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1.
Mol Ther ; 32(5): 1461-1478, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38414246

RESUMEN

Osteoarthritis (OA) is an age-related or post-traumatic degenerative whole joint disease characterized by the rupture of articular cartilage homeostasis, the regulatory mechanisms of which remain elusive. This study identifies the essential role of heterogeneous nuclear ribonucleoprotein K (hnRNPK) in maintaining articular cartilage homeostasis. Hnrnpk expression is markedly downregulated in human and mice OA cartilage. The deletion of Hnrnpk effectively accelerates the development of post-traumatic and age-dependent OA in mice. Mechanistically, the KH1 and KH2 domain of Hnrnpk bind and degrade the mRNA of WWC1. Hnrnpk deletion increases WWC1 expression, which in turn leads to the activation of Hippo signaling and ultimately aggravates OA. In particular, intra-articular injection of LPA and adeno-associated virus serotype 5 expressing WWC1 RNA interference ameliorates cartilage degeneration induced by Hnrnpk deletion, and intra-articular injection of adeno-associated virus serotype 5 expressing Hnrnpk protects against OA. Collectively, this study reveals the critical roles of Hnrnpk in inhibiting OA development through WWC1-dependent downregulation of Hippo signaling in chondrocytes and defines a potential target for the prevention and treatment of OA.


Asunto(s)
Cartílago Articular , Condrocitos , Ribonucleoproteína Heterogénea-Nuclear Grupo K , Vía de Señalización Hippo , Osteoartritis , Proteínas Serina-Treonina Quinasas , Transducción de Señal , Animales , Humanos , Masculino , Ratones , Cartílago Articular/metabolismo , Cartílago Articular/patología , Condrocitos/metabolismo , Dependovirus/genética , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Ribonucleoproteína Heterogénea-Nuclear Grupo K/metabolismo , Ribonucleoproteína Heterogénea-Nuclear Grupo K/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Osteoartritis/metabolismo , Osteoartritis/genética , Osteoartritis/etiología , Osteoartritis/patología , Osteoartritis/terapia , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo
2.
Mol Cell Biochem ; 479(4): 1011-1022, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37273040

RESUMEN

Retinoblastoma (RB) is an intraocular malignancy that is most common in children and rare in adults. Addressing novel biomarkers and therapeutic targets for RB to modulate tumor progression has become a challenge. The aim of the present study was to investigate the function of long non-coding RNAs (LncRNAs) LOXL1-AS1 in RB cell proliferation and metastasis. It was found that LOXL1-AS1 was overexpressed in RB tissues and cells. In order to evaluate cell viability and colony formation potential, the knockdown of LOXL1-AS1 has been established. Knockdown of LOXL1-AS1 was also inhibited cells migration and invasion. In addition, the proportion of cells in the G2/M phase of the sh-LOXL1-AS1 group increased significantly, and the proportion of cells in the sh-NC group decreased significantly. In the xenograft model of RB, the tumors in the sh-LOXL1-AS1 group grow slowly compared to the sh-NC group. Western blot analysis revealed that LOXL1-AS1 can regulate the progression of RB cells through MAPK signaling pathway in vitro and in vivo. These results indicated that LncRNA LOXL1-AS1 promotes proliferation, invasion and inhibits apoptosis of retinoblastoma by regulating MAPK signaling pathway, and might be expected to be a novel basis for clinical diagnosis and treatment.


Asunto(s)
ARN Largo no Codificante , Neoplasias de la Retina , Retinoblastoma , Humanos , Aminoácido Oxidorreductasas/genética , Aminoácido Oxidorreductasas/metabolismo , Apoptosis/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias de la Retina/genética , Retinoblastoma/genética , ARN Largo no Codificante/metabolismo , Transducción de Señal
3.
BMC Infect Dis ; 24(1): 335, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38509522

RESUMEN

BACKGROUND: Lung endothelial barrier injury plays an important role in the pathophysiology of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Mesenchymal stem cells (MSCs) therapy has shown promise in ARDS treatment and restoration of the impaired barrier function. It has been reported that Wnt5a shows protective effects on endothelial cells. Therefore, the study aimed to investigate whether overexpression of Wnt5a could promote the protective effects of MSCs on Lipopolysaccharide (LPS)-induced endothelial cell injury. METHODS: To evaluate the protective effects of MSCs overexpressing Wnt5a, we assessed the migration, proliferation, apoptosis, and angiogenic ability of endothelial cells. We assessed the transcription of protective cellular factors using qPCR and determined the molecular mechanism using Western blot analysis. RESULTS: Overexpression of Wnt5a upregulated the transcription of protective cellular factors in MSCs. Co-culture of MSCWnt5a promoted endothelial migration, proliferation and angiogenesis, and inhibited endothelial cell apoptosis through the PI3K/AKT pathway. CONCLUSIONS: Overexpression of Wnt5a promoted the therapeutic effect of MSCs on endothelial cell injury through the PI3K/AKT signaling. Our study provides a novel approach for utilizing genetically modified MSCs in the transplantation therapy for ARDS.


Asunto(s)
Células Madre Mesenquimatosas , Síndrome de Dificultad Respiratoria , Humanos , Lipopolisacáridos/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Células Endoteliales , Transducción de Señal , Células Madre Mesenquimatosas/metabolismo , Síndrome de Dificultad Respiratoria/terapia
4.
BMC Psychiatry ; 24(1): 434, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38862969

RESUMEN

BACKGROUND: Cognitive impairment is a recognized fundamental deficit in individuals diagnosed with schizophrenia (SZ), bipolar II disorder (BD II), and major depressive disorder (MDD), among other psychiatric disorders. However, limited research has compared cognitive function among first-episode drug-naïve individuals with SZ, BD II, or MDD. METHODS: This study aimed to address this gap by assessing the cognitive performance of 235 participants (40 healthy controls, 58 SZ patients, 72 BD II patients, and 65 MDD patients) using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) before and after 12 weeks of treatment in SZ, BD II, and MDD patients. To clarify, the healthy controls only underwent RBANS testing at baseline, whereas the patient groups were assessed before and after treatment. The severity of symptoms in SZ patients was measured using the Positive and Negative Syndrome Scale (PANSS), and depression in BD II and MDD patients was assessed using the Hamilton Depression Scale-24 items (HAMD-24 items). RESULTS: Two hundred participants completed the 12-week treatment period, with 35 participants dropping out due to various reasons. This group included 49 SZ patients, 58 BD II patients, and 53 MDD patients. Among SZ patients, significant improvements in immediate and delayed memory were observed after 12 weeks of treatment compared to their initial scores. Similarly, BD II patients showed significant improvement in immediate and delayed memory following treatment. However, there were no significant differences in RBANS scores for MDD patients after 12 weeks of treatment. CONCLUSIONS: In conclusion, the findings of this study suggest that individuals with BD II and SZ may share similar deficits in cognitive domains. It is important to note that standardized clinical treatment may have varying degrees of effectiveness in improving cognitive function in patients with BD II and SZ, which could potentially alleviate cognitive dysfunction.


Asunto(s)
Trastorno Bipolar , Trastorno Depresivo Mayor , Esquizofrenia , Humanos , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/psicología , Masculino , Femenino , Trastorno Bipolar/tratamiento farmacológico , Trastorno Bipolar/psicología , Adulto , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/fisiopatología , Esquizofrenia/complicaciones , Disfunción Cognitiva/etiología , Disfunción Cognitiva/psicología , Adulto Joven , Pruebas Neuropsicológicas , Antipsicóticos/uso terapéutico , Escalas de Valoración Psiquiátrica , Persona de Mediana Edad
5.
Acta Biochim Biophys Sin (Shanghai) ; 56(5): 776-788, 2024 05 25.
Artículo en Inglés | MEDLINE | ID: mdl-38495003

RESUMEN

Intervertebral disc degeneration (IDD) is the cause of low back pain (LBP), and recent research has suggested that inflammatory cytokines play a significant role in this process. Maslinic acid (MA), a natural compound found in olive plants ( Olea europaea), has anti-inflammatory properties, but its potential for treating IDD is unclear. The current study aims to investigate the effects of MA on TNFα-induced IDD in vitro and in other in vivo models. Our findings suggest that MA ameliorates the imbalance of the extracellular matrix (ECM) and mitigates senescence by upregulating aggrecan and collagen II levels as well as downregulating MMP and ADAMTS levels in nucleus pulposus cells (NPCs). It can also impede the progression of IDD in rats. We further find that MA significantly affects the PI3K/AKT and NF-κB pathways in TNFα-induced NPCs determined by RNA-seq and experimental verification, while the AKT agonist Sc-79 eliminates these signaling cascades. Furthermore, molecular docking simulation shows that MA directly binds to PI3K. Dysfunction of the PI3K/AKT pathway and ECM metabolism has also been confirmed in clinical specimens of degenerated nucleus pulposus. This study demonstrates that MA may hold promise as a therapeutic agent for alleviating ECM metabolism disorders and senescence to treat IDD.


Asunto(s)
Degeneración del Disco Intervertebral , FN-kappa B , Núcleo Pulposo , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Ratas Sprague-Dawley , Transducción de Señal , Triterpenos , Degeneración del Disco Intervertebral/metabolismo , Degeneración del Disco Intervertebral/tratamiento farmacológico , Degeneración del Disco Intervertebral/patología , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , FN-kappa B/metabolismo , Núcleo Pulposo/metabolismo , Núcleo Pulposo/efectos de los fármacos , Núcleo Pulposo/patología , Masculino , Triterpenos/farmacología , Ratas , Humanos , Simulación del Acoplamiento Molecular , Factor de Necrosis Tumoral alfa/metabolismo , Matriz Extracelular/metabolismo , Matriz Extracelular/efectos de los fármacos , Femenino , Células Cultivadas , Ácido Oleanólico/análogos & derivados
6.
Opt Express ; 31(24): 39638-39646, 2023 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-38041280

RESUMEN

In this work, periodic rectangular arrays were fabricated on quartz substrates using the femtosecond laser ablation technique, on which inorganic cesium lead bromide thin films were grown using the spin coating method. Enhanced photoluminescence emission was investigated using a homebuilt confocal microscope, and increased light absorption due to the engineered structures was also measured. High-performance amplified spontaneous emission with typical narrow lasing emission peaks excited using a nanosecond laser centered at 266 nm was obtained. This work provides a method to modify the performance of optoelectrical devices, which helps develop light-emitting diodes, photodetectors, solar cells, and lasers.

7.
Cancer Cell Int ; 23(1): 163, 2023 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-37568202

RESUMEN

BACKGROUND: Abnormal hyaluronic acid (HA) metabolism is a major factor in tumor progression, and the metabolic regulation of HA mainly includes HA biosynthesis and catabolism. In glioma, abnormal HA biosynthesis is intimately involved in glioma malignant biological properties and the formation of immunosuppressive microenvironment; however, the role of abnormal HA catabolism in glioma remains unclear. METHODS: HA catabolism is dependent on hyaluronidase. In TCGA and GEPIA databases, we found that among the 6 human hyaluronidases (HYAL1, HYAL2, HYAL3, HYAL4, HYALP1, SPAM1), only HYAL2 expression was highest in glioma. Next, TCGA and CGGA database were further used to explore the correlation of HYAL2 expression with glioma prognosis. Then, the mRNA expression and protein level of HYAL2 was determined by qRT-PCR, Western blot and Immunohistochemical staining in glioma cells and glioma tissues, respectively. The MTT, EdU and Colony formation assay were used to measure the effect of HYAL2 knockdown on glioma. The GSEA enrichment analysis was performed to explore the potential pathway regulated by HYAL2 in glioma, in addition, the HYAL2-regulated signaling pathways were detected by flow cytometry and Western blot. Finally, small molecule compounds targeting HYAL2 in glioma were screened by Cmap analysis. RESULTS: In the present study, we confirmed that Hyaluronidase 2 (HYAL2) is abnormally overexpressed in glioma. Moreover, we found that HYAL2 overexpression is associated with multiple glioma clinical traits and acts as a key indicator for glioma prognosis. Targeting HYAL2 could inhibit glioma progression by inducing glioma cell apoptosis and cell cycle arrest. CONCLUSION: Collectively, these observations suggest that HYAL2 overexpression could promote glioma progression. Thus, treatments that disrupt HA catabolism by altering HYAL2 expression may serve as effective strategies for glioma treatment.

8.
Cancer Cell Int ; 23(1): 105, 2023 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-37246211

RESUMEN

BACKGROUND: Copper homeostasis is associated with malignant biological behavior in various tumors. The excessive accumulation of copper can induce tumor death, which is named cuproptosis, and it is also closely related to tumor progression and the formation of the immune microenvironment. However, the associations of cuproptosis with glioblastoma (GBM) prognosis and microenvironment construction are poorly understood. METHOD: First, TCGA and GEO (GSE83300, GSE74187) merged datasets were used to analyze the association of cuproptosis-related genes (CRGs) with GBM. Then, we performed cluster analysis of CRGs in GBM from the GEO (GSE83300, GSE74187) and TCGA merged datasets. Subsequently, the prognostic risk model was constructed by least absolute shrinkage and selection operator (LASSO) according to gene expression features in CRG clusters. Next, we performed a series of in-depth analyses, including tumor mutational burden (TMB) analysis, cluster analysis, and GBM IDH status prediction. Finally, RARRES2 was identified as a target gene for GBM treatment, especially IDH wild-type GBM. In addition, we further analyzed the correlation of CRG clusters and RARRES2 expression with the GBM immune microenvironment by ESTIMATE and CIBERSORT analyses. In vitro experiments were conducted to demonstrate that targeting RARRES2 inhibits glioblastoma progression and macrophage infiltration, particularly IDH wild-type GBM. RESULTS: In the present study, we demonstrated that the CRG cluster was closely related to GBM prognosis and immune cell infiltration. Moreover, the prognostic risk model constructed with the three genes (MMP19, G0S2, RARRES2) associated with the CRG clusters could well evaluate the prognosis and immune cell infiltration in GBM. Subsequently, after further analyzing the tumor mutational burden (TMB) in GBM, we confirmed that RARRES2 in the prognostic risk model could be used as a crucial gene signature to predict the prognosis, immune cell infiltration and IDH status of GBM patients. CONCLUSION: This study fully revealed the potential clinical impact of CRGs on GBM prognosis and the microenvironment, and determined the effect of the crucial gene (RARRES2) on the prognosis and tumor microenvironment construction of GBM, meanwhile, our study also revealed over-expressed RARRES2 is related to the IDH satus of GBM, which provides a novel strategy for the treatment of GBM, particularly IDH wild-type GBM.

9.
Analyst ; 149(1): 46-58, 2023 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-37966012

RESUMEN

Chinese herbal medicines (CHMs) derived from nature have received increasing attention and become more popular. Due to their diverse production processes, complex ingredients, and different storage conditions, it is highly desirable to develop simple, rapid, efficient and trace detection methods to ensure the drug quality. Surface-enhanced Raman spectroscopy has the advantages of being time-saving, non-destructive, usable in aqueous environments, and highly compatible with various biomolecular samples, providing a promising analytical method for CHM. In this review, we outline the major advances in the application of SERS to the identification of raw materials, detection of bioactive constituents, characterization of adulterants, and detection of contaminants. This clearly shows that SERS has strong potential in the quality control of CHM, which greatly promotes the modernization of CHM.


Asunto(s)
Medicamentos Herbarios Chinos , Medicamentos Herbarios Chinos/química , Espectrometría Raman/métodos , Control de Calidad , Agua
10.
J Pediatr Hematol Oncol ; 45(2): e180-e187, 2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-36524840

RESUMEN

Primitive neuroectodermal tumors (PNET) are rare malignant tumors, but the mortality rate of the patients is extremely high. The aim of this study was to identify the hub genes and pathways involved in the pathogenesis of PNET and to screen the potential small molecule drugs for PNET. We extracted gene expression profiles from the Gene Expression Omnibus database and identified differentially expressed genes (DEGs) through Limma package in R. Two expression profiles (GSE14295 and GSE74195) were downloaded, including 33 and 5 cases separately. Four hundred sixty-eight DEGs (161 upregulated; 307 downregulated) were identified. Functional annotation and KEGG pathway enrichment of the DEGs were performed using DAVID and Kobas. Gene Ontology analysis showed the significantly enriched Gene Ontology terms included but not limited to mitosis, nuclear division, cytoskeleton, synaptic vesicle, syntaxin binding, and GABA A receptor activity. Cancer-related signaling pathways, such as DNA replication, cell cycle, and synaptic vesicle cycle, were found to be associated with these genes. Subsequently, the STRING database and Cytoscape were utilized to construct a protein-protein interaction and screen the hub genes, and we identified 5 hub genes (including CCNB1, CDC20, KIF11, KIF2C, and MAD2L1) as the key biomarkers for PNET. Finally, we identified potential small molecule drugs through CMap. Seven small molecule compounds, including trichostatin A, luteolin, repaglinide, clomipramine, lorglumide, vorinostat, and resveratrol may become potential candidates for PNET drugs.


Asunto(s)
Biomarcadores de Tumor , Perfilación de la Expresión Génica , Humanos , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Transcriptoma , Proteínas de Ciclo Celular/genética , Biología Computacional
11.
BMC Psychiatry ; 23(1): 615, 2023 08 22.
Artículo en Inglés | MEDLINE | ID: mdl-37608255

RESUMEN

BACKGROUND: Amygdala plays an important role in schizophrenia (SC), but its mechanisms are still unclear. Therefore, we investigated the relationship between the resting-state magnetic resonance imaging (rsMRI) signals of the amygdala and cognitive functions, providing references for future research in this area. METHODS: We collected 40 drug-naïve SC patients and 33 healthy controls (HC) from the Third People's Hospital of Foshan. We used rsMRI and the automatic segmentation tool to extract the structural volume and local neural activity values of the amygdala and conducted Pearson correlation analysis with the Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) scores. Finally, we compared the clinical data, as well as the volume and functional changes of the amygdala in SC patients before and after treatment. RESULTS: Compared with HC, SC had widespread cognitive impairments, significant abnormalities in left amygdala function, while the reduction in volume of SC was not significant. Further Pearson correlation analysis with Bonferroni correction showed that only Immediate memory (learning) was significantly negatively correlated with fractional amplitude of low-frequency fluctuation (FALFF, r = -0.343, p = 0.001, p' = 0.014 (Bonferroni correction)). When compared and analyzed the data difference of SC before and after treatment, we found that immediate memory and delayed memory of SC showed varying degrees of recovery after treatment (tlearning = -2.641, plearning = 0.011; tstory memory = -3.349, pstory memory = 0.001; tlist recall = -2.071, plist recall = 0.043; tstory recall = -2.424, pstory recall = 0.018). But the brain structure and function did not recover. CONCLUSION: There was significant dysfunction in the amygdala in SC, and after conventional treatment, the function of the amygdala did not improve with the improvement of clinical symptoms and cognitive function.


Asunto(s)
Disfunción Cognitiva , Esquizofrenia , Humanos , Esquizofrenia/diagnóstico por imagen , Amígdala del Cerebelo/diagnóstico por imagen , Cognición , Encéfalo , Disfunción Cognitiva/diagnóstico por imagen
12.
BMC Psychiatry ; 23(1): 465, 2023 06 26.
Artículo en Inglés | MEDLINE | ID: mdl-37365547

RESUMEN

BACKGROUND: At present, there is not enough evidence to prove the relationship between blood lipid and electrocardiogram (ECG) abnormalities in common mental disorders (CMD). This study aimed to explore the relationship between them, to detect and prevent arrhythmia or sudden death. METHODS: We collected 272 CMD patients (maintained a fixed drug dose pattern for 1 year or more), including 95 schizophrenias (SC), 90 bipolar disorders (BD) and 87 major depressive disorders (MDD), and 78 healthy controls (HC) from the Third People's Hospital of Foshan, China. We analyzed and compared their blood lipid and ECG indicators, to clarify the relationship between them. RESULTS: 350 participants were included. There were no significant differences in age, gender, total cholesterol (TC), low density lipoprotein (LDL) and QTc (p > 0.05) among subjects. And there were significant differences in body mass index (BMI), triglyceride (TG), high density lipoprotein (HDL), heart rate, PR interval and QRS width (p < 0.05). Person correlation analysis showed that QRS width was positively correlated with BMI and TG. And negatively correlated with HDL. Meanwhile, QTc was positively correlated with BMI. Multiple linear regional analysis further proved that TG (B = 3.849, p = 0.007) and LDL (B = 11.764, p = 0.018) were the risk factors, and HDL (B = -9.935, p = 0.025) was the protective factor for QRS width increase. CONCLUSION: Long term medication of CMD patients should strengthen weight management, and conduct regular blood lipid and ECG examinations to achieve early detection and intervention in order to promote their health.


Asunto(s)
Trastorno Depresivo Mayor , Humanos , HDL-Colesterol , LDL-Colesterol , Lípidos , Triglicéridos , Electrocardiografía
13.
BMC Psychiatry ; 23(1): 231, 2023 04 05.
Artículo en Inglés | MEDLINE | ID: mdl-37020192

RESUMEN

BACKGROUND: Recently studies had showed that the amygdala may take part in the cognitive impairment in schizophrenia (SC). However, the mechanism is still unclear, so we explored the relationship between the amygdala resting state magnetic resonance imaging (rsMRI) signal and cognitive function, to provide a reference for the follow-up study. METHODS: We collected 59 drug-naïve SCs and 46 healthy controls (HCs) from the Third People's Hospital of Foshan. The rsMRI technique and automatic segmentation tool were used to extract the volume and functional indicators of the SC's amygdala. The Positive and Negative Syndrome Scale (PANSS) was used to assess the severity of the disease, and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was used to assess cognitive function. Pearson correlation analysis was used to compare the relationship between the structural and functional indicators of the amygdala and PANSS and RBANS. RESULTS: (1) There was no significant difference between SC and HC in age, gender and years of education. Compared with HC, the PANSS score of SC increased and the RBANS score decreased significantly. Meanwhile, the left amygdala volume decreased (t=-3.675, p < 0.001), and the Fractional amplitude of low-frequency fluctuations (FALFF) values of bilateral amygdala increased (tL=3.916, p < 0.001; tR=3.131, p = 0.002). (2) The volumes of the left amygdala were negatively correlated with the PANSS score (rL=-0.243, p = 0.039). While the FALFF values of the bilateral amygdala were positively correlated with the PANSS score (rL=0.257, p = 0.026; rR=0.259, p = 0.026). Bilateral amygdala volumes and FALFF values were positively correlated (rL=0.445, p < 0.001; rR=0.326, p = 0.006) and negatively correlated with RBANS score (rL=-0.284, p = 0.014; rR=-0.272, p = 0.020), respectively. CONCLUSION: The abnormal volume and function of the amygdala play important roles in the disease process of SC, and are closely related to cognitive impairment.


Asunto(s)
Trastornos del Conocimiento , Disfunción Cognitiva , Esquizofrenia , Humanos , Trastornos del Conocimiento/psicología , Estudios de Seguimiento , Amígdala del Cerebelo
14.
J Biol Chem ; 297(3): 101111, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34437900

RESUMEN

Pulmonary endothelial barrier dysfunction is a major pathophysiology observed in acute respiratory distress syndrome (ARDS). Ghrelin, a key regulator of metabolism, has been shown to play protective roles in the respiratory system. However, its effects on lipopolysaccharide (LPS)-induced pulmonary endothelial barrier injury are unknown. In this study, the effects of ghrelin on LPS-induced ARDS and endothelial cell injury were evaluated in vivo and in vitro. In vivo, mice treated with LPS (3 mg/kg intranasal application) were used to establish the ARDS model. Annexin V/propidium iodide apoptosis assay, scratch-wound assay, tube formation assay, transwell permeability assay, and Western blotting experiment were performed to reveal in vitro effects and underlying mechanisms of ghrelin on endothelial barrier function. Our results showed that ghrelin had protective effects on LPS-induced ARDS and endothelial barrier disruption by inhibiting apoptosis, promoting cell migration and tube formation, and activating the PI3K/AKT signaling pathway. Furthermore, ghrelin stabilized LPS-induced endothelial barrier function by decreasing endothelial permeability and increasing the expression of the intercellular junction protein vascular endothelial cadherin. LY294002, a specific inhibitor of the PI3K pathway, reversed the protective effects of ghrelin on the endothelial cell barrier. In conclusion, our findings indicated that ghrelin protected against LPS-induced ARDS by impairing the pulmonary endothelial barrier partly through activating the PI3K/AKT pathway. Thus, ghrelin may be a valuable therapeutic strategy for the prevention or treatment of ARDS.


Asunto(s)
Ghrelina/metabolismo , Síndrome de Dificultad Respiratoria/prevención & control , Animales , Apoptosis/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Células Endoteliales/metabolismo , Endotelio Vascular/metabolismo , Femenino , Ghrelina/genética , Ghrelina/farmacología , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Inflamación/metabolismo , Uniones Intercelulares/metabolismo , Lipopolisacáridos/farmacología , Pulmón/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Síndrome de Dificultad Respiratoria/metabolismo , Transducción de Señal/efectos de los fármacos
15.
Langmuir ; 38(35): 10749-10759, 2022 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-36001401

RESUMEN

Flexspline frictional degradation causes failure of harmonic drives. This study focused on the improvement of the flexspline tribological properties. Flexspline material 40Cr was modified with a robust polydimethylsiloxane (PDMS) coating. Etched and chemically modified films were utilized to enhance the organic PDMS coating-substrate link strength. Comparing modified and unmodified 40Cr, the surface friction coefficient decreased by 82.2%. Moreover, the modified 40Cr exhibited excellent load-bearing properties. The effects of speed and lubricant-coating interaction on the tribological properties were verified. This study provides an essential theoretical basis for improving the tribological performance of harmonic drives via soft coating modification.

16.
BMC Neurol ; 22(1): 341, 2022 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-36088310

RESUMEN

BACKGROUND: People with sleep problems are more likely to have mental disorders. This study aimed to assess the effect of insomnia on the prognosis of patients with major depressive disorder (MDD). METHODS: We divided the patients into three groups according to the Insomnia Severity Index (ISI) scores. In addition, we compared the results of the Hamilton Depression Scale (HAMD) and Symptom Checklist-90 (SCL-90) scores. We evaluated the effect of insomnia at the 2nd, 4th, and 8th-week follow-up on the prognosis of MDD. RESULTS: Fifty-five patients between 19 and 58 years old, with a diagnosis of MDD via the Structured Clinical Interview for the Diagnostic and Statistical Manual-5 (DSM-5). The ISI scores of the moderate and severe group decreased significantly (P < 0.05) in the 2nd week compared to the baseline. The HAMD scores in all groups improved significantly in the 2nd week. CONCLUSIONS: This study was inspired to assess insomnia as a comorbid disorder for patients with MDD, which may bring poor treatment consequences.


Asunto(s)
Trastorno Depresivo Mayor , Trastornos del Inicio y del Mantenimiento del Sueño , Adulto , Trastorno Depresivo Mayor/complicaciones , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/epidemiología , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Humanos , Persona de Mediana Edad , Trastornos del Inicio y del Mantenimiento del Sueño/complicaciones , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Adulto Joven
17.
BMC Psychiatry ; 22(1): 654, 2022 10 21.
Artículo en Inglés | MEDLINE | ID: mdl-36271368

RESUMEN

BACKGROUND: Bipolar disorder (BD) and schizophrenia (SC) have many similarities in clinical manifestations. The acute phase of BD has psychotic symptoms, while SC also has emotional symptoms during the onset, which suggests that there is some uncertainty in distinguishing BD and SC through clinical symptoms. AIM: To explore the characteristics of brain functional activities and cognitive impairment between BD and SC. METHODS: Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) test was performed on patients in drug-naïve BD and SC (50 subjects in each group), and resting-state functional magnetic resonance imaging (rs-fMRI) scanning was performed meanwhile. Rs-fMRI data were routinely preprocessed, and the value of the fractional amplitude of low-frequency fluctuation (fALFF) was calculated. Then each part of the scores of the RBANS and the characteristics of brain function activities were compared between the two groups. Finally used Pearson correlation to analyze the correlation between cognition and brain function. RESULTS: (1) Compared with BD group, all parts of RBANS scores in SC group decreased; (2) The left inferior occipital gyrus (IOG, peak coordinates - 30, -87, -15; t = 4.78, voxel size = 31, Alphasim correction) and the right superior temporal gyrus (STG, peak coordinates 51, -12, 0; t = 5.08, voxel size = 17, AlphaSim correction) were the brain areas with significant difference in fALFF values between BD and SC. Compared with SC group, the fALFF values of the left IOG and the right STG in BD group were increased (p < 0.05); (3) Pearson correlation analysis showed that the visuospatial construction score was positively correlated with the fALFF values of the left IOG and the right STG (rleft IOG = 0.304, p = 0.003; rright STG = 0.340, p = 0.001); The delayed memory (figure recall) score was positively correlated with the fALFF value of the left IOG (rleft IOG = 0.207, p = 0.044). DISCUSSION: The cognitive impairment of SC was more serious than BD. The abnormal activities of the left IOG and the right STG may be the core brain region to distinguish BD and SC, and are closely related to cognitive impairment, which provide neuroimaging basis for clinical differential diagnosis and explore the pathological mechanism of cognitive impairment.


Asunto(s)
Trastorno Bipolar , Esquizofrenia , Humanos , Imagen por Resonancia Magnética/métodos , Trastorno Bipolar/diagnóstico por imagen , Esquizofrenia/diagnóstico por imagen , Descanso , Cognición
18.
BMC Psychiatry ; 22(1): 91, 2022 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-35130845

RESUMEN

BACKGROUND: Obesity is a serious worldwide public health problem, especially for people with mental disorders. AIM: To explore the related factors of obesity by analyzing the metabolic indexes of patients with common mental disorders in stable stage. METHODS: Five hundred seventy-six subjects with major depressive disorder (MDD), bipolar disorder (BD) or schizophrenia (SCZ) were included, who received fixed drug dose and routine drug treatment for 2 years or more. Their venous blood was collected, and the blood metabolic indexes were analyzed. RESULTS: BD and SCZ are more prone to obesity than MDD. Multiple linear regression analysis showed that the value of BMI increased with the increase of age(B = 0.084, p < 0.001), TG(B = 0.355, p = 0.024), LDL(B = 0.697, p < 0.001), LDH(B = 0.011, p = 0.002), SCr(B = 0.051, p < 0.001), UA(B = 0.014, p < 0.001), HbA1c(B = 0.702, p = 0.004) and hsCRP(B = 0.101, p < 0.001). And It decreased with the increase of HDL(B = -1.493, p < 0.001). DISCUSSION: People with mental disorders should regularly check blood indicators and strengthen weight management to reduce the risk of obesity and promote their health.


Asunto(s)
Trastorno Bipolar , Trastorno Depresivo Mayor , Trastornos Mentales , Esquizofrenia , Trastorno Bipolar/complicaciones , Trastorno Bipolar/tratamiento farmacológico , Trastorno Depresivo Mayor/complicaciones , Trastorno Depresivo Mayor/tratamiento farmacológico , Humanos , Trastornos Mentales/complicaciones , Obesidad/complicaciones , Esquizofrenia/complicaciones , Esquizofrenia/tratamiento farmacológico
19.
J Environ Manage ; 322: 116054, 2022 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-36058071

RESUMEN

Peroxymonosulfate-based advanced oxidation (PMS-AOP) is a promising technology for the degradation of environmental pollutants. PMS can be activated by various transition metals, especially cobalt-based catalysts, but pure cobalt catalyst suffers from severe metal leakage and poor cyclicality. This study synthesized NiCo2O4 using a co-precipitation hydrothermal method. The structures, morphologies, and chemical states of the prepared catalysts were hexagonal sheet structures. The activation of PMS by catalyst (NiCo2O4) is investigated in a PMS/carbonate (PC) system for Orange II degradation. The observed pseudo-first-order rate constants (k1) were assessed by the effects of different water matrices and operation conditions. The results show that kobs with NiCo2O4 were increased by 13 times than that of treatment without NiCo2O4. This was mainly due to Co3+ and Ni3+ act as electron acceptors to capture electrons from the PMS/PC system, forming a good redox cycle with HSO5-/SO5- and oxidizing Co2+/Ni2+ to produce a large amount of more active components (e.g., 1O2 and SO4⋅-). The good reusability and high stability of NiCo2O4 were demonstrated by five recycle tests. These results suggest that the NiCo2O4/PC system is an efficient and stable method of pollution remediation.


Asunto(s)
Citrus sinensis , Contaminantes Químicos del Agua , Cobalto/química , Oxidación-Reducción , Peróxidos/química , Agua , Contaminantes Químicos del Agua/química
20.
Cancer Cell Int ; 21(1): 518, 2021 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-34583688

RESUMEN

BACKGROUND: There is a lack of effective treatments for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC). Furthermore, the response rate of NPC patients to programmed death 1 (PD-1) inhibitors is approximately 20% to 30%. Thus, we aimed to explore reliable and minimally invasive prognostic indicators to predict the efficacy of PD-1 inhibitors combination therapy in RM-NPC. METHODS: The serum markers of 160 RM-NPC patients were measured before and three weeks after the first anti-PD-1 treatment. The least absolute shrinkage and selection operator (LASSO) logistic regression was carried out to select dynamic serum indicators and construct a prediction model. Furthermore, we carried out univariate, multivariate, nomogram and survival analyses to identify independent prognostic factors that were associated with 1-year progression-free survival (PFS). RESULTS: Based on two markers that were screened by Lasso logistic regression, we constructed a risk score prediction model for the prediction of anti-PD-1 efficacy at 8-12 weeks with an AUC of 0.737 in the training cohort and 0.723 in the validation cohort. Risk score and metastases were included in the nomogram, and the Kaplan-Meier survival curves demonstrated that the high-risk group has shorter PFS compared to the low-risk group. The concordance index (C-index) of the nomogram for PFS is higher than that of the TNM stage in the training and validation cohort. CONCLUSION: We proposed a strategy to monitor dynamic changes in the biochemistry markers and emphasized their importance as potential prognostic biomarkers for the treatment of advanced NPC treated with PD-1 inhibitors. Our risk score prediction model was based on the dynamic change of LDH and AST/ALT, which has predictive and prognostic value for NPC patients who were treated with PD-1 inhibitors.

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