Background: 20(S)-protopanaxadiol (PPD), a ginsenoside metabolite, has prominent benefits for the central nervous system, especially in improving learning and memory. However, its transcriptional targets in brain tissue remain unknown. Methods: In this study, we first used mass spectrometry-based drug affinity responsive target stability (DARTS) to identify the potential proteins of ginsenosides and intersected them with the transcription factor library. Second, the transcription factor PURA was confirmed as a target of PPD by biolayer interferometry (BLI) and molecular docking. Next, the effect of PPD on the transcriptional levels of target genes of PURA in brain tissues was determined by qRT-PCR. Finally, bioinformatics analysis was used to analyze the potential biological features of these target proteins. Results: The results showed three overlapping transcription factors between the proteomics of DARTS and transcription factor library. BLI analysis further showed that PPD had a higher direct interaction with PURA than parent ginsenosides. Subsequently, BLI kinetic analysis, molecular docking, and mutations in key amino acids of PURA indicated that PPD specifically bound to PURA. The results of qRT-PCR showed that PPD could increase the transcription levels of PURA target genes in brain. Finally, bioinformatics analysis showed that these target proteins were involved in learning and memory function. Conclusion: The above-mentioned findings indicate that PURA is a transcription target of PPD in brain, and PPD upregulate the transcription levels of target genes related to cognitive dysfunction by binding PURA, which could provide a chemical and biological basis for the study of treating cognitive impairment by targeting PURA.
Background: Oral health is an important element of well aging. And oral health also affects overall health, mental health, and quality of life. In this study, we sought to identify oral health influencing factors and research trends for well-aging through text analysis of research on well-aging and oral health over the past 12 years. Methods: The research data was analyzed based on English literature published in PubMed from 2012 to 2023. Aging well and oral health were used as search terms, and 115 final papers were selected. Network text analysis included keyword frequency analysis, centrality analysis, and cohesion structure analysis using the Net-Miner 4.0 program. Results: Excluding general characteristics, the most frequent keywords in 115 articles, 520 keywords (Mesh terms) were psychology, dental prosthesis and Alzheimer's disease, Dental caries, cognition, cognitive dysfunction, and bacteria. Research keywords with high degree centrality were Dental caries (0.864), Quality of life (0.833), Tooth loss (0.818), Health status (0.727), and Life expectancy (0.712). As a result of community analysis, it consisted of 4 groups. Group 1 consisted of chewing and nutrition, Group 2 consisted oral diseases, systemic diseases and management, Group 3 consisted oral health and mental health, Group 4 consisted oral frailty symptoms and quality of life. Conclusion: In an aging society, oral dysfunction affects mental health and quality of life. Preventing oral diseases for well-aging can have a positive impact on mental health and quality of life. Therefore, efforts are needed to prevent oral frailty in a super-aging society by developing and educating systematic oral care programs for each life cycle.
Purpose: This study aimed to develop and test a structural model for chemotherapy-related cognitive impairment of breast cancer patients based on a literature review and Hess and Insel's chemotherapy-related cognitive change model. Methods: The Participants consisted of 250 patients who were ${\geq}19$ years of age. The assessment tools included the Menopause Rating Scale, Symptom Experience Scale, Hospital Anxiety and Depression Scale, Everyday Cognition, and Functional Assessment of Cancer Therapy-Breast Cancer. Data were analyzed using the SPSS 21.0 and AMOS 21.0 programs. Results: The modified model was a good fit for the data. The model fit indices were ${\chi}^2=423.18$ (p<.001), ${\chi}^2/df=3.38$, CFI=.91, NFI=.91, TLI=.89, SRMR=.05, RMSEA=.09, and AIC=515.18. Chemotherapy-related cognitive impairment was directly influenced by menopausal symptoms (${\beta}=.38$, p=.002), depression and anxiety (${\beta}=.25$, p=.002), and symptom experiences (${\beta}=.19$, p=.012). These predictors explained 47.7% of the variance in chemotherapy-related cognitive impairment. Depression and anxiety mediated the relations among menopausal symptoms, symptom experiences, and with chemotherapy related cognitive impairment. Depression and anxiety (${\beta}=-.51$, p=.001), symptom experiences (${\beta}=-.27$, p=.001), menopausal symptoms (${\beta}=-.22$, p=.008), and chemotherapy-related cognitive impairment (${\beta}=-.15$, p=.024) had direct effects on the quality of life and these variables explained 91.3%. Conclusion: These results suggest that chemotherapy-related toxicity is highly associated with cognitive decline and quality of life in women with breast cancer. Depression and anxiety increased vulnerability to cognitive impairment after chemotherapy. Nursing intervention is needed to relieve chemotherapy-related toxicity and psychological factor as well as cognitive decline for quality of life in patients undergoing chemotherapy.
Purpose: Despite poor cognitive function in heart failure (HF), few studies have examined cognition and its probable implication in self-care among Korean HF patients. The purposes of this study were (1) to describe cognition in the domains of global, memory, and executive functions, (2) to explore the relationship between cognition and self-care, and (3) to determine the amount of dietary sodium intake among Korean HF patients. Methods: A pilot study was conducted: 7 HF patients (3 men, mean age 68 years) completed face-to-face interviews for neuropsychological tests of cognition and self-care including dietary sodium intake. Results: More than half of the patients had impaired global cognition, memory, or executive function; patients with more severe HF were at higher risk of poor cognitive function. Korean HF patients exhibited poor self-care, with a high dietary sodium intake (5.6 g/day), approximately twice more than the suggested guideline of 2~3 g/day for patients with stable HF. Conclusion: Cognitive dysfunction and inadequate self-care with noncompliance with dietary sodium restriction were evident in Korean HF patients. More studies are warranted that examine the prevalence of cognitive impairment and areas of deficit using neuropsychological tests in a larger sample and that examine how cognition affects self-care and compliance in salt-intake.
Background: There is recent evidence that insulin resistance is responsible for increasing the risk of developing cognitive dysfunction. To systematically review the influence of intranasal insulin treatment on the cognitive function in Alzheimer's disease patients. Methods: Randomized controlled trials comparing the cognitive effects of intranasal insulin therapy in Alzheimer's disease patients with controlled interventions were retrieved from Pubmed, Medline, Embase and Cochrane library. Meta-analysis was conducted on the cognitive measurements with a subgroup analysis by dose, gender and apolipoprotein E allele 4 (ApoE ${\varepsilon}4$) status. Results: Seven randomized controlled trials were eligible for inclusion. Intranasal insulin had a positive influence on the cognitive function as compared to placebo without a statistical significance (standardized mean difference; SMD = 0.109; 95% confidence interval; CI -0.04 to 0.26; P=0.14). In subgroup analysis, a 20 IU dose of intranasal insulin induced a significant improvement in cognitive function (SMD = 0.14; 95% CI 0.05 to 0.24; P=0.004), but 40 IU did not show this effect (SMD = -0.01; 95% CI -0.11 to 0.09; P=0.82). ApoE ${\varepsilon}4$ positive patients showed a significant decline in cognitive function as compared to ApoE ${\varepsilon}4$ positive patients in the control group (SMD = -0.213; 95% CI -0.38 to -0.04; P=0.015). Such an effect was not apparent in ApoE ${\varepsilon}4$ negative patients. Gender had no influence on the cognitive outcomes. Conclusion: The results indicate that intranasal insulin may have beneficial effect in improving the cognitive function in Alzheimer's disease patients.
Purpose: The purpose of this study was to design a mobile-application of a cognitive training program for people who have chemo-related cognitive complaints. Methods: The program was developed based on the network-based instructional system design proposed by Jung. The program consisted of several tasks centered on four cognitive domains: learning, memory, working memory, and attention. For memory learning, a target-image and all its elements (color, position, and number) were presented on the screen that had to be recognized among a number of distractor-figures. In working memory training, the previous learned target-figure according to the level of difficulty had to be remembered among many different figures. In attention training named "Find the same figure," two identical symbols in a grid-pattern filled with different images were presented on the screen, and these had to be simultaneously touched. In attention training named "Find the different figure," a different symbol in a grid pattern filled with same figures had to be selected. This program was developed to train for a minimum of 20 min/day, four days/week for six weeks. Results: This cognitive training revealed statistically significant improvement in subjective cognitive impairments (t=3.88, p=.006) at six weeks in eight cancer survivors. Conclusion: This cognitive training program is expected to offer individualized training opportunities for improving cognitive function and further research is needed to test the effect in various settings.
Objectives: This study aimed to evaluate the association between dental implants and cognitive function in community-dwelling older adults. Methods: Data were collected from the baseline survey (2016-2017) of the Korean Frailty and Aging Cohort Study. The study sample comprised 1115 community-dwelling people aged 70 years to 84 years who had 0-19 natural teeth. Dental implants and natural teeth were identified by panoramic radiography, while the cognitive function was assessed by the Korean version of the Mini-Mental State Examination (MMSE-KC). The association between dental implants and cognitive function was analyzed by multiple linear regression. Sensitivity analysis was performed to test for potential bias. Results: The mean number of natural teeth in the study population was 9.50 (standard deviation [SD], 6.42), and the mean MMSE-KC score was 24.93 (SD, 3.55). In the simple univariate analysis, tooth replacement, age, sex, smoking status, alcohol consumption, body mass index, osteoporosis, number of natural teeth, periodontitis, chewing discomfort, tooth-brushing frequency, education level, monthly household income, participation in economic activity, living alone, and marital status had a significant impact on the association. After adjusting for confounders, the association between dental implants and cognitive function remained significant (B, 0.85; standard error, 0.40; p<0.05). Age, body mass index, periodontitis, tooth-brushing frequency, and education level were also significantly associated with cognitive function. The results of the sensitivity analyses were consistent with those of the primary analysis. Conclusions: Dental implants were associated with cognitive function in older adults living in the community. Dental implants as tooth replacements may play a role in preserving cognitive function.
In this study, we have verified the memory and cognitive enhancing effect of Longanae Arillus, the fruit of Euphoria longana Lamarck, which has been used as a tonic and for the treatment of amnesia, insomnia, and palpitations in oriental medicine. To investigate the effect of Longanae Arillus water extract(LAE) on the memory and cognitive dysfunction, scopolamine (1 mg/kg, i.p.) was injected in C57BL/6 mice and several behavior tests including Y-maze, Morris water-maze, passive avoidance and fear conditioning tests were conducted. Administration of LAE (100 or 200 mg/kg/day, p.o.) effectively improved scopolamine-induced memory impairment and dysfunction. To further determine the possible molecule mechanism of LAE, we have examined the activity and/or mRNA expression of diverse proteins involved in the acetylcholine metabolism. LAE particularly increased the amount of acetylcholine in the cortex which was mediated by suppression of acetylcholine esterase (AchE) activity. In addition, LAE elevated the mRNA expression of muscarinic acetylcholine receptors (mAchRs) without affecting the mRNA levels of choline acetyltransferase (ChAT) and acetylcholine esterase (AchE). In another experiment, LAE effectively inhibited mRNA expression of pro-inflammatory cytokines such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interleukin-$1{\beta}$ (IL1-${\beta}$), which seemed to be mediated by inhibition of upstream transcription factor NF-${\kappa}B$ and extracellular-regulated kinase 1/2 (ERK1/2). These results demonstrate that Longanae Arillus can increase acetylcholine amount the cortex via regulation of AchE activity as well as mAchRs expression and decrease pro-inflammatory responses via inhibition of NF-${\kappa}B$ signaling pathway, thereby having therapeutic potential to improve memory and cognitive deficit in amnesia.
The ameliorating effect of the MeOH extract of the root of Platycodon grandiflorum on the ethanol-induced cognitive dysfunction in mice was investigated. The total MeOH extract was devided into two fractions, saponin rich fraction and non-saponin fraction. The mice with repeated administration of the total MeOH extract and those with saponin rich fraction both showed a markedly prolongεd latency time upon the step-through test (passive avoidance performance) performed after acute ethanol intoxication, while those with non-saponin rich fraction did not. The results suggest that the extracts from the root of Platycodon grandiflorum exert a beneficial effect on ethanol-induced memory impairment in mice and also suggest that these effects of the extracts might be ascribed to the saponin constituents.
The beneficial effects of hypoxic preconditioning are abolished in the diabetes. The present study was designed to investigate the protective effects and mechanisms of repeated episodes of whole body hypoxic preconditioning (WBHP) in db/db mice. The protective effects of preconditioning were explored on diabetes-induced vascular dysfunction, cognitive impairment and ischemia-reperfusion (IR)-induced increase in myocardial injury. Sixteen-week old db/db (diabetic) and C57BL/6 (non-diabetic) mice were employed. There was a significant impairment in cognitive function (Morris Water Maze test), endothelial function (acetylcholine-induced relaxation in aortic rings) and a significant increase in IR-induced heart injury (Langendorff apparatus) in db/db mice. WBHP stimulus was given by exposing mice to four alternate cycles of low (8%) and normal air O2 for 10 min each. A single episode of WBHP failed to produce protection; however, two and three episodes of WBHP significantly produced beneficial effects on the heart, brain and blood vessels. There was a significant increase in the levels of brain-derived neurotrophic factor (BDNF) and nitric oxide (NO) in response to 3 episodes of WBHP. Moreover, pretreatment with the BDNF receptor, TrkB antagonist (ANA-12) and NO synthase inhibitor (L-NAME) attenuated the protective effects imparted by three episodes of WBHP. These pharmacological agents abolished WBHP-induced restoration of p-GSK-3β/GSK-3β ratio and Nrf2 levels in IR-subjected hearts. It is concluded that repeated episodes of WHBP attenuate cognitive impairment, vascular dysfunction and enhancement in IR-induced myocardial injury in diabetic mice be due to increase in NO and BDNF levels that may eventually activate GSK-3β and Nrf2 signaling pathway to confer protection.
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