The occurrence of prion protein in surgically resected pancreatic adenocarcinoma

Background: Among the several new targets for the comprehension of the biology of pancreatic ductal adenocarcinoma (PDAC), Prion proteins (PrPc) deserve particular mention, since they share a marked neurotropism. Actually, PrPc could have also a role in tumorigenesis, as recently demonstrated. However, only few in vitro studies in cell cultures showed the occurrence of PrPc in PDAC cells. We aim to evaluate the presence of PrPc in vivo in PDAC tissues as a potential new biomarker.MethodsSamples from tumors of 23 patients undergone pancreatic resections from July 2018 to May 2020 at our institution were collected and analyzed. Immunohistochemistry and western blotting of PDAC tissues were compared with control tissues. Immunohistochemistry was used also to evaluate the localization of PrPc and of CD155, a tumoral stem-cell marker.ResultsAll cases were moderately differentiated PDAC, with perineural invasion (PNI) in 19/23 cases (83%). According to western-blot analysis, PrPc was markedly expressed in PDAC tissues (273.5 ± 44.63 OD) respect to controls (100 ± 28.35 OD, p = 0.0018). Immunohistochemistry confirmed these findings, with higher linear staining of PrPc in PDAC ducts (127.145 ± 7.56 μm vs 75.21 ± 5.01 μm, p < 0.0001). PrPc and CD155 exactly overlapped in ductal tumoral cells, highlighting the possible relationship of PrPc with cancer stemness. Finally, PrPc expression related with cancer stage and there was a potential correspondence with PNI.ConclusionsOur work provides evidence for increased levels of PrPc in PDAC. This might contribute to cancer aggressiveness and provides a potentially new biomarker. Work is in progress to decipher clinical implications.     

视黄酸诱导蛋白16蛋白质结构功能分析

目的:分析Tec激酶区作用蛋白视黄酸诱导蛋白16(RAI16)的蛋白质结构和功能信息.方法:利用相应的计算机软件及数据库,对RAI16 cDNA序列进行分析和比较,并对编码的蛋白质氨基酸序列及其二级结构进行分析和预测.结果:RAI16 cDNA序列由2863个核苷酸组成,编码759氨基酸蛋白质,RAI16蛋白包括一段由31个氨基酸组成的信号肽,没有跨膜区,亚细胞定位于内质网上,有多种二级结构形式,为一紧密包裹的球状蛋白质,是一种分泌蛋白,有多个磷酸化和蛋白酶切位点.RAI16蛋白为不稳定蛋白,不稳定系数为53.11.疏水性GRAVY(grand average of hydropathicity)值为-0.136.结论:RAI16蛋白作为一种新的胞内信号蛋白,很可能在肝癌细胞的诱导分化信号转导转录中与Tec协同发挥重要作用.     

Dynamic changes and surveillance function of prion protein expression in gastric cancer drug resistance

AIM:To explore the dynamic changes of prion protein (PrPc) in the process of gastric cancer drug resistance and the role of PrPc expression in the prognosis of gastric cancer patients receiving chemotherapy.METHODS:A series of gastric cancer cell lines resistant to different concentrations of adriamycin was established,and the expression of PrPc,Bcl-2 and Bax was detected in these cells.Apoptosis was determined using Annexin V staining.Western blotting and immunohisto-chemistry were performed to detect the ...     

Vitamin D and cognitive functioning in the elderly population in Germany

Objectives

To examine the relationship of serum 25-hydroxy vitamin D3 with cognitive functioning in higher age, using an instrument covering multiple cognitive domains in a population-based study.

Design

Follow-up study with measurement of vitamin D levels at baseline and assessment of cognitive functioning at year 5 follow-up.

Setting and participants

A subgroup of 1639 participants of the ongoing epidemiological ESTHER study of the elderly general population in Saarland State, Germany, aged 65 + years at baseline (2000-2002).

Intervention

Observational study.

Measurements

Cognitive functioning was assessed by the COGTEL phone interview developed by Kliegel et al., which was administered 5 years after ESTHER baseline. Vitamin D in baseline samples was measured by chemiluminescence methods. Additional information was obtained by standardised questionnaires.

Results

In multiple linear regression adjusted for important confounders, women in the lowest sex-specific quintile of vitamin D showed an on average 2.1 (95% confidence interval: 0.4 to 3.9) units lower COGTEL score than women in the highest quintile. A similar, albeit slightly weaker, association was seen in males (difference of 1.7 [− 0.4 to 3.8] units). Spline regression suggested non-linearity with a distinct decline in cognitive performance in the lower range of vitamin D levels.

Conclusions

Our findings support suggestions that low levels of vitamin D may be associated with reduced cognitive functioning in the elderly.     

Poor lung function accelerates cognitive decline in middle-aged and older adults: Evidence from the English Longitudinal Study of Ageing

Background/objectivePrevious studies have linked lung function to cognitive performance. However, it is not clear whether baseline lung function has an effect on the trajectory of cognitive decline during normal aging. This study aimed to examine the association of baseline lung function with long-term changes in cognition among the middle-aged and older adults.MethodsLung function as indicated by forced expiratory volume 1 s (FEV1) and forced vital capacity (FVC), was measured at the baseline examination. Cognition, including memory, time orientation, executive function and processing speed, were tested four times over six years. Generalized estimating equation (GEE) models were used to test the associations between baseline lung function and four visits of cognition in 6080 participants aged 50 years or over from the English Longitudinal Study of Ageing (ELSA).ResultsCompared to participants with higher lung function, those who had lower lung function at baseline experienced a faster rate of decline in memory (joint test: χ²_interaction = 12.07, df = 3, P = 0.007 for FVC), time orientation (joint test: χ²_interaction = 9.49, df = 3, P = 0.023 for FVC) and executive function (joint test: χ²_interaction = 9.13, df = 3, P = 0.028 for FEV1 and joint test: χ²_interaction = 12.76, df = 3, P = 0.005 for FVC). No association was found between baseline lung function and the rate of decline in processing speed (joint test: χ²_interaction = 1.29, df = 3, P=0.733 for FEV1 and joint test: χ²_interaction = 2.35, df = 3, P = 0.503 for FVC).ConclusionsPoor lung function at baseline predicted a faster rate of cognitive decline in memory, time orientation and executive function. The mechanism for this association deserves further investigation.     

The metabolic syndrome, atherosclerosis and cognitive functioning in a non-demented population: the Hoorn Study

Background

The metabolic syndrome (MetS) is associated with cognitive deficits and atherosclerotic vascular disease. We examined whether the relation between the MetS and cognitive dysfunction is mediated by measures of atherosclerosis or the presence of clinically manifest cardiovascular disease.

Methods

In 380 individuals (153 with MetS; 60–87 years) from the population based Hoorn Study, measures of atherosclerosis including carotid intima-media thickness (c-IMT), flow mediated dilation (FMD), ankle-brachial index and the presence of clinically manifest cardiovascular disease were assessed at baseline and 7 later years at follow-up. Cognitive functioning (information processing speed, memory, and attention and executive functioning) was assessed at follow-up. The relation between the MetS, atherosclerosis and cognitive functioning was assessed with linear regression analysis.

Results

Individuals with MetS showed worse performance on information processing speed (adjusted mean difference z-score ± SE: −0.22 ± 0.6; p = 0.01) and attention and executive functioning (−0.32 ± 0.07; p < 0.001), but not on the domain memory. The affected cognitive domains were also associated with measures of atherosclerosis (standardised B (95%CI) c-IMT: −0.14 (−0.24; −0.05); p < 0.01; FMD: 0.13 (0.02; 0.24), p < 0.05) and a history of clinically manifest cardiovascular disease: (−0.29 (−0.47; −0.11); p < 0.01). However, the relation between the MetS and cognitive functioning did not change after adjustment for c-IMT, FMD or a history of clinically manifest cardiovascular disease (p > 0.05).

Conclusion

In this population based cohort, the relation between the MetS and cognitive dysfunction was not mediated by atherosclerosis or a history of cardiovascular disease. These findings should stimulate future studies to elucidate alternative mechanisms underlying cognitive deficits in individuals with MetS.     

老年人握力与认知功能的关联性

目的:探讨65岁及以上老年人握力与认知功能之间的关系。方法:在武汉市65岁以上老年人中开展现况研究,由经过统一专业培训的调查人员收集握力、认知功能和生活方式等信息,分别采用多重线性回归和Logistic回归分析握力值与认知功能得分和认知障碍之间的关系。结果:本次研究对象(70.7±5.1)岁,533例老年人的平均握力为...     

老年人认知功能减退影响因素的纵向研究

目的 通过对一个社区居住的老年人群的前瞻性研究,探讨对认知功能随增的或退有重要影响的因素。方法 在北京市５５岁以上的老年与老年前期 群抽取样本,分别于１９９２年和１９９７年测查简易智能量表（ＭＭＳＦ）。结果 基线调查时在正常范围者５年后２４．４％ＭＭＳＥ评分明显下降。多分析证实,基线调查时评分在临界水平者易出现进一步下降;对认知功能痕退有预测作用的因子主要有年龄、受教育程度、地区等人口学因素,健康     

C-reactive protein is related to future cognitive impairment and decline in elderly individuals with cardiovascular disease

AimsTo explore the association of C-reactive protein (CRP) plasma levels with subsequent cognitive performance and decline among elderly individuals with pre-existing cardiovascular disease (CVD), and to assess the role of cerebrovascular indices in this relationship.MethodsCRP levels were measured in a subgroup of individuals with chronic CVD, who previously participated in a secondary prevention trial. Cognitive performance was evaluated 14.7 ± 1.9 and 19.9 ± 1.0 years after entry to the trial. A validated set of computerized cognitive tests was used (Neurotrax Computerized Cognitive Battery) to assess performance globally and in memory, executive function, visuospatial and attention domains. Linear regression and mixed models were used to assess the relationship of CRP plasma levels with cognitive scores and decline, respectively. In addition, we tested whether cerebrovascular reactivity, carotid intima media thickness and presence of carotid plaques modify these associations.ResultsAmong 536 participants (mean age at the first cognitive evaluation 72.6 ± 6.4 years; 95% males), CRP at the top tertile vs. the rest was associated with subsequent poorer performance overall (ß = −2.2 ± 1.0; p = 0.031) and on tests of executive function and attention (ß = −2.3 ± 1.1; p = 0.043 and ß = −2.0 ± 1.4; p = 0.047, respectively). Moreover, CRP levels were positively related to a greater decline in executive functions (ß = −2.4 ± 1.1; p = 0.03). These associations were independent of potential confounders and were not modified by cerebrovascular indices.ConclusionOur findings suggest that systemic chronic inflammation, potentially associated with underlying atherosclerosis, is related to cognitive impairment and decline two decades later, in elderly individuals with pre-existing CVD.     

遗传型朊蛋白病的研究进展

遗传型朊蛋白病（IPD）是由于编码朊蛋白（PrP）的PRNP基因发生突变,导致PrP发生空间构象改变而引起的神经系统退行性病变。与散发型克雅氏病（sCJD）患者相比,IPD患者的临床表型存在较大异质性,发病年龄往往较早,病程也相对较长,常规辅助检查（核磁、脑电图、14-3-3蛋白）通常无明显改变,且大多缺乏家族病史,临床上容易误诊漏诊。本文就IPD的流行病学特征、病因及发病机制、PRNP突变类型与疾病表型的相关性、3种IPD的具体临床特征、神经组织病理特征、辅助检查特点及相关研究进展等方面进行综述。     

Reductions in cognitive functioning are associated with decreases in satisfaction with aging. Longitudinal findings based on a nationally representative sample

ObjectiveThe objective of this study was to investigate the link between cognitive functioning and satisfaction with aging.MethodsData were drawn from a population-based sample, the German Ageing Survey (wave 5 and wave 6 with n = 6,384 in the analytical sample). The validated Philadelphia Geriatric Center Morale Scale was used to quantify satisfaction with aging. Cognitive functioning was measured using the digit symbol test. Linear fixed effects regressions were used.ResultsAdjusting for socioeconomics and various health-related covariates, regressions showed that decreases in cognitive functioning were associated with decreases in satisfaction with aging (β = .002, p = .02). Furthermore, regressions showed that decreases in satisfaction with aging were associated with increases in age (β=-.01, p < .001), decreases in physical functioning (β = .002, p < .01), worsening self-rated health (β=-.12, p < .001) and they were inversely associated with changes from employment to retirement (β = .11, p < .001).ConclusionStudy findings stress the importance of maintaining cognitive functioning for sustaining satisfaction with ageing. Strategies to postpone cognitive decline among middle-aged and older adults may contribute to aging satisfaction and ultimately to successful aging.     

朊病毒病实验室检测质量控制特点分析

目的分析朊病毒病重要实验室检测技术的质量控制环节,提高朊病毒病实验室诊断质量水平。方法从朊病毒常见检测方法,如脑组织的PrP^Sc免疫组化、脑组织的PrP^Sc的Westernblot检测、脑脊液中14—3-3蛋白的Westernblot检测以及血液样本中PRNP的基因检测技术等方面分析朊病毒病实验室诊断的质量控制要求。结果实验室检测过程质量控制是朊病毒检测结果准确与否的关键,有效蛋白酶K消化的时间和浓度是脑组织PrP“的Westernblot检测结果的保证,脑组织PrP^Sc的有效暴露和PrP^C的去除是朊病毒病脑组织IHC检测的核心环节,脑脊液的质量是14—3-3Westernblot检测的质量控制点,防止核酸污染是血液的PRNP序列测定的质量检测控制的关键。结论通过分析实验室检测的质量控制关键环节和控制措施,可有效加强朊病毒病实验室质量管理,提高朊病毒病实验室检测能力。     

Habitual physical activity (HPA) as a factor in sustained executive function in Alzheimer-type dementia: A cohort study

Evidence from studies on healthy older adults and mild cognitive impairment (MCI) populations suggests that physical activity interventions have a positive effect on executive function. In this study, we consider whether HPA is positively associated with executive function in Alzheimer's disease (AD). Eighty-two participants with a diagnosis of mild to moderate AD completed six measures of executive function. Objective measures of physical status were taken. In addition, informants completed questionnaires on the participants’ HPA and other lifestyle factors. A composite measure of executive function was the primary outcome. A multistage multiple regression was used to determine how much variance HPA accounted for. The final model comprised disease severity, cognitive reserve, cognitive activities, neuropsychiatric status and HPA status. The final model accounted for a total of 57% of the variance of executive performance, of which HPA itself accounted for 8% of the variance. HPA status is associated executive performance in an AD population even after controlling for key covariates. The findings encourage clinicians to recommend HPA and its cognitive benefits to AD patients and their carers.     

Anserine and carnosine supplementation in the elderly: Effects on cognitive functioning and physical capacity

The aim of this study was to investigate the potential beneficial effects of dietary anserine and carnosine (CRC) supplementation on cognitive functioning and physical activity of the elderly. The fifty-six subjects (65+) were allocated to the CRC group or placebo group at a 1:1 ratio. The double-blind procedure was used. Data were collected at the baseline and after 13-weeks of supplementation. In the follow up procedure fifty one subjects took part. Chicken meat extract (CME) containing 40% of CRC components (2:1 ratio of anserine to carnosine) was administered 2.5 g per day which allowed to rich the level of 1 g CRC in dipeptides supplement. The cognitive function, physical capacity, body measurements, blood pressure and heart rate (HR) were assessed. After supplementation Body Mass Index (BMI) decreased significantly (p < 0.05) in the CRC group performance comparing the placebo group. In two of six Senior Fitness Test the scores increased significantly (p < 0.05) in CRC group comparing to the placebo group. The perceived exertion differed significantly (p < 0.05) at the baseline and after follow up at the CRC group. The mean values of the Short Test of Mental Status (STMS) scores showed the significant (p < 0.04) increase only in CRC group, in the subscores of construction/copying, abstraction and recall. Conducted anserine and carnosine supplementation in the elderly brings promising effects on cognitive functioning and physical capacity of participants. However, further studies are needed.     

The role of cognitive event-related potentials in executive dysfunction

Frontal lobes are great and are a late-developing region of the neocortex that play a critical role in human behavior and executive function. The aim of this study was to clarify the role of event-related potentials (ERPs) in executive dysfunction and its relationship between generator mechanism and cognitive significance. We recruited 20 patients with frontal lobe lesion (FLL) and 27 age-matched controls. All patients submitted to comprehensive Frontal Test Battery and auditory ERPs measurement. In comparison with controls, the patients with FLL had significantly decreased executive function and manifested the delay of P300 latency, which reflected a delay of mental processing speed in these patients. Our findings suggest that patients with FLL may have prolonged P300 latency, which has a good correlation with executive dysfunction, poor performance, and longer P300 latencies. P300 ERPs are considered to be a useful method to identify the alteration of frontal-parietal connection.     

Effect of anesthesia on cognitive status and MMP-2 expression in rats

Objective:To investigate the effect of anesthesia on the cognitive status damage and MMP-2expression in rats.Methods:A total of 120 healthy rats were selected and randomly divided into the control group,CF3-CH(OCH2F)-CF3(Sevoflurane)group and CF3-CH2-O-CHF-CF3group(Sevoflurane)(n=40).After training for 3 d by the Morris water maze,the control group were injected with fentanyl for analgesia,the CF3-CH(OCH2F)-CF3 group and the CF3-CH2-O-CHFCF3 group were anesthesia with CF3-CH(OCH2F)-CF3 and CF3-CH2-O-CHF-CF3 on the basis of fentanyl,then rats in three groups underwent open surgery and suture conventional incision.Morris water maze was used to measure the rats cognitive ability in three groups on the 1st d,3rd d,5th d and 7th d,and the brain tissue MMP-2 expression was detected.Results:After1 d/7 d of the surgery,Morris water maze performance and MMP-2 expression were not significantly different among three groups(P0.05);After 3 d/5 d of the surgery,compared with the control group,the Morris water maze test result was significantly worsened,MMP-2expression levels were significantly increased(P0.05);After 3 d/5 d of the surgery,compared with the CF3-CH2-O-CHF-CF3 group,Morris water maze test result of CF3-CH(OCH2F)-CF3group was significantly worsened,MMP-2 expression levels were significantly increased(P0.05).Conclusions:Anesthesia can cause some injury on cognitive status,different anesthetic drugs may cause different injury,and the cognitive status injury is related to the MMP-2 expression.     

Reduced erythroid cell and erythropoietin production in response to acute anemia in prion protein-deficient (Prnp-/-) mice

Cellular prion protein (PrPc) participates in the pathogenesis of prion diseases but its normal function remains unclear. PrPc is expressed on hematopoietic cells, including erythroid precursors. We investigated the role of PrPc in erythropoiesis in vivo with phenylhydrazine-induced acute anemia. Induction of equivalent anemia in wild-type (WT) and Prnp−/− mice resulted in a higher number of circulating reticulocytes, hematocrits and spleen weights in WT mice than in Prnp−/− mice on Days 5 and 7. Examination of bone marrow erythroid precursor cells (Ter119+) on Day 5 revealed no significant differences in the number of these cells between the two types of animals. However, a higher percentage of Ter119+ cells were going through apoptosis in Prnp−/− mice than in WT mice. Plasma erythropoietin (Epo) levels and Epo mRNA in kidneys peaked on Day 3 in response to anemia for both types of animals but rose less in Prnp−/− (5500 pg/ml ) than in WT (18,000 pg/ml) animals. Administration of recombinant human Epo to mice produced an equivalent reticulocyte response in both types of animals suggesting that the potential for erythroid generation is intact in Prnp−/− animals. These observations indicate that PrPc may modulate tissue hypoxia-sensing mechanisms or effect hypoxia target gene expression.     

The impact of insomnia on cognitive functioning in older adults

OBJECTIVES: To examine whether self-reported symptoms of insomnia independently increase risk of cognitive decline in older adults. DESIGN: Longitudinal cohort study. SETTING: The four sites of the Established Populations for Epidemiologic Studies of the Elderly. PARTICIPANTS: Six thousand four hundred forty-four community-dwelling men and women age 65 and older who had no more than one error on the Short Portable Mental Status Questionnaire (SPMSQ) at baseline and an in-person interview at the third annual follow-up (FU3). MEASUREMENTS: Insomnia was defined as report of trouble falling asleep or waking up too early most of the time. Cognitive decline was defined as two or more errors on the SPMSQ at FU3. Logistic regression was used to determine risk of cognitive decline associated with insomnia, controlling for demographic, behavioral, and health-related factors. Analyses were stratified by sex and depressed mood. RESULTS: Among nondepressed men, those reporting symptoms of insomnia at both baseline and FU3 had an adjusted odds ratio (OR) of 1.49 (95% CI = 1.03-2.14) for cognitive decline, relative to those with no insomnia at FU3. Men with insomnia at FU3 only were not at increased risk (OR = 1.16, 95% CI = 0.82-1.65). These relationships were not found in women. Men and women with depressive symptoms at FU3 were at increased risk for cognitive decline independent of insomnia. CONCLUSION: Chronic insomnia independently predicts incident cognitive decline in older men. More sensitive measures of cognitive performance may identify more subtle declines and may confirm whether insomnia is associated with cognitive decline in women.     

甲状腺功能异常对老年人认知功能的影响

甲状腺功能异常在老年人中较常见,它不仅影响老年人的躯体功能,还可能引起注意力、记忆、情感等认知功能障碍.已有研究从动物实验、神经电生理、神经影像等角度对甲状腺功能与认知功能之间的关系展开探讨.此外,在临床工作中,甲状腺功能异常引起的严重认知功能损害易与老年性痴呆相混淆.因此,医务人员需重视,避免误诊.及时、合理地纠正老年人甲状腺功能异常,可能有利于认知能力的恢复.