Anti-Bacterial Agents ; pharmacology ; Child ; Humans ; Macrolides ; pharmacology ; Microbial Sensitivity Tests ; Mycoplasma pneumoniae ; drug effects

Animals ; Aorta ; drug effects ; physiology ; Blood Pressure ; drug effects ; Cadmium ; toxicity ; Female ; In Vitro Techniques ; Male ; Muscle, Smooth, Vascular ; drug effects ; physiology ; Rabbits ; Vasoconstriction ; drug effects

OBJECTIVETo determine the expression of S100-beta protein and glial fibrillary acidic protein (GFAP) in hippocampal astrocytes of rats with Alzheimer disease (AD) model rats, and observe the effect of butylphthalide on their expression.

METHODSSixty male adult rats were randomized equally into model group, butylphthalide group, and control group, and in the former two groups, AD models were established by injecting beta-amyloid protein 1-40 into the hippocampus. Sixty days later, the rats were sacrificed and the bilateral hippocampuses were taken for immunohistochemistry.

RESULTSThe number of cells positive for S100 and GFAP in the hippocampus in butylphthalide group were significantly higher than that in the control group (P/0.01), but lower than that in the model group (P/0.05).

CONCLUSIONThe expression of S100 protein and glial fibrillary acidic protein increased significantly in the hippocampal astrocytes of rats with AD, and butylphthalide can inhibit the increase of their expression.

Alzheimer Disease ; chemically induced ; metabolism ; Amyloid beta-Peptides ; Animals ; Benzofurans ; pharmacology ; Disease Models, Animal ; Glial Fibrillary Acidic Protein ; metabolism ; Hippocampus ; metabolism ; Male ; Nerve Growth Factors ; metabolism ; Neuroprotective Agents ; pharmacology ; Peptide Fragments ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; S100 Calcium Binding Protein beta Subunit ; S100 Proteins ; metabolism

OBJECTIVETo determine the effect of butylphthalide on the expressions of p38 mitogen-activated protein kinase and extra-cellular signal regulated kinases (ERKs) in the brain tissue of rats with Alzheimer's disease (AD).

METHODSSixty male adult rats were randomly divided to AD model group, butylphthalide group, and control group (n=20). AD models were established by injecting beta-amyloid protein 1-42 into the hippocampus of rats. Sixty days later, the learning and memory abilities of the rats were evaluated using Y-maze test, and the expressions of p38 and ERKs in the brain tissue of the rats were measured by immunohistochemistry. RESULTS Compared with the control group, the rats in AD model group exhibited significantly reduced learning and memory abilities, increased expressions of P38 in the hippocampus and lowered expression of ERK in the cortex (P<0.01). In comparison with the model group, the rats in the butylphthalide group showed significantly decreased P38-positive cells in the hippocampus and increased expression of ERK in the cortex (P<0.01).

CONCLUSIONSButylphthalide improves the learning and memory abilities of rats with experimental AD, the mechanism of which may involve inhibition of P38 expression and enhancement of ERK expression in the brain tissues.

Alzheimer Disease ; enzymology ; metabolism ; physiopathology ; Animals ; Benzofurans ; pharmacology ; Extracellular Signal-Regulated MAP Kinases ; metabolism ; Gene Expression Regulation, Enzymologic ; drug effects ; Hippocampus ; drug effects ; metabolism ; Male ; Memory ; drug effects ; Neuroprotective Agents ; pharmacology ; Rats ; Rats, Sprague-Dawley ; p38 Mitogen-Activated Protein Kinases ; antagonists & inhibitors

BACKGROUNDAlzheimer disease (AD) is a neurodegenerative disease related to aging. At present, its pathological mechanisms remain unclear. Family members of the renin-angiotensin system (RAS) play a role in neuronal plasticity, as well as formation of learning and memory. In this study, we explore the effects of altered angiotensin-converting enzyme (ACE), and investigate the possible mechanisms of perindopril, an ACE inhibitor, on brain structure and function in a rat model of AD, as well as the role that ACE plays in AD.

METHODSSixty Sprague-Dawley rats were selected and randomly divided into 3 groups: control, AD, and perindopril. Each group consisted of 20 rats, with 10 rats for determining pathology, and the remaining 10 rats for quantifying ACE activity. The rat AD model was established by stereotactically injecting amyloid beta protein (A-beta) 1-42 into the right hippocampus. Learning and memory functions were tested using the Y-type electric maze. The number and morphology of abnormal neurons were determined by haematoxylin and eosin staining. Amyloid deposition was measured by Congo red staining. Finally, ACE activity was estimated by spectrophotometry.

RESULTSCompared with the control group, the number of times needed to escape electrical stimuli increased (23.70 +/- 3.13, P < 0.001), the number of normal neurons in the CA1 region was reduced (density of 96.5 +/- 32.6/mm, P < 0.001), amyloid deposition was obvious, and ACE activity increased ((34.4 +/- 6.6) nmol x g(-1) x min(-1), P < 0.001) in the AD group. In the perindopril group, the number of times needed to escape electrical stimuli decreased (18.50 +/- 3.66, P < 0.001), the number of abnormal neurons increased (density of CA1 neurons was 180.8 +/- 28.5/mm, P < 0.001), amyloid deposition was reduced, and ACE activity was down-regulated ((26.2 +/- 6.2) nmol x g(-1) x min(-1), P < 0.001).

CONCLUSIONSACE activity increased in the brains of AD rats. Perindopril improved learning and memory in AD rats, which correlated with decreased ACE activity and delayed AD pathogenesis.

Alzheimer Disease ; enzymology ; pathology ; physiopathology ; Angiotensin-Converting Enzyme Inhibitors ; pharmacology ; Animals ; Brain ; drug effects ; enzymology ; pathology ; Disease Models, Animal ; Maze Learning ; drug effects ; physiology ; Neurons ; drug effects ; metabolism ; pathology ; Peptidyl-Dipeptidase A ; metabolism ; Perindopril ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate serum adiponectin level in patients with Alzheimer's disease (AD) and its correlation with the patients' cognitive function.

METHODSThis case-control study was conducted in 90 patients with a highly probable diagnosis ofAD, who were divided into mild, moderate and severe group saccording to the MMSE score. Ninety healthy subjects matched for age and gender with the AD patients were selected as the control group. The serum levels ofadiponectin in the participants were detected using enzyme-linked immunosorbent assay.

RESULTSSerum adiponectin level was significantly lower in the AD group than in the control group (P<0.05). Of the 3 subgroups of the AD patients, the moderate and severe AD groups showed significantly lower serum adiponectin level sthan the control group (P<0.05), but the difference in adiponectin levels was not significant between the mild AD group and the control group (P>0.05); serum adiponectin levels also differed significantly among the 3 subgroups of AD patients (P<0.05). Serum adiponectin level was positively correlated with the MMSE score in the AD patients (r=0.683, P<0.001).

CONCLUSIONSerum adiponectin levels are reduced in AD patients and associated with the degree of cognitive impairment.

Adiponectin ; blood ; Alzheimer Disease ; blood ; Case-Control Studies ; Cognition ; Cognitive Dysfunction ; blood ; Enzyme-Linked Immunosorbent Assay ; Humans

OBJECTIVE: To filter biomarkers of nasopharyngeal carcinoma (NPC) by constructing the homogenesis tissue gene expression profiling with the whole human genome GeneChip. METHODS: The epithelium cells of the homogenesis NPC and the pure nasopharyngeal normal tissues microdissected from nasopharyngeal biopsy which was preserved in the RNAlater were used to isolate RNA and then to harvest the aRNA through in vitro transcription, and aRNA prober was labled to hybridize to HG-U133. plus 2.0, so the expression profiling of each homogenesis tissue could be constructed. RESULTS: Some candidate biomarker genes related to the tumorigenesis of NPC had been filtered by comparing the expression profiling of NPC samples with the expression profiling of normal nasopharyngeal epithelia samples. Any genes regarding the metastasis of NPC might have been selected by comparing the expression profiling of no-metastasis samples with those of the metastasis samples. CONCLUSION Using the whole genome GeneChip to construct the expression profiling for the microdissected homogenesis tissue is effective to filter the candidate biomarker genes.
Adult ; Aged ; Biomarkers, Tumor ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; Microdissection ; Middle Aged ; Nasopharyngeal Neoplasms ; genetics ; Nasopharynx ; metabolism ; Neoplasm Proteins ; biosynthesis ; genetics ; Oligonucleotide Array Sequence Analysis ; Tumor Suppressor Proteins ; biosynthesis ; genetics

OBJECTIVE: To explore the effect of polygonum multiflorum on the fluidity of mitochondria membrane and activity of cytochrome oxidase (COX) in Alzheimer's disease (AD) model rats. METHODS: Forty-five SD rats were randomly divided into 3 groups: an AD model group, a control group, and a treatment group (n=15). AD model was established by injecting beta-amyloid protein (Abeta) 1-40 into the hippocampus of rats. The learning and memory abilities of rats were tested with the Y-electrical maze. The coefficient of viscosity of the hippocampal mitochondria membrane was determined by a spectrofluorometer, and the activity of COX was measured by an ultraviolet spectrophotometer. RESULTS: Compared with the control group, the learning and memory ability of the AD model group was significantly lower (P<0.01), while the coefficient of viscosity of the hippocampal mitochondria membrane of the AD model group rats was significantly higher (P<0.01), and COX activity was lower (P<0.01). Compared with the AD model group rats, the coefficient of viscosity of the hippocampal mitochondria membrane of the treatment group was significantly lower (P<0.05), and COX activity was significantly improved (P<0.05). CONCLUSION Polygonum multiflorum could improve the fluidity of mitochondria membrane and the activity of mitochondrial COX in the model of Alzheimer's disease.
Alzheimer Disease ; chemically induced ; metabolism ; Amyloid beta-Peptides ; Animals ; Cyclooxygenase 1 ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Female ; Hippocampus ; metabolism ; pathology ; Male ; Membrane Fluidity ; drug effects ; Membrane Proteins ; metabolism ; Mitochondria ; drug effects ; Peptide Fragments ; Polygonum ; chemistry ; Rats ; Rats, Sprague-Dawley

Objective To analyze and verify the role of senescent genes in the treatment,prognosis,and tumor microenvironment(TME)characteristics of osteoblastic osteosarcoma,bioinformatic methods were employed.Methods Senescent genes were obtained from the China National Genome Science database(https://ngdc.cncb.ac.cn/aging/index).The gene expression profile and clinical information of osteosarcoma patients were sourced from the TARGET database(https://ocg.cancer.gov/programs/target),while single-cell RNA-sequencing(scRNA-seq)data was collected from GSE162454 on the Gene Expression Omnibus(GEO)for downstream analysis.Osteosarcoma cells were classified based on scRNA-seq,and differential expression analysis between osteoblasts/chondroblasts and other cell types was conducted to identify differently expressed genes(DEGs).After matching with the senescent genes,prognostic senescent DEGs were identified through univariable and multivariable Cox regression analysis.Subsequently,the osteosarcoma senescent-related model(OSRM)was constructed,and the risk score was calculated.The role of OSRM in treatment,prognosis,and TME of osteosarcoma was further investigated.Results The analysis revealed that GSE162454 contained 6 osteosarcoma samples,with 19933 cells identified after filtering,quality control,and normalization.Seventeen cellular subtypes were identified using uniform manifold approximation and projection(UMAP)methods.A total of 4821 DEGs were found between osteoblasts/chondroblasts and other subtypes,with 132 senescent DEGs obtained after matching with the senescent gene set.In the TARGET database,4 prognostic senescent DEGs[ADH5(alcohol dehydrogenase 5),ARHGAP1(Rho GTPase activating protein 1),APOE(apolipoprotein E),and ATF4(activating transcription factor 4)]were identified through univariable and multivariable Cox analyses to construct OSRM.Based on risk score,patients were stratified into high-and low-risk groups,with the latter showing better prognosis(HR=0.13,95%CI 0.06-0.28,P<0.001)and higher sensitivity to immune checkpoint inhibitors.qRT-PCR and Western blotting confirmed the high expression of senescent genes ADH5(P<0.01),APOE(P<0.01),and ATF4(P<0.05)in the K7M2 osteosarcoma cell line,suggesting the potential for predicting the response to anti-PD-1 immunotherapy for osteosarcoma.Conclusions scRNA-seq facilitated the division of osteosarcoma into 17 cell subtypes.ADH5,ARHGAP1,APOE,and ATF4 emerged as potential cancer-promoting or suppressing senescent genes in osteosarcoma.OSRM was found to be associated with treatment response,prognosis,and TME characteristics,thereby promoting the molecular pathological diagnosis of osteoblastic osteosarcoma and prediction for anti-PD-1 immunotherapy.

[Abstract] Objective To investigate the ultrastructural changes of hippocampus in urea transporter B (UT-B) null mice and the alterations of distribution and expression level of aquaporin 4 (AQP4) in brain, and to discuss the relationship between AQP4 expression changes and depression-like behaviors in UT-B null mice. Methods Behavior differences of wild-type and UT-B null mice(10 in each group) were detected with sucrose preference and forced swimming test. The ultrastructural changes of hippocampus were observed by transmission electron microscopy (TEM). Immunohistochemistry and Western blotting were performed to detect the distribution and expression level of AQP4 in both genotypes. Results The sucrose preference index of wild-type mice and UT-B null mice were (84. 67 ± 1. 62)% and (65. 67±2. 66)%, respectively (P<0. 001). The immobility time of forced swimming was (209. 1±7. 00) seconds and (128. 6±3. 75) seconds respectively (P<0. 001). The two behavioral test results showed that UT-B null mice exhibited depression-like behavior. TEM results displayed the abnormal neurons with swelling of myelinated and unmyelinated fibers and degenerative changes, and perivascular astrocyte end-feet swelling. Immunohistochemistry results showed AQP4-immunoreactive (IR) cells were significantly reduced in cortex, hippocampus and thalamus. AQP4-IR cells were distributed in the pia matter, ependymal and cerebrovascular, but the perivascular immunostaining decreased. Western blotting analysis showed that the expression level of AQP4 in hippocampus was down-regulated by 27. 1% (P< 0. 05). Conclusion Reduced expression of AQP4 in the cerebral cortex and hippocampus of UT-B null mice might induce depressive behaviors by inference neurogenesis and cerebral metabolism.