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1.
Biochem Biophys Rep ; 40: 101840, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39483178

RESUMEN

T-2 toxin, a fungal secondary metabolite produced by toxigenic Fusarium species, poses a significant threat to grain food and feed due to its potential to cause intestinal inflammation in livestock and poultry. Macrophages play a crucial role as integral components of the body's immune system during intestinal inflammation. This study aimed to elucidate the mechanism behind the inflammatory response triggered by T-2 toxin in macrophages. Compared to the control group, gavage administration of T-2 toxin (0.33, 1, and 4 mg kg-1) led to a decrease in body weight and feed intake, along with histopathological alterations in the colon of mice. In addition, T-2 toxin induced the upregulation of macrophage-derived cytokines like IL-1ß, IL-6, and TNF-α, as well as a rise in the population of F4/80+ macrophages in the colon. T-2 toxin also led to the upregulation of IL-1ß, IL-6, and TNF-α in mouse bone marrow-derived macrophages (BMDMs). Furthermore, the transcriptomic analysis of BMDMs exposed to T-2 toxin (10 nM) identified the "TNF signaling pathway," "Lipid and atherosclerosis," "Epstein-Barr virus infection," "MAPK signaling pathway," and the "NF-kappa B signaling pathway" as the top five significantly enriched pathways. Subsequently, twelve inflammation-related genes were randomly chosen for validation through quantitative reverse transcription PCR (RT-qPCR), with the results corroborating those from the transcriptomic analysis. The comprehensive analysis of transcriptome data highlights the activation of several signaling pathways associated with the inflammatory response following T-2 toxin-induced BMDMs, offering potential therapeutic targets for the prevention and treatment of T-2 toxin-induced intestinal inflammation.

2.
IBRO Neurosci Rep ; 17: 290-299, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39391262

RESUMEN

Objective: Despite the conventional belief that motor function and sensation distal to the site of a complete spinal cord transection are irretrievable, our research has demonstrated significant motor recovery in mice, rats, and dogs by applying polyethylene glycol (PEG) topically via a syringe directly to the contact interface of transected spinal cord. However, before implementing this technology in human subjects, validating PEG's efficacy and enduring impact through experimentation on non-human primates is imperative. Methods: Two 4-year-old female Macaca fascicularis monkeys underwent complete dorsal cord transection at T10. Postoperative behavioral assessment, electrophysiologic monitoring, and neuroimaging examinations were recorded, and tissues were obtained for histological examination at the end of study. Results: The monkey whose spinal cord had been fully transected in the presence of PEG developed useful recovery already at 3 months and near-complete recovery of motor function in the hind-limbs at 18 months. The control animal without PEG remained paralyzed. Cortical somatosensory evoked potentials recovered postoperatively only in PEG-treated monkey vs none in the control. Diffusion tensor imaging showed re-establishment of continuity of the white matter in PEG-treated monkey, but not in the control. Moreover, histology revealed intact neuronal bodies, axons, and myelin tissue at the spinal cord transection site in PEG-treated monkey only. Conclusion: This report suggests that in primates, an acutely transected spinal cord can be re-fused in the presence of PEG with restoration of neural continuity and functional recovery of motor activity distal to the site of transection.

3.
Biochim Biophys Acta Rev Cancer ; 1879(6): 189184, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39303858

RESUMEN

Neuroendocrine tumors (NETs) are a diverse group of tumors that arise from neuroendocrine cells and are commonly found in various organs. A considerable proportion of NET patients were diagnosed at an advanced or metastatic stage. Alkylating agents are the primary treatment for NET, and O6-methylguanine methyltransferase (MGMT) remains the first-line of defense against DNA damage caused by these agents. Clinical trials have indicated that MGMT promoter methylation or its low/lacked expression can predict a favorable outcome with Temozolomide in NETs. Its status could help select NET patients who can benefit from alkylating agents. Therefore, MGMT status serves as a biomarker to guide decisions on the efficacy of Temozolomide as a personalized treatment option. Additionally, delving into the regulatory mechanisms of MGMT status can lead to the development of MGMT-targeted therapies, benefiting individuals with high levels of MGMT expression. This review aims to explore the polymorphism of MGMT regulation and summarize its clinical implications in NETs, which would help establish the role of MGMT as a biomarker and its potential as a therapeutic target in NETs. Additionally, we explore the benefits of combining Temozolomide and immunotherapy in MGMT hypermethylated subgroups. Future studies can focus on optimizing Temozolomide administration to induce specific immunomodulatory changes.

4.
J Nanobiotechnology ; 22(1): 479, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39134988

RESUMEN

The prevention and treatment of gastrointestinal mucosal injury caused by a plateau hypoxic environment is a clinical conundrum due to the unclear mechanism of this syndrome; however, oxidative stress and microbiota dysbiosis may be involved. The Robinia pseudoacacia L. flower, homologous to a functional food, exhibits various pharmacological effects, such as antioxidant, antibacterial, and hemostatic activities. An increasing number of studies have revealed that plant exosome-like nanoparticles (PELNs) can improve the intestinal microbiota and exert antioxidant effects. In this study, the oral administration of Robinia pseudoacacia L. flower exosome-like nanoparticles (RFELNs) significantly ameliorated hypoxia-induced gastric and small intestinal mucosal injury in mice by downregulating hypoxia-inducible factor-1α (HIF-1α) and HIF-2α expression and inhibiting hypoxia-mediated ferroptosis. In addition, oral RFELNs partially improved hypoxia-induced microbial and metabolic disorders of the stomach and small intestine. Notably, RFELNs displayed specific targeting to the gastrointestinal tract. In vitro experiments using gastric and small intestinal epithelial cell lines showed that cell death caused by elevated HIF-1α and HIF-2α under 1% O2 mainly occurred via ferroptosis. RFELNs obviously inhibited HIF-1α and HIF-2α expression and downregulated the expression of NOX4 and ALOX5, which drive reactive oxygen species production and lipid peroxidation, respectively, suppressing ferroptosis under hypoxia. In conclusion, our findings underscore the potential of oral RFELNs as novel, naturally derived agents targeting the gastrointestinal tract, providing a promising therapeutic approach for hypoxia-induced gastric and small intestinal mucosal ferroptosis.


Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Exosomas , Ferroptosis , Flores , Mucosa Gástrica , Subunidad alfa del Factor 1 Inducible por Hipoxia , Mucosa Intestinal , Intestino Delgado , Peroxidación de Lípido , Nanopartículas , Animales , Ferroptosis/efectos de los fármacos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Ratones , Exosomas/metabolismo , Exosomas/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Intestino Delgado/efectos de los fármacos , Intestino Delgado/metabolismo , Intestino Delgado/patología , Administración Oral , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Masculino , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/metabolismo , Flores/química , Nanopartículas/química , Hipoxia/tratamiento farmacológico , Hipoxia/metabolismo , Humanos , Ratones Endogámicos C57BL
5.
J Hazard Mater ; 478: 135555, 2024 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-39186842

RESUMEN

The accumulation of polyethylene microplastic (PE-MPs) in soil can significantly impact plant quality and yield, as well as affect human health and food chain cycles. Therefore, developing rapid and effective detection methods is crucial. In this study, traditional machine learning (ML) and H2O automated machine learning (H2O AutoML) were utilized to offer a powerful framework for detecting PE-MPs (0.1 %, 1 %, and 2 % by dry soil weight) and the co-contamination of PE-MPs and fomesafen (a common herbicide) in soil. The development of the framework was based on the results of the metabolic reprogramming of soybean plants. Our study stated that traditional ML exhibits lower accuracy due to the challenges associated with optimizing complex parameters. H2O AutoML can accurately distinguish between clean soil and contaminated soil. Notably, H2O AutoML can detect PE-MPs as low as 0.1 % (with 100 % accuracy) and co-contamination of PE-MPs and fomesafen (with 90 % accuracy) in soil. The VIP and SHAP analyses of the H2O AutoML showed that PE-MPs and the co-contamination of PE-MPs and fomesafen significantly interfered with the antioxidant system and energy regulation of soybean. We hope this study can provide a reliable scientific basis for sustainable development of the environment.


Asunto(s)
Glycine max , Aprendizaje Automático , Microplásticos , Contaminantes del Suelo , Glycine max/metabolismo , Glycine max/efectos de los fármacos , Contaminantes del Suelo/análisis , Contaminantes del Suelo/metabolismo , Microplásticos/toxicidad , Microplásticos/análisis , Herbicidas/análisis , Monitoreo del Ambiente/métodos , Polietileno , Suelo/química , Reprogramación Metabólica
6.
Stroke Vasc Neurol ; 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39164038

RESUMEN

BACKGROUND: The impact of lowering systolic blood pressure (SBP) following endovascular treatment (EVT) in acute large vessel occlusion stroke (LVOS) patients remains unclear. We aimed to explore the effect of the magnitude of SBP reduction (SBPr) after EVT on outcomes in LVOS patients. METHODS: We consecutively registered patients at three comprehensive stroke centres who had experienced EVT as a result of acute anterior circulation LVOS. SBPr was calculated as follows: (baseline SBP-mean SBP/baseline SBP)×100%. The 90-day modified Rankin Scale score ranging from 0 to 2 was defined as a favourable functional outcome. Based on CT scans obtained within 24 hours after procedure, symptomatic intracranial haemorrhage (sICH) was assessed according to the criteria of the European Cooperative Acute Stroke Study III. RESULTS: We enrolled 1080 patients, of which 908 (84.1%) had successful recanalisation. In the overall cohort, SBPr was correlated with lower odds of sICH (SBPr±10% as a reference, 20%-30%: OR 0.460; 95% CI: 0.245 to 0.864; p=0.016; >30%: OR 0.304; 95% CI 0.123 to 0.749; p=0.010). In patients who achieved successful reperfusion, SBPr>30% was correlated with higher odds of a poor outcome (SBPr±10% as a reference, OR 2.150; 95% CI 1.268 to 3.645; p=0.004) and SBPr has a similar tendency towards reducing the incidence of sICH. In the subgroup analyses, baseline Alberta Stroke Programme Early CT (ASPECT) score (pinteract=0.024) modified the effect of SBPr on the 90-day outcome. CONCLUSION: Among patients with EVT, a significant drop in SBP may be related to a poor functional outcome and a reduced incidence of sICH. Baseline ASPECT score may be an important interacting factor in the association of SBPr with the 90-day outcome. This study provides new insights for individualised BP management in patients with EVT.

7.
Heliyon ; 10(13): e32900, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39185496

RESUMEN

[This corrects the article DOI: 10.1016/j.heliyon.2024.e30633.].

8.
Adv Sci (Weinh) ; 11(35): e2308417, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39041891

RESUMEN

O6-methylguanine DNA methyltransferase (MGMT) removes alkyl adducts from the guanine O6 position (O6-MG) and repairs DNA damage. High MGMT expression results in poor response to temozolomide (TMZ). However, the biological importance of MGMT and the mechanism underlying its high expression in pancreatic neuroendocrine tumors (PanNETs) remain elusive. Here, it is found that MGMT expression is highly elevated in PanNET tissues compared with paired normal tissues and negatively associated with progression-free survival (PFS) time in patients with PanNETs. Knocking out MGMT inhibits cancer cell growth in vitro and in vivo. Ectopic MEN1 expression suppresses MGMT transcription in a manner that depends on ß-Catenin nuclear export and degradation. The Leucine 267 residue of MEN1 is crucial for regulating ß-Catenin-MGMT axis activation and chemosensitivity to TMZ. Interference with ß-Catenin re-sensitizes tumor cells to TMZ and significantly reduces the cytotoxic effects of high-dose TMZ treatment, and MGMT overexpression counteracts the effects of ß-Catenin deficiency. This study reveals the biological importance of MGMT and a new mechanism by which MEN1 deficiency regulates its expression, thus providing a potential combinational strategy for treating patients with TMZ-resistant PanNETs.


Asunto(s)
Metilasas de Modificación del ADN , Enzimas Reparadoras del ADN , Resistencia a Antineoplásicos , Tumores Neuroendocrinos , Neoplasias Pancreáticas , Temozolomida , beta Catenina , Animales , Femenino , Humanos , Masculino , Ratones , Antineoplásicos Alquilantes/farmacología , beta Catenina/metabolismo , beta Catenina/genética , Línea Celular Tumoral , Modelos Animales de Enfermedad , Metilasas de Modificación del ADN/metabolismo , Metilasas de Modificación del ADN/genética , Enzimas Reparadoras del ADN/genética , Enzimas Reparadoras del ADN/metabolismo , Resistencia a Antineoplásicos/genética , Resistencia a Antineoplásicos/efectos de los fármacos , Ratones Desnudos , Tumores Neuroendocrinos/genética , Tumores Neuroendocrinos/tratamiento farmacológico , Tumores Neuroendocrinos/metabolismo , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas/genética , Temozolomida/farmacología , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismo
9.
Anal Methods ; 16(28): 4783-4793, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-38961688

RESUMEN

The new generation of gene editing technologies, primarily based on CRISPR/Cas9 and its derivatives, allows for more precise editing of organisms. However, when the editing efficiency is low, only a small fraction of gene fragments is edited, leaving behind minimal traces and making it difficult to detect and evaluate the editing effects. Although a series of technologies and methods have been developed, they lack the ability for precise quantification and quantitative analysis of these products. Digital polymerase chain reaction (dPCR) offers advantages such as high precision and sensitivity, making it suitable for absolute quantification of nucleic acid samples. In the present study, we developed a novel platform for precise quantification of gene editing products based on microfluidic chip-based dPCR. The results indicated that our assay accurately identified different types of edited samples within a variety of different types, including more complex genomic crops such as tetraploid rapeseed and soybean (highly repetitive sequence). The sensitivity of this detection platform was as low as 8.14 copies per µL, with a detection limit of 0.1%. These results demonstrated the superior performance of the platform, including high sensitivity, low detection limit, and wide applicability, enabling precise quantification and assessment of gene editing efficiency. In conclusion, microfluidic chip-based dPCR was used as a powerful tool for precise quantification and assessment of gene editing products.


Asunto(s)
Sistemas CRISPR-Cas , Edición Génica , Reacción en Cadena de la Polimerasa , Edición Génica/métodos , Reacción en Cadena de la Polimerasa/métodos , Sistemas CRISPR-Cas/genética , Dispositivos Laboratorio en un Chip , Técnicas Analíticas Microfluídicas/instrumentación , Técnicas Analíticas Microfluídicas/métodos , Glycine max/genética , Brassica napus/genética
10.
Materials (Basel) ; 17(14)2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-39063738

RESUMEN

Heat treatment is important for optimizing the strength performance and improving the toughness of titanium alloys. In this study, we investigated the impact of three heat treatment methods (ß-annealing, double annealing, and solid-solution and aging treatment) on the mechanical properties and fracture morphology of Ti555211 titanium alloy. The results show that after ß-annealing treatment, the alloy retains a high strength, while showing almost no ductility, and no yield strength. The alloy after double annealing has a high elongation rate (~54%) and lower strength. After solid-solution and aging heat treatment, the alloy was able to retain both high strength and a certain degree of ductility. The optimal heat-treatment process is solid-solution treatment at 820 °C/2 h and aging at 560 °C/12 h, which results in a maximum tensile strength of 1404 MPa and an elongation rate of 11%.

11.
Hum Cell ; 37(5): 1522-1534, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39078546

RESUMEN

Pancreatic neuroendocrine tumors are the second most common tumors of the pancreas, and approximately half of patients are diagnosed with liver metastases. Currently, the improvement in the efficacy of relevant treatment methods is still limited. Therefore, there is an urgent need for in-depth research on the molecular biological mechanism of pancreatic neuroendocrine tumors. However, due to their relatively inert biology, preclinical models are extremely scarce. Here, the patient-derived organoid, and patient-derived xenograft were successfully constructed. These two models and the previously constructed cell line named SPNE1 all derived from the same patient with a grade 3 non-functional pancreatic neuroendocrine tumor, providing new tumor modeling platforms, and characterized using immunohistochemistry, whole-exome sequencing, and single-cell transcriptome sequencing. Combined with a tumor formation experiment in immunodeficient mice, we selected the model that most closely recapitulated the parental tumor. Overall, the patient-derived xenograft model most closely resembled human tumor tissue.


Asunto(s)
Tumores Neuroendocrinos , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/terapia , Tumores Neuroendocrinos/patología , Tumores Neuroendocrinos/genética , Tumores Neuroendocrinos/terapia , Animales , Modelos Animales de Enfermedad , Ratones , Xenoinjertos , Línea Celular Tumoral , Organoides , Secuenciación del Exoma
12.
J Adv Res ; 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39084403

RESUMEN

INTRODUCTION: Genetically modified (GM) crops have been widely cultivated across the world and the development of rapid, ultrasensitive, visual multiplex detection platforms that are suitable for field deployment is critical for GM organism regulation. OBJECTIVE: In this study, we developed a novel one-pot system, termed MR-DCA (Multiplex RPA and Dual CRISPR assay), for the simultaneous detection of CaMV35S and NOS genetic targets in GM crops. This innovative approach combined Multiplex RPA (recombinase polymerase amplification) with the Dual CRISPR (clustered regularly interspaced short palindromic repeat) assay technique, to provide a streamlined and efficient method for GM crop detection. METHODS: The RPA reaction used for amplification CaMV35S and NOS targets was contained in the tube base, while the dual CRISPR enzymes were placed in the tube cap. Following centrifugation, the dual CRISPR (Cas13a/Cas12a) detection system was initiated. Fluorescence visualization was used to measure CaMV35S through the FAM channel and NOS through the HEX channel. When using lateral flow strips, CaMV35S was detected using rabbit anti-digoxin (blue line), whilst NOS was identified using anti-mouse FITC (red line). Line intensity was quantified using Image J and depicted graphically. RESULTS: Detection of the targets was completed in 35 min, with a limit of detection as low as 20 copies. In addition, two analysis systems were developed and they performed well in the MR-DCA assay. In an analysis of 24 blind samples from GM crops with a wide genomic range, MR-DCA gave consistent results with the quantitative PCR method, which indicated high accuracy, applicability and semi-quantitative ability. CONCLUSION: The development of MR-DCA represents a significant advancement in the field of GM detection, offering a rapid, sensitive and portable method for multiple target detection that can be used in resource-limited environments.

13.
Sci Total Environ ; 946: 174187, 2024 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-38936741

RESUMEN

Nutrient requirement for crop growth, defined as the amount of nutrient that crops take up from soil to produce a specific grain yield, is a key parameter in determining fertilizer application rate. However, existing studies primarily focus on identifying nitrogen (N), phosphorus (P), and potassium (K) requirements solely in relation to grain yield, neglecting grain protein content, a crucial index for wheat grain quality. Addressing this gap, we conducted multi-site, multi-cultivar, and multi-year field trials across three ecological regions of China from 2016 to 2020 to elucidate variations in nutrient requirements for grain yield and grain protein. The research findings revealed that wheat grain yield ranged from 4.1 to 9.3 Mg ha-1 (average 6.9 Mg ha-1) and grain protein content ranged from 98 to 157 g kg-1 (average 127 g kg-1) across the three regions. Notably, the N requirement exhibited a nonlinear correlation with the wheat grain yield but a linear increase with increasing grain protein, while the P and K requirements positively correlated with grain yield and protein content. Regression models were formulated to determine the nutrient requirements (MENR), enabling the prediction of N, P, and K requirements for leading cultivars with varying grain yields and protein contents. Implementing nutrient requirements based on MENR projections resulted in substantial reductions in fertilizer rates: 22.0 kg ha-1 N (10.7 %), 9.9 kg ha-1 P (20.2 %), and 8.1 kg ha-1 K (16.3 %). This translated to potential savings of 0.4 Mt. N, 0.23 Mt. P, and 0.17 Mt. K, consequently mitigating 5.5 Mt. CO2 greenhouse-gas emission and yielding an economic benefit of 0.8 billion US$ annually in China. These findings underscore the significance of considering grain yield and protein content in estimating nutrient requirements for fertilizer recommendations to realize high-yielding, high-protein wheat production, and minimize overfertilization and associated environmental risks.


Asunto(s)
Grano Comestible , Fertilizantes , Nitrógeno , Fósforo , Potasio , Triticum , China , Nitrógeno/análisis , Potasio/análisis , Potasio/metabolismo , Fósforo/análisis , Grano Comestible/crecimiento & desarrollo , Triticum/crecimiento & desarrollo , Agricultura/métodos , Nutrientes/análisis
14.
Ann Clin Transl Neurol ; 11(7): 1921-1929, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38864184

RESUMEN

OBJECTIVES: A higher reperfusion grade after endovascular thrombectomy (EVT) is associated with a good prognosis. However, the effect of the number of retrievals has not yet been investigated in vertebrobasilar occlusion (VBAO). Therefore, the aim of this study was to investigate whether to continue retrieval after early modified thrombolysis in cerebral infarction (mTICI) 2b to achieve a better reperfusion grade. METHODS: We retrospectively analyzed the data of patients who underwent EVT caused by VBAO in a multicenter registry dataset. Patients who underwent successful reperfusion were included (mTICI 2b/3). Regression models were used to analyze the correlation of different reperfusion grades stratified by the number of retrieval attempts with clinical prognosis and hemorrhage transition. RESULTS: We included 432 patients: 34.5% (n = 149) had a final mTICI score of 2b and 65.5% (n = 283) had a final mTICI score of 3. Patients who obtained a mTICI of 3 after the first pass had significantly increased odds of having a good prognosis. As the number of passes increases, the chances of obtaining a good prognosis decreases. After three or more passes, the odds of achieving functional independence and favorable outcomes were comparable to those of the first mTICI 2b, regardless of the 90-day (OR 1.132 95% CI 0.367-3.487 p = 0.829; OR 1.070 95% CI 0.375-3.047 p = 0.900) or 1-year follow-up (OR 1.217 95% CI 0.407-3.637 p = 0.725; OR 1.068 95% CI 0.359-3.173 p = 0.906). INTERPRETATION: Within two retrieval attempts, mTICI 3 was better than the first retrieval to mTICI 2b. After early mTICI 2b, each retrieval should be undertaken with caution to pursue a higher reperfusion grade.


Asunto(s)
Procedimientos Endovasculares , Sistema de Registros , Trombectomía , Humanos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Estudios Retrospectivos , Insuficiencia Vertebrobasilar/cirugía , Terapia Trombolítica , Anciano de 80 o más Años , Infarto Cerebral/terapia , Evaluación de Resultado en la Atención de Salud , Pronóstico , Reperfusión
15.
Cell Prolif ; 57(11): e13694, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38938061

RESUMEN

Pancreatic cancer cells have a much higher metabolic demand than that of normal cells. However, the abundant interstitium and lack of blood supply determine the lack of nutrients in the tumour microenvironment. Although pancreatic cancer has been reported to supply extra metabolic demand for proliferation through autophagy and other means, the specific regulatory mechanisms have not yet been elucidated. In this study, we focused on transcription factor EB (TFEB), a key factor in the regulation of autophagy, to explore its effect on the phenotype and role in the unique amino acid utilisation pattern of pancreatic cancer cells (PCCs). The results showed that TFEB, which is generally highly expressed in pancreatic cancer, promoted the proliferation and metastasis of PCCs. TFEB knockdown inhibited the proliferation and metastasis of PCCs by blocking the catabolism of branched-chain amino acids (BCAAs). Concerning the mechanism, we found that TFEB regulates the catabolism of BCAAs by regulating BCAT1, a key enzyme in BCAA metabolism. BCAA deprivation alone did not effectively inhibit PCC proliferation. However, BCAA deprivation combined with eltrombopag, a drug targeting TFEB, can play a two-pronged role in exogenous supply deprivation and endogenous utilisation blockade to inhibit the proliferation of pancreatic cancer to the greatest extent, providing a new therapeutic direction, such as targeted metabolic reprogramming of pancreatic cancer.


Asunto(s)
Aminoácidos de Cadena Ramificada , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Neoplasias Pancreáticas , Transaminasas , Humanos , Aminoácidos de Cadena Ramificada/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/genética , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Línea Celular Tumoral , Transaminasas/metabolismo , Transaminasas/genética , Animales , Progresión de la Enfermedad , Ratones
16.
Curr Med Sci ; 44(3): 554-560, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38842773

RESUMEN

OBJECTIVE: This study aimed to compare the performance of standard-definition white-light endoscopy (SD-WL), high-definition white-light endoscopy (HD-WL), and high-definition narrow-band imaging (HD-NBI) in detecting colorectal lesions in the Chinese population. METHODS: This was a multicenter, single-blind, randomized, controlled trial with a non-inferiority design. Patients undergoing endoscopy for physical examination, screening, and surveillance were enrolled from July 2017 to December 2020. The primary outcome measure was the adenoma detection rate (ADR), defined as the proportion of patients with at least one adenoma detected. The associated factors for detecting adenomas were assessed using univariate and multivariate logistic regression. RESULTS: Out of 653 eligible patients enrolled, data from 596 patients were analyzed. The ADRs were 34.5% in the SD-WL group, 33.5% in the HD-WL group, and 37.5% in the HD-NBI group (P=0.72). The advanced neoplasm detection rates (ANDRs) in the three arms were 17.1%, 15.5%, and 10.4% (P=0.17). No significant differences were found between the SD group and HD group regarding ADR or ANDR (ADR: 34.5% vs. 35.6%, P=0.79; ANDR: 17.1% vs. 13.0%, P=0.16, respectively). Similar results were observed between the HD-WL group and HD-NBI group (ADR: 33.5% vs. 37.7%, P=0.45; ANDR: 15.5% vs. 10.4%, P=0.18, respectively). In the univariate and multivariate logistic regression analyses, neither HD-WL nor HD-NBI led to a significant difference in overall adenoma detection compared to SD-WL (HD-WL: OR 0.91, P=0.69; HD-NBI: OR 1.15, P=0.80). CONCLUSION: HD-NBI and HD-WL are comparable to SD-WL for overall adenoma detection among Chinese outpatients. It can be concluded that HD-NBI or HD-WL is not superior to SD-WL, but more effective instruction may be needed to guide the selection of different endoscopic methods in the future. Our study's conclusions may aid in the efficient allocation and utilization of limited colonoscopy resources, especially advanced imaging technologies.


Asunto(s)
Adenoma , Colonoscopía , Neoplasias Colorrectales , Imagen de Banda Estrecha , Humanos , Masculino , Neoplasias Colorrectales/diagnóstico por imagen , Neoplasias Colorrectales/diagnóstico , Femenino , Persona de Mediana Edad , Adenoma/diagnóstico por imagen , Adenoma/diagnóstico , Imagen de Banda Estrecha/métodos , Colonoscopía/métodos , Anciano , Método Simple Ciego , Luz , Adulto
17.
Medicine (Baltimore) ; 103(18): e38057, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38701266

RESUMEN

Patients with hypertension have a higher risk of having constipation and vice versa. The causal association between these 2 variables is not proven. We performed a retrospective Mendelian randomization analysis to determine the causal association between constipation and hypertension. Two-sample 2-way Mendelian randomization analysis was used. Genetic variants for constipation were derived from genome-wide association study data of European origin (15,902 cases and 395,721 controls). Corresponding genetic associations for hypertension were derived from European ancestry GWAS data (54,358 cases and 408,652 controls). Genetic susceptibility to hypertension was associated with an increased risk of constipation (OR: 3.459, 95% CI: 1.820-6.573, P < .001). In an inverse Mendelian randomization analysis, no causal effect of constipation on hypertension was found (OR: 0.999, 95% CI: 0.987-1.011, P = .834). In sensitivity analyses, these associations persisted and no multiple effects were found. This study suggests that there is a causal relationship between hypertension and constipation and that hypertension may increase the risk of developing constipation.


Asunto(s)
Estreñimiento , Estudio de Asociación del Genoma Completo , Hipertensión , Análisis de la Aleatorización Mendeliana , Humanos , Estreñimiento/epidemiología , Estreñimiento/genética , Hipertensión/genética , Hipertensión/epidemiología , Estudios Retrospectivos , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Factores de Riesgo
18.
Food Chem (Oxf) ; 8: 100206, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-38694166

RESUMEN

Honey adulteration with exogenous syrup has become a common phenomenon, and current detection techniques that require large instruments are cumbersome and time-consuming. In this study, a simple and efficient method was developed by integrating the rapid extraction of nucleic acids (REMD) and recombinase polymerase amplification (RPA), known as REMD-RPA, for the rapid screening of syrup adulteration in honey. First, a rapid extraction method was developed to rapidly extract corn syrup DNA in five minutes to meet the requirements of PCR and RPA assays. Then, the RPA method for detecting endogenous maize genes (ZssIIb) was established, which could detect 12 copies/µL of the endogenous maize gene within 30 min without cross-reacting with other plant-derived genes. This indicated that the RPA technique exhibited high sensitivity and specificity. Finally, the REMD-RPA detection platform was used to detect different concentrations of corn syrup adulteration, and 1 % adulteration could be detected within 30 min. The 22 commercially available samples were tested to validate the efficacy of this method, and the established RPA was able to detect seven adulterated samples in less than 30 min. Overall, the developed method is rapid, sensitive, and specific, providing technical support for the rapid field detection of honey adulteration and can serve as a reference for developing other field test methods.

19.
Heliyon ; 10(10): e30633, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38779012

RESUMEN

Background and objectives: Both myelin oligodendrocyte glycoprotein-IgG associated disorders (MOGAD) and neuromyelitis optica spectrum disorder (NMOSD) are demyelinating diseases of the central nervous system. They present similar clinical manifestations such as optica neuritis, myelitis and area postrema syndrome (APS). The distinctions of optica neuritis (ON) and myelitis between them have been elaborated to great length while their differences in APS remain to be elucidated. We aim to report the frequency of APS in patients with MOGAD as well as NNOSD patients, and to compare the characteristics of APS between patients with MOGAD and those with NMOSD. Methods: Seven MOG-IgG positive APS patients were retrospectively identified between 2017 and 2022. APS phenotypes have been previously described. The similarities and differences between MOGAD and NMOSD patients with APS was compared, including the frequency and duration of APS between the two diseases, and their incidences of accompanied subtentorial lesions have also been described and compared. Results: We reviewed a cohort of 218 MOG-IgG-positive patients, and 396 patients with NMOSD. 200 MOGAD patients and 332 NMOSD patients were included in this study. In the cohort, seven patients with MOG-IgG-positive antibody presented with APS were analyzed, four of whom had disease onset with APS. Of the 332 patients with NMOSD, 47 had APS attacks while 31 had APS at disease onset. In patients with MOGAD, 2 had nausea, 3 had vomiting, 5 had hiccups, and 1 patient presented with all three symptoms above. In patients with NMOSD, 70.2 % had nausea, vomiting and hiccups at the same time during APS attacks. Apart from the medulla oblongata, other subtentorial regions were also affected in 6/7 MOGAD patients while 14/47 NMOSD patients had other subtentorial regions involved. During an APS attack, the incidence of concomitant lesions in the brainstem and other regions was significantly greater in MOGAD than in the NMOSD cohort (P = 0.008*). Conclusion: APS is a rare, but not isolated clinical manifestation of MOGAD. APS happened more frequently with other supratentorial and subtentorial lesions in MOGAD. The symptoms of NVH (nausea, vomiting, hiccups) tended to happen respectively in MOGAD compared with NMOSD. The phenotype or mechanism of APS in MOGAD may differ from that in NMOSD.

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