Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder worldwide, causing dementia and affecting millions of individuals. One prominent characteristic in the brains of AD patients is glucose hypometabolism. In the context of galactose metabolism, intracellular glucose levels are heightened. Galactose mutarotase (GALM) plays a crucial role in maintaining normal galactose metabolism by catalyzing the conversion of β-D-galactose into α-D-galactose (α-D-G). The latter is then converted into glucose-6-phosphate, improving glucose metabolism levels. However, the involvement of GALM in AD progression is still unclear. In the present study, we found that the expression of GALM was significantly increased in AD patients and model mice. Genetic knockdown of GALM using adeno-associated virus did not change the expression of amyloid precursor protein (APP) and APP-cleaving enzymes including a disintegrin and metalloprotease 10 (ADAM10), β-site APP-cleaving enzyme 1 (BACE1), and presenilin-1 (PS1). Interestingly, genetic overexpression of GALM reduced APP and Aβ deposition by increasing the maturation of ADAM10, although it did not alter the expression of BACE1 and PS1. Further electrophysiological and behavioral experiments showed that GALM overexpression significantly ameliorated the deficits in hippocampal CA1 long-term potentiation (LTP) and spatial learning and memory in AD model mice. Importantly, direct α-D-G (20 mg/kg, i.p.) also inhibited Aβ deposition by increasing the maturation of ADAM10, thereby improving hippocampal CA1 LTP and spatial learning and memory in AD model mice. Taken together, our results indicate that GALM shifts APP processing towards α-cleavage, preventing Aβ generation by increasing the level of mature ADAM10. These findings indicate that GALM may be a potential therapeutic target for AD, and α-D-G has the potential to be used as a dietary supplement for the prevention and treatment of AD.
Animals ; ADAM10 Protein/metabolism* ; Alzheimer Disease/pathology* ; Amyloid Precursor Protein Secretases/metabolism* ; Disease Models, Animal ; Humans ; Mice ; Amyloid beta-Peptides/metabolism* ; Male ; Mice, Transgenic ; Membrane Proteins/metabolism* ; Cognitive Dysfunction/pathology* ; Mice, Inbred C57BL ; Amyloid beta-Protein Precursor/metabolism* ; Female ; Hippocampus/metabolism* ; Long-Term Potentiation/physiology*

Alzheimer's disease (AD) is a leading cause of dementia in the elderly. Mitogen-activated protein kinase phosphatase 1 (MKP-1) plays a neuroprotective role in AD. However, the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively studied. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level, thereby repressing mRNA translation. Here, we reported that the microRNA-429-3p (miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2A^APP AD model cells. We further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3'-untranslated region (3' UTR). Inhibition of miR-429-3p by its antagomir (A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ accumulation. More importantly, intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase (ERK1/2)-mediated GluA1 hyperphosphorylation at Ser831 site, thereby increasing the surface expression of GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Together, these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice, suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.

Objective:To explore differences of resting brain regional homogeneity (ReHo) between patients with major depressive disorder (MDD) and their siblings.Methods:From January to December 2013, the resting-state functional magnetic resonance imaging (fMRI) data of 87 patients with MDD and 21 healthy siblings were collected.DPABI v5.1 software was used to preprocess the resting-state fMRI data, and ReHo maps of each subject was obtained. A two-sample t-test was used to compare differences between the patients with MDD and their siblings in ReHo values throughout the brain. ReHo values within the significant brain regions were extracted out, and used to calculate Spearman correlation with the total score of 17-items Hamilton depression rating scale(HAMD-17) in the patients with MDD and their siblings respectively.The software of SPSS 20.0 was used for statistical analysis. Results:The patients with MDD exhibited lower ReHo values in the precuneus extending to the posterior cingulate cortex (PCu/PCC) compared with their siblings (cluster-size=126 voxel, cluster-level PFDR=0.033; MNI: x=-4, y=-58, z=38, t=4.30). ReHo values of the PCu/PCC in patient with MDD were positively correlated with the severity of depressive symptoms ( r=0.255, P=0.021). Conclusion:Compared with the siblings, local brain activity of the PCu/PCC in the patients with MDD was decreased, and related to the severity of depressive symptoms. It is helpful to further reveal the intrinsic neural mechanism of MDD.

Objective: To translate the Pulmonary Embolism Quality of Life (PEmb-QoL) Scale into Chinese and evaluate its reliability and validity. Methods: The Chinese version of PEmb-QoL was translated from the original, back-translated and adjusted for cultural adaptation.The reliability and validity were tested in 212 patients with PE. Results: The content validity index (CVI) of the PEmb-QoL Scale was 0.910, which indicated a desirable content validity. Factor analysis ex-tracted six common factors, which explained 82.177% of variance of the total scale, and each item had high factor loading quantity (>0.4). The test-retest reliability was 0.810, and Cronbach α was 0.894. Conclusions Chinese version of PEmb-QoL has been proved to be valid and reliable. It is a valuable tool for evaluating the quality of life among patients with pulmonary embolism disease.

Objective To study the immunoregulatory effects of emodin on macrophages during Brucella infection and to provide theoretical and experimental basis for developing new drugs to treat brucello-sis. Methods Bone marrow cells were isolated from BALB/c mice and cultured with MG-CSF to induce differentiation. Flow cytometry was used to detect the differentiation of bone marrow cells into macrophages (MΦ) by using FITC-labeled mouse anti-F4/80 antibody and PE-labeled anti-CD11b antibody. MTT meth-od was used to detect the influences of various concentrations of emodin on the survival rate of MΦ. Doxy-cycline was used as the control to compare half maximal inhibitory concentrations (IC50) of the two drugs. MΦ were cultured with Brucella at a ratio of 100 : 1 for 4 h. MΦ and Brucella were further cultured for 1, 6,12,24 and 48 h after adding emodin. Effects of emodin on the survival of MΦ were analyzed by colony counting method. ELISA was performed to detect the levels of TNF-α, IL-6 and IFN-γ in culture superna-tants. Results On day 8 of culturing,91.28% of bone marrow cells differentiated into macrophages. The IC50of emodin(608.4 μg/ml) was significantly higher than that of doxycycline(225.5 μg/ml). The logC-FU values of emodin stimulation groups (6,12,24 and 48 h) were significantly lower than those of blank control groups. Among all emodin stimulation groups, the 24 h group had the lowest logCFU value, which was also lower than that of the doxycycline treatment group. The levels of TNF-α,IL-6 and IFN-γ in 6,12 and 24 h emodin stimulations group increased significantly as compared with those of the corresponding con-trol groups. The levels of TNF-α, IL-6 and IFN-γ peaked at 24 h of culturing Brucella-infected MΦ with emodin. No significant difference in IFN-γ level was found between the 12 and 24 h emodin stimulation groups [(74.233 ±4.416) pg/ml vs (78.328 ±8.932) pg/ml]. Conclusion Emodin may enhance the ability of macrophages to kill Brucella through promoting the expression of TNF-α,IL-6 and IFN-γ.

Objective Few studies are reported on the construction of a finite element model of human complex knee joint using multimodality CT and MRI images.In this study, we developed a finite element model of the knee joint for total knee arthroplasty (TKA) using matched and fused CT and MRI data, hoping to provide a useful tool for the simulation study of knee joint biomechanics of TKA.Methods The CT and MRI image data about an intact knee of a 26-year-old male volunteer were imported into the Mimics software for the establishment of 3D models of bony and soft-tissue structures.A complete knee model was developed following the registration and fusion of the constructed 3D models based on the external landmarks.After the simulated implantation of TKA components, a finite element model of the TKA knee was constructed with the Hypermesh software.Then the finite element model was analyzed following the definition of its material behavior, boundary conditions and loading.Results The finite element model of the TKA knee, which was composed of bones, ligaments, components, polyethylene insert and bone cement, was developed from CT-MRI image registration and fusion and maintained its important spatial relationship among different structures in the TKA knee.The results obtained from the finite element analysis showed the characteristics of stress distribution in the TKA knee.Conclusion The finite element model of the knee joint for TKA can be established by matching and fusing CT and MRI image data, which can be employed as a useful tool for the study of knee joint biomechanics of TKA.

Objective To investigate the expression and clinical significance of matrix metalloproteinase(MMP-9)and tension protein homologous gene in gingival cancer tissue.Methods 50 cases in Guyuan people's hospital from June 2013to December 2016 were selected to study the expression of matrix metalloproteinase(MMP-9)and tension protein homologous gene in gingival cancer tissue.Results The positive rate of PTEN in gingival cancer group was 54.00%, the positive rate of PTEN was 94.00% in normal tissue, normal control group positive rate of PTEN was significantly higher than that of gingival cancer group(P<0.05);the positive rate of MMP-9 in gingival cancer group was 76.00%, the positive rate of control group was 20.00%, gingival cancer group was significantly higher than the normal control group(P<0.05).The expression of MMP-9 and PTEN in in gingival cancer tissue was unrealted with gender, age, and tissue differentiation, and associated with lymph node metastasis and tissue infiltration(P<0.05).Conclusion PTEN expression is low in gingival cancer tissue low, MMP-9 expression is high in gingival cancer tissues.PTEN and MMP-9 are closely related to the incidence and development of gingival cancer.Therefore, MMP-9 positivity is a risk factor for gingival cancer, while PTEN positivity is a protective factor for gingival cancer.

Humans ; Karyotype ; Leukemia, Myeloid, Acute

Objective To investigate the wall shear stress(WSS) in the common carotid artery of type 2 diabetes mellitus(DM) patients,and analyzed the spatial distribution of WSS by using quantitative visualization of blood flow shear stress analysis software.Methods Eighteen male type 2 DM subjects were enrolled as DM group and 18 age-matched healthy subjects were selected as control group.None of the participants was hypertensive,hyperlipidemic or a cigarette smoker.Intimal-medial thickness (IMT),number and size of plaques in the common carotid artery were evaluated by high-resolution echo-Doppler.Color Doppler flow images of common carotid arteries in the two groups were extracted from DICOM files.WSS in the common carotid arteries was calculated by shear stress visualization quantitative analysis software,and the corresponding spatial distribution maps of WSS were designed.Results WSS of the common carotid arteries in the control group were ranged from 4 to 14 dyne/cm2.WSS of the common carotid arteries in the DM group were ranged from 2 to 8 dyne/cm2.Compared to mean WSS value [(6.96 ± 1.17)dyne/cm2] of common carotid arteries in the control group,mean WSS value [(3.14 ± 0.79)dyne/cm2] of common carotid arteries in the DM group was significantly lower (t =9.380,P =0.000).Six diabetic participants had a plaque in one carotid artery and no lesions in the contralateral carotid.Among these subjects,mean WSS was significantly lower in the side with lesion (t =7.324,P =0.000).Therefore,IMT of common carotid arteries in participants was significantly inversely related to WSS (r =-0.76,P ＜0.01).Conclusions The common carotid arteries of DM patients are more prone to atherosclerosis which is associated with reduction of WSS.The hemodynamic profile might represent an additional factor contributing to the increased prevalence and severity of carotid atherosclerosis in diabetic patients compared with general population.

Objective To investigate the pH changes of arterial blood in patients with acute left heart failure.Methods Thirty-eight patients with acute left heart failure were selected as our subjects,who all underwent diuresis,the strong heart diuresis,dilation of blood vessels,reducing the load on the heart,and making water and electrolyte balance of conventional medication,and then parallel oxygen mask,respirator mode synchronized intermittent mandatory ventilation(SIMV).If hypoxia was not significantly improved,and positive pressure ventilation with end expiratory(PEEP) treatment was conducted.Results After treatment,the level of pH,heart rate(HR),breathing rate(RR),arterial partial pressure of oxygen(PaO2),arterial partial pressure of carbon dioxide(PaCO2) and mean arterial pressure(MAP) were (7.4 ± 0.3,86.3 ± 6.2) times/min,(22.5 ±4.8) times/min,(84.8 ±7.3) mmHg,(43.3 ±5.5) mmHg,(81.1 ±3.2) mmHg,different from those before treatment(7.1 ±0.1),(118.3 ±8.2) times/min,(36.2 ±7.1) times/min,(47.2 ±6.6) mmHg,(48.3 ±5.2) mmHg,(96.2 ±4.5) mmHg),and the differences were significant (t =5.848,19.188,9.854,23.552,4.072,16.857 respectively; P ＜ 0.01).With the progress of treatment,pH value and pHi value in patients showed a rising trend.Regression analysis showed a positive correlation and the regression equation was Y =-0.559 4 + 1.103 7X.Conclusion Patients with acute left heart failure show abnormal blood pH level and the corresponding change inside red blood cells.Then it causes changes in arterial blood oxygen carrying capacity of red blood cells,reduces the cell through the capillary capacity.Therefore,it can result in decrease of gas exchange levels in patients and hypoxia.Treatment should be considered imbalance the body of the improved state of acid-base.