RESUMEN
Pulmonary hypertension (PH) is a serious pulmonary vascular disease characterized by vascular remodeling. Circular RNAs (CircRNAs) play important roles in pulmonary hypertension, but the mechanism of PH is not fully understood, particularly the roles of circRNAs located in the nucleus. Circ-calmodulin 4 (circ-calm4) is expressed in both the cytoplasm and the nucleus of pulmonary arterial smooth muscle cells (PASMCs). This study aimed to investigate the role of endonuclear circ-calm4 in PH and elucidate its underlying signaling pathway in ferroptosis. Immunoblotting, quantitative real-time polymerase chain reaction (PCR), malondialdehyde (MDA) assay, immunofluorescence, iron assay, dot blot, and chromatin immunoprecipitation (ChIP) were performed to investigate the role of endonuclear circ-calm4 in PASMC ferroptosis. Increased endonuclear circ-calm4 facilitated ferroptosis in PASMCs under hypoxic conditions. We further identified the cartilage oligomeric matrix protein (COMP) as a downstream effector of circ-calm4 that contributed to the occurrence of hypoxia-induced ferroptosis in PASMCs. Importantly, we confirmed that endonuclear circ-calm4 formed circR-loops with the promoter region of the COMP gene and negatively regulated its expression. Inhibition of COMP restored the phenotypes related to ferroptosis under hypoxia stimulation combined with antisense oligonucleotide (ASO)-circ-calm4 treatment. We conclude that the circ-calm4/COMP axis contributed to hypoxia-induced ferroptosis in PASMCs and that circ-calm4 formed circR-loops with the COMP promoter in the nucleus and negatively regulated its expression. The circ-calm4/COMP axis may be useful for the design of therapeutic strategies for protecting cellular functionality against ferroptosis and pulmonary hypertension.
RESUMEN
Behavioral addiction (BA) is a conceptually new addictive phenotype characterized by compulsive reward-seeking behaviors despite adverse consequences. Currently, its underlying neurogenetic mechanism remains unclear. Here, this study aimed to investigate the association between cortical thickness (CTh) and genetic phenotypes in BA. We conducted a systematic search in five databases and extracted gene expression data from the Allen Human Brain Atlas. Meta-analysis of 10 studies (343 addicted individuals and 355 controls) revealed that the BA group showed thinner CTh in the precuneus, postcentral gyrus, orbital-frontal cortex, and dorsolateral prefrontal cortex (P < 0.005). Meta-regression showed that the CTh in the precuneus and postcentral gyrus were negatively associated with the addiction severity (P < 0.0005). More importantly, the CTh phenotype of BA was spatially correlated with the expression of 12 genes (false discovery rate [FDR] < 0.05), and the dopamine D2 receptor had the highest correlation (rho = 0.55). Gene enrichment analysis further revealed that the 12 genes were involved in the biological processes of behavior regulation and response to stimulus (FDR < 0.05). In conclusion, our findings demonstrated the thinner CTh in cognitive control-related brain areas in BA, which could be associated with the expression of genes involving dopamine metabolism and behavior regulation.
Asunto(s)
Conducta Adictiva , Corteza Cerebral , Humanos , Conducta Adictiva/genética , Conducta Adictiva/diagnóstico por imagen , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/patología , Masculino , Adulto , Femenino , Grosor de la Corteza Cerebral , Receptores de Dopamina D2/genética , Imagen por Resonancia MagnéticaRESUMEN
Objective: The study aims to evaluate and compare the efficacy and safety between ticagrelor and clopidogrel in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). Methods: We searched MEDLINE (via PubMed), Cochrane, Embase, and the Cochrane library databases for eligible citations (the last search was up to December 2021). Subgroup analyses were performed based on region, study design, dose, and single-center/multicenter. Meta regressions were conducted to explore the source of heterogeneity. A sensitivity analysis was conducted to assess the robustness of the results. Funnel plots and Egger's test were preformed to test publication bias of the meta-analysis. Results: A total of 29 studies were included, totaling 165,981 patients. Ticagrelor reduced the overall incidence rate of major adverse cardiovascular events (MACEs) (HR 0.74; 95% CI, 0.62, 0.89; P = 0.001; I2 = 88.3%, P < 0.001) and all-cause mortality (HR 0.85; 95% CI, 0.75, 0.97; P = 0.019; I2 = 39.7%, P = 0.052) compared with clopidogrel. However, there was a higher risk of major bleeding (HR 1.21; 95% CI, 1.02,1.44; P = 0.026, I2 = 59.3%, P = 0.012) and all bleeding (HR 1.42; 95% CI, 1.24, 1.62; P < 0.001, I2 = 76.4%, P < 0.001) with ticagrelor compared to clopidogrel. The stability of the results was demonstrated by sensitivity analysis. Furthermore, subgroup analyses and meta-regression revealed that the heterogeneity in the study may stem from factors such as whether it was conducted in a single-center or multicenter setting, as well as the geographical region. Conclusion: Ticagrelor has demonstrated superior efficacy compared to clopidogrel in ACS patients undergoing PCI, particularly in Asia and Europe. Nevertheless, it is crucial to acknowledge that the utilization of ticagrelor is linked to a heightened risk of bleeding. To provide guidance for clinical decision-making regarding the use of ticagrelor, future multicenter randomized trials that are relevant and encompass longer follow-up periods are necessary. The category of the manuscript a meta-analysis: PROSPERO registration number CRD42021274198.
RESUMEN
OBJECTIVE: Clinical practice guidelines recommend retrieving at least 12 lymph nodes for correct staging in colorectal cancer. However, it is difficult to retrieve adequate lymph nodes because of various factors. We aimed to evaluate the association between the number of retrieved lymph nodes and demographic/tumour-related characteristics in colorectal cancer. DESIGN: Systematic review and meta-analysis of primary studies. DATA SOURCES: PubMed, Embase, Cochrane and Web of Science were searched from January 2016 to June 2023. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies that evaluated the association between retrieved lymph nodes and demographic/tumour-related characteristics in colorectal cancer were included. DATA EXTRACTION AND SYNTHESIS: OR with 95% conference intervals was extracted and pooled. RESULTS: A total of 54 studies containing 2 05 821 patients were included in this meta-analysis. The results showed that fewer nodes were retrieved from elderly patients (OR=0.70, 95% CI (0.54 to 0.90), p=0.005), and from tumours located in the left colon than in the right colon (OR=0.43, 95% CI (0.33 to 0.56), p<0.001). More lymph nodes were obtained from females than males (OR=1.15, 95% CI (1.04 to 1.28), p=0.006), from the advanced T stage (T3+T4) than T1+T2 stage (OR=1.57, 95% CI (1.25 to 1.97), p<0.001) and from the N2 stage than N0 stage (OR=1.32, 95% CI (1.15 to 1.51), p<0.001). Body mass index, ethnicity, N1 stage, M stage, tumour differentiation and lymph-vascular invasion were not significantly associated with the lymph node yield. CONCLUSIONS: The study results suggest that clinicians have an increased opportunity to retrieve sufficient lymph nodes for accurate pathological staging to guide treatment decisions in patients with colorectal cancer who are young, female, with tumours located in the right colon, advanced T stage and N2 stage.
Asunto(s)
Neoplasias Colorrectales , Ganglios Linfáticos , Masculino , Humanos , Femenino , Anciano , Estadificación de Neoplasias , Ganglios Linfáticos/patología , Neoplasias Colorrectales/cirugía , Metástasis Linfática/patología , Demografía , Escisión del Ganglio Linfático , PronósticoRESUMEN
BACKGROUND: Interleukin-36s (IL-36s) are a category of inflammatory cytokines and an increasing number of studies over the past decade have found that different kinds of IL-36s play different roles in cancers. This systematic review and meta-analysis aimed to evaluate the prognostic value of IL-36s in different cancer types. METHOD: Two reviewers independently searched in PubMed, Cochrane Library and EMBASE up to December 13, 2022. We extracted the hazard ratio (HR) and the confidence intervals (CIs) of the related prognostic outcomes and analyzed the pooled HR. RESULTS: We included 12 studies including 1925 patients. In all, six studies including IL-36α, five including IL-36γ and one including IL-36ß. A high expression of IL-36α was associated with better overall survival (OS) (HR = 0.48, 95 %CI: 0.37-0.62, P < 0.001) of cancer patients. The expression of IL-36γ was not related with cancers. Further, subgroup analysis showed that the expression of IL-36γ had no correlation with the OS of colorectal cancer (CRC) and nonsmall cell lung cancer (NSCLC) patients. Interestingly, a high expression of IL-36γ played contrasting prognostic roles in hepatocellular carcinoma (HCC) (HR = 0.43, 95 %CI: 0.27-0.69, P < 0.001) patients and gastric cancer (GC) (HR = 1.58, 95 %CI: 1.33-1.87, P < 0.001) patients. The only IL-36ß related study showed the expression of IL-36ß was not correlated with the prognosis of CRC patients (P > 0.05). CONCLUSION: IL-36α, IL-36ß and IL-36γ possibly play different roles in different cancers. High expression of IL-36α may be associated with good prognostic value in cancer patients, especially in CRC patients. The association between cancers prognosis and expression of IL-36ß or IL-36γ needs further evaluation. These conclusions need more clinical prognostic data for confirmation.
Asunto(s)
Carcinoma Hepatocelular , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Hepáticas , Neoplasias Pulmonares , Humanos , Interleucina-1/metabolismo , Pronóstico , Interleucinas/metabolismoRESUMEN
BACKGROUND: Cognitive impairment is one of the major symptoms of individuals with bipolar disorder (BD). Purine system disorders may play an important role in cognitive dysfunction. So far, the relationship between cognitive deficits and purinergic metabolism in BD has been seldom discussed in previous studies. This study aims to explore its relevance and potential biological mechanisms. METHODS: In this cross-sectional study, 205 first time diagnosed drug-naive individuals with BD and 97 healthy volunteers were recruited. The uric acid(UA) level was measured using automatic biochemical analyzer, and cognitive function was assessed by Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Stroop color-word test. In addition, general information and clinical symptoms were collected and evaluated. RESULTS: In this study, the UA level of BD group (U = 8475.000, p = 0.038) was found to be significantly higher than that of the healthy controls, but the scores of RBANS (t = -11.302, p < 0.001) and Stroop color-word test (t = -6.962, p < 0.001) were significantly lower than that of the healthy controls. In gender subgroup analysis, females had lower UA level and higher RBANS scores. In correlation analysis, the cognitive function of individuals with BD was found to present a significant negative correlation with UA level in attention (r = -0.23, p = 0.001) and delayed memory(r = -0.16, p = 0.022). LIMITATIONS: This is a cross-sectional design. CONCLUSION: Elevated UA levels may be a potential mechanism of cognitive impairment in BD. This provides a new possible strategy for the prevention and treatment of cognitive impairment in BD.
Asunto(s)
Trastorno Bipolar , Trastornos del Conocimiento , Disfunción Cognitiva , Femenino , Humanos , Trastorno Bipolar/psicología , Estudios Transversales , Ácido Úrico , Disfunción Cognitiva/psicología , Trastornos del Conocimiento/psicología , Pruebas NeuropsicológicasRESUMEN
BACKGROUND: The pathophysiological mechanism of cognitive impairments of bipolar disorder (BD) has not yet been completely revealed. It is well known that Vitamin D and physical activity (PA) are associated with BD. However, specific links between Vitamin D and cognitive deficits in BD are still unclear. METHOD: The serum levels of vitamin D were measured. The cognitive performances of 102 first-diagnosed and drug-naïve BD patients were evaluated for analysis. The repeatable battery for the assessment of neuropsychological status (RBANS) and the Stroop Color-Word test was used in this study. PA was collected by international physical activity questionnaire. RESULT: Patients with BD had high levels of serum vitamin D. Furthermore, immediate and delayed memory was negatively associated with vitamin D levels in patients' group. The serum levels of vitamin D in patients with low PA were positively associated with memory. However, increased PA attenuated the protective effect of vitamin D on executive cognition. CONCLUSION: It is concluded that the increased levels of vitamin D were observed in the serum of patients with BD. Thus, it is found that more PA is less beneficial to cognition of patients with BD than longer resting.
Asunto(s)
Trastorno Bipolar , Humanos , Trastorno Bipolar/psicología , Vitamina D , Pruebas Neuropsicológicas , Cognición , Vitaminas , Ejercicio FísicoRESUMEN
BACKGROUND: To investigate the Coronavirus Disease 2019 (COVID-19) vaccination coverage and the influential factors of vaccination among patients with mental disorders, we conducted a cross-sectional study in China. METHOD: The anonymous questionnaires including demographic data, vaccination status, intention to be vaccinated and its reasons were collected in the Second Xiangya Hospital, one of the biggest four psychiatric centers in China. Mental health of these participants were measured by the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder-7 items (GAD-7). The influential factors associated with vaccination status were analyzed by Fisher exact tests and binary logistical analysis. RESULT: 1328 patients and 922 family members completed the survey. The vaccination rate of patients included was 69.4%, whereas 85.5% patients were willing to be vaccinated. Being hospitalized (aOR 0.41, 95% CI:0.27-0.60), suffering from schizophrenia (aOR 0.38, 95% CI: 0.19-0.75) and secondary school educational background (aOR 0.58, 95% CI: 0.37-0.93) were significantly associated with less likelihood to get vaccinated. Uptaking vaccines could reduce depressive (aOR 0.63, 95% CI: 0.41-0.98) or anxious symptoms (aOR 0.40, 95% CI: 0.25-0.63) in these patients for a short period. CONCLUSION: Further COVID-19 immunization programme should prioritize hospitalized psychiatric patients and schizophrenic patients since their demands for vaccination had been partly ignored during the current inoculation.
Asunto(s)
COVID-19 , Trastornos Mentales , Vacunas , Humanos , Pandemias , Cobertura de Vacunación , COVID-19/prevención & control , Estudios Transversales , Vacunas contra la COVID-19/uso terapéutico , China/epidemiología , Trastornos Mentales/epidemiologíaRESUMEN
Objective: Whether lymph node micrometastasis (LNM) increases the risk in esophageal cancer patients remains controversial. We conducted a systematic review and meta-analysis to explore the prognosis value of LNM in esophageal cancer patients. Methods: Two reviewers independently searched electronic databases, including PubMed, Embase, and the Cochrane Library, for eligible citations until February 2022. We calculated pooled estimates of the hazards ratio with a random-effects model. The certainty of evidence was determined by the Grade of Recommendations Assessment, Development, and Evaluation (GRADE) method. A sensitivity analysis was performed to assess the stability. Publication bias was assessed using funnel plots and Egger's test. We also performed subgroup analysis to explore the source of heterogeneity. Results: A total of 16 studies, with 1,652 patients, were included. The overall survival (OS) was significantly increased with LNM negativity compared with LNM positivity (HR 1.95; 95% CI, 1.53-2.49; P < 0.001; I2 = 0.0%, P = 0.930; certainty of evidence: low). Relapse-free survival (RFS) was significantly increased with LNM negativity compared with LNM positivity (HR 3.39; 95% CI, 1.87-6.16; P < 0.001; I2 = 50.18%, P = 0.060; certainty of evidence: moderate). No significant difference was observed in recurrence between the two groups (certainty of evidence: low). Sensitivity analysis revealed a stable trend. In addition, the funnel plot and Egger's test did not show significant publication bias. Conclusion: LNM positivity worsens the prognosis in esophageal cancer, and the evidence for RFS is moderate. Future relevant high-quality studies are warranted to validate our results further and provide a reference for guidelines. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier (CRD42022321768).
RESUMEN
OBJECTIVES: We aimed to comprehensively evaluate the relationship between forkhead box P3 (FOXP3+) regulatory T cell (Treg) expression and diffuse large B-cell lymphoma (DLBCL) prognosis and to explore the sources of heterogeneity of the results. DESIGN: Systematic review and meta-analysis. DATA SOURCES: We searched the Cochrane Library, PubMed, Embase and Web of Science databases up to 5 December 2021. ELIGIBILITY CRITERIA: We included studies that analysed the prognostic significance of FOXP3+ Tregs in DLBCL. We included studies reported in Chinese or English that reported HRs and related 95% CIs for prognosis. DATA EXTRACTION AND SYNTHESIS: We extracted data from eligible studies. HRs and 95% CIs were used to assess the prognostic value. RESULTS: Fourteen eligible studies were identified. FOXP3+ Treg expression was not associated with overall survival (OS) (HR=0.72, 95% CI 0.45 to 1.16) or progression-free survival (HR=0.86, 95% CI 0.54 to 1.38). The three approaches used to measure FOXP3+ Treg expression (pinteraction<0.001) may be the source of the heterogeneity of the results. Subgroup analysis found that a higher expression of FOXP3+ Tregs was associated with better OS in all populations and in Asians when FOXP3+ Treg expression was measured by the number of positive cells (HR=0.36 (95% CI 0.22 to 0.58) in the former, HR=0.33 (95% CI 0.20 to 0.55) in the latter) or the percentage of positive cells (HR=0.49 (95% CI 0.27 to 0.89) in the former, HR=0.38 (95% CI 0.21 to 0.70) in the latter). However, when measured by the score, inverse results were found (HR=1.56, 95% CI 1.01 to 2.42). CONCLUSIONS: Approaches to measuring FOXP3+ Treg expression might be the major source of heterogeneity in studies of the prognostic significance of FOXP3+ Tregs in DLBCL. FOXP3+ Treg expression might be used to predict the prognosis of patients with DLBCL when FOXP3+ Treg expression is calculated by the number or the percentage of positive cells, especially in Asian populations.
Asunto(s)
Linfoma de Células B Grandes Difuso , Linfocitos T Reguladores , Humanos , Pronóstico , Supervivencia sin Progresión , Factores de Transcripción Forkhead/metabolismoRESUMEN
OBJECTIVES: Cognitive impairment and abnormal glycolipid metabolism are common clinical features of bipolar disorder (BD). The purpose of this study was to investigate the relationship between conventional glycolipid metabolism indicators and cognitive impairment in patients with BD. METHODS: A total of 132 drug-naïve patients with BD and 129 healthy controls (HC) were recruited in the study. Five serum glycolipid metabolism indicators were measured and cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Stroop Color-Word Test (Stroop test) for each participant. RESULTS: The scores of immediate memory, attention, language and delayed memory in BD group were significantly lower than those in HC group (P < 0.05). The triglyceride (TG) level in BD group was higher than that in HC group (P = 0.011), and the total cholesterol and high-density lipoprotein cholesterol (HDL) levels were lower than those in HC group (P = 0.026; P = 0.001). Regression analysis showed that TG level was significantly correlated with RBANS total score (ß = 0.245, P = 0.008), attention (ß = 0.289, P = 0.03) and delayed memory (ß = 0.221, P = 0.023). Fasting blood glucose (FBG) level was significantly correlated with language subscale score (ß = -0.187, P = 0.046) in BD. LIMITATIONS: Cross-sectional design and limited control variables. CONCLUSIONS: Elevated FBG and TG levels may be associated with cognitive dysfunction in BD patients. Improving glycolipid metabolism in patients with BD may help to improve certain domain-specific cognitive functions.
Asunto(s)
Trastorno Bipolar , Disfunción Cognitiva , Preparaciones Farmacéuticas , Trastorno Bipolar/complicaciones , Disfunción Cognitiva/etiología , Estudios Transversales , Glucolípidos , Humanos , Pruebas NeuropsicológicasRESUMEN
Pulmonary endarterectomy (PEA) is used to treat chronic thromboembolic pulmonary hypertension (CTEPH) patients, and it can effectively remove organized thrombotic materials and proliferative intima as well as improve hemodynamics. It has been reported that the levels of several inflammatory factors were altered in the peri-operative period of PEA. Even though their specific role remains unknown, this could have some relevance. In this study, we reviewed the recently published data addressing these factors in PEA, attempting to understand their potential implications.
RESUMEN
BACKGROUND: Bipolar disorder (BD) is a severe mental illness that affects more than 1% the world's population with high recurrence rates and a series of comorbidities. Cognitive dysfunction is an endophenotype of BD, but sex influences in cognitive impairment remains unclear. METHOD: We evaluated the performance of 139 patients with first-diagnosed, drug-naïve BD (44 males and 95 females) and 92 healthy controls (24 males and 68 females) using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) scale and the Stroop color-word test. RESULT: Immediate memory, visuospatial/constructional ability, language, attention, delayed memory, total RBANS score, and Stroop color-word scores were significantly lower in patients with first-diagnosed, drug-naïve BD than healthy participants. Thus, male patients had worse attention and delayed memory scores compared with female patients with BD. Importantly, a worse performance in visuospatial/constructional ability was negatively associated with the Young Mania Rating Scale score in male patients only. CONCLUSION: Male patients with first-diagnosed, drug-naïve bipolar disorder had worse cognitive dysfunction than female patients in attention and delayed memory. Cognitive deficits were correlated with mania severity only in male patients. These findings reveal the sexual dimorphism in the cognitive deficits of early BD patients with mild and moderated symptoms for further pathophysiological exploration.
Asunto(s)
Trastorno Bipolar , Preparaciones Farmacéuticas , Trastorno Bipolar/diagnóstico , Trastorno Bipolar/epidemiología , Cognición , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas , Caracteres SexualesRESUMEN
BACKGROUND: MicroRNA-495 (miR-495) is a post-translational modulator that performs several functions, and it is involved in several disease states. On the other hand, the physiological functions of miR-495 in H2O2 stimulated mouse spinal cord neuronal dysfunction have not yet been fully understood. METHODS: In this study, we speculated that miR-495 may regulate the expression of STAT3 in the processes of neuronal proliferation and apoptosis following spinal cord injury (SCI). Cell viability was assessed with methyl thiazolyl tetrazolium (MTT) assay. Caspase-3 activity was assayed with ELISA. Cellular apoptotic changes were measured with TUNEL assay. Intracellular ROS production was determined by measuring uptake of dichlorodihydrofluorescein diacetate (DCFH-DA; PCR was used to assay the mRNA expression of STAT3 gene bearing predicted targeting positions for miR-495, while qRT-PCR was used to measure miR-495 mRNA. RESULTS: The results demonstrated that treatment of SCNs with H2O2 led to a significant decrease in cell survival, while it enhanced apoptosis. The H2O2 treatment induced cell membrane dysfunction, and increased ROS levels and DNA damage. Interestingly, the expression of miR-495 was markedly suppressed when SCNs were exposed to H2O2. However, miR-495 overexpression reversed H2O2-induced cytotoxicity and apoptosis in SCNs. Moreover, H2O2 exposure elevated protein and mRNA concentrations of STAT3 in SCNs. Bioinformatics analysis showed likely binding domains of miR-495 in the 3'-untranslated regions of STAT3 in SCNs. MiR-495 loss-of-function and gain-of-function significantly up-regulated and down-regulated both STAT3 mRNA and protein expressions, respectively, in SCNs. CONCLUSIONS: miR-495 overexpression inhibited H2O2-induced SCN dysfunction. This mechanism was mediated through the down-regulation of STAT3 expression.
RESUMEN
BACKGROUND: Spinal cord injury (SCI) has an immediate and devastating impact on the control over various movements and sensations. However, no effective therapies for SCI currently exist. METHODS: To identify and analyze SCI subtypes, we obtained the expression profile data of the 1,057 genes (889 intersection genes) in GSE45550 using weighted gene co-expression network analysis (WGCNA), and 14 co-expression gene modules were identified. Next, we filtered out the network degree top 10 (degree >80) genes, considered the final key SCI genes. A multifactor regulatory network (105 interaction pairs), consisting of messenger RNAs (mRNAs), long non-coding RNAs (lncRNAs), and transcription factors (TFs) was constructed. This network was involved in the co-expression of key genes. We selected the top 10 regulatory factors (degree >4) as core regulators in the multifactor regulatory network. RESULTS: The results of functional enrichment analysis of the target gene expressing the core regulatory factor [1,059] showed that these target genes were enriched in pathways for human cytomegalovirus infection, chronic myeloid leukemia, and pancreatic cancer. Further, we used the key genes in the co-expression network to categorize the SCI samples in GSE45550. The expression levels of the top 6 genes (CCNB2, CCNB1, CKS2, COL5A1, KIF20A, and RACGAP1) may act as potential marker genes for different SCI subtypes. On the basis of these different subtypes, 8 SCI core gene CDK1-associated drugs were also found to provide potential therapeutic options for SCI. CONCLUSIONS: These results may provide a novel therapeutic strategy for the treatment of SCI.
RESUMEN
OBJECTIVE: To analyze the network alteration characteristics of brain structure network in patients with delayed encephalopathy after CO poisoning (DEACMP) based on diffusion tensor imaging (DTI), and to explore the structural correlation neuroimaging mechanism of DEACMP cognitive impairment. METHODS: DTI scanning was performed in 33 patients with DEACMP and 25 healthy controls (HCs) who were matched in age and sex. The whole brain was divided into 90 regions by automated anatomical marker templates. The continuous tracing method was used to reconstruct the brain fiber bundle connection and construct the brain structure weighted network. The global and regional properties were computed by graph theoretical analysis. To compare the brain network regional properties between the DEACMP group and the HCs group, two-sample t test (false discovery rate correction, P < 0.05) was utilized. The correlations between the brain structural network properties and clinical parameters were further analyzed. RESULTS: Both of the two groups were found to follow the efficient small-world characteristics. The shortest path length of the DEACMP group increased (Lp = 0.86 ± 0.05), whereas global efficiency (Eglob = 9.60 ± 2.65) and local efficiency (Eloc = 17.98 ± 3.89) decreased. Moreover, the core nodes of the DEACMP group's default network, highlighting network, central execution network, and visual area, were decreased (P < 0.05, FDR correction). The left amygdala node degree of DEACMP group was positively correlated with MMSE and MoCA scores of the clinical scale (r = 0.863, P = 0.001, r = 0.525, P = 0.021). The node degree value of the left lingual gyrus was positively correlated with MoCA score (r = 0.406, P = 0.019) and negatively correlated with CDR score (r = -0.563, P = 0.016). The efficiency value of the right dorsolateral superior frontal gyrus in the DEACMP group was negatively correlated with the CDR score (r = -0.377, P = 0.031). CONCLUSION: By comparing the differences and changes in the topological properties and nodes of the brain structure network between DEACMP group and HCs group, the degree of related brain regions, especially the damage of higher brain functions in DEACMP patients, was verified, which was helpful to understand the cognitive damage caused by CO poisoning and to predict the efficacy of late remodeling. Small-worldness is a dynamic reorganization of the small-world topology and its community structure from the brain network to provide system-wide flexibility and adaptability (Barbey in Trends Cogn Sci 22(1):8-20, 2018). The combination with DTI is helpful for the accurate localization of brain structural damage, especially in DEACMP patients.
Asunto(s)
Encefalopatías/diagnóstico por imagen , Encefalopatías/etiología , Intoxicación por Monóxido de Carbono/complicaciones , Imagen de Difusión Tensora , Trastornos Neurocognitivos/diagnóstico por imagen , Trastornos Neurocognitivos/etiología , Adulto , Anciano , Algoritmos , Estudios de Casos y Controles , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Masculino , Persona de Mediana EdadRESUMEN
Glutamine (Gln) is a non-essential amino acid central for generating building blocks and cellular energy in tumours and rapidly proliferating non-transformed cells. However, the influence of Gln on regulating chromosomal stability of transformed and non-transformed cells remain poorly understand. We hypothesised that Gln is required for maintaining a homeostatic level of chromosomal stability. To this end, transformed cells HeLa and A375 and non-transformed cells NCM460 and HUVEC cells were intervened with varying concentrations of Gln (10, 1, 0.1 and 0.01 mM), with or without cisplatin (0.1 µg/ml), for 24 h. The cytokinesis-block micronucleus (MN) assay was used to determine chromosomal instability (CIN), the extent of which is reflected by the frequency of MN, nucleoplasmic bridge (NPB) and nuclear bud (NB). We demonstrated an unexpected decrease in the spontaneous rate of MN, but not NPB and NB, after Gln restriction in HeLa and A375 cells. Gln restriction reduced cisplatin-induced MN, but not NPB and NB, in HeLa and A375 cells. We further revealed that Gln restriction suppressed the proliferation of HeLa cells with high CIN induced by nocodazole, partially explaining why Gln restriction decreased the frequency of spontaneous and cisplatin-induced MN in transformed cells. In contrast, Gln restriction increased MN and NB, but not NPB, in NCM460 cells. In HUVEC cells, Gln restriction increased MN, NPB and NB. Meanwhile, Gln restriction sensitised NCM460 cells to cisplatin-induced genotoxicity. A similar but more pronounced pattern was observed in HUVEC cells. Collectively, these results suggest that the in vitro influences of Gln metabolism on CIN depend on cellular contexts: Transformed cells require high Gln to fine tune their CIN in an optimal rate to maximise genomic heterogeneity and fitness, whereas non-transformed cells need high Gln to prevent CIN.
RESUMEN
INTRODUCTION: Spinal cord injury (SCI) causes most severe motor and sensory dysfunctions. In Chinese traditional medicine, the agonist of a purinergic receptor is believed to have a positive effect on SCIs, and 2-Methylthio-adenosine-5'-diphosphate (2-MesADP) is a selective agonist of the P2Y purinergic receptor. METHODS: To investigate its therapeutic function and molecular mechanism in SCI, transcriptome analysis associated with weighted gene co-expression network analysis (WGCNA) was carried out at various time points after T9 crush injury. RESULTS: 2-MesADP demonstrated recovery of limb motor function at the 6 weeks after injury, accompanied by neuronal regeneration and axon remyelination at 2 and 6 weeks. Furthermore, gene profiling revealed alternated gene expression with the treatment of 2-MesADP. These genes were assigned to a total of 38 modules, followed by gene ontology analysis; of these, 18 represented neuronal apoptosis and regeneration, immune response, synaptic transmission, cell cycle, and angiogenesis. In the neuronal apoptosis and regeneration module, Nefh, NeuroD6, and Dcx in the 2-MesADP group were noticed due to their interesting expression pattern. The gene expression patterns of Mag, Mog, and Cnp, which played key roles in myelination, were significantly changed with the treatment of 2-MesADP. Wnt signal pathway was the most important pathway in 2-MesADP treatment for acute SCI. CONCLUSION: 2-MesADP enhanced locomotor recovery in mouse SCI by altering the expression of neuronal apoptosis and remyelination-related genes and Wnt signaling pathways.
Asunto(s)
Adenosina Difosfato/análogos & derivados , Regulación de la Expresión Génica/efectos de los fármacos , Locomoción/fisiología , Agonistas Purinérgicos/farmacología , Recuperación de la Función/efectos de los fármacos , Traumatismos de la Médula Espinal , Tionucleótidos/farmacología , Adenosina Difosfato/farmacología , Animales , Proteína Doblecortina , Humanos , Ratones , Regeneración Nerviosa/efectos de los fármacos , Recuperación de la Función/fisiología , Remielinización/efectos de los fármacos , Traumatismos de la Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/patología , Traumatismos de la Médula Espinal/fisiopatologíaRESUMEN
OBJECTIVE: To observe the structural changes of gray matter nuclei in patients with acute carbon monoxide intoxication by diffusion tensor imaging (DTI), quantify the degree of deep gray matter damage in the brain by adopting imaging technology and research the characteristics of the damage and its pertinence with memory and cognitive impairment. METHODS: Twenty-five patients with acute carbon monoxide intoxication and 25 healthy volunteers matched in sex and age were examined by routine head MRI and diffusion tensor imaging (DTI). Bilateral hippocampus, dater nucleus, thalamus, amygdala, globus pallidus and putamen were taken as regions of interest. The mean diffusion coefficient (MD), anisotropic fraction (FA) and appearance of deep gray matter nucleus in patients with acute carbon monoxide intoxication were analyzed. It found that the change of diffusion coefficient (ADC) and its clinical correlation with cognitive impairment were generated by carbon monoxide intoxication. RESULTS: Compared with the healthy control group, the FA values of bilateral globus pallidus, hippocampus, dater nucleus and putamen decreased, while the FA values of amygdala and thalamus had no statistical significance; the MD values and ADC values of hippocampus, globus pallidus and putamen increased, while the MD and ADC values of dater nucleus, thalamus and amygdala had no statistical significance, either. CONCLUSION: DTI is capable of sensitively reflecting the damage of gray matter nuclei caused by acute carbon monoxide intoxication and quantifying the degree of hypoxic brain damage in a certain extent, and may be related to cognitive impairment.
Asunto(s)
Traumatismos Difusos del Encéfalo/diagnóstico por imagen , Intoxicación por Monóxido de Carbono/diagnóstico por imagen , Imagen de Difusión Tensora/métodos , Sustancia Gris/diagnóstico por imagen , Enfermedad Aguda , Adulto , Anciano , Amígdala del Cerebelo/diagnóstico por imagen , Anisotropía , Estudios de Casos y Controles , Cognición , Femenino , Globo Pálido/diagnóstico por imagen , Hipocampo/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Pruebas de Estado Mental y Demencia , Persona de Mediana Edad , Giro Parahipocampal/diagnóstico por imagen , Putamen/diagnóstico por imagen , Tálamo/diagnóstico por imagen , Vigilia , Adulto JovenRESUMEN
Polycarbonate (PC)/Poly(styrene-co-acrylonitrile) (SAN)-organic silica bead (OSB) anisotropic light-scattering materials containing novel spindle-shaped core-shell particles through simple, low-cost hot stretching methods are prepared in situ, which have excellent and easily tunable optical properties. The effects of OSB particle size, OSB mass fraction and stretching ratio on the morphology of the spindle-shaped core-shell particles and the scattering properties of PC/SAN-OSB composites were studied in detail. The results show that smaller particle size OSB and smaller draw ratio are more conducive to the production of spindle-shaped core-shell particles. And because of the multiple scattering effects of the spindle-shaped core-shell particles, they have a significant compensation effect on the pattern short-axis light-scattering range of the PC anisotropic materials while ensuring that the pattern long-axis direction light-scattering range is not impaired.