Poor subjective sleep quality and trait impulsivity in patients with bipolar disorder.

BACKGROUND: Sleep disturbance and impulsivity are key components of mood vulnerability in bipolar disorder (BD), but few studies have assessed the association between these two symptoms among patients with BD. METHODS: Forty-seven euthymic patients with bipolar I disorder (BDI) or bipolar II disorder (BDII) and 58 age- and sex-matched healthy controls were enrolled in this cross-sectional study. Trait impulsivity was measured using the Barratt Impulsiveness Scale Version 11 (BIS-11), which yielded 3 second-order factors: attention, motor, and non-planning. Subjective sleep quality was assessed using the self-reported Pittsburgh Sleep Quality Index (PSQI). General linear models (GLMs) were used to assess the associations between subjective poor sleep and trait impulsivity with multiple testing corrections. RESULTS: Patients with BD scored higher in BIS-11 and PSQI than healthy controls. PSQI total scores positively correlated with BIS-11 total scores, while sleep disturbance and daytime dysfunction were associated with attentional impulsiveness after controlling for covariates. Participants with higher PSQI total scores (>10) had higher scores in BIS-11 total, attention, and non-planning than those with low PSQI scores (≤5). CONCLUSION: These findings support the hypothesis that poor sleep quality might lead to impulsivity and add to the growing evidence that improving sleep quality may be a therapeutic target for patients with BD.

Treatment Efficacy of Pharmacotherapies for Frontotemporal Dementia: A Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The neuropsychiatric symptoms of frontotemporal dementia (FTD) have a profound negative impact on disease outcomes and care burden. Available pharmacotherapies might be supported by small-scale randomized controlled trials (RCTs); however, clinical recommendations might not be conclusive. METHODS: We systematically searched several databases from inception to April 30, 2022, for RCTs of drug therapy in patients with FTD and neuropsychiatric symptoms (primary outcome). Secondary outcomes included changes in caregiver stress, daily interactive activities, cognitive function, and acceptability (adverse event or dropout rates). The network meta-analysis (NMA) procedure was performed under the frequency model, showing effect sizes as standardized mean differences (SMD) or odds ratios (OR) with 95% confidence intervals (95% CIs). RESULTS: Seven RCTs with 243 participants were included. Compared with placebo, high-dose oxytocin (72 international units) was associated with the greatest improvement in patients' neuropsychiatric symptoms (SMD = -1.17, 95% CIs = -2.25 to -0.08, z = -2.10, p = 0.035). Piracetam significantly worsened neuropsychiatric symptoms (SMD = 3.48, 95% CIs = 1.58 to 5.37, z = 3.60, p < 0.001) and caregiver stress (SMD = 2.40, 95% CIs = 0.80-4.01, z = 2.94, p = 0.003). Trazodone had significantly higher rates of adverse events (OR = 9.53, 95% CIs = 1.85-49.20, z = 2.69, p = 0.007). No pharmacological intervention significantly benefited cognitive function. CONCLUSIONS: This study provides the first NMA for clinical recommendation to support the use of high-dose oxytocin and caution regarding the use of piracetam for neuropsychiatric symptoms in patients with FTD.

A longitudinal study of the association between pro-inflammatory cytokines and mood symptoms in bipolar disorder.

BACKGROUND: Because of a relative dearth of longitudinal studies, the directionality of the relationship between mood and inflammation among patients with bipolar disorder (BD) is still unclear. We aimed to investigate the longitudinal associations of pro-inflammatory markers with mood symptom severity in BD. METHODS: Hundred and thirty-two adult patients with BD were enrolled. At the baseline and 1-year follow-up visit, all participants received mood assessment with Montgomery Åsberg depression rating scale (MADRS) and Young mania rating scale, and underwent blood draws to quantify metabolic profile and serum levels of the pro-inflammatory markers, including soluble interleukin-6 receptor, soluble tumor necrosis factor-α receptor type 1 (sTNF-αR1), monocyte chemoattractant protein-1, and C-reactive protein. A four-factor model of MADRS, consisting of sadness, negative thoughts, detachment, and neurovegetative symptoms, were applied. RESULTS: At baseline, 65 patients with BD were in depressed state, and 67 patients with BD were in euthymic state. Among patients in depressed state, baseline MADRS total score positively correlated with sTNF-αR1 level at follow-up. While baseline sTNF-αR1 level positively predicted sadness symptom in euthymic patients with BD who later developed depression (n = 22), sadness in patients with bipolar depression predicted later increase in serum sTNF-αR1 level even after remission (n = 17). Moreover, lithium had a stronger effect of lowering peripheral sTNF-αR1 level as compared with other mood stabilizers. CONCLUSION: Our results indicate the bidirectional inflammation-depression relationship in BD.

Health-related quality of life and mild behavioral impairment in older adults without dementia.

BACKGROUND: The Mild Behavioral Impairment Checklist (MBI-C) was developed to assess neuropsychiatric symptoms (NPS) and to identify mild behavioral impairment (MBI). This study validated the Taiwanese version of the MBI-C and examined its association of health-related quality of life (HR-QoL). METHODS: We recruited 242 older individuals without dementia (129 amnestic mild cognitive impairment, 113 cognitively normal). Their family completed the MBI-C, the Neuropsychiatric Inventory Questionnaire (NPI-Q), and instrumental activities of daily living scale. Participants completed the Geriatric Depression Scale (GDS-15), the Mini-Mental State Examination, the 12-item word recall test, the category verbal fluency test and the EuroQol 5 dimensions questionnaire (EQ-5D). Cronbach's α was used to evaluate the internal consistency of the MBI-C. Linear regression models were used to examined the association between MBI-C score and HR-QoL assessed using ED-5D. RESULTS: The prevalence of MBI was 12% of all participants. Cronbach's α of the MBI-C was 0.893. The optimal cut-off point of MBI-C was 7.5 for identifying MBI, with a sensitivity of 100% and specificity of 85%. The MBI-C total score (ß = -0.01, 95% confidence interval [CI] = -0.02 to -0.01, p < 0.001), MBI-C subdomain of decreased motivation (ß = -0.04, 95% CI = -0.05 to -0.02, p < 0.001) and emotional dysregulation (ß = -0.02, 95% CI = -0.04 to -0.004, p = 0.01) were factors related to EQ-5D index scores. CONCLUSION: Among older adults without dementia, the Taiwanese version of the MBI-C has good reliability and validity for detecting MBI. The total and subdomains of MBI-C were associated with decreased HR-QoL among individuals without dementia.

A national survey on health-related quality of life for people with dementia in residential long-term care institutions.

BACKGROUND: Health-related quality of life (HRQoL) is an essential outcome parameter in geriatric research; however, the available evidence is mixed regarding the factors associated with HRQoL among people with dementia. We aimed to identify factors that contribute to HRQoL among people with dementia in residential long-term care (LTC) institutions. METHODS: We randomly selected 299 of 1607 registered residential LTC institutions in Taiwan. A cross-sectional survey was conducted between 2019 and 2020, including items on demographic characteristics, comorbidities, the EuroQol-5 dimensions-5 levels (EQ-5D-5L; utility and visual analog scale [VAS] scores), the Mini-Mental State Examination (MMSE), the Clinical Dementia Rating (CDR), behavioral and psychological symptoms of dementia, activities of daily living (ADL), and instrumental ADL (IADL). RESULTS: In total, 1313 people with dementia from 267 institutions were enrolled (mean age, 76.4 ± 12.7 years). The mean EQ-5D-5L utility and VAS scores were 0.10 (standard deviation [SD] = 0.48) and 66.57 (SD = 20.67), respectively. In multivariate linear regression analysis, higher scores for ADL, IADL, and CDR sum of boxes were associated with higher utility scores. Higher VAS scores were associated with higher ADL and MMSE scores. Lower utility scores and VAS scores were associated with more frequent depressive symptoms. CONCLUSION: ADL, dementia severity, cognitive function, and depressive symptoms influenced the HRQoL of people with dementia in residential LTC institutions. Longitudinal studies should be conducted to better understand how HRQoL changes over time among people with disabilities.

Determinants of long-term care service use by persons with dementia: A national dementia registry study conducted in Taiwan.

BACKGROUND: This study investigated the determinants and use of Taiwan's long-term care (LTC) Plan Version 2.0 (LTC 2.0) services by persons with dementia (PWDs) and their caregivers. METHODS: In total, 1268 PWD-caregiver dyads were enrolled for analysis from a national dementia registry. Andersen's Behavioral Model of Health Services Use was used to investigate the association of LTC service use with several factors, namely the demographic data of PWDs and their caregivers, migrant caregiver employment, monthly household income, caregiver burden as determined by the Zarit Burden Interview (ZBI), Mini-Mental State Examination score, Clinical Dementia Rating scores, neuropsychiatric inventory scores for the behavioral and psychological symptoms of dementia, and PWDs' activities of daily living (ADLs). RESULTS: Among the studied family caregivers, 81.4% did not use LTC resources. A multivariable logistic analysis revealed that aberrant motor behaviors (odd ratio [OR] = 1.31, 95% confidence interval [CI] = 1.10-1.56, p = 0.003), dysfunction in ADLs (OR = 1.06, 95% CI = 1.02-1.10, p = 0.002), higher ZBI scores (OR = 1.02, 95% CI = 1.01-1.03, p = 0.004), not residing with family members (OR = 1.88, 95% CI = 1.32-2.66, p < 0.001), and not employing a migrant caregiver (OR = 4.41, 95% CI = 2.59-7.51, p < 0.001) were the factors most significantly associated with LTC service use. CONCLUSION: Factors such as whether PWDs live alone, specific neuropsychiatric symptoms, and impaired function should be considered in future policy amendments to provide required activities and care resources for PWDs and their caregivers.

Inflammation, cognitive dysfunction, and suicidal ideation among patients with major depression.

BACKGROUND: Dysregulated proinflammatory cytokines have been shown to be associated with suicidal behavior. Cognitive deficits in working memory and inhibitory control have been demonstrated in depressed patients and people with suicidal ideation (SI). However, the association between proinflammatory cytokines, SI, and cognitive deficits in patients with major depressive disorder (MDD) remains unclear. METHODS: A total of 77 patients with MDD and age-/sex-matched 60 healthy individuals were recruited. MDD patients were divided into two groups: with SI (n = 36) and no SI (n = 41). SI was defined by a score of ≥2 in item 3 of the 17-item Hamilton Rating Scale for Depression. Levels of proinflammatory cytokines, including soluble interleukin-6 receptor, soluble tumor necrosis factor-α receptor type 1, and C-reactive protein (CRP), were measured, and cognitive function was assessed using 2-back task and Go/No-Go task. RESULTS: Patients with SI had higher levels of CRP than those without SI and controls (P = .007). CRP was positively associated with SI (ß = 0.21, P = .037), independent of cognitive function and depressive symptoms. Furthermore, SI was associated with cognitive deficits in working memory and inhibitory control after adjusting for confounding factors (P < .05). CONCLUSION: Our findings suggest that higher levels of serum CRP and deficits in working memory and inhibitory control may be associated with higher SI among patients with MDD.

RETRACTED - Risk factors for mild behavioral impairment in non-demented geriatrics: a population-based survey in Taiwan.

OBJECTIVES: To investigate potential risk factors for mild behavioral impairment (MBI) among non-demented geriatrics. DESIGN: Population-based, cross-sectional survey. SETTING: Taiwan Alzheimer Disease Association (TADA) Database. PARTICIPANTS: Participants were selected by multistage random sampling of all Taiwan counties. They received in-person interviews between December 2011 and March 2013. MEASUREMENTS: Demographic data, lifestyle and habits, medical comorbidities, cognitive status measured by the Taiwanese Mini-Mental Status Examination (TMSE) and presence of MCI of the participants were collected. Subjects were distributed to the MBI and non-MBI groups. These factors had been evaluated for their effects on MBI in the univariate and multivariable logistic regression models. RESULTS: In total, 6,196 non-demented participants aged 65 years or older, including 409 MBI and 5,787 non-MBI participants, were recruited. After adjustment for age, sex, education, body mass index, lifestyle and habits, medical comorbidities, and MCI, good sleep was associated with lower risk of MBI (OR 0.09, 95% CI 0.07 - 0.12). Low body weight (OR 2.01, 95% CI 1.21-3.33), low-to-medium education (OR 1.40, 95%CI 1.06-1.85; OR 2.32, 95% CI 1.67-3.21), medical comorbidities of hypertension (OR 1.56, 95% CI 1.25-1.95), hyperlipidemia (OR 1.29, 95% CI 1.00-1.67), cancer (OR 2.05, 95% CI 1.37-3.06) were significantly associated with increased MBI risk. MCI neither increased nor decreased risk of MBI (OR 1.00, 95% CI 0.76-1.32). CONCLUSIONS: Good sleep was associated with lower MBI risk. Underweight, lower education, medical comorbidities of cancer, hypertension, hyperlipidemia were predictive of MBI.

Pro-inflammatory cytokines and cognitive dysfunction among patients with bipolar disorder and major depression.

AIM: Bipolar disorder and major depressive disorder (MDD) have been demonstrated to be associated with proinflammatory states and cognitive function deficits. We aimed to investigate the differences of cognitive function and proinflammatory cytokines between patients with bipolar I disorder (BDI), bipolar II disorder (BDII), and MDD. METHODS: Thirty-seven patients with BDI, 33 with BDII, 25 with MDD, and 54 age-, sex-matched controls were enrolled. All patients had a clinical global impression-severity scale ≤2. Serum levels of proinflammatory markers, including soluble interleukin-6 receptor, C-reactive protein, and soluble tumor necrosis factor receptor 1 (sTNF-αR1) were measured. Performance in the Word List Memory Task (WLMT), Wisconsin Card Sorting Task (WCST), 2-back task, Go/No-Go task, and divided attention task was assessed. RESULTS: Patients with BDI had higher levels of sTNF-αR1 than patients with MDD and controls (P < 0.001). Patients with BDI performed worse on WLMT, WCST, 2-back task, divided attention_visual and divided attention_auditory tasks than the other three groups (all P < 0.05). Furthermore, sTNF-αR1 levels were negatively correlated with cognitive function measured using the WLMT and divided attention_auditory (all P < 0.05). CONCLUSIONS: Patients with BDI had higher levels of sTNF-αR1 and cognitive function impairments than the remaining groups. Future studies are needed to explore the pathophysiology of sTNF-αR1 in the contribution of cognitive alterations.

Familial coaggregation of major psychiatric disorders among first-degree relatives of patients with obsessive-compulsive disorder: a nationwide study.

BACKGROUND: Whether the first-degree relatives (FDRs) of patients with obsessive-compulsive disorder (OCD) have an increased risk of the major psychiatric disorders, namely schizophrenia, bipolar disorder, OCD, major depressive disorder (MDD), autism spectrum disorder (ASD), and attention deficit hyperactivity disorder (ADHD), remains unclear. METHODS: Using the Taiwan National Health Insurance Research Database with the whole population sample size (n = 23 258 175), 89 500 FDRs, including parents, offspring, siblings, and twins, of patients with OCD were identified in our study. The relative risks (RRs) of major psychiatric disorders were assessed among FDRs of patients with OCD. RESULTS: FDRs of patients with OCD had higher RRs of major psychiatric disorders, namely OCD (RR 8.11, 95% confidence interval (CI) 7.68-8.57), bipolar disorder (RR 2.85, 95% CI 2.68-3.04), MDD (RR 2.67, 95% CI 2.58-2.76), ASD (RR 2.38, 95% CI 2.10-2.71), ADHD (RR 2.19, 95% CI 2.07-2.32), and schizophrenia (RR 1.97, 95% CI 1.86-2.09), compared with the total population. Different familial kinships of FDRs, such as parents, offspring, siblings, and twins consistently had increased risks for these disorders. In addition, a dose-dependent relationship was found between the numbers of OCD probands and the risk of each major psychiatric disorder. CONCLUSIONS: The FDRs, including parents, offspring, siblings, and twins, of patients with OCD have a higher risk of OCD, schizophrenia, bipolar disorder, MDD, ADHD, and ASD. The familial co-aggregation of OCD with OCD and other major psychiatric disorders was existent in a dose-dependent manner. Given the increased risks of psychiatric disorders, medical practitioners should closely monitor the mental health of the FDRs of patients with OCD.

Liposome Consolidated with Cyclodextrin Provides Prolonged Drug Retention Resulting in Increased Drug Bioavailability in Brain.

Although butylidenephthalide (BP) is an efficient anticancer drug, its poor bioavailability renders it ineffective for treating drug-resistant brain tumors. However, this problem is overcome through the use of noninvasive delivery systems, including intranasal administration. Herein, the bioavailability, drug stability, and encapsulation efficiency (EE, up to 95%) of BP were improved by using cyclodextrin-encapsulated BP in liposomal formulations (CDD1). The physical properties and EE of the CDD1 system were investigated via dynamic light scattering, transmission electron microscopy, UV-Vis spectroscopy, and nuclear magnetic resonance spectroscopy. The cytotoxicity was examined via MTT assay, and the cellular uptake was observed using fluorescence microscopy. The CDD1 system persisted for over 8 h in tumor cells, which was a considerable improvement in the retention of the BP-containing cyclodextrin or the BP-containing liposomes, thereby indicating a higher BP content in CDD1. Nanoscale CDD1 formulations were administered intranasally to nude mice that had been intracranially implanted with temozolomide-resistant glioblastoma multiforme cells, resulting in increased median survival time. Liquid chromatography-mass spectrometry revealed that drug biodistribution via intranasal delivery increased the accumulation of BP 10-fold compared to oral delivery methods. Therefore, BP/cyclodextrin/liposomal formulations have potential clinical applications for treating drug-resistant brain tumors.

Epigenetic targeting DNMT1 of pancreatic ductal adenocarcinoma using interstitial control release biodegrading polymer reduced tumor growth through hedgehog pathway inhibition.

Annually, 48,000 people die from pancreatic ductal adenocarcinoma (PDAC), ranking it the fourth among cancer-related deaths in the United States. Currently, anti-cancer drugs are not effective against PDAC, and only extends survival by 3 months. Aberrant DNA methylation has been shown to play an important role during carcinogenesis in PDAC, with approximately 80% of tumor overexpressing the DNA methyltransferase 1 (DNMT1) protein. In the present study, we used DNMTs as a screening platform to find a new DNMT inhibitor, n-butylidenephthalide (n-BP), which is identified from a Chinese herbal drug. n-BP could inhibit DNMT1 expression in both dose-dependent and time-dependent manner. It also displays an effect in suppressing growth of PDAC cells and inducing cell cycle arrest at G0/G1 phase leading apoptosis. Growth suppression can be restored by the overexpression of DNMT1 in PDAC cells. Furthermore, we found n-BP-mediated DNMT1 suppression influenced the protein stability rather than changing the RNA expression. Through microarray studies, we found that the patched domain contained 4 (PTCHD4) is the potential downstream gene of DNMT1. Following silencing of PTCHD4 expression by siRNA, n-BP decreased tumor growth inhibition. Finally, in vivo, two animal models were used to evaluate the efficacy and survival after n-BP treatment by interstitial control release polymer delivery. The results show that n-BP could effectively inhibit PDAC tumor volume growth and extend animal survival. In summary, n-BP may inhibit the growth of human PDAC cells though reducing DNMT1 and increasing the expression of PTCHD4 both in vitro and in vivo.

Increased risk of type 2 diabetes among the siblings of patients with schizophrenia.

BACKGROUND: Research suggests an association between metabolic disorders, such as type 2 diabetes mellitus (T2DM), and schizophrenia. However, the risk of metabolic disorders in the unaffected siblings of patients with schizophrenia remains unclear. METHODS: Using the Taiwan National Health Insurance Research Database, 3135 unaffected siblings of schizophrenia probands and 12,540 age-/sex-matched control subjects were included and followed up to the end of 2011. Individuals who developed metabolic disorders during the follow-up period were identified. RESULTS: The unaffected siblings of schizophrenia probands had a higher prevalence of T2DM (3.4% vs. 2.6%, p = 0.010) than the controls. Logistic regression analyses with the adjustment of demographic data revealed that the unaffected siblings of patients with schizophrenia were more likely to develop T2DM (odds ratio [OR]: 1.39, 95% confidence interval [CI]: 1.10-1.75) later in life compared with the control group. Moreover, only female siblings of schizophrenia probands had an increased risk of hypertension (OR: 1.47, 95% CI: 1.07-2.01) during the follow-up compared with the controls.DiscussionThe unaffected siblings, especially sisters, of schizophrenia probands had a higher prevalence of T2DM and hypertension compared with the controls. Our study revealed a familial link between schizophrenia and T2DM in a large sample. Additional studies are required to investigate the shared pathophysiology of schizophrenia and T2DM.

Non-Canonical Regulation of Type I Collagen through Promoter Binding of SOX2 and Its Contribution to Ameliorating Pulmonary Fibrosis by Butylidenephthalide.

Pulmonary fibrosis is a fatal respiratory disease that gradually leads to dyspnea, mainly accompanied by excessive collagen production in the fibroblast and myofibroblast through mechanisms such as abnormal alveolar epithelial cells remodeling and stimulation of the extracellular matrix (ECM). Our results show that a small molecule, butylidenephthalide (BP), reduces type I collagen (COL1) expression in Transforming Growth Factor beta (TGF-ß)-induced lung fibroblast without altering downstream pathways of TGF-ß, such as Smad phosphorylation. Treatment of BP also reduces the expression of transcription factor Sex Determining Region Y-box 2 (SOX2), and the ectopic expression of SOX2 overcomes the inhibitory actions of BP on COL1 expression. We also found that serial deletion of the SOX2 binding site on 3'COL1 promoter results in a marked reduction in luciferase activity. Moreover, chromatin immunoprecipitation, which was found on the SOX2 binding site of the COL1 promoter, decreases in BP-treated cells. In an in vivo study using a bleomycin-induced pulmonary fibrosis C57BL/6 mice model, mice treated with BP displayed reduced lung fibrosis and collagen deposition, recovering in their pulmonary ventilation function. The reduction of SOX2 expression in BP-treated lung tissues is consistent with our findings in the fibroblast. This is the first report that reveals a non-canonical regulation of COL1 promoter via SOX2 binding, and contributes to the amelioration of pulmonary fibrosis by BP treatment.

Targeting Cellular Stress Mechanisms and Metabolic Homeostasis by Chinese Herbal Drugs for Neuroprotection.

Traditional Chinese medicine has been practiced for centuries in East Asia. Herbs are used to maintain health and cure disease. Certain Chinese herbs are known to protect and improve the brain, memory, and nervous system. To apply ancient knowledge to modern science, some major natural therapeutic compounds in herbs were extracted and evaluated in recent decades. Emerging studies have shown that herbal compounds have neuroprotective effects or can ameliorate neurodegenerative diseases. To understand the mechanisms of herbal compounds that protect against neurodegenerative diseases, we summarize studies that discovered neuroprotection by herbal compounds and compound-related mechanisms in neurodegenerative disease models. Those compounds discussed herein show neuroprotection through different mechanisms, such as cytokine regulation, autophagy, endoplasmic reticulum (ER) stress, glucose metabolism, and synaptic function. The interleukin (IL)-1ß and tumor necrosis factor (TNF)-α signaling pathways are inhibited by some compounds, thus attenuating the inflammatory response and protecting neurons from cell death. As to autophagy regulation, herbal compounds show opposite regulatory effects in different neurodegenerative models. Herbal compounds that inhibit ER stress prevent neuronal death in neurodegenerative diseases. Moreover, there are compounds that protect against neuronal death by affecting glucose metabolism and synaptic function. Since the progression of neurodegenerative diseases is complicated, and compound-related mechanisms for neuroprotection differ, therapeutic strategies may need to involve multiple compounds and consider the type and stage of neurodegenerative diseases.

n-Butylidenephthalide Regulated Tumor Stem Cell Genes EZH2/AXL and Reduced Its Migration and Invasion in Glioblastoma.

Glioblastoma (GBM) is one of the most common and aggressive types of brain tumor. Due to its highly recurrent rate and poor prognosis, the overall survival time with this type of tumor is only 20-21 months. Recent knowledge suggests that its recurrence is in part due to the presence of cancer stem cells (CSCs), which display radioresistant, chemoresistant, self-renewal and tumorigenic potential. Enhancers of Zeste 2 (EZH2) and AXL receptor tyrosine kinase (AXL) are both highly expressed in GBM. Additionally, they are an essential regulator involved in CSCs maintenance, migration, invasion, epithelial-to-mesenchymal transition (EMT), stemness, metastasis and patient survival. In this study, we used a small molecule, n-butylidenephthalide (BP), to assess the anti-GBM stem-like cells potential, and then tried to find out the associated genes involved with regulation in migration and invasion. We demonstrated that BP reduced the expression of AXL and stemness related genes in a dose-dependent manner. The migratory and invasive capabilities of GBM stem-like cells could be reduced by AXL/EZH2. Finally, in the overexpression of AXL, EZH2 and Sox2 by transfection in GBM stem-like cells, we found that AXL/EZH2/TGF-ꞵ1, but not Sox2, might be a key regulator in tumor invasion, migration and EMT. These results might help in the development of a new anticancer compound and can be a target for treating GBM.

Brain tumor senescence might be mediated by downregulation of S-phase kinase-associated protein 2 via butylidenephthalide leading to decreased cell viability.

Developing an effective drug for treating human glioblastoma multiform (GBM) has been investigated persistently. A pure compound butylidenephthalide (BP), isolated from Angelica sinensis, has been shown the activities to arrest the growth and initiate apoptosis of GBM in our previous reports. In this study, we further demonstrated that BP treatment accelerates the cell senescence in a dose-dependent manner in vitro and in vivo. S-phase kinase-associated protein 2 (Skp2), a proto-oncogene, is generally upregulated in cancer. We found that it was downregulated in BP-treated GBM cells. The downregulation of Skp2 is parallel with increasing p16 and p21 expression which causes G0/G1 arrest and tumor cell senescence. We also found that restoring the Skp2 protein level by exogenous overexpression prevents the BP-induced cell senescence. Therefore, the linkage between cell senescence and Skp2 expression is strengthened. Promoter binding analysis further detailed that the BP-mediated SP1 reduction might involve in the Skp2 downregulation. In summary, these results emphasize that BP-triggered senescence in GBM cells is highly associated with its control on Skp2 regulation.

Changes in cognitive function after a 12-week POWER rehabilitation in older adults with schizophrenia and frailty.

BACKGROUND: The effectiveness of isolated resistance training (RT) on cognitive function among older adults with schizophrenia is insufficiently investigated. This study investigated the effectiveness of 12-weeks POWER rehabilitation, a novel RT regimen, on cognitive function among older patients with schizophrenia and frailty. METHODS: Thirty-two older adults with schizophrenia and frailty were enrolled and randomized to receive either a 12-week, twice weekly POWER rehabilitation, or without add-on training. Cognitive functioning was assessed using mini-mental state examination (MMSE), digit symbol substitution test, color trail task (CTT), and digit span task (DST). Physical performance was assessed by walking speed and hand grip strength. The generalized estimating equations was used to compare pre- and post-training outcome measure between groups. RESULTS: Between-group analysis revealed significant improvement in CTT1 and hand grip strength in the intervention group compared to the controls. Subgroup analyses showed CTT1 performance significantly improved after 12 weeks of POWER rehabilitation in the intervention group (time, p < .001), independent of age, educational level, global cognition, depressive symptoms, and psychotropic medication use. Increased hand grip strength was significantly associated with improved performance in MMSE, CTT1, and DST forward at study endpoint. CONCLUSION: A 12-week POWER rehabilitation for older patients with schizophrenia and frailty is safe and feasible, and may benefit physical and some domains of cognitive functioning.

Predictors of live-in migrant caregiver employment for people with dementia in Taiwan.

BACKGROUND: With the increasing number of individuals with dementia, families have hired an increasing number of live-in migrant caregivers (LIMCs). Currently, limited evidence is available regarding the influence of long-term care resource utilization on the hiring of LIMCs for caring for individuals with dementia in Taiwan. METHODS: We recruited individuals with dementia who did not hire LIMCs and their primary family caregivers from nine hospitals in Taiwan as baseline. Multivariable logistic regression was used to evaluate the utilization of long-term care resources for individuals with dementia and other factors that may affect the decision to hire LIMCs. RESULTS: The users of non-long-term care resources had the highest likelihood of hiring LIMCs (odds ratio [OR] = 4.24, 95% CI, 2.30-7.84). Compared with spouses, nonimmediate family caregivers (OR = 3.40, 95% CI, 1.16-9.90) were significantly more likely to hire LIMCs. A higher likelihood of hiring LIMCs was observed for those with Lewy body dementia compared with other individuals (OR = 2.31, 95% CI, 1.03-5.14). Compared with individuals who did not hire LIMCs, those who hired LIMCs exhibited higher scores on the Neuropsychiatric Inventory (NPI) and higher severity of individual NPI items. CONCLUSION: Hiring LIMCs is strongly correlated with the utilization of non-long-term care resources and is influenced by the dynamics between individuals with dementia and their primary family caregivers. A higher likelihood of hiring LIMCs was observed for individuals with Lewy body dementia and individuals with elevated NPI scores compared with their counterparts. Given these observations, various support strategies and interventions should be tailored to the specific requirements of individuals with dementia and their families.