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Aberrant energy metabolism in the brain is a common pathological feature in the preclinical Alzheimer's Disease (AD). Recent studies have reported the early elevations of glycolysis-involved enzymes in AD brain and cerebrospinal fluid according to a large-scale proteomic analysis. It's well-known that astrocytes exhibit strong glycolytic metabolic ability and play a key role in the regulation of brain homeostasis. However, its relationship with glycolytic changes and cognitive deficits in early AD patients is unclear. Here, we investigated the mechanisms by which astrocyte glycolysis is involved in early AD and its potential as a therapeutic target. Our results suggest that Aß-activated microglia can induce glycolytic-enhanced astrocytes in vitro, and that these processes are dependent on the activation of the AKT-mTOR-HIF-1α pathway. In early AD models, the increase in L-lactate produced by enhanced glycolysis of astrocytes leads to spatial cognitive impairment by disrupting synaptic plasticity and accelerating Aß aggregation. Furthermore, we find rapamycin, the mTOR inhibitor, can rescue the impaired spatial memory and Aß burden by inhibiting the glycolysis-derived L-lactate in the early AD models. In conclusion, we highlight that astrocytic glycolysis plays a critical role in the early onset of AD and that the modulation of glycolysis-derived L-lactate by rapamycin provides a new strategy for the treatment of AD.
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High mobility group protein B1 (HMGB1) acts as a pathogenic inflammatory response to mediate ranges of conditions such as epilepsy, septic shock, ischemia, traumatic brain injury, Parkinson's disease, Alzheimer's disease and mass spectrometry. HMGB1 promotes inflammation during sterile and infectious damage and plays a crucial role in disease development. Mobilization from the nucleus to the cytoplasm is the first important step in the release of HMGB1 from activated immune cells. Here, we demonstrated that Sirtuin 2 (SIRT2) physically interacts with and deacetylates HMGB1 at 43 lysine residue at nuclear localization signal locations, strengthening its interaction with HMGB1 and causing HMGB1 to be localized in the cytoplasm. These discoveries are the first to shed light on the SIRT2 nucleoplasmic shuttle, which influences HMGB1 and its degradation, hence revealing novel therapeutic targets and avenues for neuroinflammation treatment.
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In plant environments, there exist heterogeneous microbial communities, referred to as the plant microbiota, which are recruited by plants and play crucial roles in promoting plant growth, aiding in resistance against pathogens and environmental stresses, thereby maintaining plant health. These microorganisms, along with their genomes, collectively form the plant microbiome. Research on the plant microbiome can help unravel the intricate interactions between plants and microbes, providing a theoretical foundation to reduce pesticide use, enhance agricultural productivity, and promote environmental sustainability. Despite significant progress in the field of research, unresolved challenges persist due to ongoing technological limitations and the complexities inherent in studying microorganisms at small scales. Recently, synthetic community (SynCom) has emerged as a novel technique for microbiome research, showing promising prospects for applications in the plant microbiome field. This article systematically introduces the origin and distribution of plant microbiota, the processes of their recruitment and colonization, and the mechanisms underlying their beneficial functions for plants, from the aspects of composition, assembly, and function. Furthermore, we discuss the principles, applications, challenges, and prospects of SynCom for promoting plant health.
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OBJECTIVE: To evaluate the prognostic factors and survival outcomes of patients with surgically treated high-grade neuroendocrine carcinoma of the cervix (NECC). METHODS: This multicenter, retrospective study involved 98 cervical cancer patients with stage IA2-IIA2 and IIIC1/2p high-grade NECC. We divided the patients into two groups based on histology: the pure and mixed groups. All clinicopathologic variables were retrospectively evaluated. Cox regression and Kaplan-Meier methods were used for analysis. RESULTS: In our study, 60 patients were in the pure group and 38 patients were in the mixed group. Cox multivariate analysis showed that mixed histology was a protective factor impacting overall survival (OS) (P = 0.026) and progression free survival (PFS) (P = 0.018) in surgically treated high-grade NECC. Conversely, survival outcomes were negatively impacted by ovarian preservation (OS: HR, 20.84; 95% CI: 5.02-86.57, P < 0.001), age >45 years (OS: HR, 4.50; 95% CI: 1.0-18.83, P = 0.039), tumor size >4 cm (OS: HR, 6.23; 95% CI: 2.34-16.61, P < 0.001), parity >3 (OS: HR, 4.50; 95% CI: 1.02-19.91, P = 0.048), and perineural invasion (OS: HR, 5.21; 95% CI: 1.20-22.53, P = 0.027). Kaplan-Meier survival curves revealed notable differences in histologic type (OS: P = 0.045; PFS: P = 0.024), chemotherapy (OS: P = 0.0056; PFS: P = 0.0041), ovarian preservation (OS: P = 0.00031; PFS: P = 0.0023), uterine invasion (OS: P < 0.0001; PFS: P < 0.0001), and depth of stromal invasion (OS: P = 0.043; PFS: P = 0.022). CONCLUSION: Patients with mixed histologic types who undergo surgery for high-grade NECC have a better prognosis. Meanwhile, ovarian preservation, tumor size >4 cm, parity >3, age >45 years and perineural invasion were poor prognostic predictors. Therefore, patients with high-risk factors should be considered in clinical practice.
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BACKGROUND: The risks associated with negative doctor-patient relationships have seriously hindered the healthy development of medical and healthcare and aroused widespread concern in society. The number of public comments on doctor-patient relationship risk events reflects the degree to which the public pays attention to such events. AIM: To explore public emotional differences, the intensity of comments, and the positions represented at different levels of doctor-patient disputes. METHODS: Thirty incidents of doctor-patient disputes were collected from Weibo and TikTok, and 3655 related comments were extracted. The number of comment sentiment words was extracted, and the comment sentiment value was calculated. The Kruskal-Wallis H test was used to compare differences between each variable group at different levels of incidence. Spearman's correlation analysis was used to examine associations between variables. Regression analysis was used to explore factors influencing scores of comments on incidents. RESULTS: The study results showed that public comments on media reports of doctor-patient disputes at all levels are mainly dominated by "good" and "disgust" emotional states. There was a significant difference in the comment scores and the number of partial emotion words between comments on varying levels of severity of doctor-patient disputes. The comment score was positively correlated with the number of emotion words related to positive, good, and happy) and negatively correlated with the number of emotion words related to negative, anger, disgust, fear, and sadness. CONCLUSION: The number of emotion words related to negative, anger, disgust, fear, and sadness directly influences comment scores, and the severity of the incident level indirectly influences comment scores.
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BACKGROUND: Intracranial high-density areas (HDAs) have attracted considerable attention for predicting clinical outcomes; however, whether HDAs predict worse neurological function and mental health remains controversial and unclear, which requires further investigation. AIM: To investigate the predictive value of intracranial HDAs for neurological function and mental health after endovascular treatment. METHODS: In this prospective study, 96 patients with acute ischemic stroke (AIS) who accepted endovascular mechanical thrombectomy (EMT) were included. The enrolled patients underwent cranial computed tomography (CT) examination within 24 hours after EMT. Clinical data in terms of National Institutes of Health Stroke Scale (NIHSS), the 3-month modified Rankin Scale (mRS), self-rating depression scale (SDS), and self-rating anxiety scale (SAS) scores were collected and compared between patients with HDAs and non-HDAs and between patients with good and poor clinical prognosis. RESULTS: Compared to patients without HDAs, patients with HDAs presented severe neurological deficits (admission NIHSS score: 18 ± 3 vs 19 ± 4), were more likely to have post-stroke disabilities (mRS < 3: 35% vs 62%), and suffered more severe depression (SDS score: 58 ± 16 vs 64 ± 13) and anxiety disorder (SAS score: 52 ± 8 vs 59 ± 10). Compared to patients with a good prognosis, patients with a poor prognosis presented severe neurological deficits (admission NIHSS score: 17 ± 4 vs 20 ± 3), were more likely to have HDAs on CT images (64% vs 33%), and suffered more severe depression (SDS score: 55 ± 19 vs 65 ± 11) and anxiety (SAS score: 50 ± 8 vs 58 ± 12). Multivariate analysis revealed that HDAs were independent negative prognostic factors. CONCLUSION: In conclusion, HDAs on CT images predicted poor prognosis and severe depressive and anxiety symptoms in patients with AIS who underwent EMT.
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The SwissTargetPrediction was employed to predict the potential drug targets of the active component of Si-Miao-Yong-An decoction (SMYAD). The therapeutic targets for HF were searched in the Genecard database, and Cytoscape3.9.1 software was used to construct the "drug-component-target-disease network" diagram. In addition, the String platform was used to construct Protein-Protein Interaction (PPI) network, and the DAVID database was used for GO and KEGG analysis. AutoDockTools-1.5.6 software was used for molecular docking verification. Network pharmacology studies have shown that AKT 1, ALB, and CASP 3 are the key targets of action of SMYAD against heart failure. The active compounds are quercetin and kaempferol.
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Tumor necrosis factor α (TNFα) exhibits diverse biological functions; however, its regulatory roles in myogenesis are not fully understood. In the present study, we explored the function of TNFα in myoblast proliferation, differentiation, migration, and myotube fusion in primary myoblasts and C2C12 cells. To this end, we constructed TNFα muscle-conditional knockout ( TNFα-CKO) mice and compared them with flox mice to assess the effects of TNFα knockout on skeletal muscles. Results indicated that TNFα-CKO mice displayed phenotypes such as accelerated muscle development, enhanced regenerative capacity, and improved exercise endurance compared to flox mice, with no significant differences observed in major visceral organs or skeletal structure. Using label-free proteomic analysis, we found that TNFα-CKO altered the distribution of several muscle development-related proteins, such as Hira, Casz1, Casp7, Arhgap10, Gas1, Diaph1, Map3k20, Cfl2, and Igf2, in the nucleus and cytoplasm. Gene set enrichment analysis (GSEA) further revealed that TNFα deficiency resulted in positive enrichment in oxidative phosphorylation and MyoD targets and negative enrichment in JAK-STAT signaling. These findings suggest that TNFα-CKO positively regulates muscle growth and development, possibly via these newly identified targets and pathways.
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Ratones Noqueados , Desarrollo de Músculos , Músculo Esquelético , Regeneración , Factor de Necrosis Tumoral alfa , Animales , Desarrollo de Músculos/fisiología , Ratones , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/genética , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiología , Línea Celular , Diferenciación Celular , Mioblastos/metabolismo , Mioblastos/fisiologíaRESUMEN
AIMS: Necroptosis is one of programmed death that may aggravate spinal cord injury (SCI). We aimed to investigate the effect and mechanism of exendin-4 (EX-4) on the recovery of motor function and necroptosis after SCI. METHODS: The SD rats with left hemisection in the T10 spinal cord as SCI model were used. The behavior tests were measured within 4 weeks. The effects of EX-4 on necroptosis-associated proteins and autophagy flux were explored. In addition, the SHSY5Y cell model was introduced to explore the direct effect of EX-4 on neurons. The effect of lysosome was explored using mTOR activator and AO staining. RESULTS: EX-4 could improve motor function and limb strength, promote the recovery of autophagy flux, and accelerate the degradation of necroptosis-related protein at 3 d after injury in rats. EX-4 reduced lysosome membrane permeability, promoted the recovery of lysosome function and autophagy flux, and accelerated the degradation of necroptosis-related proteins by inhibiting the phosphorylation level of mTOR in the SHSY5Y cell model. CONCLUSION: Our results demonstrated that EX-4 may improve motor function after SCI via inhibiting mTOR phosphorylation level and accelerating the degradation of necroptosis-related proteins in neurons. Our findings may provide new therapeutic targets for clinical treatment after SCI.
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Autofagia , Exenatida , Necroptosis , Neuronas , Ratas Sprague-Dawley , Traumatismos de la Médula Espinal , Animales , Autofagia/efectos de los fármacos , Traumatismos de la Médula Espinal/tratamiento farmacológico , Traumatismos de la Médula Espinal/patología , Ratas , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Exenatida/farmacología , Exenatida/uso terapéutico , Necroptosis/efectos de los fármacos , Humanos , Recuperación de la Función/efectos de los fármacos , Recuperación de la Función/fisiología , Serina-Treonina Quinasas TOR/metabolismo , Línea Celular Tumoral , Fármacos Neuroprotectores/farmacología , MasculinoRESUMEN
OBJECTIVE: To explore the role of different cells and molecules in the pathogenesis of allergic rhinitis (AR) with positive Artemisia allergen by detecting their expression levels. METHODS: From January 2021 to December 2022,200 AR patients diagnosed in the Otolaryngology Clinic of Ordos Central Hospital were selected as the AR group, and 50 healthy people who underwent physical examination in the hospital during the same period were randomly selected as the healthy control (HC) group. The levels of GATA-3mRNA, RORγtmRNA and FoxP3mRNA in peripheral blood mononuclear cells were detected by real-time fluorescence quantitative PCR (qRT-PCR). The proportions of Th2, Th17 and Treg cells were detected by flow cytometry. The concentrations of IL-4, IL-5, IL-17 and IL-10 in serum were detected by enzyme-linked immunosorbent assay. The differences of transcription gene level, immune cell ratio and cytokine concentration between the two groups were analyzed. RESULTS: There was no difference in age and gender between the two groups. The levels of GATA-3mRNA and RORγtmRNA transcription genes in peripheral blood mononuclear cells, the percentage of Th2, Th17 and Treg immune cells, the levels of eosinophils and basophils in peripheral blood, the concentrations of IL-4, IL-5, IL-17, IL-10 cytokines and IgE in serum of AR patients were significantly higher than those in HC group (P < 0.05). IL-4 and IL-17 were positively correlated with total IgE level. CONCLUSION: The secretion of immune cells and cytokines in peripheral blood of AR patients is abnormal. Th2, Th17, Treg specific transcription factors and related cells and cytokines are involved in the occurrence and development of allergic rhinitis.
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Introduction: Sweet sorghum juice is a typical production feedstock for natural, eco-friendly sweeteners and beverages. Clostridium tyrobutyricum is one of the widely used microorganisms in the food industry, and its principal product, bio-butyric acid is an important food additive. There are no published reports of Clostridium tyrobutyricum producing butyric acid using SSJ as the sole substrate without adding exogenous substances, which could reach a food-additive grade. This study focuses on tailoring a cost-effective, safe, and sustainable process and strategy for their production and application. Methods: This study modeled the enzymolysis of non-reducing sugars via the first/second-order kinetics and added food-grade diatomite to the hydrolysate. Qualitative and quantitative analysis were performed using high-performance liquid chromatography, gas chromatography-mass spectrometer, full-scale laser diffraction method, ultra-performance liquid chromatography-tandem mass spectrometry, the cell double-staining assay, transmission electron microscopy, and Oxford nanopore technology sequencing. Quantitative real-time polymerase chain reaction, pathway and process enrichment analysis, and homology modeling were conducted for mutant genes. Results: The treated sweet sorghum juice showed promising results, containing 70.60 g/L glucose and 63.09 g/L fructose, with a sucrose hydrolysis rate of 98.29% and a minimal sucrose loss rate of 0.87%. Furthermore, 99.62% of the colloidal particles and 82.13% of the starch particles were removed, and the concentrations of hazardous substances were effectively reduced. A food microorganism Clostridium tyrobutyricum TGL-A236 with deep utilization value was developed, which showed superior performance by converting 30.65% glucose and 37.22% fructose to 24.1364 g/L bio-butyric acid in a treated sweet sorghum juice (1:1 dilution) fermentation broth. This titer was 2.12 times higher than that of the original strain, with a butyric acid selectivity of 86.36%. Finally, the Genome atlas view, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and evolutionary genealogy of genes: Non-supervised Orthologous (eggNOG) functional annotations, three-dimensional structure and protein cavity prediction of five non-synonymous variant genes were obtained. Conclusion: This study not only includes a systematic process flow and in-depth elucidation of relevant mechanisms but also provides a new strategy for green processing of food raw materials, improving food microbial performance, and ensuring the safe production of food additives.
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Clinical surgery can lead to severe neuroinflammation and cognitive dysfunctions. It has been reported that astrocytes mediate memory formation and postoperative cognitive dysfunction (POCD), however, the thalamic mechanism of astrocytes in mediating POCD remains unknown. Here, we report that reactive astrocytes in zona incerta (ZI) mediate surgery-induced recognition memory impairment in male mice. Immunostaining results showed that astrocytes are activated with GABA transporter-3 (GAT-3) being down-expressed, and neurons were suppressed in the ZI. Besides, our work revealed that reactive astrocytes caused increased tonic current in ZI neurons. Up-regulating the expression of GAT-3 in astrocytes ameliorates surgery-induced recognition memory impairment. Together, our work demonstrates that the reactive astrocytes in the ZI play a crucial role in surgery-induced memory impairment, which provides a new target for the treatment of surgery-induced neural dysfunctions.
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Astrocitos , Proteínas Transportadoras de GABA en la Membrana Plasmática , Trastornos de la Memoria , Regulación hacia Arriba , Zona Incerta , Animales , Masculino , Proteínas Transportadoras de GABA en la Membrana Plasmática/metabolismo , Trastornos de la Memoria/metabolismo , Ratones , Regulación hacia Arriba/efectos de los fármacos , Astrocitos/metabolismo , Zona Incerta/metabolismo , Ratones Endogámicos C57BL , Neuronas/metabolismo , Neuronas/efectos de los fármacos , Complicaciones Cognitivas Postoperatorias/metabolismo , Complicaciones Cognitivas Postoperatorias/prevención & control , Reconocimiento en Psicología/efectos de los fármacos , Reconocimiento en Psicología/fisiologíaRESUMEN
Background: Breast cancer remains a pressing global health concern, necessitating accurate diagnostics for effective interventions. Deep learning models (AlexNet, ResNet-50, VGG16, GoogLeNet) show remarkable microcalcification identification (>90%). However, distinct architectures and methodologies pose challenges. We propose an ensemble model, merging unique perspectives, enhancing precision, and understanding critical factors for breast cancer intervention. Evaluation favors GoogleNet and ResNet-50, driving their selection for combined functionalities, ensuring improved precision, and dependability in microcalcification detection in clinical settings. Methods: This study presents a comprehensive mammogram preprocessing framework using an optimized deep learning ensemble approach. The proposed framework begins with artifact removal using Otsu Segmentation and morphological operation. Subsequent steps include image resizing, adaptive median filtering, and deep convolutional neural network (D-CNN) development via transfer learning with ResNet-50 model. Hyperparameters are optimized, and ensemble optimization (AlexNet, GoogLeNet, VGG16, ResNet-50) are constructed to identify the localized area of microcalcification. Rigorous evaluation protocol validates the efficacy of individual models, culminating in the ensemble model demonstrating superior predictive accuracy. Results: Based on our analysis, the proposed ensemble model exhibited exceptional performance in the classification of microcalcifications. This was evidenced by the model's average confidence score, which indicated a high degree of dependability and certainty in differentiating these critical characteristics. The proposed model demonstrated a noteworthy average confidence level of 0.9305 in the classification of microcalcification, outperforming alternative models and providing substantial insights into the dependability of the model. The average confidence of the ensemble model in classifying normal cases was 0.8859, which strengthened the model's consistent and dependable predictions. In addition, the ensemble models attained remarkably high performances in terms of accuracy, precision, recall, F1-score, and area under the curve (AUC). Conclusion: The proposed model's thorough dataset integration and focus on average confidence ratings within classes improve clinical diagnosis accuracy and effectiveness for breast cancer. This study introduces a novel methodology that takes advantage of an ensemble model and rigorous evaluation standards to substantially improve the accuracy and dependability of breast cancer diagnostics, specifically in the detection of microcalcifications.
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One major obstacle in the treatment of cancer is the presence of proteins resistant to cancer therapy, which can impede the effectiveness of traditional approaches such as radiation and chemotherapy. This resistance can lead to disease progression and cause treatment failure. Extensive research is currently focused on studying these proteins to create tailored treatments that can circumvent resistance mechanisms. CLU (Clusterin), a chaperone protein, has gained notoriety for its role in promoting resistance to a wide range of cancer treatments, including chemotherapy, radiation therapy, and targeted therapy. The protein has also been discovered to have a role in regulating the immunosuppressive environment within tumors. Its ability to influence oncogenic signaling and inhibit cell death bolster cancer cells resistant against treatments, which poses a significant challenge in the field of oncology. Researchers are actively investigating to the mechanisms by which CLU exerts its resistance-promoting effects, with the ultimate goal of developing strategies to circumvent its impact and enhance the effectiveness of cancer therapies. By exploring CLU's impact on cancer, resistance mechanisms, tumor microenvironment (TME), and therapeutic strategies, this review aims to contribute to the ongoing efforts to improve cancer treatment outcomes.
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Clusterina , Resistencia a Antineoplásicos , Neoplasias , Microambiente Tumoral , Humanos , Clusterina/metabolismo , Neoplasias/inmunología , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Animales , Microambiente Tumoral/inmunologíaRESUMEN
The increased incidence of obesity, which become a global health problem, requires more functional food products with minor side and excellent effects. Calebin A (CbA) is a non-curcuminoid compound, which is reported to be an effective treatment for lipid metabolism and thermogenesis. However, its ability and mechanism of action in improving obesity-associated hyperglycemia remain unclear. This study was designed to explore the effect and mechanism of CbA in hyperglycemia via improvement of inflammation and glucose metabolism in the adipose tissue and liver in high-fat diet (HFD)-fed mice. After 10 weeks fed HFD, obese mice supplemented with CbA (25 and 100 mg/kg) for another 10 weeks showed a remarkable reducing adiposity and blood glucose. CbA modulated M1/M2 macrophage polarization, ameliorated inflammatory cytokines, and restored adiponectin as well as Glut 4 expression in the adipose tissue. In the in vitro study, CbA attenuated pro-inflammatory markers while upregulated anti-inflammatory IL-10 in LPS + IFNγ-generated M1 phenotype macrophages. In the liver, CbA attenuated steatosis, inflammatory infiltration, and protein levels of inflammatory TNF-α and IL-6. Moreover, CbA markedly upregulated Adiponectin receptor 1, AMPK, and insulin downstream Akt signaling to improve glycogen content and increase Glut2 protein. These findings indicated that CbA may be a novel therapeutic approach to treat obesity and hyperglycemia phenotype targeting on adipose inflammation and hepatic insulin signaling.
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Tejido Adiposo , Dieta Alta en Grasa , Glucosa , Hiperglucemia , Inflamación , Hígado , Macrófagos , Obesidad , Animales , Dieta Alta en Grasa/efectos adversos , Ratones , Hiperglucemia/tratamiento farmacológico , Hiperglucemia/metabolismo , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Masculino , Glucosa/metabolismo , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inflamación/patología , Células RAW 264.7 , Ratones Obesos , Ratones Endogámicos C57BL , Transducción de Señal/efectos de los fármacos , Citocinas/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Glucemia/metabolismo , Glucemia/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismoRESUMEN
Metastasis is one of the key factors of treatment failure in late-stage colorectal cancer (CRC). Metastatic CRC frequently develops resistance to chemotherapeutic agents. This study aimed to identify the novel regulators from "hidden" proteins encoded by long noncoding RNAs (lncRNAs) involved in tumor metastasis and chemoresistance. Methods: CRISPR/Cas9 library functional screening was employed to identify the critical suppressor of cancer metastasis in highly invasive CRC models. Western blotting, immunofluorescence staining, invasion, migration, wound healing, WST-1, colony formation, gain- and loss-of-function experiments, in vivo experimental metastasis models, multiplex immunohistochemical staining, immunohistochemistry, qRT-PCR, and RT-PCR were used to assess the functional and clinical significance of FOXP3, PRDM16-DT, HNRNPA2B1, and L-CHEK2. RNA-sequencing, co-immunoprecipitation, qRT-PCR, RT-PCR, RNA affinity purification, RNA immunoprecipitation, MeRIP-quantitative PCR, fluorescence in situ hybridization, chromatin immunoprecipitation and luciferase reporter assay were performed to gain mechanistic insights into the role of PRDM16-DT in cancer metastasis and chemoresistance. An oxaliplatin-resistant CRC cell line was established by in vivo selection. WST-1, colony formation, invasion, migration, Biacore technology, gain- and loss-of-function experiments and an in vivo experimental metastasis model were used to determine the function and mechanism of cimicifugoside H-1 in CRC. Results: The novel protein PRDM16-DT, encoded by LINC00982, was identified as a cancer metastasis and chemoresistance suppressor. The down-regulated level of PRDM16-DT was positively associated with malignant phenotypes and poor prognosis of CRC patients. Transcriptionally regulated by FOXP3, PRDM16-DT directly interacted with HNRNPA2B1 and competitively decreased HNRNPA2B1 binding to exon 9 of CHEK2, resulting in the formation of long CHEK2 (L-CHEK2), subsequently promoting E-cadherin secretion. PRDM16-DT-induced E-cadherin secretion inhibited fibroblast activation, which in turn suppressed CRC metastasis by decreasing MMP9 secretion. Cimicifugoside H-1, a natural compound, can bind to LEU89, HIS91, and LEU92 of FOXP3 and significantly upregulated PRDM16-DT expression to repress CRC metastasis and reverse oxaliplatin resistance. Conclusions: lncRNA LINC00982 can express a new protein PRDM16-DT to function as a novel regulator in cancer metastasis and drug resistance of CRC. Cimicifugoside H-1 can act on the upstream of the PRDM16-DT signaling pathway to alleviate cancer chemoresistance.
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Neoplasias Colorrectales , Proteínas de Unión al ADN , Resistencia a Antineoplásicos , Regulación Neoplásica de la Expresión Génica , Metástasis de la Neoplasia , ARN Largo no Codificante , Factores de Transcripción , Animales , Humanos , Ratones , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/metabolismo , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Resistencia a Antineoplásicos/genética , Ribonucleoproteína Heterogénea-Nuclear Grupo A-B/metabolismo , Ribonucleoproteína Heterogénea-Nuclear Grupo A-B/genética , Ratones Endogámicos BALB C , Ratones Desnudos , Oxaliplatino/farmacología , Oxaliplatino/uso terapéutico , Empalme del ARN/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genéticaRESUMEN
BACKGROUND: Hemorrhage is the most common major complication after liver biopsy. Hemothorax is one type of bleeding and is very rare and dangerous. Several cases of hemothorax subsequent to liver biopsy have been documented, primarily attributed to injury of the intercostal artery or inferior phrenic artery and a few resulting from lung tissue damage; however, no previous case report of hemothorax caused by injury of musculophrenic artery after liver biopsy has been reported. CASE PRESENTATION: A 45-year-old native Chinese woman diagnosed with primary biliary cirrhosis due to long-term redness in urination and abnormal blood test indicators was admitted to our hospital for an ultrasound-guided liver biopsy to clarify pathological characteristics and disease staging. A total of 2 hours after surgery, the patient complained of discomfort in the right chest and abdomen. Ultrasound revealed an effusion in the right thorax and hemothorax was strongly suspected. The patient was immediately referred to the interventional department for digital subtraction angiography. Super-selective angiography of the right internal thoracic artery was performed which revealed significant contrast medium extravasation from the right musculophrenic artery, the terminal branch of the internal thoracic artery. Embolization was performed successfully. The vital signs of the patient were stabilized after the transarterial embolization and supportive treatment. CONCLUSION: This case draws attention to the musculophrenic artery as a potential source of hemorrhage after percutaneous liver biopsy.
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Embolización Terapéutica , Hemotórax , Hígado , Humanos , Hemotórax/etiología , Femenino , Persona de Mediana Edad , Hígado/patología , Hígado/diagnóstico por imagen , Hígado/irrigación sanguínea , Ultrasonografía Intervencional , Biopsia Guiada por Imagen/efectos adversos , Angiografía de Substracción DigitalRESUMEN
Purpose: This study aimed to analyze the expression and prognosis of SRY-box transcription factor 11 (SOX11) in neuroblastoma (NB), as well as the biological function and potential regulatory mechanism of SOX11 in NB. Methods: Public RNA sequencing was used to detect the expression level of SOX11. The Kaplan-Meier curve and hazard ratios (HR) were used to determine the prognostic value of SOX11 in NB. Functional analyses were performed using CCK8, wound healing assay, and transwell invasion assay. Finally, the potential target genes of SOX11 were predicted by Harmonizonme (Ma'ayan Laboratory) and Cistrome Data Browser (Cistrome Project) database to explore the potential molecular mechanism of SOX11 in NB. Results: Compared with normal adrenal tissue, the expression of SOX11 in NB tissue was significantly upregulated. The Kaplan-Meier curve showed that high expression of SOX11 was associated with poor prognosis in children with NB (HR, 1.719; P = 0.049). SOX11 knockdown suppressed the migration capacity of SK-N-SH cells but did not affect proliferation and invasion capacity. Enhancer of zeste homolog 2 (EZH2) may be a potential downstream target gene for the transcription factor SOX11 to play a role in NB. Conclusion: The transcription factor SOX11 was significantly upregulated in NB. SOX11 knockdown suppressed the migration capacity of NB cell SK-N-SH. SOX11 may promote the progression of NB by targeting EZH2.
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AIM: To report a technique used with intermittent sliding-lock-knot (ISLK) fixation for limbal conjunctival autografts in pterygium surgery and compared with those of routine intermittent (RI) fixation. METHODS: Consecutive patients with primary pterygium who had undergone pterygium excision combined with limbal conjunctival autograft transplantation between March 2021 and March 2022 at our institute were retrospectively analyzed. Primary outcome measures were mean duration of surgery and suture removal, degree of conjunctival hyperemia on postoperative day 1, pain score at suture removal, postoperative symptoms at 6mo, including conjunctival hyperemia, foreign body sensation, and graft stability. RESULTS: Ninety-eight patients underwent monocular surgery and were divided into ISLK (51 eyes) and RI (47 eyes) groups according to the type of conjunctiva autograft fixation method planned. There was no significant difference in mean duration of surgery between the two groups (18.59±2.39min vs 18.15±2.20min, P=0.417); however, compared to the RI group, shorter suture removal times were observed in the ISLK group [0.58min (0.42-0.87) vs 3.00min (2.21-4.15), P<0.001]. The degree of conjunctival hyperemia on postoperative day 1 was milder in the ISLK group (P<0.001). Pain scores at suture removal were lower in the ISLK group than in RI group [1 (0-3) vs 2 (1-4), P<0.001]. Postoperative symptoms at 6mo were comparable between the groups (P=0.487), with no recurrence. CONCLUSION: ISLK is an innovative method for limbal conjunctival autograft fixation after pterygium excision. Compared to RI fixation, ISLK facilitates suture removal and reduces discomfort, with comparable surgery duration and less conjunctival hyperemia.