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A GGGGCC hexanucleotide repeat expansion in intron 1 of chromosome 9 open reading frame 72 ( C9ORF72 ) gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Repeat-associated non-ATG translation of dipeptide repeat proteins (DPRs) contributes to the neuropathological features of c9FTD/ALS. Among the five DPRs, arginine-rich poly-PR are reported to be the most toxic. Here, we generate a transgenic mouse line that expresses poly-PR (GFP-PR 28 ) specifically in neurons. GFP-PR 28 homozygous mice show decreased survival time, while the heterozygous mice show motor imbalance, decreased brain weight, loss of Purkinje cells and lower motor neurons, and inflammation in the cerebellum and spinal cord. Transcriptional analysis shows that in the cerebellum, GFP-PR 28 heterozygous mice show differential expression of genes related to synaptic transmission. Our findings show that GFP-PR 28 transgenic mice partly model neuropathological features of c9FTD/ALS, and show a role for poly-PR in neurodegeneration. Repeat-associated non-ATG translation of dipeptide repeat proteins (DPRs) contributes to disease manifestation in FTD/ALS associated with the hexanucleotide repeat expansion of the C9ORF72 gene. Here the authors show that a transgenic mouse line expressing poly-PR28 in neurons displays some signs of neuronal loss that mirrors that seen in the disease.

Parkinson's disease (PD) is the second most common neurodegenerative disorder. Although its pathogenesis remains unclear, growing evidencce suggests that microglia-mediated neuroinflammation contributes greatly to the progression of PD. P7C3, an aminopropyl carbazole, possesses significant neuroprotective effects in several neurodegenerative disease animal models, including PD. In this study, we designed to investigate the effects of P7C3 on neuroinflammation. We showed that P7C3 specially suppressed the expression of lipopolysaccharide (LPS)-induced pro-inflammatory factors but not influenced the anti-inflammatory factors in microglia. The inhibition of the nuclear factor κB (NF-κB) signaling pathway was involved in the mechanisms of the anti-inflammatory effects by P7C3. LPS-induced activation of IκB kinase (IKK), degradation of the inhibitory κB alpha (IκBα) and nuclear translocation of NF-κB can be attenuated by the pretreatment of P7C3 in microglia. Furthermore, in LPS-treated microglia, P7C3-pretreatment decreased the toxicity of conditioned media to MES23.5 cells (a dopaminergic (DA) cell line). Most importantly, the anti-inflammatory effects of P7C3 were observed in LPS-stimulated mouse model. In general, our study demonstrates that P7C3 inhibits LPS-induced microglial activation through repressing the NF-κB pathway both and , providing a theoretical basis for P7C3 in anti-inflammation.

Background Mutations or deletions in DJ-1/PARK7 gene are causative for recessive forms of early onset Parkinson’s disease (PD). Wild-type DJ-1 has cytoprotective roles against cell death through multiple pathways. The most commonly studied mutant DJ-1(L166P) shifts its subcellular distribution to mitochondria and renders cells more susceptible to cell death under stress stimuli. We previously reported that wild-type DJ-1 binds to Bcl-X L and stabilizes it against ultraviolet B (UVB) irradiation-induced rapid degradation. However, the mechanisms by which mitochondrial DJ-1(L166P) promotes cell death under death stimuli are largely unknown. Results We show that DJ-1(L166P) is more prone to localize in mitochondria and it binds to Bcl-X L more strongly than wild-type DJ-1. In addition, UVB irradiation significantly promotes DJ-1(L166P) translocation to mitochondria and binding to Bcl-X L . DJ-1(L166P) but not wild-type DJ-1 dissociates Bax from Bcl-X L , thereby leading to Bax enrichment at outer mitochondrial membrane and promoting mitochondrial apoptosis pathway in response to UVB irradiation. Conclusion Our findings suggest that wild-type DJ-1 protects cells and DJ-1(L166P) impairs cells by differentially regulating mitochondrial Bax/Bcl-X L functions.

Kindergarten teachers’ emotions are an essential factor in their physical and psychological wellbeing. Previous studies mainly focused on the relationship between kindergarten teachers’ emotions and their students’ emotions while ignoring the important relationships between kindergarten teachers’ emotions and their own wellbeing (e.g., teachers’ health, job satisfaction, burnout). Therefore, this study explores teacher emotions as predictor variables, illness symptoms, and job satisfaction as criterion variables, and emotional exhaustion as a mediator. In total, 1997 kindergarten teachers completed the Teacher’s Emotion Scale, the Occupational Emotional Exhaustion Scale, the Illness Symptoms Scale, and the Job Satisfaction Scale. Results revealed that enjoyment negatively predicted illness symptoms and positively predicted job satisfaction via the mediating role of emotional exhaustion. The opposite relationships were found with anger, also confirming the mediating role of emotional exhaustion. Anxiety positively predicted illness symptoms, completely mediated by emotional exhaustion, but no relationship was found with job satisfaction. The function of emotions in teachers’ physical and mental health, implications for kindergartens’ research and practice, and suggestions for future research are discussed.

Epigenetic dysregulation that leads to alterations in gene expression and is suggested to be one of the key pathophysiological factors of Parkinson’s disease (PD). Here, we found that α-synuclein preformed fibrils (PFFs) induced histone H3 dimethylation at lysine 9 (H3K9me2) and increased the euchromatic histone methyltransferases EHMT1 and EHMT2, which were accompanied by neuronal synaptic damage, including loss of synapses and diminished expression levels of synaptic-related proteins. Furthermore, the levels of H3K9me2 at promoters in genes that encode the synaptic-related proteins SNAP25, PSD95, Synapsin 1 and vGLUT1 were increased in primary neurons after PFF treatment, which suggests a linkage between H3K9 dimethylation and synaptic dysfunction. Inhibition of EHMT1/2 with the specific inhibitor A-366 or shRNA suppressed histone methylation and alleviated synaptic damage in primary neurons that were treated with PFFs. In addition, the synaptic damage and motor impairment in mice that were injected with PFFs were repressed by treatment with the EHMT1/2 inhibitor A-366. Thus, our findings reveal the role of histone H3 modification by EHMT1/2 in synaptic damage and motor impairment in a PFF animal model, suggesting the involvement of epigenetic dysregulation in PD pathogenesis.

ObjectiveWe focus on providing the first comprehensive national dataset on the incidence, injury aetiology and mortality of TSCI in China.MethodsA multi-stage stratified cluster sampling method was used. We included TSCI cases from all hospitals in three regions, nine provinces and 27 cities in China via search of electronic medical records and retrospectively analysed the characteristics of TSCI in China from 2009 to 2018. We estimated the incidence of TSCI in the total population and subgroups.ResultsThere were 5954 actual cases in 2009, corresponding to a total estimated TSCI incidence of 45.1 cases per million population (95% CI, 44.0–46.3). There were 10,074 actual cases in 2018, corresponding to a total estimated TSCI incidence of 66.5 cases per million population (95% CI, 65.2–67.8) (P < 0.001; annual average percentage change (AAPC), 4.4%). From 2009 to 2018, the incidence of almost all sex/age groups showed an increasing trend over time (P < 0.001; AAPC, 0.7–8.8%). The elderly population (aged 65–74) displayed the highest incidence of TSCI (with an average annual incidence of 127.1 cases per million [95% CI, 119.8–134.3]).ConclusionsThe TSCI incidence increased significantly from 2009 to 2018. The incidence in the elderly populations was consistently high and continues to increase over time. The mortality of TSCI patients in hospitals is relatively low and continues to decrease each year, but elderly individuals remain at a high risk of hospital death.

Background: Mutations or deletions in DJ-1/PARK7 gene are causative for recessive forms of early onset Parkinson's disease (PD). Wild-type DJ-1 has cytoprotective roles against cell death through multiple pathways. The most commonly studied mutant DJ-1(L166P) shifts its subcellular distribution to mitochondria and renders cells more susceptible to cell death under stress stimuli. We previously reported that wild-type DJ-1 binds to Bcl-X sub(L) and stabilizes it against ultraviolet B (UVB) irradiation-induced rapid degradation. However, the mechanisms by which mitochondrial DJ-1(L166P) promotes cell death under death stimuli are largely unknown. Results: We show that DJ-1(L166P) is more prone to localize in mitochondria and it binds to Bcl-X sub(L) more strongly than wild-type DJ-1. In addition, UVB irradiation significantly promotes DJ-1(L166P) translocation to mitochondria and binding to Bcl-X sub(L). DJ-1(L166P) but not wild-type DJ-1 dissociates Bax from Bcl-X sub(L), thereby leading to Bax enrichment at outer mitochondrial membrane and promoting mitochondrial apoptosis pathway in response to UVB irradiation. Conclusion: Our findings suggest that wild-type DJ-1 protects cells and DJ-1(L166P) impairs cells by differentially regulating mitochondrial Bax/Bcl-X sub(L) functions.

Purpose of ReviewSystemic lupus erythematosus (SLE) is a complex, potentially fatal autoimmune disease with no complete cure. Current treatments for SLE are limited by suboptimal efficacy and increased risk of infections and malignancies, and cannot meet the clinical demands of patients with SLE. Artemisinin and its derivatives (artemisinins), a new class of anti-malarial drugs, have recently been reported to have an immunosuppressive effect on lupus patients. In this review, we evaluate the therapeutic properties and potential mechanisms of artemisinins for the treatment of SLE.Recent FindingsBoth clinical and animal studies suggest that artemisinins have potential beneficial effects for SLE. The beneficial effects associated with artemisinin treatment include improving symptoms, reducing level of antibodies and proteinuria, ameliorating renal damage, and diminishing the dosage of prednisone use. Animal studies suggest that mechanisms of action of artemisinins may include regulating T cell subsets, inhibiting activation of B cells and production of inflammatory cytokines, as well as blocking the NF-κB signal transduction pathway, thus playing a role in anti-inflammation and immunomodulation.SummaryArtemisinin family drugs are a promising potential new medication that may challenge the current treatment paradigms available for SLE.

Dilated cardiomyopathy (DCM), characterized by ventricular dilation and systolic dysfunction, has a 10-year survival rate of 25%. The number of young and middle-aged patients with DCM is increasing, with progressive physical limitations and psychosocial distress substantially impairing quality of life. However, illness experiences in this population remain underexplored, particularly in non-Western contexts. Social media platforms such as Zhihu and Weibo offer a novel avenue for exploring patient narratives and peer support. A qualitative descriptive study was conducted to explore the multidimensional experiences of young and middle-aged Chinese patients with DCM through the social narratives shared on social media. A qualitative reflexive thematic analysis was conducted on 872 questions and responses from Zhihu, a Chinese Q&A platform. Data were extracted using a Python (Python Software Foundation) application programming interface, manually filtered, and analyzed with NVivo 14.0 (Lumivero). Thematic codes were developed iteratively, with researcher reflexivity and team discussions ensuring analytical rigor. Five themes emerged: (1) bodily control loss (persistent sleep disturbances, severe respiratory compromise, and physical activity limitations), (2) enmeshed in emotional turmoil (anxiety over survival challenges, guilt over burdening family, and heterogeneous responses to death), (3) social and family role disruption (impacts on academic and career paths and family responsibility interruptions), (4) support needs in health care (urgent demand for information on diseases and treatments and desire for continuous care and guidance), and (5) life reconstruction-between disease and life (lifestyle modifications, exploring diversified treatment paths, peer support and experience sharing, and reconstructing the meaning of life). This study provides an interpretive account of the intertwined physical, psychological, and social experiences of young and middle-aged patients with DCM in China, emphasizing the influence of life-course stage and sociocultural context. Patients' perceptions of family responsibilities, societal role expectations, and death shape their understanding of illness and their processes of meaning reconstruction. These findings underscore the importance of incorporating life-stage and culturally sensitive perspectives in future research and highlight the potential value of tailored psychological support and digital health platforms in improving access to illness-related information and ensuring continuity of care.

Sustainable and safe delivery of brain-targeted drugs is highly important for successful therapy in Parkinson's disease (PD). This study was designed to formulate biodegradable poly(ethylene glycol)-poly(lactic-co-glycolic acid) (PEG-PLGA) nanoparticles (NPs), which were surface-modified with lactoferrin (Lf), for efficient intranasal delivery of rotigotine to the brain for the treatment of PD. Rotigotine NPs were prepared by nanoprecipitation, and the effect of various independent process variables on the resulting properties of NPs was investigated by a Box-Behnken experimental design. The physicochemical and pharmaceutical properties of the NPs and Lf-NPs were characterized, and the release kinetics suggested that both NPs and Lf-NPs provided continuous, slow release of rotigotine for 48 h. Neither rotigotine NPs nor Lf-NPs reduced the viability of 16HBE and SH-SY5Y cells; in contrast, free rotigotine was cytotoxic. Qualitative and quantitative cellular uptake studies demonstrated that accumulation of Lf-NPs was greater than that of NPs in 16HBE and SH-SY5Y cells. Following intranasal administration, brain delivery of rotigotine was much more effective with Lf-NPs than with NPs. The brain distribution of rotigotine was heterogeneous, with a higher concentration in the striatum, the primary region affected in PD. This strongly suggested that Lf-NPs enable the targeted delivery of rotigotine for the treatment of PD. Taken together, these results demonstrated that Lf-NPs have potential as a carrier for nose-to-brain delivery of rotigotine for the treatment of PD.