Natural medicinal materials are a significant resource for the identification of compounds with specific biological properties. In this study, we employed multipotent C17.2 neural stem cells as a ...model for screening natural compounds that possess neural differentiation-inducing properties. We show here for the first time that, out of the 67 compounds tested, the flavonoid baicalin is a potent differentiation-inducing agent. Baicalin increased the number of cells bearing extended neurites and the expression levels of a number of neuronal markers. Importantly, baicalin promoted the expression of several key neurogenic transcriptional factors. Moreover, we demonstrated that baicalin enhanced the phosphorylation/activation of Erk1/2. Inhibition of Erk1/2 activation by the MEK inhibitor U0126 attenuated the neuronal differentiation-inducing effect of baicalin. Taken together, our findings suggest that baicalin induces neuronal differentiation of C17.2 neural stem cells and that this is mediated by activation of Erk1/2. Our work lays the foundation for exploring baicalin for the promotion of neural regeneration after injury or disease.
The ribonucleoprotein (RNP) complex is the essential transcription-replication machinery of the influenza virus. It is composed of the trimeric polymerase (PA, PB1 and PB2), nucleoprotein (NP) and ...RNA. Elucidating the molecular mechanisms of RNP assembly is central to our understanding of the control of viral transcription and replication and the dependence of these processes on the host cell. In this report, we show, by RNP reconstitution assays and co-immunoprecipitation, that the interaction between NP and polymerase is crucial for the function of the RNP. The functional association of NP and polymerase involves the C-terminal '627' domain of PB2 and it requires NP arginine-150 and either lysine-627 or arginine-630 of PB2. Using surface plasmon resonance, we demonstrate that the interaction between NP and PB2 takes place without the involvement of RNA. At 33, 37 and 41°C in mammalian cells, more positive charges at aa. 627 and 630 of PB2 lead to stronger NP-polymerase interaction, which directly correlates with the higher RNP activity. In conclusion, our study provides new information on the NP-PB2 interaction and shows that the strength of NP-polymerase interaction and the resulting RNP activity are promoted by the positive charges at aa. 627 and 630 of PB2.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Identifying baicalin‐regulated genes for neuronal differentiation: Baicalin is a potent neuronal‐differentiation‐inducing compound. This study explored the gene expression regulated through ...baicalin‐induced differentiation of C17.2 neural stem cells by using a DNA microarray followed by qPCR validation. The expression of 15 genes was significantly regulated among the 58 differentially expressed genes important for nervous system development and function.
•Verbal working memory deterioration was a novel early sign of psychotic relapse.•Digital monitoring of working memory was viable in managing relapse.•Relapse was also predicted by worse medication ...adherence and less resilience.
Relapse prevention is an important goal in the clinical management of psychosis. Cognitive deficits/deterioration can provide useful insights for monitoring relapse in psychosis patients.
This was a prospective, naturalistic 1-year follow-up study involving 110 psychosis patients with full clinical remission. Relapse, defined as the recurrence of psychotic symptoms, was monitored monthly along with digital tracking of verbal and visual working memory using a mobile app developed for this study. Cognitive deterioration was defined as worsening performance over 2 months prior to relapse or study termination, whichever was earlier. Other clinical, cognitive, functioning, and psychosocial variables were also collected.
At 1 year, 18 (16.36%) patients relapsed, of which 6 (33.33%) required hospitalization. Relapse was predicted by verbal working memory deterioration 2 months prior to relapse (p = 0.029), worse medication adherence (p = 0.018), and less resilience (p = 0.014).
Verbal working memory deterioration is a novel early sign of relapse. It is a clearly defined, objectively measurable, and reproducible marker that can help clinicians and healthcare workers identify patients at risk of relapse and make decisions about maintenance therapy. Moreover, digital monitoring is a viable tool in the management of relapse.
Cigarette smoking has been proposed as a major risk factor for aging-related pathological changes and Alzheimer's disease (AD). To date, little is known for how smoking can predispose our brains to ...dementia or cognitive impairment. This study aimed to investigate the cigarette smoke-induced pathological changes in brains. Male Sprague-Dawley (SD) rats were exposed to either sham air or 4% cigarette smoke 1 hour per day for 8 weeks in a ventilated smoking chamber to mimic the situation of chronic passive smoking. We found that the levels of oxidative stress were significantly increased in the hippocampus of the smoking group. Smoking also affected the synapse through reducing the expression of pre-synaptic proteins including synaptophysin and synapsin-1, while there were no changes in the expression of postsynaptic protein PSD95. Decreased levels of acetylated-tubulin and increased levels of phosphorylated-tau at 231, 205 and 404 epitopes were also observed in the hippocampus of the smoking rats. These results suggested that axonal transport machinery might be impaired, and the stability of cytoskeleton might be affected by smoking. Moreover, smoking affected amyloid precursor protein (APP) processing by increasing the production of sAPPβ and accumulation of β-amyloid peptide in the CA3 and dentate gyrus region. In summary, our data suggested that chronic cigarette smoking could induce synaptic changes and other neuropathological alterations. These changes might serve as evidence of early phases of neurodegeneration and may explain why smoking can predispose brains to AD and dementia.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Foodborne pathogens, particularly antimicrobial-resistant (AMR) bacteria, remain a significant threat to global health. Given the limitations of conventional culture-based approaches, which are ...limited in scope and time-consuming, metagenomic sequencing of food products emerges as a promising solution. This method provides a fast and comprehensive way to detect the presence of pathogenic microbes and antimicrobial resistance genes (ARGs). Notably, nanopore long-read sequencing provides more accurate bacterial taxonomic classification in comparison to short-read sequencing. Here, we revealed the impact of food types and attributes (origin, retail place, and food processing methods) on microbial communities and the AMR profile using nanopore metagenomic sequencing. We analyzed a total of 260 food products, including raw meat, sashimi, and ready-to-eat (RTE) vegetables. Clostridium botulinum, Acinetobacter baumannii, and Vibrio parahaemolyticus were identified as the top three foodborne pathogens in raw meat and sashimi. Importantly, even with low pathogen abundance, higher percentages of samples containing carbapenem and cephalosporin resistance genes were identified in chicken and RTE vegetables, respectively. In parallel, our results demonstrated that fresh, peeled, and minced foods exhibited higher levels of pathogenic bacteria. In conclusion, this comprehensive study offers invaluable data that can contribute to food safety assessments and serve as a basis for quality indicators.
•Clostridium botulinum, Acinetobacter baumannii, and Vibrio parahaemolyticus were the top three foodborne pathogens in raw meat and sashimi.•In ready-to-eat (RTE) vegetables, even with low pathogen abundance, higher percentages of samples containing cephalosporin resistance genes were identified.•Imported food samples from China showed a prevalence of Clostridium botulinum and Acinetobacter baumannii.•Fresh, peeled, and minced foods exhibited higher levels of pathogenic bacteria.•Chilled samples had a notable percentage of high-risk ARGs, despite having a low level of pathogenic bacteria.
Objective
As Hong Kong faced the 5th wave of the COVID‐19 pandemic, the facilitators and hurdles toward effective vaccination is important for healthcare professionals to understand the vaccination ...gap among patients with epilepsy.
Methods
A cross‐sectional, pragmatic study of COVID‐19 vaccination was performed at a tertiary epilepsy center with regards to patterns of vaccination and any unusually high rate of adverse events. Patients having recent visits at the epilepsy center (4 months) had their anonymized electronic linkage records examined 12 months after the inception of vaccination program for types of vaccines, seizure demographics, and adverse events following immunization (AEFI).
Results
A total of 200 patients with epilepsy and their anonymized data were analyzed. The vaccine uptake was approximately 60% of that of the general population. Twice as many patients with epilepsy chose to receive mRNA vaccine as compared with inactivated vaccine. The proportion of patients who kept up‐to‐date with all available dosing was 7%. Patients with epilepsy with genetic etiology were least likely to receive vaccination (13/38, 34%, P = .02). There was no unreasonably high rate of unacceptable side effects after vaccination among patients with epilepsy. Only 3 patients reported worsening of seizures without meeting the criteria for AEFI. Refractory epilepsy, allergy to antiseizure medications and elder age (≥65) did not confer any significant difference in vaccination patterns or adverse effects.
Significance
A vaccination gap exists among epilepsy patients which calls for actionable strategies for improving vaccine uptake, including education and outreach programs.
Parental self-efficacy has been found to be a critical determinant of the efficacy of interventions intended to enhance the parental management of childhood eczema.
The psychometric properties of a ...translated Chinese version of the Parental Self-Efficacy with Eczema Care Index (C-PASECI) were examined.
The PASECI was translated in a 2-stage process involving both forward and backward translation. Subsequently, the psychometric properties of the C-PASECI were examined in a cohort of 147 Chinese parents or caregivers of children with eczema. Specifically, the internal consistency, 2-day test-retest reliability and construct validity were assessed.
The C-PASECI received a Cronbach's αof 0.97, and the intraclass correlation coefficients of each item ranged from 0.93 to 0.99. Negative correlations were observed among the C-PASECI, Children's Dermatology Life Quality Index and Scoring Atopic Dermatitis Scale scores, indicating the acceptable convergent validity of the C-PASECI. The moderate correlation observed between the C-PASECI and General Self-Efficacy Scale (Pearson's r = 0.53, p < 0.001) reflected the acceptable concurrent validity of the C-PASECI. The results of confirmatory factor analysis supported the factorial validity of the C-PASECI.
The C-PASECI appears to be a reliable and valid measure of parental self-efficacy in Chinese parents or caregivers of children with eczema.
Introduction: It is now clear that circulating cell-free ribonucleic acids (ccfRNAs), including messenger RNA (mRNA) and miRNA, are potential cancer biomarkers. As ccfmiRNA is relatively more stable ...than ccfmRNA, research should concentrate on developing novel methods to preserve the stability of ccfmRNA and standardization of the protocol which includes extraction, detection, and multicenter validation.
Areas covered: This literature review concentrates on the potential of ccfRNA being used as a biomarker in cancer, with special focus on mRNAs and microRNAs (miRNAs).
Expert opinion: With the advancement of high-throughput technologies such as RNA sequencing, a panel of biomarkers will be used for the diagnosis, prognosis and therapeutic monitoring of cancer patients. In order to achieve this important target, bioinformatics education to pathologists, scientists, and technologists in molecular diagnostic laboratories is essential. Moreover, the panel of these new ccfRNAs biomarkers has to obtain approval or clearance from an authority such as the US Food and Drug Administration (FDA), and the standard of utilizing these new protocols has to be recognized via accreditation exercise. Therefore, there is still a long way to go before an extensively use of ccfRNA biomarkers in cancer patients can be realized.
PDF
