Rationale:
Accumulating evidence demonstrated that long noncoding RNAs (lncRNAs) involved in the regulation of the immune system and displayed a cell-type-specific pattern in immune cell subsets. ...Given the vital role of tumor-infiltrating lymphocytes in effective immunotherapy, we explored the tumor-infiltrating immune cell-associated lncRNA (TIIClncRNA) in low-grade glioma (LGG), which has never been uncovered yet.
Methods:
This study utilized a novel computational framework and 10 machine learning algorithms (101 combinations) to screen out TIIClncRNAs by integratively analyzing the sequencing data of purified immune cells, LGG cell lines, and bulk LGG tissues.
Results:
The established TIIClnc signature based on the 16 most potent TIIClncRNAs could predict outcomes in public datasets and the Xiangya in-house dataset with decent efficiency and showed better performance when compared with 95 published signatures. The TIIClnc signature was strongly correlated to immune characteristics, including microsatellite instability, tumor mutation burden, and interferon γ, and exhibited a more active immunologic process. Furthermore, the TIIClnc signature predicted superior immunotherapy response in multiple datasets across cancer types. Notably, the positive correlation between the TIIClnc signature and CD8, PD-1, and PD-L1 was verified in the Xiangya in-house dataset.
Conclusions:
The TIIClnc signature enabled a more precise selection of the LGG population who were potential beneficiaries of immunotherapy.
IntroductionMany patients with frontal brain damage show serious cognitive function deficits, which hamper their quality of life and result in poor clinical outcomes. Preclinical research has shown ...that sulforaphane can significantly improve spatial localisation and working memory impairment after brain injury. The primary aim of this double-blind randomised controlled clinical trial is to assess the efficacy of sulforaphane for improving cognitive function in patients with frontal brain damage.Methods and analysisNinety eligible patients will be randomly allocated to an active treatment or a placebo group in a 2:1 ratio. Participants will undergo a series of cognitive and neuropsychiatric tests at baseline (week 0) and after 12 weeks to determine the effect of sulforaphane on cognition. Magnetic resonance spectrum of the brain will be studied using the 3T MRIs of the brain to detect brain metabolites markers, including N-acetyl aspartate, glutamate (Glu), glutathione (GSH) and γ-aminobutyric acid (GABA). Blood brain-derived neurotrophic factor, Glu, GSH and GABA levels and gut microbiota will also be assessed over this period. This study will also evaluate long-term outcomes of brain trauma, brain tumours and cerebrovascular disease via exploratory analyses. The primary outcome will be the difference in scores of a battery of cognitive tests after 12 weeks of sulforaphane treatment. The secondary outcomes will be changes in the Functional Activities Questionnaire (FAQ), the Patient Health Questionnaire (PHQ-9), the Self-Rating Anxiety Scale, the changes in T1-weighted MRI and resting-state functional MRI findings, and changes in brain and blood metabolic markers and gut microbiota at weeks 0 and 12. We expect that sulforaphane will yield favourable results in treating memory and learning deficits for patients with frontal brain damage. Cognitive functional treatment may also improve brain trauma, brain tumours and cerebrovascular outcomes.Ethics and disseminationThe study protocol has been approved by the Medical Ethics committee of the Xiangya Hospital of Central South University (No. 2017121019). The results will be disseminated in peer-reviewed journals and at international conferences.Trial registration numberThis trial was registered on Clinicaltrials.gov on 31 January 2020 (NCT04252261). The protocol version is V.1.0 (20 December 2019).
Regenerative medicine mainly relies on heterologous transplantation, often hindered by sample availability and ethical issues. Furthermore, patients are required to take immunosuppressive medications ...to prevent adverse side effects. Stem cell-derived 3D-organoid culture has provided new alternatives for transplantation and regenerative medicine. Scholars have combined organoids with tissue engineering technology to improve reproducibility, the accuracy of constitution and throughput, and genetic correction to achieve a more personalized therapy. Here, we review the available applications of organoids in regenerative medicine and the current challenges concerning this field.
The coronavirus disease 2019 (COVID-19) pandemic has presented numerous challenges to public health, including the emergence of subjective dry eye symptoms among individuals. However, there is ...currently a dearth of comprehensive knowledge regarding the associated factors with subjective dry eye symptoms in the general population.
A nationwide survey in China was carried out from 20 June to 31 August 2022, involving 21 916 participants. Subjective dry eye symptoms were assessed using the Ocular Surface Disease Index-6. We employed random forest classification to select potential associated factors based on the socioecological model. We also conducted univariate and multivariable logistic regression analyses to explore the factors associated with subjective dry eye symptoms. Network analyses were employed to explore the network structure of subjective dry eye symptoms and associated factors.
The item "watching TV (or similar task)" displayed the highest node strength and exhibited the highest predictability within the network. The results of the multivariate logistic regression analysis demonstrated significant associations between subjective dry eye symptoms and several factors, including loneliness (odds ratio (OR) = 1.29; 95% confidence interval (CI) = 1.26 to 1.32), problematic Internet use (OR = 1.08; 95% CI = 1.08 to 1.09), family communication (OR = 1.01; 95% CI = 1.00 to 1.01), the presence of depression (OR = 1.53; 95% CI = 1.39 to 1.68) and anxiety (OR = 1.31; 95% CI = 1.17 to 1.47) symptoms, older age (OR = 1.01; 95% CI = 1.01 to 1.01), self-rated health status (OR = 0.99; 95% CI = 0.98 to 0.99), family health (OR = 0.97; 95% CI = 0.96 to 0.97), health literacy (OR = 0.98; 95% CI = 0.97 to 0.99) and the agreeableness personality trait (OR = 0.97; 95% CI = 0.95 to 0.99).
These findings have important implications for public health interventions targeting the prevention and management of subjective dry eye symptoms in the general population. Strategies addressing individual risk factors and supporting psychological well-being may prove beneficial in mitigating the burden associated with subjective dry eye symptoms.
Cognitive impairment is a core feature of schizophrenia, which is aggravated by antipsychotics-induced metabolic disturbance and lacks effective pharmacologic treatments in clinical practice. Our ...previous study demonstrated the efficiency of metformin in alleviating metabolic disturbance following antipsychotic administration. Here we report that metformin could ameliorate cognitive impairment and improve functional connectivity (FC) in prefrontal regions. This is an open-labeled, evaluator-blinded study. Clinically stable patients with schizophrenia were randomly assigned to receive antipsychotics plus metformin (N = 48) or antipsychotics alone (N = 24) for 24 weeks. The improvement in cognition was assessed by the MATRICS Consensus Cognitive Battery (MCCB). Its association with metabolic measurements, and voxel-wise whole-brain FC with dorsolateral prefrontal cortex (DLPFC) subregions as seeds were evaluated. When compared to the antipsychotics alone group, the addition of metformin resulted in significantly greater improvements in the MCCB composite score, speed of processing, working memory, verbal learning, and visual learning. A significant time × group interaction effect of increased FC between DLPFC and the anterior cingulate cortex (ACC)/middle cingulate cortex (MCC), and between DLPFC subregions were observed after metformin treatment, which was positively correlated with MCCB cognitive performance. Furthermore, the FC between left DLPFC A9/46d to right ACC/MCC significantly mediated metformin-induced speed of processing improvement; the FC between left A46 to right ACC significantly mediated metformin-induced verbal learning improvement. Collectively, these findings demonstrate that metformin can improve cognitive impairments in schizophrenia patients and is partly related to the FC changes in the DLPFC. Trial Registration: The trial was registered with ClinicalTrials.gov (NCT03271866). The full trial protocol is provided in Supplementary Material.
Recent breakthroughs in human pluripotent stem cell-derived cerebral organoids provide a valuable platform for investigating the human brain after different drugs treatments and for understanding the ...complex genetic background to human pathology. Here, we identified tranylcypromine, which is used to treat refractory depression, caused human-induced pluripotent stem cell-derived brain organoids neurotoxicity, leading to decreased proliferation activity and apoptosis induction. Moreover, tranylcypromine treatment affects neurons and astrocytes, which impairs cell density and arrangement. Finally, staining of histone demethylation-related genes revealed that tranylcypromine suppresses the transcriptional activity of BHC110/LSD1-targeted genes and increases the expression of histone di-methylated K4. These results show that human brain organoids can be applied as an
model for CNS drug screening to evaluate structural, cellular, and molecular changes in the normal brains or brains of patients with neuropsychiatric disorders after drug treatments.
Abstract
Background and Hypothesis
Antipsychotic-induced weight gain is associated with alterations to the composition of the gut microbiota. The purpose of this study was to determine the effect of ...probiotics plus dietary fiber on antipsychotic-induced weight gain.
Study Design
Two sequential, randomized clinical trials were conducted. In Study 1, 90 drug-naïve, first-episode schizophrenia patients were randomized to receive either olanzapine plus probiotics or olanzapine monotherapy for 12 weeks. In Study 2, 60 drug-naïve, first-episode schizophrenia patients were randomly assigned to receive either olanzapine plus probiotics and dietary fiber or olanzapine monotherapy for 12 weeks.
Study Results
In Study 1, no significant differences in weight gain were observed between the two groups. The insulin resistance index (IRI) was lower in the olanzapine plus probiotics group compared with the olanzapine monotherapy group at week 12 (estimated mean difference, −0.65, 95% confidence interval (CI), −1.10 to −0.20; p = .005). In Study 2, weight gain was lower in the probiotics plus dietary fiber group than in the olanzapine monotherapy group at week 12 (estimated mean difference −3.45 kg, 95% CI, −5.91 to −1.00; p = .007). At week 12, IRI increased significantly in the olanzapine monotherapy group (mean, 1.74; standard deviation (SD) = 1.11, p < .001), but not in the olanzapine plus probiotics and dietary fiber group (mean 0.47, SD = 2.16, p = .35) with an estimated mean difference of −0.95 between the two groups 95% CI, −1.77 to −0.14; p = .022).
Conclusions
These results provide support for the efficacy and safety of probiotics plus dietary fiber in attenuating antipsychotic-induced weight gain in drug-naïve, first-episode schizophrenia patients.
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