMP/PKA signaling pathway. [ABSTRACT FROM AUTHOR]

BACKGROUND: Astrocytes play an important role in the pathology of central nervous system diseases. The phenotypic and functional changes in astrocytes suggest that it may be an effective therapeutic target for central nervous system diseases. Our previous studies have confirmed that astragaloside can inhibit the lipopolysaccharide-induced astrocyte inflammatory response. Whether astragaloside can regulate the phenotype and function of astrocytes through Notch-1 and its downstream signaling pathway remains unclear. OBJECTIVE: To explore the effect of astragaloside on astrocyte activation and inflammatory response induced by inflammation and its possible mechanism. METHODS: Cerebral cortex astrocytes derived from neonatal C57BL/6 mouse were cultured in vitro. CCK-8 assay was used to determine the optimum concentration of astragaloside and Notch active inhibitor DAPT. The astrocytes were divided into five groups: PBS group, lipopolysaccharide group, lipopolysaccharide + astragaloside group, lipopolysaccharide + DAPT group and lipopolysaccharide + DAPT + astragaloside group. The secretion level of inflammatory factors was detected by ELISA, and the level of nitric oxide was detected by Griess method. The astrocytes and splenic mononuclear cells were co-cultured in Transwell chamber to observe the migration of CD4T cells. The expression of astrocyte activation marker GFAP, A1 marker C3 and A2 marker S100A10 as well as Notch 1 and Jag-1 was detected by immunofluorescence staining. The expressions of CFB, C3, S100A10, PTX3, Notch-1, Jag-1, and Hes were detected by western blot assay. RESULTS AND CONCLUSION: (1) According to the results of CCK8 assay, the final concentration of astragaloside was selected as 25 μmol/L and the final concentration of DAPT was 50 μmol/L for follow-up experiments. (2) Compared with PBS group, interleukin-6, interleukin-12 and nitric oxide secretion levels in the lipopolysaccharide group were significantly increased (P < 0.05, P < 0.05, P < 0.01). Compared with the lipopolysaccharide group, interleukin-6 (all P < 0.05), interleukin-12 (P > 0.05, P < 0.05, P < 0.05) and nitric oxide (P < 0.05, P < 0.01, P < 0.01) secretion significantly reduced in the lipopolysaccharide + astragaloside group, lipopolysaccharide +DAPT group, lipopolysaccharide + DAPT + astragaloside group. (3) Compared with the PBS group, the expression of GFAP that is the marker of activated astrocytes and the migration of CD4 T cells were significantly increased in the lipopolysaccharide group (P < 0.01). Compared with the lipopolysaccharide group, astrocyte activation was significantly inhibited and CD4 T cell migration was significantly reduced in the lipopolysaccharide + astragaloside, lipopolysaccharide +DAPT, lipopolysaccharide + DAPT + astragaloside group (P < 0.05, P < 0.05, P < 0.01). (4) Compared with the PBS group, the expressions of A1 markers C3 and CFB in the lipopolysaccharide group were increased (P < 0.01, P < 0.05), and the expressions of A2 markers S100A10 and PTX3 were decreased (P < 0.01, P < 0.05). Compared with the lipopolysaccharide group, C3 (all P < 0.01) and CFB (both P < 0.05) were significantly reduced and S100A10 (all P < 0.01) and PTX3 (P < 0.05, P < 0.05 and P > 0.05) were increased in the lipopolysaccharide + astragaloside, lipopolysaccharide +DAPT, lipopolysaccharide + DAPT + astragaloside group. (5) Compared with the PBS group, the expressions of Jag-1, Notch-1 and Hes in the lipopolysaccharide group were significantly increased (all P < 0.01). Compared with the lipopolysaccharide group, the expressions of Jag-1 (all P < 0.01), Notch-1 (all P < 0.01) and Hes (P < 0.05, P < 0.01 and P < 0.01) were significantly reduced in the lipopolysaccharide + astragaloside, lipopolysaccharide +DAPT, lipopolysaccharide + DAPT + astragaloside group. (6) The results indicate that astragaloside can promote the transformation of astrocytes from A1 to A2 by regulating Notch-1 signaling pathway, reduce the secretion of inflammatory factors and the migration of CD4 T cells, and thus inhibit astrocyte activation and inflammatory response. [ABSTRACT FROM AUTHOR]

BACKGROUND: Abnormal mitochondrial dynamics is closely related to oxidative stress after affecting neurodegenerative diseases. Our previous studies have shown that eriodictyol can reduce nerve injury in Alzheimer’s disease, but whether it has a regulatory effect on mitochondrial dynamics is not clear. OBJECTIVE: To explore the mechanism of eriodictyol on SH-SY5Y cell apoptosis induced by hydrogen peroxide (H2O2). METHODS: SH-SY5Y cells were divided into three groups: PBS control group, H2O2 (250 μmol/L) group, and H2O2 (250 μmol/L) plus eriodictyol (10 μmol/L) treatment group (eriodictyol group). The intervention was performed for 24 hours. The kits were utilized to observe the level of malondialdehyde and the activity of superoxide dismutase. Cell morphology was observed under the microscope. TUNEL staining was used to observe the apoptosis. JC-1 staining was used to observe mitochondrial membrane potential. The expression levels of apoptotic proteins and mitochondrial fusion and fission protein-related proteins were detected by immunofluorescence staining and western blot assay. RESULTS AND CONCLUSION: (1) A significant decrease of malondialdehyde levels and a significant increase of superoxide dismutase activity were found in eriodictyol treated group, when compared with the H2O2 group. (2) Compared with the PBS control group, the H2O2 group showed decreased cell density, cytosolic hypertrophy, increased apoptosis, decreased mitochondrial membrane potential, decreased Bcl-2 expression, and increased Bax expression. Compared with the H2O2 group, above indexes were significantly improved in the eriodictyol group. (3) Compared with PBS control group, the expression levels of mitochondrial fission-related proteins dynamin-related protein 1 (p-DRP1) and mitochondrial fission protein 1 (FIS1) were elevated and the expression levels of mitochondrial fusion-related proteins optic atrophic protein 1 (OPA1) and mitofusin 2 (Mfn2) were decreased in the H2O2 group. Compared with the H2O2 group, eriodictyol treatment decreased the expression levels of p-DRP1 and FIS1 and increased the expression of OPA1 and Mfn2. (4) The results indicate that eriodictyol can inhibit H2O2-induced apoptosis in SH-SY5Y cells by regulating mitochondrial dynamics. [ABSTRACT FROM AUTHOR]

BACKGROUND: Bushen Yizhi Anti-aging Prescription exerts different therapeutic effects on Alzheimer′s disease, and our previous studies have suggested that Bushen Yizhi anti-aging prescription can significantly improve the cognitive function of APP/PS1 Tg mice by simultaneously promoting the polarization of spleen macrophages and central microglia to M2 type. OBJECTIVE: To explore the therapeutic effect and mechanisms of Bushen Yizhi Anti-aging Prescription on Alzheimer’s disease model mice (APP/PS1 Tg). METHODS: Totally 20 male APP/PS1 transgene mice aged 8 months were randomly assigned to APP/PS1 transgenic model group and Bushen Yizhi Anti-aging Prescription intervention group. Another age- and sex-matched wild-type male mice were used as wild-type control group. All mice were fed for 8 weeks. Morris Water Maze and Y-maze test were used to evaluate cognitive function of mice in the three groups. M1 microglial surface marker nitric oxide synthase, interleukin-6 and M2 microglial surface marker arginase-1 and interleukin-10 in mouse hippocampus were analyzed by immunohistochemistry. Expressions of Iba-1, inducible nitric oxide synthase, arginase-1, interleukin-6, interleukin-10, Toll-like receptor 4, myeloid differentiation factor 88 and nuclear factor-κB were examined by western blot. Flow cytometry was used to analyze the expression of M1 (CD16/32, interleukin-12) and M2-type mononuclear macrophages (CD206, interleukin-10) in mouse spleen. The study protocol was approved by the Animal Ethics Committee of Shanxi Datong Univerisity. RESULTS AND CONCLUSION: Compared the wild-type control group, the model group showed decreased cognitive function and the microglia in the brain were activated and transformed into M1, while the mononuclear macrophages in the spleen also transformed into M1. After treatment with Bushen Yizhi Antiaging Prescription, the cognitive function of APP/PS1 Tg mice was significantly improved (P < 0.05), the activation of microglia was inhibited (P < 0.01), the transformation from M1 microglia to M2 was promoted (P < 0.05), and the expressions of Toll-like receptor 4, myeloid differentiation factor 88 and nuclear factor-κB were down-regulated (P < 0.01). All these findings indicate that Bushen Yizhi Anti-aging Prescription reverses cognitive impairment and facilitates microglia M2 polarization via the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB signaling pathway in APP/PS1 transgenic mice. [ABSTRACT FROM AUTHOR]

BACKGROUND: Studies have shown that bone marrow mesenchymal stem cell therapy can effectively fill the neurons lost in Alzheimer’s disease patients, but the specific mechanism of action needs to be further clarified. OBJECTIVE: To explore the therapeutic effects of bone marrow mesenchymal stem cells in APP/PS1 double transgenic mice with Alzheimer’s disease and its mechanism. METHODS: APP/PS1 double transgenic mice were selected as the research objects and were randomly divided into model and bone marrow mesenchymal stem cell groups (n=10 per group). Ten wild-type C57BL/6 mice of the same month and the same sex were selected as the normal control group. The mice were treated with bone marrow mesenchymal stem cells (1×106 /time) or normal saline, and repeated administration once a week, for 2 months via nasal cavity. Morris water maze test was applied to examine cognitive function of mice. Western blot assay was used to detect the expression of related factors of pathological markers, inflammatory molecules and oxidative stress proteins in the brain tissues of mice. RESULTS AND CONCLUSION: Bone marrow mesenchymal stem cells effectively improved the cognitive dysfunction of Alzheimer’s disease mice, increased the expression of APP protein and decreased expression of phosphorylated tau protein, reduced the expression of Toll like receptor 2, inducible nitric oxide synthase, nuclear transcription factor kappa B and increased the expression of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1. It is concluded that bone marrow mesenchymal stem cells have a potential role in the treatment of Alzheimer’s disease; the mechanism exerts the effects of the anti-inflammation and antioxidation through nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling pathway. [ABSTRACT FROM AUTHOR]

BACKGROUND: The pathogenesis of Alzheimer’s disease is closely related to abnormal mitochondrial dynamics. Our previous research demonstrated that Fasudil has neuroprotective effect. However, it is needed to explore whether Fasudil has beneficial effect on regulating mitochondiral dynamics. OBJECTIVE: To investigate the effect and mechanism of ROCK inhibitor on cognitive function and neuronal apoptosis in Alzheimer’s disease mice. METHODS: Amyloid precursor protein/presenilin-1 (APP/PS1) transgenic mice were randomly divided into the Fasudil group (25 mg/kg/d) and normal saline group (equivalent volume normal saline), and wild-type C57BL/6 mice at the same age and gender served as normal controls (same volume normal saline). Administration in each group was given via intraperitoneal injection once daily for 2 months. Spatial cognition of mice was detected by Morris water maze test and Y maze test. Nissl staining was used to observe and analyze the number and morphology of neurons. TUNEL staining was applied to observe neuronal apoptosis. The protein levels of NeuN, Bax, Bcl-2, Cleaved Caspase-3, dynamin-related protein 1 (DRP1), mitochondrial fission protein 1 (FIS1), optic atrophic protein 1 (OPA1), mitofusin 1 (Mfn1), and mitofusin 2 (Mfn2) in hippocampus tissue were determined by western blot test. The expression of NeuN and DRP1 was detected by immunofluorescence staining. RESULTS AND CONCLUSION: Fasudil ameliorated cognitive impairment and improved loss of learning, memory and exploration function in APP/PS1 mice. Compared with the normal control group, the number of survived neurons was decreased, the apoptotic rate of neurons was increased, the expression of Bax and Cleaved Caspase-3 was increased, but the expression of NeuN and Bcl-2 was decreased in APP/PS1 mice. These changes were all strongly reversed by a 2-month treatment of Fasudil. Fasudil markedly down-regulated the expression of DRP1 and FIS1, but remarkably up-regulated the expression of OPA1, Mfn1, and Mfn2. These findings indicate that Fasudil significantly improves the spatial cognitive function in APP/PS1 mice, which may be related to restoring the mitochondrial fission and fusion imbalance so as to inhibit neuronal apoptosis. [ABSTRACT FROM AUTHOR]

BACKGROUND: More and more evidences show that ROCK signaling pathway is involved in inflammation and oxidative stress. Fasudil is an effective Rho kinase inhibitor. Our previous series of studies have proved that fasudil has neuroprotective effects. However, it is still unclear that whether fasudil has protective effect on oxidative damage to astrocytes and its possible mechanisms. OBJECTIVE: To explore the protective effect and mechanism of fasudil on lipopolysaccharide-induced oxidative injury in astrocytes. METHODS: Primary C57BL/6 mouse astrocytes were cultured and divided into PBS control group, lipopolysaccharide stimulation group (1 mg/L), lipopolysaccharide (1 mg/L) combined with fasudil (15 mg/L) treatment group. After 24 hours of treatment, MTT assay was used to detect the viability of astrocytes. The content of malondialdehyde and the activity of superoxide dismutase in astrocytes were measured using the kit to evaluate the level of oxidative stress. Immunofluorescence staining was used to detect the expression of cleaved-caspase-3, the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and the expression of heme oxygenase-1 (HO-1) in astrocytes. Western blot assay was used to detect the total Nrf2, nuclear Nrf2 and HO-1 protein levels. RESULTS AND CONCLUSION: (1) Compared with the PBS control group, the astrocyte viability in the lipopolysaccharide stimulation group was reduced, and fasudil treatment improved the cell damage induced by lipopolysaccharide. (2) Compared with the PBS control group, lipopolysaccharide resulted in a significant decrease in the activity of superoxide dismutase and a significant increase in the level of malondialdehyde in astrocytes (P < 0.01). Fasudil significantly increased the activity of superoxide dismutase (P < 0.01) and reduced the level of malondialdehyde (P < 0.01). (3) Compared with the PBS control group, the expression of cleaved-caspase-3 was significantly increased in the lipopolysaccharide stimulation group. Compared with the lipopolysaccharide stimulation group, the expression of cleaved-caspase-3 was decreased in the lipopolysaccharide combined with fasudil treatment group. (4) Fasudil could promote the nuclear translocation of Nrf2 and significantly increase the expression of total Nrf2, nucleus Nrf2 and HO-1 after lipopolysaccharide stimulation. (5) The results indicate that fasudil can inhibit lipopolysaccharide-induced astrocytic injury by regulating the Nrf2/HO-1 signaling pathway. [ABSTRACT FROM AUTHOR]