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Alzheimer's disease (AD) is a central nervous system degenerative disease that is prone to occur in the pre-senile period and senile period . It is characterized by behavioral impairment and progressive cognitive impairment, with an insidious onset and progressive aggravation. It not only has cognitive decline, but also is accompanied by other neurological and psychiatric symptoms. Memory loss is the core symptom of the disease. Diabetes mellitus (DM) is a disease characterized by hyperglycemia. In recent years, with the increasing incidence of the two diseases, more and more studies have reported the correlation between AD and DM. This article reviews the correlation between AD and DM from the aspects of correlation research, pathological mechanism and drug treatment through the review of relevant literature, with a view to providing guidance for clinical practice.
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Objective To investigate the relieving effects of knockdown of long non-coding RNA(lncRNA)taurine up-regulated gene 1 (TUG1) on inhibiting nucleotide binding oligomerization domain like receptor protein 1 (NLRP1) inflammasome and the progression of Alzheimer’ s disease. Methods Wild-type (WT group, 10 mice) or amyloid precursor protein (APP) / presenilin-1 (PS1) transgenic mice (30 mice) with a genetic background of C57 / BL6 aged 9-10 weeks were used in this study. APP / PS1 transgenic mice were randomly divided into model group, model+lncRNA TUG1 short hairpin RNA (shRNA) group and model + shRNA non target (NT) group (n = 10) . Blood samples, cerebral cortex tissues, primary microglial cells and primary astrocytes were collected from mice 12 weeks of age on day 1 (3-month-old) and 32 weeks of age on day 1 (8-month-old), with 5 mice per group at each time point. Real-time PCR analysis was used to detect the expression levels of lncRNA TUG1 and macrophage migration inhibitory factor (MIF) mRNA in cerebral cortex tissues and primary microglial cells, and C1r and C1s mRNA levels in primary astrocytes of 3-month-old and 8-month-old mice in the above 4 groups, respectively. ELISA was used to determine the MIF in plasma samples of the above 4 groups of mice. Primary microglia and astrocytes from the cerebral cortex of 3-month-old and 8-month-old mice were co-cultured. CCK-8 method was used to determine the proliferation ability of the above cells. Western blotting was used to determine the expression levels of MIF, pro interleukin-1β (pro-IL-1β), apoptosis associated speck-like protein containing a caspase recrult domain(ASC), Caspase-1 (p20), Caspase-1 (full), NLRP1 and NLRP3 in cerebral cortex tissues of 3-month-old and 8-month-old mice. Immunofluorescent staining was used to determine amyloid beta(Aβ) in cerebral cortex of 8-month-old mice. Results At the age of 3-month-old and 8-month-old, compared with the WT group, the relative expression level of lncRNA TUG1 and MIF in cerebral cortex tissues and primary microglia of model group mice was significantly up-regulated, with primary microglial cells and astrocytes proliferation ability enhanced (P0. 05) . There was no significant difference between the model group and the model+shRNA NT group mice of all the above factors (P>0. 05) . Conclusion In APP / PS1 transgenic mice, up-regulation of lncRNA TUG1 and MIF are positively associated with the activation of NLRP1 inflammasome in mice cerebral cortex tissues and primary microglia. Knock-down of lncRNA TUG1 can ameliorate the progression of Alzheimer’ s disease.
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Obｊective To investigate the protective mechanism of tricholoma matsutake polysaccharides(TMP) against 1-methy-4-pehnyl-pyridine ion (MPP
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Alzheimer' s disease (AD) is a progressive neurodegenerative disorder histologically characterized by the presence of senile plaques and neurofibrillary tangles (NFTs) found in and around pyramidal neurons in cortical tissue. Mounting evidence suggests regional increased iron load and dyshomeostasis have been associated with oxidative stress, oxidation of proteins and lipids, and cell death, and appears to be a risk factor for more rapid cognitive decline, thereby involved in multiple aspects of the pathophysiology of AD. Ferroptosis is a newly identified iron-dependent lipid peroxidation-driven cell death and emerging evidences have demonstrated the involvement of ferroptosis in the pathological process of AD. Notably, some novel compounds targeting ferroptosis can relieve AD-related pathological symptoms in AD cells and animal model and exhibit potential clinical benefits in AD patients. This review systematically summarizes the growing molecular and clinical evidence implicating ferroptosis in the pathogenesis of AD, and then reviews the application of ferroptosis inhibitors in mouse/cell models to provide valuable information for future treatment and prevention of AD.
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Aim To investigate the effect of safflower yellow (SY) on learning and memory ability of APP/ PS1 mice at different disease stages, and to explore the mechanism of SY anti- Alzheimer's disease by using 3-,6- and 9-month-old APP/PS 1 transgenic mice as experimental animal models. Methods Behavioral experiments were conducted to observe the effects of SY on learning and memory of APP/PS1 mice of different months. ELISA was used to detect the effect of SY on the expression of inflammatory factors in cortex of mice of different months. Western blot was used to detect the microglia activation marker protein, and its mechanism of action was further analyzed. Results SY could enhance the learning and memory ability of mice aged 3, 6 and 9 months, reduce the content of IL-6 and increase the content of TGF-β1 in brain tissue, up-regulate the expression levels of arginase-1 (arg-1) and triggering receptor expressed on myeloid cells 2 (tREM2) in brain tissue of mice of different months, and down-regulate the expression levels of inducible nitric oxide synthase (iNOS), Toll-like receptors 4 (tlr4) and nuclear factor-kappa B (nf-KB). Conclusions Compared with 3- and 9-month-old mice, SY is the most effective in improving learning memory in 6-month-old APP/PS1 mice. SY inhibits TLR4/NF-KB pathway activation by inducing TREM2 expression in brain tissue of APP/PS 1 transgenic mice, promotes microglia phenotype shift to anti-inflammatory phenotype, reduces chronic neuroinflammatory response, and improves learning memory in APP/PS1 mice at all months of age.
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Objectives@#In the Philippines, there has been a lack of information on the concordance between classifications of Hansen’s disease or leprosy clinically, histopathologically, and with AFS results. The study ultimately aimed to determine the concordance between the clinical diagnosis, histopathological results, and AFS results of patients with leprosy seen at the Dr. Jose N. Rodriguez Memorial Hospital and Sanitarium (DJNRMHS). @*Methods@#This is a descriptive, retrospective, single-center study conducted at the DJNRMHS, a tertiary government hospital and one of the last remaining sanitaria in the country located in northern Metro Manila in the Philippines. The study reviewed and included all the patient records from the years 2017-2019 which included skin biopsy results and slit-skin smear with AFS. Leprosy patients were then classified based on the following classifications: World Health Organization (WHO) and Ridley-Jopling classifications; and the concordance of clinical diagnosis vs the histopathologic findings and clinical diagnosis vs AFS results were determined using kappa testing.
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Lepra , BiopsiaRESUMEN
@#Introduction: The human tau protein is a key protein involved in various neurodegenerative disease (NDs) including Parkinson’s disease (PD). The protein has high tendency to aggregate into oligomers, subsequently generating insoluble mass in the brain. Symptoms of PD include tremor, bradykinesia, rigidity, and postural instability. Currently drugs for PD treatment are only symptom-targeted while effective therapeutic treatment remains a challenge. The objective of this study is to identify novel promising anti-PD drugs using computational techniques. Method: ligand-based (LB) receptor modelling was conducted using LigandScout, validated and subjected to Glide XP docking, virtual screening, ADMET, and molecular dynamics predictions. Results: The adopted LB modelling generated pharmacophoric features of 5 hydrogen bond donors, 1 aromatic rings, and 7 hydrogen bond acceptors. The validation result indicated GH score of 0.73 and EF of 36.30 as validation protocols, probing it to be an ideal model. Using 3D query of the modelling a total of 192 compounds were retrieved from interbioscreen database containing 70,436 natural compounds. Interestingly, ligands 1, 2, 3, 4 and 5 orderly indicated higher binding affinities to the receptor with Glide XP docking of -7.451, -7.368, -7.101, -6.878, and -6.789 compared to a clinical drug Anle138b with -4.552 kcal/mol respectively. Furthermore, molecular dynamics and pkCSM pharmacokinetics demonstrated ligands 1, 2, & 4 having better stability and low toxicity profiles compared to the reference. Conclusion: In summary, the study pave way for discovery of small molecules that could be recommended as adjuvant /single candidate as ant-PD candidates upon further translational study.
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@#Alzheimer’s disease (AD) is classified as one of neurodegenerative disease caused by neuronal death. It is characterized as memory impairment, including the inability to produce new memories. Since AD has low treatment effectiveness, proteomics research opens possibilities for advancement. Proteomics is the study of proteomes produced by the disease-bearing host to identify and understand diseases. In this case, to investigate the use of protein as a reliable molecular entity and their involvement in AD. Therefore, this review focused on three main applications of proteomics; the potential use of proteomics as a diagnostic tool for AD, the use of proteomics to assess the treatment progression of AD and the advancement in AD research. The review discussed three research areas utilizing the proteomics approach: ageing, behavioural, and demographic research of AD populations. Proteomic approaches have also been shown to be effective to discover the biomarkers for infectious diseases, cancers, heart diseases, and neurological disorders. Although much work remained to be done, the proteomics approach is an interesting method to be carried out in detecting AD at an earlier stage and will be very useful for AD treatment and management in the future.
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Objective To explore the relationship between serum levels of tyrosine hydroxylase (TH) and the risk of cerebral infarction in Parkinson's patients. Methods A total of 129 patients with confirmed Parkinson's disease who were hospitalized in our hospital were selected, among the 58 patients had Parkinson's disease complicated with cerebral infarction (complicated with cerebral infarction group), and the remaining 71 patients had Parkinson's disease alone (control group). Blood TH levels and other potential related information were collected retrospectively at the time of diagnosis. Comparative analysis of data was performed using SPSS software. Results Comparing the serum TH expression levels in patients with Parkinson's disease and patients with cerebral infarction at admission , the serum TH level in patients with cerebral infarction was lower. Results also showed that the levels of CRP, IL-6, MDA, and Hcy were higher in patients with cerebral infarction, while PON-1 level was lower. In addition, patients with cerebral infarction had lower motor ability (higher UPDRS Ⅲ score). Further regression analysis was carried out with the occurrence of Parkinson's disease complicated with cerebral infarction as the dependent variable and the potential influencing factors as the independent variable. The results indicated that factors such as low expression of TH, high expression of inflammatory factors, and high expression of oxidative stress factors were positively correlated with the risk of complications of the two diseases. Conclusion The low expression of TH, inflammatory state and high oxidative stress state are the potential risk factors for Parkinson's disease complicated with cerebral infarction, which deserves clinical attention.
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Objective@# The present study was aimed to investigate the neuroprotective effect of Croton hirtus (CH) extract against streptozotocin (STZ) in rats. @*Methods@#(i) The sub-chronic toxicity consisted of 24 adult rats of either sex weighing from 160 to 200 g were divided into four groups with six rats in each group. Rats in group 1 received Dimethyl sulfoxide (DMSO) mixed with saline; rats in groups 2, 3, and 4 received 100, 200, and 400 mg/kg of methanolic extract of CH (MECH) orally by gavage administration for 28 d, respectively. The functional observation battery and locomotor activity were graded as part of their neurobehavioral activity and the brain regions, including cortex and hippocampus, were analyzed for neuropathological abnormalities. (ii) The main research consisted of 30 adult male Wistar rats weighing from 160 to 200 g, which were divided into five groups and six rats in each group, including control (I), STZ (II), Donepezil (III), MECH (100 mg/kg, IV), and MECH (200 mg/kg, V) groups. Rats in group I received citrate buffer orally and DMSO mixed with saline for 14 d. Rats in group II received STZ via intracerebroventricular injection (3 mg/kg, bilateral ICV-STZ) on days 1 and 3 followed by DMSO mixed with saline for 14 d. Rats in groups III, IV, and V received STZ administration on days 1 and 3 followed by Donepezil [3 mg/(kg·d), p.o.] and MECH [100 and 200 mg/(kg·d), p.o.] for 14 d. Rats were tested for learning and memory parameters such as Morris water maze (MWM) and passive avoidance test (PAT). They were sacrificed after completing behavioural experiments; brains were harvested to estimate the acetylcholinesterase (AChE), lipid peroxidation (LPO), glutathione (GSH), and superoxide dismutase (SOD) by using UV-Visible Spectrophotometer; caspase-3 was evaluated by total fluorescence emission spectra; amyloid β (Aβ) levels were detected using enzyme-linked immuosorbent assay (ELISA); and histopathological examination was conducted in the CA1 region of the hippocampus.@*Results @# (i) The sub-chronic toxicity results revealed that open field test parameters including line crossing, rearing, entering the middle square, defecating, or urinating did not differ significantly in the MECH rats (P > 0.05). The histopathological observation did not show any lesions in the neuronal cells and inflammation in both the regions in MECH rats compared with control rats. (ii) The main study findings demonstrated that STZ-treated rats showed asignificant increase in impairment in learning and memory parameters (P < 0.001), the levels of AChE, caspase-3, Aβ (1-40 and 1-42), and LPO were increased significantly (P < 0.001), and significant decrease was found in the levels of SOD (P < 0.001) and GSH (P < 0.01). Moreover, neuronal damage was found in the hippocampus. In contrast, STZ-induced behavioural and biochemical impairments in rats were considerably decreased by treatment with MECH dose-dependently. @*Conclusion@#MECH significantly prevented the memory deficit induced by STZ due to antioxidant action. Restoration of cholinergic functioning may be the cause of behavioural improvement. Therefore, MECH may be able to treat cognitive disorders like Alzheimer's disease (AD).
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Objective@#To investigate the preliminary screening results of Alzheimer's disease (AD) among the elderly in Ningbo City, Zhejiang Province and analyze the influencing factors, so as to provide insights into prevention and control of AD in the elderly. @*Methods@#A multi-stage stratified proportional sampling method was used to select the registered residents aged 60 years and older in Ningbo City as subjects. Demographic characteristics, lifestyle factors, physical conditions and social activities of the subjects was evaluated with questionnaires. AD was screened using the Mini-Mental State Examination (MMSE), and factors affecting the positive rate of AD preliminary screening were identified using a multivariable logistic regression model.@*Results@#A total of 34 027 elderly residents were investigated, with an mean age of (71.71±6.89) years. There were 15 115 males (44.42%) and 18 912 females (55.58%), 16 146 residents living in rural areas (47.45%) and 17 881 residents living in urban areas (52.55%). The positive rate of AD preliminary screening was 7.28% (2 476 cases). Multivariable logistic regression analysis showed that age (70 to 74 years, OR=1.357; 75 to 79 years, OR=1.807; 80 to 84 years, OR=2.782; 85 years and older, OR=4.907), gender (female, OR=1.118), residence (urban areas, OR=0.713), marital status (unmarried, OR=3.078; widowed/separated/divorced, OR=1.301), educational level (primary school, OR=0.629; junior high school and above, OR=0.609), occupation before retirement (others, OR=0.741), family genetic history (no, OR=0.651), household disposable monthly income (1 000 to 1 999 Yuan, OR=0.636; 2 000 to 2 999 Yuan, OR=0.569; 3 000 Yuan and above, OR=0.448), exercise (seldom, OR=0.855; regular, OR=0.780), number of chronic diseases (2~5, OR=1.328), hearing loss (no, OR=0.764), smell loss (no, OR=0.615), chronic constipation (no, OR=0.696), major negative life events (no, OR=0.804), subjective memory loss (no, OR=0.583), sleep quality (general, OR=0.640; good, OR=0.616), living style (living with spouse, OR=0.300; living alone, OR=0.315; living with children, OR=0.350) and social activities (2-3 times/week, OR=0.584; 4 times/week and more, OR=0.409) were factors affecting the positive rate of AD preliminary screening. @*Conclusions @#The positive rate of AD preliminary screening among the elderly in Ningbo City is relatively high. Age, gender, economic conditions, exercise, social activities and physical conditions were factors affecting the positive rate of AD preliminary screening.
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@#Objective To review and analyze the clinical manifestations of common aortitis in cardiac surgery. Methods We screened 41 552 patients who were hospitalized in the Department of Cardiac Surgery of Zhongshan Hospital, Fudan University from 2010 to 2020, analyzed the patients' clinical data, and classified according to the type of diseases. Then we summarized all their clinical manifestations. Results In our center 145 patients were operated for aortitis diseases, including 75 males and 70 females, with the age of 24-76 (45.6±11.3) years. There were 61 patients of Takayasu's arteritis, 51 patients of Behcet's disease, 8 patients of syphilitic aortitis, 8 patients of systemic lupus erythematosus, 2 patients of Kawasaki disease, 4 patients of ankylosing spondylitis, 10 patients of dry syndrome, and 1 patient of scleroderma. Conclusion Aortitis is not uncommon in cardiac surgery, and awareness of the disease should be enhanced. So that we can distinguish various types of aortitis and to make proper management to improve patients' prognosis.
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@#Studies suggest that synaptic damage is closely associated with cognitive dysfunction, and lemur tyrosine kinase 1 (LMTK1) is a key kinase that affects synaptic growth. Dihydroergotamine (DHE) is an ergot alkaloid derivative with high biological activity, which could regulate cognition, memory processing and motor control.This study aims to investigate the effect of DHE on synapse atrophy and plasticity as well as cognition in Alzheimer’s disease (AD) model animals.SAMR1 mice were selected as control group (n = 12).SAMP8 mice were randomly divided into 3 groups (n = 12 for each group):AD group, DHE low-dose group and high-dose group.The DHE groups were injected DHE intraperitoneally daily for 8 weeks.Immunofluorescence experiments, Golgi staining experiment, electrophysiological experiment, Morris water maze experiment (MWM) and Western blot experiment were conducted to investigate the effect of DHE on synaptic morphology, synaptic plasticity, cognitive function as well as the phosphorylation level of LMTK1 downstream TBC1D9B in AD model mice.Subsequently, the LMTK1 silencing and overexpression cells were constructed.Immunofluorescence experiments were used to study the effect of DHE on synaptic length of nerve cell after LMTK1 silencing and overexpression.In the hippocampus of AD mice, the postsynaptic marker PSD95 was significantly increased after DHE administration, which suggested that DHE could increase the synaptic density. In Golgi staining experiment, synaptic atrophy was observed in the hippocampal of AD mice, which could be improved by high-dose DHE.Compared with normal mice, the long-term potentiation (LTP) level of AD model mice was significantly reduced (P < 0.000 1), DHE could increase LTP significantly.The MWM experiment further showed that DHE could improve cognitive function in AD mice.WB experiments showed that the level of P-LMTK1 in the hippocampus of AD mice increased significantly, and the level of downstream P-TBC1D9B decreased significantly after DHE administration.Cell immunofluorescence experiments in vitro had shown that DHE significantly improved synaptic atrophy in overexpressed C17.2 cells, while its improvement disappeared when LMTK1 was silenced. This research suggests DHE may improve synaptic atrophy and cognitive dysfunction in AD by targeting on LMTK1.
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@#Alzheimer''s disease (AD) has brought to us huge medical and economic burdens, and so discovery of its therapeutic drugs is of great significance.In this paper, we utilized knowledge graph embedding (KGE) models to explore drug repurposing for AD on the publicly available drug repurposing knowledge graph (DRKG).Specifically, we applied four KGE models, namely TransE, DistMult, ComplEx, and RotatE, to learn the embedding vectors of entities and relations on DRKG.By using three classical knowledge graph evaluation metrics, we then evaluated and compared the performance of these models as well as the quality of the learned embedded vectors.Based on our results, we selected the RotatE model for link prediction and identified 16 drugs that might be repurposed for the treatment of AD.Previous studies have confirmed the potential therapeutic effects of 12 drugs against AD, i.e., glutathione, haloperidol, capsaicin, quercetin, estradiol, glucose, disulfire, adenosine, paroxetine, paclitaxel, glybride and amitriptyline.Our study demonstrates that drug repurposing based on KGE may provide new ideas and methods for AD drug discovery.Moreover, the RotatE model effectively integrates multi-source information of DRKG, enabling promising AD drug repurposing.The source code of this paper is available at https://github.com/LuYF-Lemon-love/AD-KGE.
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@#Coronavirus disease 2019 (COVID-19) is a highly contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). More than one-third of patients with COVID-19 experience neurological symptoms, including confusion, headaches, and decreased/disordered taste. Alzheimer's disease (AD) is a slowly progressive neurodegenerative disease and the most common type of dementia. Alzheimer's disease patients are at high risk and susceptible to infection with COVID-19, which may cause severe illness and even death. There appears to be an interaction between AD and COVID-19, and on the one hand, patients with COVID-19 seem to be more likely to develop AD. AD patients, on the other hand, may be more susceptible to severe COVID-19. Therefore, understanding the common link between COVID-19 and AD may help to develop treatment strategies. Risk factors common to AD and COVID-19 are aging, ApoE ε4 allele, β-amyloid (Aβ) deposition, angiotensin-converting enzyme (ACE), neuroinflammation, oxidative stress. Here, this article focuses on the relationship between COVID-19 and AD, explores common risk factors and potential pathogenesis, and provides help for early prevention, treatment and recovery.
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Objective @#To investigate the effect of aluminum exposure on expression of miR-497-5p, wingless murine breast cancer virus integration site family member 3a (Wnt3a), β-catenin protein, glycogen synthase kinase-3β (GSK-3β) protein and tau protein in rat adrenal pheochromocytoma PC12 cells, so as to provide insight into unraveling the mechanisms underlying aluminum exposure-induced abnormal phosphorylation of tau protein.@* Methods@# PC12 cells were exposed to Al(mal)3 at concentrations of 0, 100, 200, 400 μmol/L for 24 h. The viability of PC12 cells was measured using cell counting kit-8 (CCK-8) assay. The relative expression of miR-497-5p and Wnt3a was detected using a real-time fluorescent quantitative PCR (RT-qPCR) assay, and the expression of Wnt3a, β-catenin, GSK-3β, P-GSK-3β (Ser9), tau and p-tau (Ser396) proteins were determined using Western blotting. @*Results @#The viability of PC12 cells appeared a tendency towards a decline with the increase of aluminum dose (Ftrend=323.473, P=0.001). RT-qPCR assay detected that the relative miR-497-5p expression appeared a tendency towards a rise with the increase of aluminum dose (Ftrend=14.888, P=0.031), and the relative Wnt3a expression appeared a tendency towards a decline with the increase of aluminum dose (Ftrend=165.934, P<0.001). The miR-497-5p expression negatively correlated with the relative Wnt3a expression (r=-0.693, P=0.012). The expression of Wnt3a (Ftrend=357.656, P=0.001), β-catenin (Ftrend=208.750, P=0.001) and p-GSK-3β (Ser9) proteins (Ftrend=512.583, P<0.001) appeared a tendency towards a decline with the increase of aluminum dose, and the expression of GSK-3β (Ftrend=39.965, P<0.001), tau (Ftrend=277.929, P=0.006) and p-tau (Ser396) proteins (Ftrend=96.247, P=0.002) appeared a tendency towards a rise with the increase of aluminum dose. @*Conclusion@# Up-regulation of miR-497-5p and GSK-3β expression and down-regulation of Wnt3a and β-catenin expression may be a mechanism underlying aluminum exposure-induced abnormal phosphorylation of tau protein.
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Abstract@#Alzheimer's disease (AD) is a neurodegenerative disease characterized by deposition of β-amyloid (Aβ). Liver X receptors (LXRs), a member of the nuclear receptor transcription factor superfamily, are widely expressed in brain, which may be involved in the development and progression of AD. Based on the international and national publications pertaining to the association between LXRs and AD from 2010 to 2022, this review summarizes the advances on the involvement of LXRs in the regulation of cholesterol metabolism, inflammatory response and synapse formation in the pathogenesis of AD was reviewed, so as to provide insights into the prevention and treatment of AD.
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@#Abstract: Objective This study aimed to investigate the expression of CD73 in colonic tissues in Crohn's disease (CD) and its significance and possible mechanism of action. Methods Thirty male BALB/c mice were randomly divided into normal control group, model group and intervention group. The control group was fed normally, and the model group was treated with TNBS+40% alcohol enema to establish a mouse model of Crohn's disease induced by chronic inflammation. The intervention group was treated with AB-680 intraperitoneally on the second day of each enema based on the model group. Mice body weight, fecal traits and fecal occult blood were recorded for disease activity index (DAI) score of inflammatory bowel disease. The animals were sacrificed at 7th week, their colonic tissues were removed, weighed and measured. The tissue inflammation was observed by standard hematoxylin-eosin (HE) staining. Masson staining was used to measure the area of collagen in colon tissue of mice. CD73 was detected by fluorescence quantitative PCR and immunohistochemistry. The expression levels of TGF-β, TNF-α and IL-6 in colon tissue of mice were determined by ELISA. Results The DAI score was (0.10±0.16) in the control group, (2.80±0.79) in the model group, and (3.07±0.34) in the intervention group. Compared with the control group, the DAI scores of the model and intervention groups were increased significantly (P<0.05). Compared with the model group, the DAI score of the intervention group was significantly increased (P<0.05). HE staining showed that there was no inflammation in the colon of the control group, while the colon of the model group and the intervention group showed typical inflammatory manifestations such as edema and congestion, inflammatory cell infiltration, and mucosal ulcer. The area ratio of collagen in the control group was (4.95±0.82)%, in the model group was (24.62±1.46)%, and in the intervention group was (54.47±2.75)%. Compared with the control group, the area ratio of collagen in the model group and the intervention group was significantly increased (P<0.05). Compared with the model group, the area ratio of collagen in the intervention group was significantly increased (P<0.05). Compared with the control group, the expression of CD73 in colon tissue of the model group and the intervention group was significantly increased (P<0.05). Compared with the model group, the expression of CD73 in colon tissue of the intervention group was decreased (P<0.05). Compared with the control group, the expressions of TGF-β, TNF-α and IL-6 in the model group and the intervention group were significantly increased (P<0.05). Compared with the model group, the expression of TGF-β, TNF-α and IL-6 in the intervention group decreased (P<0.05). Conclusions CD73 is upregulated in colon tissue of CD mice, it can inhibit inflammatory reaction and improve fibrosis by up-regulating TGF-β expression. On the other hand, CD73 can aggravate the inflammatory response in CD intestinal inflammation and fibrosis by up-regulating the expression of IL-6 and TNF-α. Therefore, CD73 may play a bidirectional regulatory role in intestinal inflammation and fibrosis of CD.
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Alzheimer’s disease (AD) is a progressive neurodegenerative disease with the early symptom of A β plaque, tau hyperphosphorylation neuronal tangle formation in cells. At present, accumulated evidence shows that the changes of GABA receptors are closely related to AD. Some studies have shown that the expression level of each subunit of the GABA receptor changes in AD patients. Therefore, it is speculated that the changes of GABA subunits may be related to the pathogenesis of AD, but there is no better methods to improve AD by targeting GABA receptors. In order to further understand the relationship between the changes of GABA receptors and AD, this paper first reviewed the changes of GABA receptors in AD patients and animal models’ brains and found that there was differential expression in GABA(A) receptor subunits in AD patients. Then we summarized the changes of GABA receptor subunits in Alzheimer database. Based on the data, we found that a few GABA subunits had significant changes. The evidence shows that the change of GABA receptors alters the neural activity in the brain. Other studies have found that the treatment of mice with GABA receptor agonists and antagonists can improve the cognitive ability of mice. We hope that understanding the differential expression of GABA receptors in AD will provide a more accurate target for the treatment of AD.
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[Abstract] Objective To study whether the regulation of mammalian target of rapamycin complex 2(mTORC2) / Akt signaling pathway has a protective effect on SH-SY5Y cell line damaged by 6-hydroxydopamine (6-OHDA), and to clarify its molecular mechanism. Methods SH-SY5Y cells treated with retinoic acid (RA) were given 6-OHDA, mTORC2 signaling pathway inhibitor PP242 and agonist A-443654 respectively. The changes of cell number in each group were investigated by immunofluorescent staining; The total protein was extracted and the expression level and interaction of key proteins in mTORC2 signaling pathway were determined by Western blotting and co-immunoprecipitation (CoIP); The apoptosis rate of cells in each group was detected by flow cytometry. At the same time, the co-culture Parkinson’ s disease (PD) model was made using SH-SY5Y cell line and Bv-2 cell line; MTT colorimetric method was used to detect the cell viability of each group; ELISA was used to detect the content of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in cell culture supernatant. Results The number of tyrosine hydroxylase(TH) / proliferating cell nuclear antigen (PCNA) / hochest-, TH / 5-bronmo-2’ -deoxyuridine(BrdU) -labeled positive cells in 6-OHDA-lesioned PD cell model group was significantly lower than that in the normal group; The apoptosis rate was higher; The expression of Rictor, p-Akt and regulated in DNA damage and development 1(REDD1) was increased; There was an interaction between Rictor and p-Akt or REDD1; The cell viability was significantly reduced in the co-culture model; the content of TNF-α and IL-β increased in the cell culture supernatant. With further up-regulation of the abovementioned protein expressions, the cell survival, apoptosis and pro-inflammatory cytokine levels in A-443654 group were significantly ameliorated, while PP242 group showed the opposite changes. Conclusion A-443654 activates mTORC2 signaling pathway by p-Akt, which increases the expression of Rictor and REDD1 protein. These changes contribute to the amelioration in cell survival rate, apoptosis rate, and the proliferation and differentiation and decreasion of apoptosis rate of SH-SY5Y cells. These result improved 6-OHDA-induced cell damage and inhibited the release of pro-inflammatory cytokines.