The mitochondria-targeted small molecule SS31 delays progression of behavioral deficits by attenuating ß-amyloid plaque formation and mitochondrial/synaptic deterioration in APP/PS1 mice.

Alzheimer's disease (AD) is a common neurodegenerative disorder characterized by progressive cognitive dysfunction and an impaired ability to carry out daily life functions. Mitochondrial dysfunction and ß-amyloid (Aß) deposition are the most common causes of AD. Antioxidants have been shown to delay brain aging and AD development; however, it remains unknown whether the antioxidant peptide SS31 can protect mitochondrial and synaptic function and delay the progression of behavioral deficits in early-stage AD in vivo. Therefore, in this study we compared mitochondrial and synaptic changes, as well as the protective effects of SS31, in APP/PS1 transgenic mice and C57BL/6J control mice. The APP/PS1 transgenic mice exhibited elevated expression of Aß40/Aß42 and mitochondrial fission protein DLP1 and reduced expression of synaptophysin (SYN) and postsynaptic density protein 95 (PSD95) reductions, as well as increased levels of neuronal apoptosis and ROS in the hippocampus, and long-term treatment with SS31 reversed these effects. Furthermore, the cognitive impairments observed in APP/PS1 transgenic mice were reversed by SS31 treatment. Our findings show that SS31 lowers ROS and Aß levels, protecting mitochondrial homeostasis and synaptic integrity, and ultimately improving behavioral deficits in early-stage AD. This suggests that SS31 is a potential pharmacological agent for treating or slowing the progression of AD.

Ginsenoside Rh4 inhibits breast cancer growth through targeting histone deacetylase 2 to regulate immune microenvironment and apoptosis.

High expression of histone deacetylase 2 (HDAC2) is recognized as a marker of invasive breast cancer (BC). HDAC2 is not only responsible for enhancing tumor cell growth, development, and anti-apoptosis, but also plays a significant role in regulating PD-L1 on the surface of tumor cells. Continuous expression of PD-L1 allows tumor cells to escape immune surveillance. There is not much research on how HDAC2 affects the immune system in breast cancer. Ginsenoside Rh4 (Rh4) is a major rare saponin in heat-treated ginseng, which is widely applied in treating and preventing various diseases because of its potent medicinal value and stable safety. However, it is unclear how Rh4 affects the tumor immune microenvironment in breast cancer. Therefore, this paper aims to investigate the effect of Rh4 on HDAC2 in breast cancer, specifically the effect of HDAC2 on apoptosis and the immune microenvironment to inhibit breast cancer growth. According to our study, ginsenoside Rh4 has been shown to significantly suppress breast cancer cell proliferation without any adverse effects. The molecular docking results of Rh4 and HDAC2 indicate a binding energy of -6.06 kcal/mol, suggesting the potential of Rh4 as a targeting modulator of HDAC2. Mechanistically, Rh4 induces apoptosis of breast cancer cells by the HDAC2-mediated caspase pathway and inhibits the HDAC2-mediated JAK/STAT pathway to regulate the immune microenvironment, which inhibits breast cancer growth. Specifically, Rh4 was shown for the first time to blockade immune checkpoints (PD-1/PD-L1) and increase levels of T-lymphocytes in the tumor. In a word, our study establishes a theoretical framework for applying Rh4 as an immune checkpoint inhibitor as part of breast cancer treatment.

Assessing executive function following the early stage of mild Ischemic stroke with three brief screening tests.

OBJECTIVE: Executive dysfunction following stroke is well documented, but less is known about whether it occurs in mild stroke patients. The purpose of the study was to investigate executive impairment in this population and explore the correlation between executive function tests and cognitive tests of other domains. METHODS: Cross-sectional study was undertaken to compare 139 mild ischemic stroke patients (National Institute of Health Stroke Scale (NIHSS) ≤ 7) aged 40-80 with 131 normal controls matched age, gender and levels of education. All participants were administered a neuropsychological test battery including three measures of executive functioning: Clock Drawing Test (CDT), Trial Making Test-A and B (TMT-A and B), and Stroop Color Word Test (SCWT). The CDT was evaluated using three quantitative scoring rubrics, with a total score of 3,10,18, respectively and a qualitative scoring method with six types of errors. Spearman's correlations were made to analyze the correlation between executive function tests and other neuropsychological tests. RESULTS: Control group performed better than stroke group on most executive function tests at a statistical significance. Qualitative CDT showed that errors of "graphic difficulties", "conceptual deficits" and "spatial and/or planning deficits" occurred frequently in the early stage of mild stroke. Correlation data clarified that among the executive function tests, time for TMT-B correlated with global cognition most. CONCLUSION: Executive dysfunction is common following even mild strokes, and that relatively brief measures such as CDT, TMT and SCWT can be employed for it before discharge as part of rehabilitation planning.

Trends in cognitive function assessed by a battery of neuropsychological tests after mild acute ischemic stroke.

OBJECTIVE: The aim of this study is to investigate the domain-specific trends of cognitive function up to 12 months after mild acute ischemic stroke. METHODS: Enrolment of consecutive cohort of patients with mild acute ischemic stroke with recorded clinical characteristics and extensive neuropsychological assessments, including five cognitive domains. The Montreal cognitive assessment of the Beijing version (MoCA-Bj) was used to assess overall cognition. All patients completed all domain-specific examinations were categorised into three groups according to the time between the stroke onset and neuropsychological profiling, the time duration including less than one month (n = 174), one month to six months (n = 65) and over six months (n = 39). RESULTS: The final cohort consisted of 278 patients. The executive (χ2 = 6.95, P<0.05) and memory dysfunctions (χ2 = 9.6, P<0.01) showed strong improvement, especially in executive function, which prevalence was 48.85% at <1- month group and 25.64% at >6 months group. The prevalence of attention and information processing also had a declining trend, the differences, however, were not statistically significant (χ2 = 0.23 and 2.25, respectively, P>0.05). There was no significant change in language function (χ2 = 0.46, P>0.05) and the MoCA (χ2 = 0.59, P>0.05) at 3-time point groups. In 195 first-ever stroke patients, the results of memory (χ2 = 6.94 P<0.05) and executive dysfunctions (χ2 = 6.25 P<0.05) also showed significant improvement. CONCLUSION: There is varying degree of improvement tendency in executive and memory dysfunctions after mild acute ischemic stroke. Early cognitive assessments after mild acute ischemic stroke do not reflect the cognitive level of stable period.

Progress of Drug Nanocrystal Self-Stabilized Pickering Emulsions: Construction, Characteristics In Vitro, and Fate In Vivo.

A drug nanocrystal self-stabilized Pickering emulsion (DNSPE) is a novel Pickering emulsion with drug nanocrystals as the stabilizer. As a promising drug delivery system, DNSPEs have attracted increasing attention in recent years due to their high drug loading capacity and ability to reduce potential safety hazards posed by surfactants or specific solid particles. This paper comprehensively reviews the progress of research on DNSPEs, with an emphasis on the main factors influencing their construction, characteristics and measurement methods in vitro, and fate in vivo, and puts forward issues that need to be studied further. The review contributes to the advancement of DNSPE research and the promotion of their application in the field of drug delivery.

Chinese version of the auditory verbal learning test: normative study and clinical applications in Chinese-speaking population in Shijiazhuang city.

OBJECTIVE: The purposes were to establish standardized values for the Auditory Verbal Learning Test (AVLT) in the communities of Shijiazhuang city (China), with particular focus on the influences of age, education and sex, and to detect the discriminant validity data of the AVLT in patients with acute ischemic stroke (AIS). METHODS: 406 Chinese-speaking subjects (age: 50-84 years old) from Shijiazhuang city, were brought into this study. Using linear regression analyses, standardized values were developed for three variables of interest, including scores on short-term memory (sum of AVLT trials 1-3), delayed recall (AVLT trial 4), and an index representing recognition memory corrected for false-positive identifications (AVLT trial 5). 177 patients with AIS were included to probe the discriminant validity of the AVLT. RESULTS: The linear regression analysis showed statistically significant effect of age and sex on all trials of the AVLT. Years of education contributed significantly to trial 1-3 and trial 4 but not trial 5. Based on the results obtained, trail 1-3 and trail 4 of AVLT norms were stratified by age (3 strata), education (2 strata), and sex (2 strata). Trail 5 norms were stratified by age (3 strata) and sex (2 strata). Moreover, AIS groups performed significantly worse on most AVLT trials than matched cognitively healthy controls. CONCLUSIONS: Normative data stratified by age, education and sex for the Chinese-speaking community-residents in Shijiazhuang was presented for use in research and clinical settings. The AVLT measures adequately differentiated between the cognitive performance (especially memory decline) of healthy adults and patients with AIS.

A derivant of ginsenoside CK and its inhibitory effect on hepatocellular carcinoma.

Epidemiological studies have shown that hepatocellular carcinoma (HCC) is a main cause of tumor death worldwide. Accumulating data indicate that ginsenoside CK is an effective compound for preventing HCC growth and development. However, improvement of pharmaceutical effect of the ginsenoside CK is still needed. In our study, we performed acetylation of ginsenoside CK (CK-3) and investigated the antitumor effects of the derivative in vitro and in vivo. The cytotoxicity analysis revealed that compared with CK, CK-3 could inhibit the proliferation of multiple tumor cell lines at a lower concentration. Treating with CK-3 on HCC cells arrested cell cycle in G2/M phase and induced cell apoptosis through AO/EB staining, TUNEL analysis and flow cytometry. Meanwhile, CK-3 significantly inhibited tumor growth in an HCC xenograft model and showed no side effect on the function of the main organs. Mechanistically, whole transcriptome analysis revealed that the antitumor effect of CK-3 was involved in the Hippo signaling pathway. The immunoblotting and immunofluorescence results illustrated that CK-3 directly facilitated the phosphorylation of YAP1 and decreased the expression of the main transcription factor TEAD2 in HCC cell lines and tumor tissue sections. Collectively, our results demostrate the formation of a new derivative of ginsenoside CK and its regulatory mechanism in HCC, which could activate the Hippo-YAP1-TEAD2 signaling pathway to regulate HCC progression. This research could provide a new direction for traditional Chinese medicine in the therapy of tumors.

The montreal cognitive assessment and mini-mental state examination visuoexecutive subtests in acute ischemic stroke patients and their correlations with demographic and clinical factors.

Visuoexecutive impairment is common among acute ischemic stroke patients. This study aimed to examine the ability of the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) visuoexecutive subtests to detect visuoexecutive abnormality in acute ischemic stroke patients and to identify the predictors for their impairments. 336 patients who completed the MMSE and MoCA were enrolled in this study. We compared the proportion of participants with incorrect MoCA visuoexecutive tasks and MMSE pentagon copying. Multivariate logistic regression analysis was used to evaluate the associations between the visuoexecutive dysfunction and demographic and clinical characteristics in the samples. Among all the participants, the MoCA detected more visuoexecutive dysfunction than the MMSE (88.69% vs. 45.83%, respectively; p < 0.001). The predictors identified by the univariate analysis included the factors of gender, age, educational level, smoking, alcohol consumption, Oxfordshire Community Stroke Project (OCSP), previous strokes, initial NIHSS score and number of old lacunar infarctions, while from the multivariate logistic regression analysis, the factors of age, educational level, NIHSS score, previous strokes and number of old lacunar infarctions served as predictive factors for the visuoexecutive impairment in acute stroke patients. In conclusion, visuoexecutive impairment is associated with the factors of the educational level, stroke severity, stroke history and number of old lacunar infarctions. Our findings may guide the clinicians to intervene the risks for the patients at an early stage after stroke and form the basis for good rehabilitation plans.

Clock-drawing test in vascular mild cognitive impairment: Validity of quantitative and qualitative analyses.

INTRODUCTION: The clock-drawing test (CDT) has been used as a screening tool to identify cognitive deficit in patients with dementia. However, it has not been extensively evaluated for categorizing patients with vascular mild cognitive impairment (vMCI). This study aimed to examine the discrimination of vMCI using various CDT scoring methods. METHOD: A total of 120 vMCI patients and 119 normal control (NC) subjects were tested using three CDT quantitative scoring systems: the one from the Montreal Cognitive Assessment (MoCA) (CDT3) and the systems of Rouleau (CDT10) and Babins (CDT18). We used a revised scoring method to evaluate the effectiveness in differentiating vMCI patients from NC subjects, which combined the CDT10 quantitative score and three qualitative errors with a significantly higher prevalence in vMCI group (called hereinafter CDTcomb, including CDTcomb13 and CDTcomb16 based on different weights of the three error types). The sensitivity and specificity of the CDT methods were determined by the receiver operating characteristic (ROC) curve. The results of the scoring systems were compared with those of the Mini-Mental State Examination (MMSE). RESULTS: The results of the ROC analyses with the CDT3, CDT10, and CDT18 systems produced a sensitivity of 71.1%, 81.8%, and 60.3%, and a specificity of 66.12%, 58.68%, and 73.55%, respectively, for the diagnosis of vMCI. Compared with the separate MMSE score, the combination of MMSE with the CDT3, CDT10 and CDT18 scores did not increase the sensitivity and specificity. When three qualitative errors were incorporated into the CDT10 quantitative score, CDTcomb13 and CDTcomb16 provided a sensitivity of 87.6% and 86.78%, and a specificity of 74.79% and 80.67%, respectively, in differentiating vMCI patients from the NC group. CONCLUSION: Our findings suggest that the combination of CDT quantitative score with qualitative observations of the clock-drawing errors can provide a better discrimination between vMCI patients and cognitively normal subjects.

Clock-drawing test: Normative data of three quantitative scoring methods for Chinese-speaking adults in Shijiazhuang City and clinical utility in patients with acute ischemic stroke.

OBJECTIVE: The clock-drawing test (CDT) is a widely used screening tool for detecting cognitive decline. However, normative data for Chinese individuals are scarce. Our study aimed to provide standardized values for the three quantitative CDT scoring methods that were tailored for Chinese-speaking adults in Shijiazhuang City and explore the discriminant validity of the CDT scores in patients with acute ischemic stroke. METHODS: We conducted the CDT among 418 healthy individuals aged between 35 and 84 years. The CDT was administered and scored by five raters using the method derived from the Montreal Cognitive Assessment (MoCA), Rouleau's, and Babins' scoring systems. The influence of age, education, and sex on the performance in the CDT was analyzed. Furthermore, 336 patients with acute ischemic stroke were enrolled to explore the discriminant validity of CDT scores. RESULTS: In all three scoring systems, CDT scores were significantly correlated with age and years of education but not with sex. Normative data stratified for age and years of education were established. Interrater and intersystem reliability were high in our study. CDT total scores and subscores showed significant differences between stroke patients and healthy individuals. CONCLUSIONS: Our study provides CDT normative data using three quantitative scoring methods for Chinese-speaking adults in Shijiazhuang City. Age and education level were the key factors that affected the CDT scores. CDT total scores and subscores provided good discriminant validity for patients with acute ischemic stroke.