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Long-time hypoxia induced cardiomyocyte apoptosis is an important mechanism of myocardial ischemia (MI) injury. Interestingly, long noncoding RNA myocardial infarction-associated transcript (LncMIAT) has been involved in the regulation of MI injury; however, the underlying mechanism by which LncMIAT affects the progression of hypoxia-induced cardiomyocyte apoptosis remains unclear. In the present study, hypoxia was found to promote cardiomyocyte apoptosis through an increased expression of LncMIAT in vitro. Biological investigations and dual-luciferase gene reporter assay further revealed that LncMIAT was able to bind with miR-708-5p to upregulate the p53-mediated cell death of the cardiomyocytes. Silencing of LncMIAT or overexpression of miR-708-5p led to a significant reduction in p53-mediated cardiomyocyte apoptosis. The methylated RNA immunoprecipitation (MeRIP)-qPCR results showed that hypoxia exerted its effects on LncMIAT through AKLBH5-N6-methyladenosine (m6A) methylation and therefore hypoxia was shown to trigger HL-1 cardiomyocyte apoptosis via the m6A methylation-mediated LncMIAT/miR-708-5p/p53 axis. Silencing of AKLBH5 significantly alleviated the m6A methylation-mediated LncMIAT upregulation and p53-mediated cardiomyocyte apoptosis, while promoted miR-708-5p expression. Taken together, the present study highlighted that LncMIAT could act as a key biological target during hypoxia-induced cardiomyocyte apoptosis. In addition, it was shown that hypoxia could promote cardiomyocyte apoptosis through regulation of the m6A methylation-mediated LncMIAT/miR-708-5p/p53 signaling axis.
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Free radical damage and oxidative stress are thought to play a crucial role in the development of neurodegenerative diseases. Walnut peptides, especially walnut oligopeptides, have been shown to protect nerve cells from oxidative stress and inflammatory damage, as well as improve memory function. In this study, walnut peptides were obtained from walnut meal through enzymatic hydrolysis, ultrafiltration, and gel filtration chromatography. A novel oligopeptide called AQ was successfully isolated and its chemical structure was identified as AASCDQ using ESI-MS/MS. AQ demonstrated remarkable scavenging activity against O2- free radicals (81.00%), DPPH free radicals (79.40%), and ABTS free radicals (67.09%) at a concentration of 1 mg mL-1. Furthermore, AQ exhibited strong neuroprotective effects against hydrogen peroxide-induced damage in SH-SY5Y cells, reducing cell injury and apoptosis. AQ also effectively inhibited the secretion of pro-inflammatory factors NO (IC50 = 46.03 ± 0.32 µM) and suppressed the expression of IL-6 and TNF-α in RAW264.7 cells stimulated by LPS. In vivo experiments demonstrated that AQ promoted angiogenesis in the quail chick chorioallantoic membrane assay and reduced ROS accumulation in Caenorhabditis elegans, thereby extending its lifespan. The anti-inflammatory mechanism of AQ was further confirmed by western blotting. In summary, the novel oligopeptide AQ possesses potential neuroprotective effects, including antioxidant, anti-inflammatory, angiogenic, and anti-aging properties, making it a promising candidate for the development of functional foods and pharmaceutical products.
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Caenorhabditis elegans , Juglans , Fármacos Neuroprotectores , Oligopéptidos , Animales , Juglans/química , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/química , Ratones , Caenorhabditis elegans/efectos de los fármacos , Células RAW 264.7 , Humanos , Oligopéptidos/farmacología , Oligopéptidos/química , Estrés Oxidativo/efectos de los fármacos , Apoptosis/efectos de los fármacos , Antiinflamatorios/farmacología , Antiinflamatorios/química , Hidrolisados de Proteína/farmacología , Hidrolisados de Proteína/química , Especies Reactivas de Oxígeno/metabolismo , Nueces/química , Antioxidantes/farmacología , Antioxidantes/químicaRESUMEN
BACKGROUND: Clinical studies have shown that diabetic peripheral neuropathy (DPN) has been on the rise, with most patients presenting with severe and progressive symptoms. Currently, most of the available prediction models for DPN are derived from general clinical information and laboratory indicators. Several Traditional Chinese medicine (TCM) indicators have been utilised to construct prediction models. In this study, we established a novel machine learning-based multi-featured Chinese-Western medicine-integrated prediction model for DPN using clinical features of TCM. MATERIALS AND METHODS: The clinical data of 1581 patients with Type 2 diabetes mellitus (T2DM) treated at the Department of Endocrinology of the First Affiliated Hospital of Anhui University of Chinese Medicine were collected. The data (including general information, laboratory parameters and TCM features) of 1142 patients with T2DM were selected after data cleaning. After baseline description analysis of the variables, the data were divided into training and validation sets. Four prediction models were established and their performance was evaluated using validation sets. Meanwhile, the accuracy, precision, recall, F1 score and area under the curve (AUC) of ROC were calculated using ten-fold cross-validation to further assess the performance of the models. An explanatory analysis of the results of the DPN prediction model was carried out using the SHAP framework based on machine learning-based prediction models. RESULTS: Of the 1142 patients with T2DM, 681 had a comorbidity of DPN, while 461 did not. There was a significant difference between the two groups in terms of age, cause of disease, systolic pressure, HbA1c, ALT, RBC, Cr, BUN, red blood cells in the urine, glucose in the urine, and protein in the urine (p < 0.05). T2DM patients with a comorbidity of DPN exhibited diverse TCM symptoms, including limb numbness, limb pain, hypodynamia, thirst with desire for drinks, dry mouth and throat, blurred vision, gloomy complexion, and unsmooth pulse, with statistically significant differences (p < 0.05). Our results showed that the proposed multi-featured Chinese-Western medicine-integrated prediction model was superior to conventional models without characteristic TCM indicators. The model showed the best performance (accuracy = 0.8109, precision = 0.8029, recall = 0.9060, F1 score = 0.8511, and AUC = 0.9002). SHAP analysis revealed that the dominant risk factors that caused DPN were TCM symptoms (limb numbness, thirst with desire for drinks, blurred vision), age, cause of disease, and glycosylated haemoglobin. These risk factors were exerted positive effects on the DPN prediction models. CONCLUSIONS: A multi-feature, Chinese-Western medicine-integrated prediction model for DPN was established and validated. The model improves early-stage identification of high-risk groups for DPN in the diagnosis and treatment of T2DM, while also providing informative support for the intelligent management of chronic conditions such as diabetes.
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Diabetes Mellitus Tipo 2 , Neuropatías Diabéticas , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Neuropatías Diabéticas/diagnóstico , Neuropatías Diabéticas/epidemiología , Neuropatías Diabéticas/etiología , Hipoestesia , Medicina Tradicional China , Factores de RiesgoRESUMEN
Background: Myocardial infarction (MI) remains one of the major causes of high morbidity and mortality worldwide. Danggui Buxue Decoction (DBD)-an ancient Chinese herbal decoction-has been used to prevent coronary heart disease, which was called "chest palsy" in ancient clinics. However, the mechanism of DBD in the treatment of MI remains unclear. The aim of this study was to explore the effect and mechanism of DBD on MI by combining network pharmacology with in vivo experiments. Materials and methods: First, public databases were used to identify the key active chemicals and possible targets of DBD. The MI targets were obtained from the Therapeutic Target Database, and the function of the target genes in relation to linked pathways was investigated. Subsequently, Cytoscape software was used to build a target-signaling pathway network. Finally, the efficacy of DBD therapy on MI was validated using in vivo investigations combined with molecular docking. Results: In traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP), 27 bioactive compounds were screened from DBD. A total of 213 common targets were obtained, including 507 DBD targets and 2566 MI targets. Enrichment analysis suggests that PI3K/AKT is a potential signaling pathway for DBD-based protection. Immunofluorescence and protein blotting confirmed PI3K/AKT1, ERK2, and CASPASE-9 as the target proteins. Molecular docking analysis showed that quercetin, kaempferol, isoflavanones, isorhamnetin, hederagenin, and formononetin had high binding affinity to AKT1, ERK2, and CASPASE-9. Conclusions: This study demonstrated that the therapeutic benefit of DBD on MI may be mediated via target proteins in the PI3K/AKT pathway, such as AKT1, ERK2, and CASPASE-9. Our study data can help to provide ideas and identify new treatment targets for MI.
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Osteoarthritis (OA) is a chronic joint disease characterized by progressive degeneration of articular cartilage. A challenge in the development of disease-modifying drugs is effective delivery to chondrocytes. The unique structure of the joint promotes rapid clearance of drugs through synovial fluid, and the dense and avascular cartilage extracellular matrix (ECM) limits drug penetration. Here, we show that poly(lactide-co-glycolic acid) nanoparticles coated in chondrocyte membranes (CM-NPs) were preferentially taken up by rat chondrocytes ex vivo compared with uncoated nanoparticles. Internalization of the CM-NPs was mediated primarily by E-cadherin, clathrin-mediated endocytosis, and micropinocytosis. These CM-NPs adhered to the cartilage ECM in rat knee joints in vivo and penetrated deeply into the cartilage matrix with a residence time of more than 34 days. Simulated synovial fluid clearance studies showed that CM-NPs loaded with a Wnt pathway inhibitor, adavivint (CM-NPs-Ada), delayed the catabolic metabolism of rat and human chondrocytes and cartilage explants under inflammatory conditions. In a surgical model of rat OA, drug-loaded CM-NPs effectively restored gait, attenuated periarticular bone remodeling, and provided chondroprotection against cartilage degeneration. OA progression was also mitigated by CM-NPs-Ada in a canine model of anterior cruciate ligament transection. These results demonstrate the feasibility of using chondrocyte membrane-coated nanoparticles to improve the pharmacokinetics and efficacy of anti-OA drugs.
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Cartílago Articular , Nanopartículas , Osteoartritis , Ratas , Animales , Perros , Humanos , Condrocitos/metabolismo , Osteoartritis/tratamiento farmacológico , Osteoartritis/metabolismo , Articulación de la Rodilla , Cartílago Articular/metabolismoRESUMEN
BACKGROUND: Dilated cardiomyopathy (DCM) is a leading cause of heart failure. Cuproptosis is involved in various diseases, although its role in DCM is still unclear. Here, this study aims to investigate the feasibility of using genes related to cuproptosis as diagnostic biomarkers for DCM and the association of their expression with immune infiltration and drug target in cardiac tissue. METHODS: Gene expression data from nonfailure (NF) and DCM samples were retrieved from the GEO database. Cuproptosis scores were calculated using single-sample gene set enrichment analysis (ssGSEA). Weighted gene co-expression network analysis (WGCNA) was used to screen key modules associated with DCM and cuproptosis. Random forest and least absolute shrinkage and selection operator (LASSO) were applied to identify signature genes. Finally, immune cell infiltration was assessed using ssGSEA. mRNA-miRNA-lncRNA regulatory networks and chemical-drug regulatory networks based on signature genes were analyzed by Cytoscape. RESULTS: 8 modules were aggregated by WGCNA, among which MEblue was significantly associated with cuproptosis scores and DCM. A diagnostic model made up of six signature genes including SEPTIN1, CLEC11A, ISG15, P3H3, SDSL, and INKA1 was selected. Furthermore, immune infiltration studies showed significant differences between DCM and NF. Drugs networks and ceRNA regulatory network based on six signature genes were successfully constructed. CONCLUSION: Six signature genes (SEPTIN1, CLEC11A, ISG15, P3H3, SDSL, and INKA1) were identified as novel diagnostic biomarkers in DCM. In addition, the expression of these genes was associated with immune cell infiltration, suggesting that cuproptosis may be involved in the immune regulation of DCM.
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Cardiomiopatía Dilatada , MicroARNs , Humanos , Cardiomiopatía Dilatada/diagnóstico , Cardiomiopatía Dilatada/genética , Sistemas de Liberación de Medicamentos , Bases de Datos Factuales , BiomarcadoresRESUMEN
OBJECTIVE: To observe the effect of Danzhi Jiangtang capsule (DJC) on the clinical indexes and vascular endothelial function indexes in patients with impaired glucose tolerance (IGT). METHODS: A total of 106 patients were enrolled and randomly assigned to the treatment group and control group following a four-week washout period. The patients in the control group received a general lifestyle intervention, while those in the treatment group received DJC (2.0 g 3× a day) in conjunction with the intervention given to the control group patients. The physiological and biochemical levels, vascular endothelial function indices, and traditional Chinese medicine (TCM) syndrome ratings of the patients in the two groups were compared after 12 weeks of therapy. RESULTS: In the control group, the diastolic blood pressure (DBP) was significantly improved compared with those before treatment (83.31 ± 6.47 vs. 79.21 ± 6.17, p < .01) (CI: 1.45, 6.73; Cohen's d: 10.51), as was the case with the nitric oxide (NO) levels and TCM syndrome points (35.71 ± 4.58 vs. 43.96 ± 5.17, 9.57 ± 2.63 vs. 5.38 ± 1.79, p < .001) (CI: -10.28, -6.24; 3.12, 5.18; Cohen's d: 0.90). In the treatment group, the levels of fasting blood glucose, endothelin and vascular endothelial growth factor were significantly improved compared with control group (4.92 ± 0.21 vs. 5.59 ± 0.31, 59.37 ± 13.25 vs. 72.13 ± 12.37, 19.25 ± 2.80 vs. 26.76 ± 1.88, p < .001) (CI: 0.55, 0.78; 7.40, 18.13; 6.52, 8.50; Cohen's d: 4.94, 0.41, 1.32), as was the case with 2-h post-load plasma glucose and total cholesterol (TC) (8.33 ± 0.62 vs. 8.89 ± 1.55, 4.61 ± 1.05 vs. 5.22 ± 1.12, p < .05) (CI: 0.07, 1.07; 0.15, 1.06; Cohen's d: 0.40, 0.51). CONCLUSIONS: Treatment with DJC could significantly improve the physiological and biochemical indicators, vascular endothelial function, and TCM syndrome points of IGT patients, indicating that DJC could be a potential drug to treat patients with IGT of Qi-Yin deficiency type.
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Intolerancia a la Glucosa , Humanos , Intolerancia a la Glucosa/tratamiento farmacológico , Deficiencia Yin , Qi , Factor A de Crecimiento Endotelial VascularRESUMEN
OBJECTIVE: To investigate blood group serological manifestations and molecular mechanism of para-Bombay phenotype. METHODS: The serological manifestations of para-Bombay phenotype was identified by serological assay. Molecular mechanism of para-Bombay phenotype was detected by PCR amplification. RESULTS: Eighteen cases of para-Bombay phenotype were detected through serology and PCR, including 5 cases of Amh, 4 cases of Bmh, and 10 cases of Omh. Eight cases produced anti-HI antibody. CONCLUSIONS: Blood group serology combined with molecular biology can accurately identify para-Bombay phenotype. Special transfusion strategy should be adopted for individual with para-Bombay phenotype to avoid hemolytic reactions.
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Cobalt carbonyl/nitrosyl complexes, (PPh3)(CO)2Co(NO) (1) and (PPh3)2(CO)Co(NO) (2), were obtained by reacting (CO)3Co(NO) with one equiv. and two equiv. of PPh3, respectively. The process of isoelectronic replacement of CO with NO+ resulted in the formation of a cationic complex {Co(NO)2}10 [(PPh3)2Co(NO)2][BF4] (3). Complex (PPh3)(SPh)Co(NO)2 (4), which contains a thiophenolate ligand, was synthesized by ligand exchange of complex 3 with [PPh4][SPh] in a 1 : 1 molar ratio in THF solution. The addition of one equiv. of [PPh4][SPh] to complex 4 led to the formation of complex [PPh4][(SPh)2Co(NO)2] (5). The interconversions among complexes 1-5 were substantiated with the application of IR spectroscopy and X-ray single-crystal diffraction techniques. Notably, complex 4 exhibited commendable NOs (nitric oxide species: NO+/ËNO/NO-) transfer capabilities in the presence of [Fe(TPP)Cl] (5,10,15,20-tetraphenyl-21H,23H-porphine iron(III) chloride).
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Manipulating the tumor immune contexture towards a more active state can result in better therapeutic outcomes. Here we describe an easily accessible bacterial biomineralization-generated immunomodulator, which we name Ausome (Au + [exo]some). Ausome comprises a gold nanoparticle core covered by bacterial components; the former affords an inducible hyperthermia effect, while the latter mobilizes diverse immune responses. Multiple pattern recognition receptors actively participate in Ausome-initiated immune responses, which lead to the release of a broad spectrum of pro-inflammatory cytokines and the activation of effector immune cells. Upon laser irradiation, tumor-accumulated Ausome elicits a hyperthermic response, which improves tissue blood perfusion and contributes to enhanced infiltration of immunostimulatory modules, including cytokines and effector lymphocytes. This immune-modulating strategy mediated by Ausome ultimately brings about a comprehensive immune reaction and selectively amplifies the effects of local antitumor immunity, enhancing the efficacy of well-established chemo- or immuno-therapies in preclinical cancer models in female mice.
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Hipertermia Inducida , Nanopartículas del Metal , Neoplasias , Femenino , Animales , Ratones , Oro , Nanopartículas del Metal/uso terapéutico , Hipertermia , Receptores Toll-Like , Neoplasias/terapia , Citocinas , InmunidadRESUMEN
Recent studies on osteosarcoma and matrix stiffness are still mostly performed in a 2D setting, which is distinct from in vivo conditions. Therefore, the results from the 2D models may not reflect the real effect of matrix stiffness on cell phenotype. Here, we employed a 3D bioprinted osteosarcoma model, to study the effect of matrix stiffness on osteosarcoma cells. Through density adjustment of GelMA, we constructed three osteosarcoma models with distinct matrix stiffnesses of 50, 80, and 130 kPa. In this study, we found that osteosarcoma cells proliferated faster, migrated more actively, had a more stretched morphology, and a lower drug sensitivity in a softer 3D matrix. When placed in a stiffer matrix, osteosarcoma cells secrete more MMP and VEGF, potentially to fight for survival and attract vascular invasion. Transcriptomic analysis showed that matrix stiffness could impact the signaling pathway of integrin α5-MAPK. The transplantation of 3D printed models in nude mice showed that cells encapsulated in the softer hydrogel were more likely to form subcutaneous tumors. These results suggest that matrix stiffness plays an important role in the development of osteosarcoma in a 3D environment and that inhibition of integrin α5 could block the signal transduction of matrix stiffness.
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Neoplasias Óseas , Osteosarcoma , Ratones , Animales , Hidrogeles/farmacología , Gelatina , Biomimética/métodos , Ratones Desnudos , Integrina alfa5 , Impresión TridimensionalRESUMEN
Whether and how shared intentionality (SI) influences the establishment of a novel interpersonal communication system is poorly understood. To investigate this issue, we designed a coordinating symbolic communication game (CSCG) and applied behavioral, functional near-infrared spectroscopy (fNIRS)-based hyperscanning, and hyper-transcranial alternating current stimulation (hyper-tACS) methods. Here we show that SI is a strong contributor to communicative accuracy. Moreover, SI, communicative accuracy, and interpersonal neural synchronization (INS) in the right superior temporal gyrus (rSTG) are higher when dyads successfully establish a novel communication system. Furthermore, the SI influences communicative accuracy by increasing INS. Additionally, using time series and long short-term memory neural network analyses, we find that the INS can predict communicative accuracy at the early formation stage of the communication system. Importantly, the INS partially mediates the relationship between the SI and the communicative accuracy only at the formation stage of the communication system. In contrast, when the communication system is established, SI and INS no longer contribute to communicative accuracy. Finally, the hyper-tACS experiment confirms that INS has a causal effect on communicative accuracy. These findings suggest a behavioral and neural mechanism, subserved by the SI and INS, that underlies the establishment of a novel interpersonal communication system.
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Relaciones Interpersonales , Lóbulo Temporal , Lóbulo Temporal/fisiología , Comunicación , Espectroscopía Infrarroja Corta/métodosRESUMEN
OBJECTIVE: Assumptions on the natural history of ductal carcinoma in situ (DCIS) are necessary to accurately model it and estimate overdiagnosis. To improve current estimates of overdiagnosis (0-91%), the purpose of this review was to identify and analyse assumptions made in modelling studies on the natural history of DCIS in women. METHODS: A systematic review of English full-text articles using PubMed, Embase, and Web of Science was conducted up to February 6, 2023. Eligibility and all assessments were done independently by two reviewers. Risk of bias and quality assessments were performed. Discrepancies were resolved by consensus. Reader agreement was quantified with Cohen's kappa. Data extraction was performed with three forms on study characteristics, model assessment, and tumour progression. RESULTS: Thirty models were distinguished. The most important assumptions regarding the natural history of DCIS were addition of non-progressive DCIS of 20-100%, classification of DCIS into three grades, where high grade DCIS had an increased chance of progression to invasive breast cancer (IBC), and regression possibilities of 1-4%, depending on age and grade. Other identified risk factors of progression of DCIS to IBC were younger age, birth cohort, larger tumour size, and individual risk. CONCLUSION: To accurately model the natural history of DCIS, aspects to consider are DCIS grades, non-progressive DCIS (9-80%), regression from DCIS to no cancer (below 10%), and use of well-established risk factors for progression probabilities (age). Improved knowledge on key factors to consider when studying DCIS can improve estimates of overdiagnosis and optimization of screening.
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Neoplasias de la Mama , Carcinoma Ductal de Mama , Carcinoma Intraductal no Infiltrante , Femenino , Humanos , Carcinoma Intraductal no Infiltrante/patología , Neoplasias de la Mama/patología , Progresión de la Enfermedad , Simulación por Computador , Detección Precoz del Cáncer , Carcinoma Ductal de Mama/patologíaRESUMEN
Previous findings have shown a strong relationship between sports and interpersonal cooperative behavior. Physical activity is the basic form of sport. In this study, we investigated the effect of physical activity on interpersonal cooperative behavior and its inter-brain correlates. Eighty college students were recruited and randomly divided into the experimental or control group (20 dyads per each). The experimental group performed a 30-min of moderate intensity single-person cycling exercise, while the control group performed a 30-min single-person sitting. Interpersonal cooperative behavior was measured by a Prisoner's Dilemma task before and after the intervention, while neural activities in the frontal cortex in each dyad were measured by the near-infrared spectroscopy-based hyperscanning approach. The results showed that the average cooperation rate and cooperation efficiency of the experimental dyads were significantly higher after the exercise intervention compared to that before intervention, but not in control group. Meanwhile, the interpersonal neural synchronization (INS) in the left frontal cortex was significantly increased after intervention only in experimental dyads. Moreover, the INS increased in left frontal cortex was positively correlated with the cooperation improvement. Taken together, these results indicate that one single-person bicycling can improve interpersonal cooperation behavior, which may be associated with enhanced interpersonal neural synchronization in the left frontal cortex.
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Ciclismo , Encéfalo , Humanos , Mapeo Encefálico/métodos , Conducta Cooperativa , Lóbulo Frontal/diagnóstico por imagen , Relaciones InterpersonalesRESUMEN
Osteosarcoma is the most prevalent bone malignant tumor in children and teenagers. The bone defect, recurrence, and metastasis after surgery severely affect the life quality of patients. Clinically, bone grafts are implanted. Primary bioceramic scaffolds show a monomodal osteogenesis function. With the advances in three-dimensional printing technology and materials science, while maintaining the osteogenesis ability, scaffolds become more patient-specific and obtain additional anti-tumor ability with functional agents being loaded. Anti-tumor therapies include photothermal, magnetothermal, old and novel chemo-, gas, and photodynamic therapy. These strategies kill tumors through novel mechanisms to treat refractory osteosarcoma due to drug resistance, and some have shown the potential to reverse drug resistance and inhibit metastasis. Therefore, multifunctional three-dimensional printed bioceramic scaffolds hold excellent promise for osteosarcoma treatments. To better understand, we review the background of osteosarcoma, primary 3D-printed bioceramic scaffolds, and different therapies and have a prospect for the future.
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Senile osteoporosis is characterized by age-related bone loss and bone microarchitecture deterioration. However, little is known to date about the mechanism that maintains bone homeostasis during aging. In this study, we identify adenosine monophosphate-activated protein kinase alpha 1 (AMPKα1) as a critical factor regulating the senescence and lineage commitment of mesenchymal stem cells (MSCs). A phospho-mutant mouse model shows that constitutive AMPKα1 activation prevents age-related bone loss and promoted MSC osteogenic commitment with increased bone-derived insulin-like growth factor 1 (IGF-1) secretion. Mechanistically, upregulation of IGF-1 signalling by AMPKα1 depends on cAMP-response element binding protein (CREB)-mediated transcriptional regulation. Furthermore, the essential role of the AMPKα1/IGF-1/CREB axis in promoting aged MSC osteogenic potential is confirmed using three-dimensional (3D) culture systems. Taken together, these results can provide mechanistic insight into the protective effect of AMPKα1 against skeletal aging by promoting bone-derived IGF-1 secretion.
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Factor I del Crecimiento Similar a la Insulina , Osteoporosis , Ratones , Animales , Factor I del Crecimiento Similar a la Insulina/metabolismo , Huesos/metabolismo , Envejecimiento/metabolismo , Osteogénesis , Osteoporosis/prevención & controlRESUMEN
Cognitive impairments are common in patients with schizophrenia. Changes in total cholesterol (TC) may be involved in the development of schizophrenia and associated with cognitive function. This study aimed to investigate differences in serum TC level and cognitive function between schizophrenia patients and healthy controls and explore the relationship between serum TC level and cognitive function in patients with schizophrenia. A total of 105 schizophrenia patients and 105 healthy controls were recruited. Results showed that patients with schizophrenia had significantly lower scores on the overall RBANS scale and subscales (i.e., immediate memory, language, attention, and delayed memory) than those of healthy controls. Pearson's correlation analyses showed that in patients with schizophrenia, serum TC levels were positively associated with RBANS subscale scores of immediate memory and language. Furthermore, multivariate regression analyses showed that serum TC level was positively associated with the immediate memory index in patients with schizophrenia. However, no significant association was found between serum TC level and RBANS score in the healthy control group. Our results suggest that elevated serum TC level may be related to improved cognitive function in patients with schizophrenia, especially that of immediate memory.
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Disfunción Cognitiva , Esquizofrenia , Humanos , Memoria a Corto Plazo , Esquizofrenia/complicaciones , Pruebas Neuropsicológicas , Cognición , Disfunción Cognitiva/etiología , ColesterolRESUMEN
Analogical reasoning is important for human. We have found that a short executive attention intervention improved analogical reasoning performance in healthy young adults. Nevertheless, previous electrophysiological evidence was limited for comprehensively characterizing the neural mechanisms underlying the improvement. And although we hypothesized that the intervention improved active inhibitory control and attention shift first and then relation integration, it is still unclear whether there are two sequential cognitive neural activities were indeed changed during analogical reasoning. In the present study, we combined hypothesis with multivariate pattern analysis (MVPA) to explore the effects of the intervention on electrophysiology. Results showed that in the resting state after the intervention, alpha and high gamma power and the functional connectivity between the anterior and middle in the alpha band could discriminate the experimental group from the active control group, respectively. These indicated that the intervention influenced the activity of multiple bands and the interaction of frontal and parietal regions. In the analogical reasoning, alpha, theta, and gamma activities could also fulfill such discrimination, and furthermore, they were sequential (alpha first, theta, and gamma later). These results directly supported our previous hypothesis. The present study deepens our understanding about how executive attention contributes to higher-order cognition.
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Cognición , Solución de Problemas , Adulto Joven , Humanos , Solución de Problemas/fisiología , Cognición/fisiología , AtenciónRESUMEN
Psychological pain is a robust predictor of suicide attempts in patients with major depressive disorder (MDD). However, whether suicide and psychological pain share a common neural basis remains unclear. Patients with MDD (n = 64) and healthy controls (HC) (n = 35) were recruited and patients were allocated to two groups: those with a history of suicide attempts (MDD-SA) (n = 25) and those without such a history (MDD-NSA) (n = 39). All participants completed the measurements and underwent functional magnetic resonance imaging to investigate the resting-state static and dynamic brain functional networks in default mode (DMN), central executive (CEN), salience (SN), and basal ganglia (BGN) networks. The MDD-SA group scored higher in pain avoidance than the MDD-NSA and HC groups. Functional connectivity within the dorsal DMN in the MDD-SA group was greater than that in the MDD-NSA and HC groups, and was significantly correlated with pain avoidance and suicide attempts. Dynamic functional connectivity analysis revealed that the proportion of State I in the fraction windows in the MDD-SA group was higher than those in the MDD-NSA and HC groups. Therefore, the increased functional connectivity within the dorsal DMN and segregation of networks may represent potential biological markers for suicide attempts related to psychological pain processing.
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Trastorno Depresivo Mayor , Humanos , Trastorno Depresivo Mayor/diagnóstico por imagen , Mapeo Encefálico/métodos , Intento de Suicidio , Vías Nerviosas/diagnóstico por imagen , Descanso , Encéfalo/diagnóstico por imagen , Dolor/diagnóstico por imagenRESUMEN
Detecting and correcting execution errors is crucial for safe and efficient goal-directed behavior. Despite intensive investigations on error processing, the cognitive foundations of this process remain unclear. Based on the presumed relation between executive attention (EA) and error processing, we implemented a seven-day EA intervention by adopting the Posner cueing paradigm to test the potential causal link from EA to error processing in healthy adults. The experimental group (high EA, HEA) was trained on the Posner cueing paradigm, with a ratio of invalid cue (IC) trials to valid cue (VC) trials of 5:1 and a corresponding ratio of 1:1 in the active control group (low EA, LEA). We found that the EA intervention improved EA across intervention sessions. Critically, after the EA intervention, the HEA group showed that post-error accuracy (PEA) was restored to the same level as the post-correct accuracy (in comparison with the LEA group). However, post-error slowing and the flanker effect were not modulated by the EA intervention. Furthermore, we observed that the changes in the accuracy of VC trials positively predicted the changes in PEA and that the two groups were classified according to the changes in PEA with a 61.3% accuracy. Based on these results, we propose that EA causally drives error processing. And the capabilities of the "actively catch" more attention resources and the automatic mismatch processing developed after EA intervention is transferable to error processing, thereby directly resulting in the gains in post-error adjustments. Our work informs the potential cognitive mechanisms underlying this causal link.