Objective:To investigate the effect of aucubin(AU)on mitochondrial autophagy in the hippocampus of ischemic stroke(IS)rats by regulating the pten-induced kinase protein 1(PINK1)/cytoplasmic E3-ubiquitin ligase(Parkin)signaling pathway.Methods:The IS rat model was established by middle cerebral artery occlusion(MCAO),and was randomly divided into IS group,low-dose AU group(AU-L),medium-dose AU group(AU-M),high-dose AU group(AU-H),and high-dose AU combined with 3-MA group(AU-H+3-MA).The rats without liga-tion were used as the Sham surgery group.Zea Longa score was used to evaluate the neurological function of rats.TTC staining was used to detect the percentage of cerebral infarction volume.The microstructures of mitochondria were observed by transmission electron microscopy,and the changes of autophagy protein-microtubule associated protein light chain 3B(LC3B)and p62 were detected by immunohistochemistry.Hippocampal apoptosis was detected by TUNEL.PINK1/Parkin-related protein expression in hippocampus was detected by Western blot.Results:Neurological function score of IS rats was increased(P＜0.05),cerebral infarction was observed by TTC staining,the expression of mito-chondrial autophagy protein p62 in hippocampus was up-regulated(P＜0.05),the expression of LC3B was down-regu-lated(P＜0.05),the number of autophagosomes was decreased(P＜0.05),and apoptosis in hippocampus was in-creased(P＜0.05),the expression of PINK1 and ARKIN protein in hippocampus was down-regulated(P＜0.05).After AU intervention,the neural function score of rats was decreased,the percentage of cerebral infarction volume was reduced,the positive expression of p62 in hippocampus was down-regulated(P＜0.05),the positive expression of LC3B was up-regulated(P＜0.05),and the number of autophagosomes was increased(P＜0.05),the apoptosis of hippocampus was decreased(P＜0.05),and the expression of PINK1 and ARKIN protein in hippocampus was in-creased(P＜0.05).3-MA blocked the therapeutic effect of AU and aggravated the nerve injury in rats.Conclusion:AU promotes hippocampal mitochondrial autophagy and improves neurological damage in IS rats by activating the PINK1/Parkin signaling pathway.

Objective:To investigate the effect of aucubin(AU)on mitochondrial autophagy in the hippocampus of ischemic stroke(IS)rats by regulating the pten-induced kinase protein 1(PINK1)/cytoplasmic E3-ubiquitin ligase(Parkin)signaling pathway.Methods:The IS rat model was established by middle cerebral artery occlusion(MCAO),and was randomly divided into IS group,low-dose AU group(AU-L),medium-dose AU group(AU-M),high-dose AU group(AU-H),and high-dose AU combined with 3-MA group(AU-H+3-MA).The rats without liga-tion were used as the Sham surgery group.Zea Longa score was used to evaluate the neurological function of rats.TTC staining was used to detect the percentage of cerebral infarction volume.The microstructures of mitochondria were observed by transmission electron microscopy,and the changes of autophagy protein-microtubule associated protein light chain 3B(LC3B)and p62 were detected by immunohistochemistry.Hippocampal apoptosis was detected by TUNEL.PINK1/Parkin-related protein expression in hippocampus was detected by Western blot.Results:Neurological function score of IS rats was increased(P＜0.05),cerebral infarction was observed by TTC staining,the expression of mito-chondrial autophagy protein p62 in hippocampus was up-regulated(P＜0.05),the expression of LC3B was down-regu-lated(P＜0.05),the number of autophagosomes was decreased(P＜0.05),and apoptosis in hippocampus was in-creased(P＜0.05),the expression of PINK1 and ARKIN protein in hippocampus was down-regulated(P＜0.05).After AU intervention,the neural function score of rats was decreased,the percentage of cerebral infarction volume was reduced,the positive expression of p62 in hippocampus was down-regulated(P＜0.05),the positive expression of LC3B was up-regulated(P＜0.05),and the number of autophagosomes was increased(P＜0.05),the apoptosis of hippocampus was decreased(P＜0.05),and the expression of PINK1 and ARKIN protein in hippocampus was in-creased(P＜0.05).3-MA blocked the therapeutic effect of AU and aggravated the nerve injury in rats.Conclusion:AU promotes hippocampal mitochondrial autophagy and improves neurological damage in IS rats by activating the PINK1/Parkin signaling pathway.

OBJECTIVES: Stroke patients may have various sensory-motor disorders, such as spasticity, muscle weakness or sensory damage. Spasticity affects 20% to 40% of stroke patients. Patients with spasticity may have problems such as pain, motor function damage, and the decreased range of motion, which leads to decline of activity and quality of daily life. Extracorporeal shock wave therapy (ESWT) is a technique that can improve post-stroke spasticity. Whole body vibration (WBV), as a passive neuromuscular muscle stimulation technique, can improve the posture control, muscle strength, and muscle work of different people. At present, there are still few studies using WBV combined with ESWT for the treatment of hemiplegic patients with stroke. This study aims to explore the effects of WBV combined with ESWT on spasticity of the affected lower limb and gait function in stroke patients. METHODS: From March 2020 to March 2021, 50 hemiplegic patients with stroke were treated in the Department of Rehabilitation Medicine of the First Hospital of Changsha and they were assigned into a control group and a combined group, 25 cases per group. Both groups carried out conventional treatment, while the control group undertook the ESWT and fake WBV based on conventional treatment, and the combined group undertook ESWT after WBV and conventional treatment. Modified Ashworth Scale (MAS), Lower Extremity portion of the Fugl-Meyer Motor Assessment (FMA-LE), Berg Balance Scale (BBS), and parameters of three-dimensional gait analysis including kinematic parameters (peak value of hip flexion and knee flexion) and spatiotemporal parameters (velocity, cadence and stride length) were assessed before and after 4-week treatment between the 2 groups. RESULTS: After 4 weeks of treatment, MAS scores in 2 groups were lower than before (both P<0.05), and the combined group was lower than the control group (P<0.001); BBS and FMA-LE scores were higher than those before treatment (both P<0.05), and the combined group was higher than the control group (both P<0.001); in the control group, the walking speed, stride frequency, and stride length were higher than those before treatment (all P<0.05), and there was no significant difference between the peak value of flexion hip and peak value of flexion knee (both P<0.05); the peak value of hip flexion, peak value of knee flexion, step speed, step frequency, and stride length in the combined group were higher than those before treatment (all P<0.05), and were higher than those in control group (P<0.05 or P<0.001). CONCLUSIONS WBV combined with ESWT can improve the spasticity and motor function of the affected lower extremity, balance, and gait in hemiplegic patients with stroke.
Extracorporeal Shockwave Therapy ; Gait ; Hemiplegia/therapy* ; Humans ; Muscle Spasticity/therapy* ; Stroke/complications* ; Stroke Rehabilitation/methods* ; Treatment Outcome ; Vibration/therapeutic use*

Objective To investigate serum adiponectin level in patients with Alzheimer's disease (AD) and its correlation with the patients' cognitive function. Methods This 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. Results Serum 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). Conclusion Serum adiponectin levels are reduced in AD patients and associated with the degree of cognitive impairment.

Objective To investigate serum adiponectin level in patients with Alzheimer's disease (AD) and its correlation with the patients' cognitive function. Methods This 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. Results Serum 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). Conclusion Serum adiponectin levels are reduced in AD patients and associated with the degree of cognitive impairment.

OBJECTIVETo determine the association between the polymorphism of angiotensin converting enzyme (ACE) gene and Alzheimer's disease (AD).

METHODSThis case-control study involved 201 AD patients and 257 healthy subjects matched for age and gender as the control group. Polymerase chain reaction amplification and matrix-assisted laser desorption/ ionization time of flight mass spectrometry were used to examine the rs4291, rs4309, and rs4343 of ACE gene, and the difference in genotypes, allelotype frequencies and haplotype frequencies were analyzed between the two groups.

RESULTSNo statistic difference was found in the genotype and allelotype frequencies of rs4291 locus between AD and control groups (P>0.05). A significant difference was found in the genotype and allelotype frequencies of rs4309 between the two groups with a significant increase in the C allelotype frequency in AD group (OR=1.917, 95% CI=1.431-2.568, P<0.05). The difference in the genotype frequency of rs4343 was not significant between the two groups, but the allelotype frequencies differed significantly with a decreased A allelotype frequency in AD group(OR=0.714, 95% CI=0.532-0.957, P=0.024). Analysis of the linkage disequilibrium among the loci of rs4291, rs4309 and rs4343 showed a D' all above 0.65 between one another. Haplotype analysis confirmed the existence of 5 haplotypes, namely ATA, ACA, TCA, TCG and TTG, indicating a negative correlation between haplotype ATA and AD occurrence (OR=0.558, 95% CI=0.420-0.741, P<0.05) and positive correlations of haplotype ACA and TCA with AD occurrence (ACA: OR=4.883, 95% CI=2.267-10.518, P<0.05; TCA: OR=2.269, 95% CI=1.083-4.754, P<0.05).

CONCLUSIONThe polymorphism of rs4291 may have no relation with the incidence of AD. Polymorphisms of s4309 and rs4343 may be related to AD, and ATA, ACA and TCA haplotypes composed of rs4291/rs4309/rs4343 may be related to AD.

Alzheimer Disease ; genetics ; Case-Control Studies ; Gene Frequency ; Genotype ; Haplotypes ; Humans ; Linkage Disequilibrium ; Peptidyl-Dipeptidase A ; genetics ; Polymorphism, Single Nucleotide

Objective To determine the association between the polymorphism of angiotensin converting enzyme (ACE) gene and Alzheimer's disease (AD). Methods This case-control study involved 201 AD patients and 257 healthy subjects matched for age and gender as the control group. Polymerase chain reaction amplification and matrix-assisted laser desorption/ionization time of flight mass spectrometry were used to examine the rs4291, rs4309, and rs4343 of ACE gene, and the difference in genotypes, allelotype frequencies and haplotype frequencies were analyzed between the two groups. Results No statistic difference was found in the genotype and allelotype frequencies of rs4291 locus between AD and control groups (P>0.05). A significant difference was found in the genotype and allelotype frequencies of rs4309 between the two groups with a significant increase in the C allelotype frequency in AD group (OR=1.917, 95% CI=1.431-2.568, P<0.05). The difference in the genotype frequency of rs4343 was not significant between the two groups, but the allelotype frequencies differed significantly with a decreased A allelotype frequency in AD group(OR=0.714, 95%CI=0.532-0.957, P=0.024). Analysis of the linkage disequilibrium among the loci of rs4291, rs4309 and rs4343 showed a D’all above 0.65 between one another. Haplotype analysis confirmed the existence of 5 haplotypes, namely ATA, ACA, TCA, TCG and TTG, indicating a negative correlation between haplotype ATA and AD occurrence (OR=0.558, 95% CI=0.420-0.741, P<0.05) and positive correlations of haplotype ACA and TCA with AD occurrence (ACA:OR=4.883, 95%CI=2.267-10.518, P<0.05;TCA:OR=2.269, 95%CI=1.083-4.754, P<0.05). Conclusion The polymorphism of rs4291 may have no relation with the incidence of AD. Polymorphisms of s4309 and rs4343 may be related to AD, and ATA, ACA and TCA haplotypes composed of rs4291/rs4309/rs4343 may be related to AD.

Objective To determine the association between the polymorphism of angiotensin converting enzyme (ACE) gene and Alzheimer's disease (AD). Methods This case-control study involved 201 AD patients and 257 healthy subjects matched for age and gender as the control group. Polymerase chain reaction amplification and matrix-assisted laser desorption/ionization time of flight mass spectrometry were used to examine the rs4291, rs4309, and rs4343 of ACE gene, and the difference in genotypes, allelotype frequencies and haplotype frequencies were analyzed between the two groups. Results No statistic difference was found in the genotype and allelotype frequencies of rs4291 locus between AD and control groups (P>0.05). A significant difference was found in the genotype and allelotype frequencies of rs4309 between the two groups with a significant increase in the C allelotype frequency in AD group (OR=1.917, 95% CI=1.431-2.568, P<0.05). The difference in the genotype frequency of rs4343 was not significant between the two groups, but the allelotype frequencies differed significantly with a decreased A allelotype frequency in AD group(OR=0.714, 95%CI=0.532-0.957, P=0.024). Analysis of the linkage disequilibrium among the loci of rs4291, rs4309 and rs4343 showed a D’all above 0.65 between one another. Haplotype analysis confirmed the existence of 5 haplotypes, namely ATA, ACA, TCA, TCG and TTG, indicating a negative correlation between haplotype ATA and AD occurrence (OR=0.558, 95% CI=0.420-0.741, P<0.05) and positive correlations of haplotype ACA and TCA with AD occurrence (ACA:OR=4.883, 95%CI=2.267-10.518, P<0.05;TCA:OR=2.269, 95%CI=1.083-4.754, P<0.05). Conclusion The polymorphism of rs4291 may have no relation with the incidence of AD. Polymorphisms of s4309 and rs4343 may be related to AD, and ATA, ACA and TCA haplotypes composed of rs4291/rs4309/rs4343 may be related to AD.

OBJECTIVETo investigate the presence of β-amyloid peptide (Aβ) deposition in the cerebellum and the expression of related miRNAs in the cerebellum of a mouse model of Alzheimer disease.

METHODSTwelve 12-month-old APPswe/PSδE9 double transgenic mice and 12 wild-type C57 mice were sacrificed and the brain tissues were taken for examination. The right hemisphere was stained with Congo red to observe the deposition of amyloid substances, and from the left hemisphere, the hippocampus and the cerebellum were dissected for detecting the expression of miRNA-135a-5p, miRNA-298-5p, miRNA-466b-3p and miR-669f-3p using real-time PCR.

RESULTSCongo red staining revealed the presence of Aβ deposition in both the hippocampus and the cerebellum of the transgenic mice but not in the control mice. Real-time PCR showed a significantly lower expression of the 4 miRNAs in the hippocampus in the transgenic mice than in the control mice (P<0.05). The expression of miRNA-135a-5p, miRNA-298-5p, and miR-669f-3p in the cerebellum was significantly lower in the transgenic mice than in the control mice (P<0.05). The expression of miRNA-298-5p and miR-669f-3p in the hippocampus was significantly lower than that in the cerebellum of the transgenic mice (P<0.05).

CONCLUSIONβ deposition also occurs in the cerebellum of APPswe/PSδE9 double transgenic mice, and its formation might be related to the down-regulation of miRNA-135a-5p, miRNA-298-5p, and miR-669f-3p.

Alzheimer Disease ; metabolism ; Amyloid beta-Peptides ; metabolism ; Animals ; Cerebellum ; metabolism ; Disease Models, Animal ; Hippocampus ; metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; MicroRNAs ; metabolism

Objective To investigate the presence of β-amyloid peptide (Aβ) deposition in the cerebellum and the expression of related miRNAs in the cerebellum of a mouse model of Alzheimer disease. Methods Twelve 12-month-old APPswe/PS△E9 double transgenic mice and 12 wild-type C57 mice were sacrificed and the brain tissues were taken for examination. The right hemisphere was stained with Congo red to observe the deposition of amyloid substances, and from the left hemisphere, the hippocampus and the cerebellum were dissected for detecting the expression of miRNA-135a-5p, miRNA-298-5p, miRNA-466b-3p and miR-669f-3p using real-time PCR. Results Congo red staining revealed the presence of Aβdeposition in both the hippocampus and the cerebellum of the transgenic mice but not in the control mice. Real-time PCR showed a significantly lower expression of the 4 miRNAs in the hippocampus in the transgenic mice than in the control mice (P<0.05). The expression of miRNA-135a-5p, miRNA-298-5p, and miR-669f-3p in the cerebellum was significantly lower in the transgenic mice than in the control mice (P<0.05). The expression of miRNA-298-5p and miR-669f-3p in the hippocampus was significantly lower than that in the cerebellum of the transgenic mice (P<0.05). Conclusion Aβdeposition also occurs in the cerebellum of APPswe/PS△E9 double transgenic mice, and its formation might be related to the down-regulation of miRNA-135a-5p, miRNA-298-5p, and miR-669f-3p.