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BACKGROUND: The pentose phosphate pathway (PPP) is a critical metabolic pathway that generates NADPH and ribose-5-phosphate for nucleotide biosynthesis and redox homeostasis. In this study, we investigated a potential regulatory role for Krüppel-like factor 8 (KLF8) in the control of PPP in lung adenocarcinoma (LUAD) cells. METHODS: Based on a comprehensive set of experimental approaches, including cell culture, molecular techniques, and functional assays, we revealed a novel mechanism by which KLF8 promotes the activation of glucose-6-phosphate dehydrogenase (G6PD), a component enzyme in the PPP. RESULTS: Our findings demonstrate that KLF8 inhibits the acetylation of G6PD, leading to its increased enzymatic activity. Additionally, we observed that KLF8 activates the transcription of SIRT2, which has been implicated in regulating G6PD acetylation. These results highlight the interplay between KLF8, G6PD, and protein acetylation in the regulation of PPP in LUAD. CONCLUSIONS: Understanding the intricate molecular mechanisms underlying the metabolic reprogramming driven by KLF8 in lung cancer provides valuable insights into potential therapeutic strategies targeting the PPP. This study emphasizes the significance of KLF8 as a key modulator of metabolic pathways and indicates the potential of targeting the KLF8-G6PD axis for lung cancer treatment.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Vía de Pentosa Fosfato/fisiología , Sirtuina 2/genética , Sirtuina 2/metabolismo , Adenocarcinoma del Pulmón/genética , Neoplasias Pulmonares/genética , Pulmón/metabolismo , Factores de Transcripción de Tipo Kruppel/genética , Factores de Transcripción de Tipo Kruppel/metabolismoRESUMEN
Alzheimer's disease (AD) is a biological, clinical continuum that covers the preclinical, prodromal, and clinical phases of the disease. Early diagnosis and identification of the stages of Alzheimer's disease (AD) are crucial in clinical practice. Ideally, biomarkers should reflect the underlying process (pathological or otherwise), be reproducible and non-invasive, and allow repeated measurements over time. However, the currently known biomarkers for AD are not suitable for differentiating the stages and predicting the trajectory of disease progression. Some objective parameters extracted using electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) are widely applied to diagnose the stages of the AD continuum. While electroencephalography (EEG) has a high temporal resolution, fMRI has a high spatial resolution. Combined EEG and fMRI (EEG-fMRI) can overcome single-modality drawbacks and obtain multi-dimensional information simultaneously, and it can help explore the hemodynamic changes associated with the neural oscillations that occur during information processing. This technique has been used in the cognitive field in recent years. This review focuses on the different techniques available for studying the AD continuum, including EEG and fMRI in single-modality and multi-modality settings, and the possible future directions of AD diagnosis using EEG-fMRI.
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Enfermedad de Alzheimer , Encéfalo , Electroencefalografía , Imagen por Resonancia Magnética , Humanos , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/fisiopatología , Enfermedad de Alzheimer/diagnóstico , Electroencefalografía/métodos , Imagen por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Imagen Multimodal/métodosRESUMEN
Pollution from electronic-waste (E-waste) dismantling is of great concern. This study investigated the concentrations of polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), and polybrominated diphenyl ethers (PBDEs) in 253 cropland soil samples around an abandoned E-waste dismantling site in Taizhou city, Zhejiang province in China, using an analytical method which simultaneously extracted, purified and determined the identity and quantity of the three types of persistent organic pollutants. Meanwhile, their spatial distributions, pollution characteristics, and risk assessments were further analyzed. Total PCBs in the test soils ranged from below method detection limits (ND) to 2985.25 µg kg-1 on a dry weight basis (d.w.), and the spatial distribution indicated a "hot spot" of PCBs pollution in the study area. The PAHs were detected in all samples with total concentrations ranging from 4.99 to 2723.06 µg kg-1 d.w. The distribution of PBDEs showed the pollution characteristics of "family-run workshops", with a total content range of ND ~ 899.34 µg kg-1 d.w., of which BDE209 was typically the dominant congener, accounting for 74.05% of the total PBDEs content in the test soils, with the highest content reaching 857.72 µg kg-1 d.w. Results showed that the ecological and lifetime carcinogenic risks of PCBs and PAHs were low in the study area, but the health risk caused by oral ingestion and dermal contact accounted for the highest proportion of the total exposure risks, while inhalation could be ignored. PBDEs in soils of the study area were a potential chronic non-carcinogenic risk, particularly for children. Therefore, in order to protect human health and environment, it is necessary to regulate the management of E-waste dismantling sites and pollution control.
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Residuos Electrónicos , Bifenilos Policlorados , Niño , Humanos , Bifenilos Policlorados/análisis , Monitoreo del Ambiente , Residuos Electrónicos/análisis , Éteres Difenilos Halogenados/análisis , Granjas , China , Suelo , Medición de RiesgoRESUMEN
BACKGROUND: Subjective cognitive decline (SCD) may serve as a symptomatic indicator for preclinical Alzheimer's disease; however, SCD is a heterogeneous entity regarding clinical progression. We aimed to investigate whether spatial navigation could reveal subcortical structural alterations and the risk of progression to objective cognitive impairment in SCD individuals. METHODS: One hundred and eighty participants were enrolled: those with SCD (n = 80), normal controls (NCs, n = 77), and mild cognitive impairment (MCI, n = 23). SCD participants were further divided into the SCD-good (G-SCD, n = 40) group and the SCD-bad (B-SCD, n = 40) group according to their spatial navigation performance. Volumes of subcortical structures were calculated and compared among the four groups, including basal forebrain, thalamus, caudate, putamen, pallidum, hippocampus, amygdala, and accumbens. Topological properties of the subcortical structural covariance network were also calculated. With an interval of 1.5 years ± 12 months of follow-up, the progression rate to MCI was compared between the G-SCD and B-SCD groups. RESULTS: Volumes of the basal forebrain, the right hippocampus, and their respective subfields differed significantly among the four groups (p < 0.05, false discovery rate corrected). The B-SCD group showed lower volumes in the basal forebrain than the G-SCD group, especially in the Ch4p and Ch4a-i subfields. Furthermore, the structural covariance network of the basal forebrain and right hippocampal subfields showed that the B-SCD group had a larger Lambda than the G-SCD group, which suggested weakened network integration in the B-SCD group. At follow-up, the B-SCD group had a significantly higher conversion rate to MCI than the G-SCD group. CONCLUSION: Compared to SCD participants with good spatial navigation performance, SCD participants with bad performance showed lower volumes in the basal forebrain, a reorganized structural covariance network of subcortical nuclei, and an increased risk of progression to MCI. Our findings indicated that spatial navigation may have great potential to identify SCD subjects at higher risk of clinical progression, which may contribute to making more precise clinical decisions for SCD individuals who seek medical help.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Navegación Espacial , Humanos , Pruebas Neuropsicológicas , Enfermedad de Alzheimer/complicaciones , Disfunción Cognitiva/psicología , Progresión de la EnfermedadRESUMEN
Brain dynamics and the associations with spatial navigation in individuals with subjective cognitive decline (SCD) remain unknown. In this study, a hidden Markov model (HMM) was inferred from resting-state functional magnetic resonance imaging data in a cohort of 80 SCD and 77 normal control (NC) participants. By HMM, 12 states with distinct brain activity were identified. The SCD group showed increased fractional occupancy in the states with less activated ventral default mode, posterior salience, and visuospatial networks, while decreased fractional occupancy in the state with general network activation. The SCD group also showed decreased probabilities of transition into and out of the state with general network activation, suggesting an inability to dynamically upregulate and downregulate brain network activity. Significant correlations between brain dynamics and spatial navigation were observed. The combined features of spatial navigation and brain dynamics showed an area under the curve of 0.854 in distinguishing between SCD and NC. The findings may provide exploratory evidence of the reconfiguration of brain network dynamics underlying spatial deficits in SCD.
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Disfunción Cognitiva , Imagen por Resonancia Magnética , Humanos , Imagen por Resonancia Magnética/métodos , Encéfalo/fisiología , Disfunción Cognitiva/psicología , Mapeo Encefálico/métodos , ProbabilidadRESUMEN
Cerebral small vessel disease (CSVD) is a common disease that seriously endangers people's health, and is easily overlooked by both patients and clinicians due to its near-silent onset. Dynamic functional connectivity (DFC) is a new concept focusing on the dynamic features and patterns of brain networks that represents a powerful tool for gaining novel insight into neurological diseases. To assess alterations in DFC in CSVD patients, and the correlation of DFC with cognitive function. We enrolled 35 CSVD patients and 31 normal control subjects (NC). Resting-state functional MRI (rs-fMRI) with a sliding-window approach and k-means clustering based on independent component analysis (ICA) was used to evaluate DFC. The temporal properties of fractional windows and the mean dwell time in each state, as well as the number of transitions between each pair of DFC states, were calculated. Additionally, we assessed the functional connectivity (FC) strength of the dynamic states and the associations of altered neuroimaging measures with cognitive performance. A dynamic analysis of all included subjects suggested four distinct functional connectivity states. Compared with the NC group, the CSVD group had more fractional windows and longer mean dwell times in state 4 characterized by sparse FC both inter-network and intra-networks. Additionally, the CSVD group had a reduced number of windows and shorter mean dwell times compared to the NC group in state 3 characterized by highly positive FC between the somatomotor and visual networks, and negative FC in the basal ganglia and somatomotor and visual networks. The number of transitions between state 2 and state 3 and between state 3 and state 4 was significantly reduced in the CSVD group compared to the NC group. Moreover, there was a significant difference in the FC strength between the two groups, and the altered temporal properties of DFC were significantly related to cognitive performance. Our study indicated that CSVD is characterized by altered temporal properties in DFC that may be sensitive neuroimaging biomarkers for early disease identification. Further study of DFC alterations could help us to better understand the progressive dysfunction of networks in CSVD patients.
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[This retracts the article DOI: 10.1515/med-2022-0417.].
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Acute lung injury (ALI) is a respiratory disorder characterized by acute respiratory failure. circRNA mus musculus (mmu)-circ_0001679 was reported overexpressed in septic mouse models of ALI. Here the function of circ_0001679 in sepsis-induced ALI was investigated. In vitro models and animal models with ALI were, respectively, established in mouse lung epithelial (MLE)-12 cells and C57BL/6 mice. Pulmonary specimens were harvested for examination of the pathological changes. The pulmonary permeability was examined by wet-dry weight (W/D) ratio and lung permeability index. The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß in the bronchoalveolar lavage fluid (BALF), the lung tissues, and the supernatant of MLE-12 cells were measured by enzyme linked immunosorbent assay . Apoptosis was determined by flow cytometry. Bioinformatics analysis and luciferase reporter assay were used to assess the interactions between genes. We found that circ_0001679 was overexpressed in lipopolysaccharide (LPS)-stimulated MLE-12 cells. circ_0001679 knockdown suppressed apoptosis and proinflammatory cytokine production induced by LPS. Moreover, circ_0001679 bound to mmu-miR-338-3p and miR-338-3p targeted dual-specificity phosphatases 16 (DUSP16). DUSP16 overexpression reversed the effect of circ_0001679 knockdown in LPS-stimulated MLE-12 cells. Furthermore, circ_0001679 knockdown attenuated lung pathological changes, reduced pulmonary microvascular permeability, and suppressed inflammation in ALI mice. Overall, circ_0001679 knockdown inhibits sepsis-induced ALI progression through the miR-338-3p/DUSP16 axis.
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BACKGROUND Circular RNAs (circRNAs) are frequently aberrantly expressed in non-small cell lung cancer (NSCLC) and are considered to exert a pivotal role in the occurrence and development of NSCLC via targeting and negatively regulating microRNAs (miRNAs). We aimed to investigate the role of hsa_circ_0109320 in the proliferation, invasion and apoptosis of NSCLC, and explore its underlying molecular mechanism. MATERIAL AND METHODS Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis was performed to determine the circ_0109320 and miR-595 expression in tissues or cells. Western blot analysis was conducted to examine the cleaved caspase-3, Bax, Bcl-2, and E2F7 protein expression. Transwell detection was used to evaluate the invasion level of NSCLC cell lines. RESULTS The results of present study indicated that circ_0109320 expression in NSCLC patients was upregulated significantly in tumor tissues compared with tissues adjacent to carcinoma. Upregulated circ_0109320 level was significantly associated with TNM stages as well as lymph node metastasis of NSCLC. Moreover, downregulation of circ_0109320 attenuated proliferation and invasion while promoting apoptosis in NSCLC cells. We further confirmed that circ_0109320 could sponge miR-595 to upregulate E2F7 expression. Silencing of miR-595 or overexpression of E2F2 could partially reversed the inhibitory role of circ_0109320 knockdown in NSCLC cells. These data provided evidence that the suppression of circ_0109320 attenuates NSCLC cell proliferation and invasion and enhances apoptosis through the miR-595/E2F7 pathway. CONCLUSIONS Circ_0109320/miR-595/E2F2 axis may exert a pivotal role in the pathological mechanism of NSCLC progression, and it has potential application in the future treatment of NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas/genética , MicroARNs/genética , ARN Circular/genética , Adulto , Anciano , Anciano de 80 o más Años , Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Proliferación Celular/genética , Progresión de la Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Neoplasias Pulmonares/patología , Masculino , MicroARNs/metabolismo , Persona de Mediana Edad , Invasividad Neoplásica , ARN/genética , ARN Circular/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa/métodosRESUMEN
Herein, we described 2 patients with posterior spinal artery syndrome (PSAS) caused by vertebral artery dissection. The patients complained of sudden neck pain or walking instability. Neurological examination revealed sensory loss, muscle weakness, and sensory ataxia. Angiography showed double lumen sign or intimal flap in the vertebral artery. T2-weighted imaging and diffusion-weighted imaging of MRI showed a hyperintense lesion in the dorsal side of the cervical spinal cord at different times after onset. Both patients had good outcome after antiplatelet therapy and physiotherapy. A review of previously reported PSAS cases was also conducted in order to improve the understanding and awareness of this rare myelopathy.
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Enfermedades Vasculares de la Médula Espinal/etiología , Disección de la Arteria Vertebral/complicaciones , Adulto , Femenino , Marcha , Trastornos Neurológicos de la Marcha/etiología , Trastornos Neurológicos de la Marcha/fisiopatología , Trastornos Neurológicos de la Marcha/terapia , Humanos , Masculino , Dolor de Cuello/etiología , Dolor de Cuello/fisiopatología , Dolor de Cuello/terapia , Modalidades de Fisioterapia , Inhibidores de Agregación Plaquetaria/uso terapéutico , Recuperación de la Función , Enfermedades Vasculares de la Médula Espinal/diagnóstico por imagen , Enfermedades Vasculares de la Médula Espinal/fisiopatología , Enfermedades Vasculares de la Médula Espinal/terapia , Resultado del Tratamiento , Disección de la Arteria Vertebral/diagnóstico por imagen , Disección de la Arteria Vertebral/fisiopatología , Disección de la Arteria Vertebral/terapiaRESUMEN
OBJECTIVE: To determine the expression levels of KIF18A in lung adenocarcinoma and its relationship with the clinicopathologic features of patients undergoing radical colectomy and explore the potential role in the progression of lung adenocarcinoma. METHODS: Immunohistochemical assays were performed to explore the expression levels of KIF18A in 82 samples of lung adenocarcinoma and corresponding normal tissues. According to the levels of KIF18A expression in lung adenocarcinoma tissue samples, patients were classified into the KIF18A high expression group and low expression group. Clinical data related to the perioperative clinical features (age, gender, smoking, tumor size, differentiation, clinical stage, and lymph node metastasis), the potential correlation between KIF18A expression levels, and clinical features were analyzed, and the effects of KIF18A on lung adenocarcinoma cell proliferation, migration, and invasion were measured by colony formation assay, MTT assay, wound healing assay, and transwell assays. The possible effects of KIF18A on tumor growth and metastasis were measured in mice through tumor growth and tumor metastasis assays in vivo. RESULTS: KIF18A in lung adenocarcinoma tissues. Further, KIF18A was significantly associated to clinical characteristic features including the tumor size (P = 0.033) and clinical stage (P = 0.041) of patients with lung adenocarcinoma. Our data also investigated that KIF18A depletion dramatically impairs the proliferation, migration, and invasion capacity of lung adenocarcinoma cells in vitro and inhibits tumor growth and metastasis in mice. CONCLUSIONS: Our study reveals the involvement of KIF18A in the progression and metastasis of lung adenocarcinoma and provides a novel therapeutic target for the treatment of lung adenocarcinoma.