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Enolase 1 (ENO1) is a glycolytic enzyme that plays essential roles in various pathological activities including cancer development. However, the mechanisms underlying ENO1-contributed tumorigenesis are not well explained. Here, we uncover that ENO1, as an RNA-binding protein, binds to the cytosine-uracil-guanine-rich elements of YAP1 messenger RNA to promote its translation. ENO1 and YAP1 positively regulate alternative arachidonic acid (AA) metabolism by inverse regulation of PLCB1 and HPGD (15-hydroxyprostaglandin dehydrogenase). The YAP1/PLCB1/HPGD axis-mediated activation of AA metabolism and subsequent accumulation of prostaglandin E2 (PGE2) are responsible for ENO1-mediated cancer progression, which can be retarded by aspirin. Finally, aberrant activation of ENO1/YAP1/PLCB1 and decreased HPGD expression in clinical hepatocellular carcinoma samples indicate a potential correlation between ENO1-regulated AA metabolism and cancer development. These findings underline a new function of ENO1 in regulating AA metabolism and tumorigenesis, suggesting a therapeutic potential for aspirin in patients with liver cancer with aberrant expression of ENO1 or YAP1.
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Carcinogênese , Neoplasias Hepáticas , Humanos , Ácido Araquidônico , Linhagem Celular Tumoral , Proliferação de Células , Carcinogênese/genética , Transformação Celular Neoplásica , Fosfopiruvato Hidratase/genética , Fosfopiruvato Hidratase/metabolismo , Neoplasias Hepáticas/genética , Aspirina/farmacologia , Proteínas de Ligação a DNA/genética , Biomarcadores Tumorais , Proteínas Supressoras de Tumor/genéticaRESUMO
Community-acquired pneumonia (CAP) is a leading cause of hospitalization and mortality in the elderly. The peripheral blood neutrophil CD64 (nCD64) index is increasingly recognized for its association with poor pneumonia prognosis. A comprehensive investigation involving 128 elderly patients diagnosed with CAP, including 96 with non-severe CAP and 32 with severe CAP, from January 2020 to January 2021 was performed. The nCD64 index, CD4+, CD8+, C-reactive protein (CRP), white blood cell (WBC) count, procalcitonin (PCT), neutrophil (NEUT), and B lymphocyte count were determined using flow cytometry. Our findings reveal that patients with severe CAP exhibited significantly higher levels of nCD64 index, NEUT, WBC, CRP, and PCT. Intriguingly, lower CRP, nCD64 index, CURB-65 score, and PCT were associated with a higher survival rate. Notably, the nCD64 index demonstrated remarkable predictive efficiency for 28-d survival in CAP patients [area under the curve (AUC) = 0.907], surpassing other markers and even showing enhanced predictive power when combined with the CURB-65 score (AUC = 0.905). Furthermore, a negative association was observed between the nCD64 index and both CD4+, CD4+/CD8+ ratios, and B lymphocytes, highlighting its potential role in immune dysregulation. These findings underscore the critical importance of the nCD64 index in the early diagnosis, risk stratification, and prognostic evaluation of infections and immune responses in elderly CAP patients.
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Infecções Comunitárias Adquiridas , Pneumonia , Humanos , Idoso , Prognóstico , Neutrófilos , Proteína C-Reativa/análise , Pneumonia/diagnóstico , Contagem de Leucócitos , Infecções Comunitárias Adquiridas/diagnósticoRESUMO
BACKGROUND: Both genetic factors and environmental air pollution contribute to the risk of stroke. However, it is unknown whether the association between air pollution and stroke risk is influenced by the genetic susceptibilities of stroke and its risk factors. METHODS: This prospective cohort study included 40â 827 Chinese adults without stroke history. Satellite-based monthly fine particulate matter (PM2.5) estimation at 1-km resolution was used for exposure assessment. Based on 534 identified genetic variants from genome-wide association studies in East Asians, we constructed 6 polygenic risk scores for stroke and its risk factors, including atrial fibrillation, blood pressure, type 2 diabetes, body mass index, and triglyceride. The Cox proportional hazards model was applied to evaluate the hazard ratios and 95% CIs for the associations of PM2.5 and polygenic risk score with incident stroke and the potential effect modifications. RESULTS: Over a median follow-up of 12.06 years, 3147 incident stroke cases were documented. Compared with the lowest quartile of PM2.5 exposure, the hazard ratio (95% CI) for stroke in the highest quartile group was 2.72 (2.42-3.06). Among individuals at high genetic risk, the relative risk of stroke was 57% (1.57; 1.40-1.76) higher than those at low genetic risk. Although no statistically significant interaction was found, participants with both the highest PM2.5 and high genetic risk showed the highest risk of stroke, with ≈4× that of the lowest PM2.5 and low genetic risk group (hazard ratio, 3.55 [95% CI, 2.84-4.44]). Similar upward gradients were observed in the risk of stroke when assessing the joint effects of PM2.5 and genetic risks of blood pressure, type 2 diabetes, body mass index, atrial fibrillation, and triglyceride. CONCLUSIONS: Long-term exposure to PM2.5 was associated with a higher risk of incident stroke across different genetic susceptibilities. Our findings highlighted the great importance of comprehensive assessment of air pollution and genetic risk in the prevention of stroke.
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Poluentes Atmosféricos , Poluição do Ar , Fibrilação Atrial , Diabetes Mellitus Tipo 2 , Acidente Vascular Cerebral , Adulto , Humanos , Material Particulado/efeitos adversos , Material Particulado/análise , Estudos Prospectivos , Fibrilação Atrial/complicações , Estudo de Associação Genômica Ampla , Exposição Ambiental/efeitos adversos , Incidência , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/induzido quimicamente , Poluição do Ar/efeitos adversos , Fatores de Risco , Predisposição Genética para Doença , Triglicerídeos , Poluentes Atmosféricos/efeitos adversosRESUMO
BACKGROUND: Previous studies focusing on assessing the effects of remnant cholesterol (RC) and low-density lipoprotein cholesterol (LDL-C) on stroke may not consider their mutual influence. We aimed to explore the associations of RC and discordant high RC with LDL-C with stroke, ischemic stroke (IS), and hemorrhagic stroke. METHODS: This prospective cohort study was conducted based on 3 cohorts of the China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk in China) project. RC was calculated as non-high-density lipoprotein cholesterol minus LDL-C estimated by Martin/Hopkins equations. Concordant/discordant categories for RC versus LDL-C were determined based on cut-points of 130 mg/dL for LDL-C and equivalent percentile (32.50 mg/dL) for RC. Cox models were used to estimate adjusted hazard ratios and 95% CIs for incident stroke. RESULTS: Among 113 448 participants recruited at baseline, a total of 98 967 participants were eligible for the final analysis (mean age of 51.44 years; 40.45% were men). During 728 776.87 person-years of follow-up, 2859 stroke cases, 1811 IS cases, and 849 hemorrhagic stroke cases were observed. RC was positively associated with stroke and IS, but not hemorrhagic stroke, with adjusted hazard ratios (95% CIs) of 1.06 (1.02-1.10), 1.09 (1.04-1.13), and 0.95 (0.88-1.03) for per SD increase in RC. Compared with low LDL-C/low RC group, low LDL-C/high RC group had higher risks of stroke (adjusted hazard ratio, 1.15 [95% CI, 1.02-1.30]) and IS (1.19, 1.03-1.38), while high LDL-C/low RC group had no increased risk of stroke (1.07 [0.95-1.20]) and IS (1.09 [0.94-1.25]). CONCLUSIONS: Higher RC was associated with increased risks of stroke and IS but not hemorrhagic stroke. Discordantly high RC, not discordantly high LDL-C, conferred higher risks of stroke and IS. Our findings support further lowering RC by interventions to reduce residual IS risk.
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LDL-Colesterol , Colesterol , Acidente Vascular Cerebral , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , LDL-Colesterol/sangue , Estudos Prospectivos , China/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/sangue , Colesterol/sangue , Adulto , Fatores de Risco , Estudos de Coortes , Idoso , AVC Isquêmico/epidemiologia , AVC Isquêmico/sangue , Acidente Vascular Cerebral Hemorrágico/epidemiologia , Acidente Vascular Cerebral Hemorrágico/sangue , Triglicerídeos/sangue , População do Leste AsiáticoRESUMO
Patients treated with Pt-based anticancer drugs (PtII) often experience severe side effects and are susceptible to cancer recurrence due to the limited bioavailability of PtII and tumor-induced immunosuppression. The exposure of phosphatidylserine on the cell's outer surface induced by PtII results in profound immunosuppression through the binding of phosphatidylserine to its receptors on immune cells. Here, we report a novel approach for enhanced cancer chemoimmunotherapy, where a novel nuclear-targeting lipid PtIV prodrug amphiphile was used to deliver a small interfering RNA (siXkr8) to simultaneously amplify Pt-DNA adducts and reduce the level of exposure of phosphatidylserine. This drug delivery vehicle is engineered by integrating the PtIV prodrug with self-assembly performance and siXkr8 into a lipid nanoparticle, which shows tumor accumulation, cancer cell nucleus targeting, and activatable in a reduced microenvironment. It is demonstrated that nuclear-targeting lipid PtIV prodrug increases the DNA cross-linking, resulting in increased Pt-DNA adduct formation. The synergistic effects of the PtIV prodrug and siXkr8 contribute to the improvement of the tumor immune microenvironment. Consequently, the increased Pt-DNA adducts and immunogenicity effectively inhibit primary tumor growth and prevent tumor recurrence. These results underscore the potential of utilizing the nuclear-targeting lipid PtIV prodrug amphiphile to enhance Pt-DNA adduct formation and employing siXkr8 to alleviate immunosuppression during chemotherapy.
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Antineoplásicos , Neoplasias , Pró-Fármacos , Humanos , Pró-Fármacos/farmacologia , Adutos de DNA , Fosfatidilserinas , RNA Interferente Pequeno , Antineoplásicos/farmacologia , Neoplasias/tratamento farmacológico , RNA de Cadeia Dupla , Linhagem Celular Tumoral , Cisplatino , Microambiente TumoralRESUMO
The length of hypocotyl affects the height of soybean and lodging resistance, thus determining the final grain yield. However, research on soybean hypocotyl length is scarce, and the regulatory mechanisms are not fully understood. Here, we identified a module controlling the transport of sucrose, where sucrose acts as a messenger moved from cotyledon to hypocotyl, regulating hypocotyl elongation. This module comprises four key genes, namely MYB33, SWEET11, SWEET21 and GA2ox8c in soybean. In cotyledon, MYB33 is responsive to sucrose and promotes the expression of SWEET11 and SWEET21, thereby facilitating sucrose transport from the cotyledon to the hypocotyl. Subsequently, sucrose transported from the cotyledon up-regulates the expression of GA2ox8c in the hypocotyl, which ultimately affects the length of the hypocotyl. During the domestication and improvement of soybean, an allele of MYB33 with enhanced abilities to promote SWEET11 and SWEET21 has gradually become enriched in landraces and cultivated varieties, SWEET11 and SWEET21 exhibit high conservation and have undergone a strong purified selection and GA2ox8c is under a strong artificial selection. Our findings identify a new molecular pathway in controlling soybean hypocotyl elongation and provide new insights into the molecular mechanism of sugar transport in soybean.
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Optical zoom is an essential function for many imaging systems including consumer electronics, biomedical microscopes, telescopes, and projectors. However, most optical zoom imaging systems have discrete zoom rates or narrow zoom ranges. In this work, a continuous optical zoom imaging system with a wide zoom range is proposed. It consists of a solid lens, two Alvarez lenses, and a camera with an objective. Each Alvarez lens is composed of two cubic phase plates, which have inverted freeform surfaces concerning each other. The movement of the cubic phase masks perpendicular to the optical axis is realized by the actuation of the dielectric elastomer. By applying actuation voltages to the dielectric elastomer, cubic phase masks are moved laterally and then the focal lengths of the two Alvarez lenses are changed. By adjusting the focal lengths of these two Alvarez lenses, the optical magnification is tuned. The proposed continuous optical zoom imaging system is built and the validity is verified by the experiments. The experimental results demonstrate that the zoom ratio is up to 10×, i.e., the magnification continuously changes from 1.58× to 15.80× when the lateral displacements of the cubic phase masks are about 1.0 mm. The rise and fall response times are 150â ms and 210â ms, respectively. The imaging resolution can reach 114 lp/mm during the optical zoom process. The proposed continuous optical imaging system is expected to be used in the fields of microscopy, biomedicine, virtual reality, etc.
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Ghost imaging (GI) has been widely used in the applications including spectral imaging, 3D imaging, and other fields due to its advantages of broad spectrum and anti-interference. Nevertheless, the restricted sampling efficiency of ghost imaging has impeded its extensive application. In this work, we propose a novel foveated pattern affine transformer method based on deep learning for efficient GI. This method enables adaptive selection of the region of interest (ROI) by combining the proposed retina affine transformer (RAT) network with minimal computational and parametric quantities with the foveated speckle pattern. For single-target and multi-target scenarios, we propose RAT and RNN-RAT (recurrent neural network), respectively. The RAT network enables an adaptive alteration of the fovea of the variable foveated patterns spot to different sizes and positions of the target by predicting the affine matrix with a minor number of parameters for efficient GI. In addition, we integrate a recurrent neural network into the proposed RAT to form an RNN-RAT model, which is capable of performing multi-target ROI detection. Simulations and experimental results show that the method can achieve ROI localization and pattern generation in 0.358â ms, which is a 1 × 105 efficiency improvement compared with the previous methods and improving the image quality of ROI by more than 4â dB. This approach not only improves its overall applicability but also enhances the reconstruction quality of ROI. This creates additional opportunities for real-time GI.
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Chilling stress caused by extreme weather is threatening global rice (Oryza sativa L.) production. Identifying components of the signal transduction pathways underlying chilling tolerance in rice would advance molecular breeding. Here, we report that OsMST6, which encodes a monosaccharide transporter, positively regulates the chilling tolerance of rice seedlings. mst6 mutants showed hypersensitivity to chilling, while OsMST6 overexpression lines were tolerant. During chilling stress, OsMST6 transported more glucose into cells to modulate sugar and abscisic acid signaling pathways. We showed that the transcription factor OsERF120 could bind to the DRE/CRT element of the OsMST6 promoter and activate the expression of OsMST6 to positively regulate chilling tolerance. Genetically, OsERF120 was functionally dependent on OsMST6 when promoting chilling tolerance. In summary, OsERF120 and OsMST6 form a new downstream chilling regulatory pathway in rice in response to chilling stress, providing valuable findings for molecular breeding aimed at achieving global food security.
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Temperatura Baixa , Proteínas de Transporte de Monossacarídeos , Oryza , Proteínas de Plantas , Plântula , Fatores de Transcrição , Oryza/genética , Oryza/metabolismo , Oryza/fisiologia , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Plântula/fisiologia , Plântula/genética , Plântula/metabolismo , Proteínas de Transporte de Monossacarídeos/metabolismo , Proteínas de Transporte de Monossacarídeos/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Regulação da Expressão Gênica de PlantasRESUMO
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic interstitial lung disease characterized by progressive dyspnea and decreased lung function, yet its exact etiology remains unclear. It is of great significance to discover new drug targets for IPF. METHODS: We obtained the cis-expression quantitative trait locus (cis-eQTL) of druggable genes from eQTLGen Consortium as exposure and the genome wide association study (GWAS) of IPF from the International IPF Genetics Consortium as outcomes to simulate the effects of drugs on IPF by employing mendelian randomization analysis. Then colocalization analysis was performed to calculate the probability of both cis-eQTL of druggable genes and IPF sharing a causal variant. For further validation, we conducted protein quantitative trait locus (pQTL) analysis to reaffirm our findings. RESULTS: The expression of 45 druggable genes was significantly associated with IPF susceptibility at FDR < 0.05. The expression of 23 and 15 druggable genes was significantly associated with decreased forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLco) in IPF patients, respectively. IPF susceptibility and two significant genes (IL-7 and ABCB2) were likely to share a causal variant. The results of the pQTL analysis demonstrated that high levels of IL-7 in plasma are associated with a reduced risk of IPF (OR = 0.67, 95%CI: 0.47-0.97). CONCLUSION: IL-7 stands out as the most promising potential drug target to mitigate the risk of IPF. Our study not only sheds light on potential drug targets but also provides a direction for future drug development in IPF.
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Estudo de Associação Genômica Ampla , Fibrose Pulmonar Idiopática , Análise da Randomização Mendeliana , Humanos , Fibrose Pulmonar Idiopática/genética , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/diagnóstico , Análise da Randomização Mendeliana/métodos , Estudo de Associação Genômica Ampla/métodos , Locos de Características Quantitativas , Predisposição Genética para Doença , Feminino , Terapia de Alvo Molecular/métodos , MasculinoRESUMO
Given that combination with multiple biomarkers may well raise the predictive value of wound age, it appears critically essential to identify new features under the limited cost. For this purpose, the present study explored whether the gene expression ratios provide unique time information as an additional indicator for wound age estimation not requiring the detection of new biomarkers and allowing full use of the available data. The expression levels of four wound-healing genes (Arid5a, Ier3, Stom, and Lcp1) were detected by real-time polymerase chain reaction, and a total of six expression ratios were calculated among these four genes. The results showed that the expression levels of four genes and six ratios of expression changed time-dependent during wound repair. The six expression ratios provided additional temporal information, distinct from the four genes analyzed separately by principal component analysis. The overall performance metrics for cross-validation and external validation of four typical prediction models were improved when six ratios of expression were added as additional input variables. Overall, expression ratios among genes provide temporal information and have excellent potential as predictive markers for wound age estimation. Combining the expression levels of genes with ratio-expression of genes may allow for more accurate estimates of the time of injury.
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Contusões , Ratos , Animais , Humanos , Ratos Sprague-Dawley , Contusões/genética , Contusões/metabolismo , Músculo Esquelético/metabolismo , Cicatrização/genética , Biomarcadores/metabolismoRESUMO
The present study is aimed to address the challenge of wound age estimation in forensic science by identifying reliable genetic markers using low-cost and high-precision second-generation sequencing technology. A total of 54 Sprague-Dawley rats were randomly assigned to a control group or injury groups, with injury groups being further divided into time points (4 h, 8 h, 12 h, 16 h, 20 h, 24 h, 28 h, and 32 h after injury, n = 6) to establish rat skeletal muscle contusion models. Gene expression data were obtained using second-generation sequencing technology, and differential gene expression analysis, weighted gene co-expression network analysis (WGCNA) and time-dependent expression trend analysis were performed. A total of six sets of biomarkers were obtained: differentially expressed genes at adjacent time points (127 genes), co-expressed genes most associated with wound age (213 genes), hub genes exhibiting time-dependent expression (264 genes), and sets of transcription factors (TF) corresponding to the above sets of genes (74, 87, and 99 genes, respectively). Then, random forest (RF), support vector machine (SVM) and multilayer perceptron (MLP), were constructed for wound age estimation from the above gene sets. The results estimated by transcription factors were all superior to the corresponding hub genes, with the transcription factor group of WGCNA performed the best, with average accuracy rates of 96% for three models' internal testing, and 91.7% for the highest external validation. This study demonstrates the advantages of the indicator screening system based on second-generation sequencing technology and transcription factor level for wound age estimation.
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Contusões , Músculo Esquelético , Ratos Sprague-Dawley , Animais , Músculo Esquelético/lesões , Músculo Esquelético/metabolismo , Contusões/genética , Fatores de Tempo , Máquina de Vetores de Suporte , Sequenciamento de Nucleotídeos em Larga Escala , Ratos , Perfilação da Expressão Gênica , Marcadores Genéticos , Masculino , Genética Forense/métodosRESUMO
Brominated byproducts and toxicity generation are critical issues for ozone application to wastewater containing bromide. This study demonstrated that ultraviolet/ozone (UV/O3, 100 mJ/cm2, 1 mg-O3/mg-DOC) reduced the cytotoxicity of wastewater from 14.2 mg of pentol/L produced by ozonation to 4.3 mg of pentol/L (1 mg/L bromide, pH 7.0). The genotoxicity was also reduced from 1.65 to 0.17 µg-4-NQO/L by UV/O3. Compared with that of O3 alone, adsorbable organic bromine was reduced from 25.8 to 5.3 µg/L by UV/O3, but bromate increased from 32.9 to 71.4 µg/L. The UV/O3 process enhanced the removal of pre-existing precursors (highly unsaturated and phenolic compounds and poly aromatic hydrocarbons), while new precursors were generated, yet the combined effect of UV/O3 on precursors did not result in a significant change in toxicity. Instead, UV radiation inhibited HOBr concentration through both rapid O3 decomposition to reduce HOBr production and decomposition of the formed HOBr, thus suppressing the AOBr formation. However, the hydroxyl radical-dominated pathway in UV/O3 led to a significant increase of bromate. Considering both organic bromine and bromate, the UV/O3 process effectively controlled both cytotoxicity and genotoxicity of wastewater to mammalian cells, even though an emphasis should be also placed on managing elevated bromate. Futhermore, other end points are needed to evaluate the toxicity outcomes of the UV/O3 process.
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Bromo , Águas Residuárias , Bromo/química , Bromo/toxicidade , Bromatos/química , Processos Fotoquímicos , Raios Ultravioleta , Ozônio/química , Purificação da Água/métodos , Águas Residuárias/toxicidade , Mamíferos , Animais , Células CHO , CricetulusRESUMO
Colorectal cancer (CRC) is a prevalent form of gastrointestinal malignancy with challenges in chemotherapy resistance and side effects. Effective and low toxic drugs for CRC treatment are urgently needed. Ferroptosis is a novel mode of cell death, which has garnered attention for its therapeutic potential against cancer. Baicalein (5, 6, 7-trihydroxyflavone) is the primary flavone extracted from the dried roots of Scutellaria baicalensis that exhibits anticancer effects against several malignancies including CRC. In this study, we investigated whether baicalein induced ferroptosis in CRC cells. We showed that baicalein (1-64 µM) dose-dependently inhibited the viability of human CRC lines HCT116 and DLD1. Co-treatment with the ferroptosis inhibitor liproxstatin-1 (1 µM) significantly mitigated baicalein-induced CRC cell death, whereas autophagy inhibitor chloroquine (25 µM), necroptosis inhibitor necrostatin-1 (10 µM), or pan-caspase inhibitor Z-VAD-FMK (10 µM) did not rescue baicalein-induced CRC cell death. RNA-seq analysis confirmed that the inhibitory effect of baicalein on CRC cells is associated with ferroptosis induction. We revealed that baicalein (7.5-30 µM) dose-dependently decreased the expression levels of GPX4, key regulator of ferroptosis, in HCT116 and DLD1 cells by blocking janus kinase 2 (JAK2)/STAT3 signaling pathway via direct interaction with JAK2, ultimately leading to ferroptosis in CRC cells. In a CRC xenograft mouse model, administration of baicalein (10, 20 mg/kg, i.g., every two days for two weeks) dose-dependently inhibited the tumor growth with significant ferroptosis induced by inhibiting the JAK2/STAT3/GPX4 axis in tumor tissue. This study demonstrates that ferroptosis contributes to baicalein-induced anti-CRC activity through blockade of the JAK2/STAT3/GPX4 signaling pathway, which provides evidence for the therapeutic application of baicalein against CRC.
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Neoplasias Colorretais , Ferroptose , Flavanonas , Janus Quinase 2 , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Fator de Transcrição STAT3 , Flavanonas/farmacologia , Flavanonas/uso terapêutico , Humanos , Ferroptose/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/antagonistas & inibidores , Animais , Janus Quinase 2/metabolismo , Janus Quinase 2/antagonistas & inibidores , Camundongos , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/antagonistas & inibidores , Camundongos Nus , Camundongos Endogâmicos BALB C , Transdução de Sinais/efeitos dos fármacos , Linhagem Celular Tumoral , Células HCT116 , Ensaios Antitumorais Modelo de Xenoenxerto , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a DrogaRESUMO
As the number of patients increases, physicians are dealing with more and more cases of degenerative spine pathologies on a daily basis. To reduce the workload of healthcare professionals, we propose a modified Swin-UNet network model. Firstly, the Swin Transformer Blocks are improved using a residual post-normalization and scaling cosine attention mechanism, which makes the training process of the model more stable and improves the accuracy. Secondly, we use the log-space continuous position biasing method instead of the bicubic interpolation position biasing method. This method solves the problem of performance loss caused by the large difference between the resolution of the pretraining image and the resolution of the spine image. Finally, we introduce a segmentation smooth module (SSM) at the decoder stage. The SSM effectively reduces redundancy, and enhances the segmentation edge processing to improve the model's segmentation accuracy. To validate the proposed method, we conducted experiments on a real dataset provided by hospitals. The average segmentation accuracy is no less than 95%. The experimental results demonstrate the superiority of the proposed method over the original model and other models of the same type in segmenting the spinous processes of the vertebrae and the posterior arch of the spine.
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PURPOSE: The aim of this study is to investigate the role of the neutrophil to lymphocyte ratio (NLR) in patients diagnosed with the chronic obstructive pulmonary disease-obstructive sleep apnea (COPD-OSA) overlap syndrome and comorbid pulmonary hypertension (PH). PATIENTS AND METHODS: We enrolled a consecutive of stable COPD patients and conducted spirometry measurements, nocturnal polysomnography (PSG), and echocardiography for all participants. Clinical laboratory data were collected. RESULTS: A total of 178 patients with stable COPD were enrolled among whom 33.14% (59/178) were diagnosed with OSA. Of the patients with overlap syndrome, 35.59% (21/59) showed comorbid PH, compared to 34.45% (41/119) in COPD patients without OSA. There was no significant difference in the occurrence of PH between COPD with and without OSA. NLR was significantly higher in patients with overlap syndrome compared to those with either disease alone. The difference in NLR between COPD-OSA patients with and without PH was not significant. Correlation analysis revealed that NLR was associated with age, total sleep time spent with oxygen saturation below 90% (T90), CRP, pulmonary artery systolic pressure (PASP), and minimum peripheral capillary oxygen saturation (SpO2min) in all COPD patients. NLR was identified as an independent factor contributing to OSA in COPD. The median cut-off value for detecting OSA in stable COPD was 2.49. However, NLR was not found to be a predictor for PH in COPD-OSA overlap syndrome. CONCLUSIONS: NLR can serve as a predictive marker for comorbid OSA in patients with COPD. NLR is expected to increase its clinical application as a convenient and cost-effective biomarker for COPD-OSA overlap syndrome.
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Linfócitos , Neutrófilos , Doença Pulmonar Obstrutiva Crônica , Apneia Obstrutiva do Sono , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/sangue , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Hipertensão Pulmonar/sangue , Hipertensão Pulmonar/diagnóstico , Polissonografia , Contagem de Linfócitos , ComorbidadeRESUMO
PURPOSE: To investigate whether or not intermittent hypoxia (IH), the main characteristic of obstructive sleep apnea (OSA) may affect the myofibroblast differentiation and extracellular matrix (ECM) production of lung fibroblast through the HIF-1α-TGF-ß/Smad pathway and assess the interventional role of a HIF-1α inhibitor, 2-methoxyestradiol (2-ME2). METHOD: The human lung fibroblast MRC5 cells were exposed to normoxia or IH conditions, and the expression of myofibroblast differentiation marker α-smooth muscle actin (α-SMA) and ECM protein collagen I were evaluated. To clarify the underlying mechanism, the expression level of HIF-1α, TGF-ß, and p-Smads/Smads were measured and the effects of inhibiting HIF-1α with 2-ME2 on the α-SMA expression level and ECM production through the TGF-ß/Smad pathway were assessed. Si HIF-1α was applied to genetically inhibit HIF-1α in MRC5 cells, and the related proteins were assessed. RESULTS: IH increased the protein and mRNA expression of Collagen I and α-SMA of MRC5 cells in a time-dependent manner. IH activated the protein and mRNA level of HIF-1α and TGF-ß and increased the phosphorylation of Smad2/Smad3 of MRC5 cells in a time-dependent manner. 2-ME2 inhibited the activation of HIF-1α induced by IH and decreased overexpression of TGF-ß, p-Smad2/Smad2, and p-Smad3/Smad3, which in turn partially reversed the upregulation of α-SMA and Collagen I induced by IH in MRC5 cells. When HIF-1α was successfully silenced by si-HIF-1α, upregulation of TGF-ß induced by intermittent hypoxia was partially decreased. CONCLUSIONS: This study showed that IH contributes to myofibroblast differentiation and excessive ECM production of MRC5 cells through activation of the HIF-1α-TGF-ß/Smad pathway. 2-ME2 partially attenuated myofibroblast differentiation induced by IH by inhibiting the HIF-1α-TGF-ß/Smad pathway.
Assuntos
Miofibroblastos , Fator de Crescimento Transformador beta , Humanos , Colágeno/metabolismo , Matriz Extracelular/metabolismo , Hipóxia/metabolismo , Miofibroblastos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator de Crescimento Transformador beta/metabolismoRESUMO
PURPOSE: Obstructive sleep apnea (OSA) is a common sleep-breathing disorder. Numerous investigations have found a strong inherent relationship between OSA and hypothyroidism. Studies suggest that lymphocytes may be involved in the development of hypothyroidism in patients with OSA. This study aimed to assess the association between lymphocytes and hypothyroidism in OSA patients. PATIENTS AND METHODS: This study involved 920 patients with OSA who underwent nocturnal sleep monitoring, thyroid function testing, and routine blood tests. In patients with OSA, logistic regression analysis indicated independent predictors of hypothyroidism. The cutoff level of lymphocyte count was determined using a receiver operating characteristic (ROC) analysis to predict the occurrence of hypothyroidism in individuals with OSA. RESULTS: This study comprised 920 OSA patients (617 males and 303 women), 879 with normal thyroid function, and 41 with hypothyroidism, with a hypothyroidism incidence of 4.46%. In the entire OSA population and male OSA patients, the number of lymphocytes was significantly higher in the hypothyroid group than in the control group (p = 0.002 and 0.020, respectively). In addition, among the OSA population younger than 60 years old and patients with mild to moderate OSA, lymphocytes were found to be considerably more in the hypothyroid group than in the euthyroid group. Lymphocyte count, ESS, and sex were all independent predictors of hypothyroidism development in OSA patients. According to ROC curve analysis, the risk of hypothyroidism increases with increasing lymphocyte count in the total patient population, with an optimal diagnostic cutoff point of 2.5 (× 10*9/L). CONCLUSIONS: The prevalence of hypothyroidism in patients with OSA increases as the number of lymphocytes increases. Lymphocyte count can be used as an independent predictor of the occurrence of hypothyroidism, and it has a diagnostic value for OSA combined with hypothyroidism.
Assuntos
Hipotireoidismo , Apneia Obstrutiva do Sono , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Hipotireoidismo/complicações , Hipotireoidismo/epidemiologia , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/diagnóstico , Sono , Curva ROC , LinfócitosRESUMO
BACKGROUND: As the Omicron variant of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) emerges, the neurological manifestations correlated with this epidemic have garnered increasing attention. This study was primarily intended to compare seizures in febrile children with and without SARS-CoV-2 infection and to conduct short-term follow-up of the SARS-CoV-2-infected patients. METHODS: Retrospective analysis of patients admitted to the Children's Hospital of Chongqing Medical University for fever and seizures between October 1 and December 30, 2022. Based on the results of SARS-CoV-2 Reverse Transcription-Polymerase Chain Reaction(RT-PCR) at the time of admission, the patients were divided into a Coronavirus disease 2019(COVID-19) positive group and a COVID-19 negative group. Aside from that, we followed up COVID-19-positive patients for 3 months after their discharge from the hospital. The follow-up included monitoring for post-discharge seizures. RESULTS: Compared with the COVID-19-negative group, the COVID-19-positive group had a higher proportion of seizure duration ≥ 15 min(18.7%VS5.1%;P = 0.001), seizure ≥ 2 time(54.4%VS41.0%; P = 0.024), status epilepticus(15.4%VS5.1%; P = 0.005), and Electroencephalogram (EEG) abnormalities(29.4%VS13.6%; P = 0.016). Among the 161 individuals under follow-up, 21 (13.0%)experienced a recurrence of seizures. CONCLUSIONS: Although the incidence of seizure duration ≥ 15 min, number of seizures ≥ 2 time, and status epilepticus was higher in the COVID-19-positive group, the majority of patients had a favorable prognosis. Nonetheless, patients with COVID-19 who present with seizures and persistent impaired consciousness need to be alerted to serious neurological disorders such as acute necrotizing encephalopathy. Owing to the consideration that some patients may experience a recurrence of seizures within a short period of time, it is paramount to provide guardians with education about the emergency management of seizures and to follow up with patients over time.
Assuntos
COVID-19 , Estado Epiléptico , Criança , Humanos , COVID-19/complicações , SARS-CoV-2 , Estudos Retrospectivos , Seguimentos , Assistência ao Convalescente , Alta do Paciente , Convulsões/etiologiaRESUMO
Background: Acute pancreatitis (AP) is a clinically frequent acute abdominal condition, which refers to an inflammatory response syndrome of edema, bleeding, and even necrosis caused by abnormal activation of the pancreas's own digestive enzymes. Intestinal damage can occur early in the course of AP and is manifested by impaired intestinal mucosal barrier function, and inflammatory reactions of the intestinal mucosa, among other factors. It can cause translocation of intestinal bacteria and endotoxins, further aggravating the condition of AP. Therefore, actively protecting the intestinal mucosal barrier, controlling the progression of intestinal inflammation, and improving intestinal dynamics in the early stages of AP play an important role in enhancing the prognosis of AP. Methods: The viability and apoptosis of RAW264.7 cells treated with Esculentoside A (EsA) and/or lipopolysaccharide were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry, respectively. The expression of apoptosis-related proteins and NF-κB signaling pathway-related proteins were detected by western blot (WB). An enzyme-linked immunosorbent assay was used to measure TNF-α and IL-6 secretion. Results: In vitro experiments demonstrated that EsA not only promoted the apoptosis of inflammatory cells but also reduced the secretion of TNF-α and IL-6 in a dose-dependent manner. Additionally, it inhibited the activation of the NF-κB signaling pathway by decreasing the expression of phosphorylated-p65(p-p65) and elevating the expression of IκBα. Similarly, in vivo experiments using a rat AP model showed that EsA inhibited the expression of p-p65 elevating the expression of IκBα in the intestinal tissues of the rat AP model and promoting the apoptosis of inflammatory cells in the intestinal mucosa in vivo experiments, while improving the pathological outcome of the pancreatic and intestinal tissues. Conclusion: Our results suggest that EsA can reduce intestinal inflammation in the rat AP model and that EsA may be a candidate for treating intestinal inflammation in AP and further arresting AP progression.