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1.
Curr Issues Mol Biol ; 46(9): 10335-10350, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39329967

RESUMEN

Anthocyanins, flavonoid pigments, are responsible for the purple and red hues in potato tubers. This study analyzed tubers from four potato cultivars-red RR, purple HJG, yellow QS9, and white JZS8-to elucidate the genetic mechanisms underlying tuber pigmentation. Our transcriptomic analysis identified over 2400 differentially expressed genes between these varieties. Notably, genes within the flavonoid biosynthesis pathway were enriched in HJG and RR compared to the non-pigmented JZS8, correlating with their higher levels of anthocyanin precursors and related substances. Hierarchical clustering revealed inverse expression patterns for the key genes involved in anthocyanin metabolism between pigmented and non-pigmented varieties. Among these, several MYB transcription factors displayed strong co-expression with anthocyanin biosynthetic genes, suggesting a regulatory role. Specifically, the expression of 16 MYB genes was validated using qRT-PCR to be markedly higher in pigmented HJG and RR versus JZS8, suggesting that these MYB genes might be involved in tuber pigmentation. This study comprehensively analyzed the transcriptome of diverse potato cultivars, highlighting specific genes and metabolic pathways involved in tuber pigmentation. These findings provide potential molecular targets for breeding programs focused on enhancing tuber color.

2.
ACS Nano ; 18(36): 25155-25169, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39189792

RESUMEN

Steviol glycosides (SGs) are a class of high-potency noncalorie natural sweeteners made up of a common diterpenoid core and varying glycans. Thus, the diversity of glycans in composition, linkage, and isomerism results in the tremendous structural complexity of the SG family, which poses challenges for the precise identification and leads to the fact that SGs are frequently used in mixtures and their variances in biological activity remain largely unexplored. Here we show that a wild-type aerolysin nanopore can detect and discriminate diverse SG species through the modulable electro-osmotic flow effect at varied applied voltages. At low voltages, the neutral SG molecule was drawn and stuck in the pore entrance due to an energy barrier around R220 sites. The ensuing binding events enable the identification of the majority of SG species. Increasing the voltage can break the barrier and cause translocation events, allowing for the unambiguous identification of several pairs of SGs differing by only one hydroxyl group through recognition accumulation from multiple sensing regions and sites. Based on nanopore data of 15 SGs, a deep learning-based artificial intelligence (AI) model was created to process the individual blockage events, achieving the rapid, automated, and precise single-molecule identification and quantification of SGs in real samples. This work highlights the value of nanopore sensing for precise structural analysis of complex glycans-containing glycosides, as well as the potential for sensitive and rapid quality assurance analysis of glycoside products with the use of AI.


Asunto(s)
Aprendizaje Profundo , Diterpenos de Tipo Kaurano , Nanoporos , Diterpenos de Tipo Kaurano/química , Diterpenos de Tipo Kaurano/análisis , Glucósidos/química , Glucósidos/análisis , Glicósidos/química , Glicósidos/análisis
3.
Genes Nutr ; 19(1): 17, 2024 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-39182019

RESUMEN

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver ailment that can lead to serious conditions such as cirrhosis and hepatocellular carcinoma. Hepatic Nogo-B regulates glucose and lipid metabolism, and its inhibition has been shown to be protective against metabolic syndrome. Increasing evidence suggests that imbalances in the gut microbiota (GM) and lipid metabolism disorders are significant contributors to NAFLD progression. Nevertheless, it is not yet known whether Nogo-B can affect NAFLD by influencing the gut microbiota and metabolites. Hence, the aim of the present study was to characterize this process and explore its possible underlying mechanisms. METHODS: A NAFLD model was constructed by administering a high-fat diet (HFD) to Nogo-B-/- and WT mice from the same litter, and body weight was measured weekly in each group. The glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed to assess blood glucose levels. At the end of the 12-week period, samples of serum, liver, and intestinal contents were collected and used for serum biochemical marker and inflammatory factor detection; pathology evaluation; and gut microbiome and metabolomics analysis. Spearman's correlation analysis was performed to determine possible correlations between differential gut microbiota and differential serum metabolites between groups. RESULTS: Nogo-B deficiency attenuated the effects of the HFD, including weight gain, liver weight gain, impaired glucose tolerance, hepatic steatosis, elevated serum lipid biochemicals levels, and liver function. Nogo-B deficiency suppressed M1 polarization and promoted M2 polarization, thus inhibiting inflammatory responses. Furthermore, Nogo-B-/--HFD-fed mice presented increased gut microbiota richness and diversity, decreased Firmicutes/Bacteroidota (F/B) ratios, and altered serum metabolites compared with those of WT-HFD-fed mice. During analysis, several differential gut microbiota, including Lachnoclostridium, Harryflintia, Odoribacter, UCG-009, and unclassified_f_Butyricoccaceae, were screened between groups. These microbiota were found to be positively correlated with upregulated purine metabolism and bile acid metabolites in Nogo-B deficiency, while they were negatively correlated with downregulated corticosterone and tricarboxylic acid cyclic metabolites in Nogo-B deficiency. CONCLUSION: Nogo-B deficiency delayed NAFLD progression, as demonstrated by reduced hepatocellular lipid accumulation, attenuated inflammation and liver injury, and ameliorated gut microbiota dysbiosis and metabolic disorders. Importantly, Odoribacter was strongly positively correlated with ALB and taurodeoxycholic acid, suggesting that it played a considerable role in the influence of Nogo-B on the progression of NAFLD, a specific feature of NAFLD in Nogo-B-/- mice. The regulation of bile acid metabolism by the gut microbiota may be a potential target for Nogo-B deficiency to ameliorate NAFLD.

4.
Apoptosis ; 29(9-10): 1564-1583, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39066845

RESUMEN

Anoikis-Related Genes (ARGs) lead to the organism manifesting resistance to anoikis and are associated with unfavorable prognostic outcomes across various malignancies.Therefore, it is crucial to identify the pivotal target genes related to anoikis in HCC .We found that ARGs were significantly correlated with prognosis and immune responses in HCC. The core gene, SPP1, notably promoted anoikis resistance and metastasis in HCC through both in vivo and in vitro studies. The PI3K-Akt-mTOR pathway played a critical role in anoikis suppression within HCC contexts. Our research unveiled SPP1's role in enhancing PKCα phosphorylation, which in turn activated the PI3K-Akt-mTOR cascade. Additionally, SPP1 was identified as a key regulator of MDSCs and Tregs migration, directly affecting their immunosuppressive capabilities.These findings indicate that in HCC, SPP1 promoted anoikis resistance and facilitated immune evasion by modulating MDSCs and Tregs.


Asunto(s)
Anoicis , Carcinoma Hepatocelular , Neoplasias Hepáticas , Osteopontina , Anoicis/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/patología , Humanos , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Animales , Osteopontina/genética , Osteopontina/metabolismo , Ratones , Línea Celular Tumoral , Metástasis de la Neoplasia , Vigilancia Inmunológica , Invasividad Neoplásica , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Linfocitos T Reguladores/inmunología , Transducción de Señal , Evasión Inmune , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Serina-Treonina Quinasas TOR/metabolismo , Serina-Treonina Quinasas TOR/genética , Células Supresoras de Origen Mieloide/inmunología , Células Supresoras de Origen Mieloide/metabolismo , Pronóstico , Masculino , Movimiento Celular/genética
5.
Inflamm Res ; 73(9): 1435-1444, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39020021

RESUMEN

OBJECTIVE: A coagulation factor called fibrinogen is produced by the liver and is proteolyzed by thrombin to become fibrin. The latest studies have revealed that fibrin(ogen) palys an essential role in the regulation of cardiovascular disease. Understanding the relationship and mechanism between fibrin(ogen) and cardiovascular disease is of great significance for maintaining overall health. The objective of this review is to discuss the specific involvement and underlying mechanisms of fibrin(ogen) in cardiovascular disease. METHODS: A review was conducted using the PubMed database to identify and analyze the emerging role of fibrinogen in cardiovascular disease. RESULTS: The literature review revealed that fibrin(ogen) plays a pivotal role in maintaining cardiovascular disease and are involved in the pathogenesis of cardiovascular disease. Fibrin(ogen) mainly influence various pathophysiological processes, such as participating in thrombosis formation, stimulating the inflammatory response, and other molecular pathways. CONCLUSION: This review focuses on the involvement of fibrin(ogen) in cardiovascular disease, with a particular emphasis on the main functions and underlying mechanisms by which fibrin(ogen) influence the pathogenesis and progression of these conditions. This review underscores the potential of fibrin(ogen) as therapeutic targets in managing cardiovascular disease.


Asunto(s)
Enfermedades Cardiovasculares , Fibrinógeno , Humanos , Enfermedades Cardiovasculares/metabolismo , Animales , Fibrinógeno/metabolismo , Inflamación/metabolismo , Trombosis/metabolismo
6.
ACS Nano ; 18(19): 12412-12426, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38693619

RESUMEN

Glycans play vital roles in nearly all life processes of multicellular organisms, and understanding these activities is inseparable from elucidating the biological significance of glycans. However, glycan research has lagged behind that of DNA and protein due to the challenges posed by structural heterogeneity and isomerism (i.e., structures with equal molecular weights) the lack of high-efficiency structural analysis techniques. Nanopore technology has emerged as a sensitive single-molecule biosensor, shining a light on glycan analysis. However, a significant number of glycans are small and uncharged, making it challenging to elicit identifiable nanopore signals. Here we introduce a R-binaphthyl tag into glycans, which enhances the cation-π interaction between the derivatized glycan molecules and the nanopore interface, enabling the detection of neutral glycans with an aerolysin nanopore. This approach allows for the distinction of di-, tri-, and tetrasaccharides with monosaccharide resolution and has the potential for group discrimination, the monitoring of enzymatic transglycosylation reactions. Notably, the aerolysin mutant T240R achieves unambiguous identification of six disaccharide isomers, trisaccharide and tetrasaccharide linkage isomers. Molecular docking simulations reveal that multiple noncovalent interactions occur between residues R282, K238, and R240 and the glycans and R-binaphthyl tag, significantly slowing down their translocation across the nanopore. Importantly, we provide a demonstration of the kinetic translocation process of neutral glycan isomers, establishing a solid theoretical foundation for glycan nanopore analysis. The development of our technology could promote the analysis of glycan structural isomers and has the potential for nanopore-based glycan structural determination and sequencing.


Asunto(s)
Toxinas Bacterianas , Nanoporos , Polisacáridos , Proteínas Citotóxicas Formadoras de Poros , Polisacáridos/química , Toxinas Bacterianas/química , Toxinas Bacterianas/genética , Proteínas Citotóxicas Formadoras de Poros/química , Proteínas Citotóxicas Formadoras de Poros/genética , Simulación del Acoplamiento Molecular , Mutación
7.
Front Med ; 18(3): 499-515, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38806989

RESUMEN

Cardiac fibrosis caused by ventricular remodeling and dysfunction such as post-myocardial infarction (MI) can lead to heart failure. RNA N6-methyladenosine (m6A) methylation has been shown to play a pivotal role in the occurrence and development of many illnesses. In investigating the biological function of the m6A reader YTHDF1 in cardiac fibrosis, adeno-associated virus 9 was used to knock down or overexpress the YTHDF1 gene in mouse hearts, and MI surgery in vivo and transforming growth factor-ß (TGF-ß)-activated cardiac fibroblasts in vitro were performed to establish fibrosis models. Our results demonstrated that silencing YTHDF1 in mouse hearts can significantly restore impaired cardiac function and attenuate myocardial fibrosis, whereas YTHDF1 overexpression could further enhance cardiac dysfunction and aggravate the occurrence of ventricular pathological remodeling and fibrotic development. Mechanistically, zinc finger BED-type containing 6 mediated the transcriptional function of the YTHDF1 gene promoter. YTHDF1 augmented AXL translation and activated the TGF-ß-Smad2/3 signaling pathway, thereby aggravating the occurrence and development of cardiac dysfunction and myocardial fibrosis. Consistently, our data indicated that YTHDF1 was involved in activation, proliferation, and migration to participate in cardiac fibrosis in vitro. Our results revealed that YTHDF1 could serve as a potential therapeutic target for myocardial fibrosis.


Asunto(s)
Tirosina Quinasa del Receptor Axl , Fibrosis , Infarto del Miocardio , Proteínas Proto-Oncogénicas , Proteínas de Unión al ARN , Proteínas Tirosina Quinasas Receptoras , Animales , Ratones , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismo , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Proteínas Tirosina Quinasas Receptoras/genética , Proteínas Tirosina Quinasas Receptoras/metabolismo , Infarto del Miocardio/genética , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Masculino , Ratones Endogámicos C57BL , Transducción de Señal , Miocardio/patología , Miocardio/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Remodelación Ventricular/genética , Modelos Animales de Enfermedad , Adenosina/análogos & derivados , Adenosina/metabolismo , Fibroblastos/metabolismo
8.
ACS Omega ; 9(2): 2606-2614, 2024 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-38250387

RESUMEN

In the field of optoelectronic applications, the vigorous development of organic-inorganic hybrid perovskite materials, such as methylammonium lead triiodide (MAPbI3), has spurred continuous research on methods to enhance the photodetection performance. Periodic nanoarrays can effectively improve the light absorption of perovskite thin films. However, there are still challenges in fabricating tunable periodic patterned and large-area perovskite nanoarrays. In this study, we present a cost-effective and facile approach utilizing nanosphere lithography and dry etching techniques to create a large-area Si nanopillar array, which is employed for patterning MAPbI3 thin films. The scanning electron microscopy (SEM) and X-ray diffraction (XRD) results reveal that the introduction of nanopillar structures did not have a significant adverse effect on the crystallinity of the MAPbI3 thin film. Light absorption tests and optical simulations indicate that the nanopillar array enhances the light intensity within the perovskite films, leading to photodetectors with a responsivity of 11.2 A/W and a detectivity of 7.3 × 1010 Jones at 450 nm in wavelength. Compared with photodetectors without nanostructures, these photodetectors exhibit better visible light absorption. Finally, we demonstrate the application of these photodetector arrays in a prototype image sensor.

9.
Adv Mater ; 36(6): e2310427, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38012003

RESUMEN

Here, a facile fabrication approach for the high-quality 1D perovskite triangular nanowire (TNW) array synthesis through space-confined effect is reported. A soft stamp containing 1D triangular linear array pattern is used to confine the MAPbX3 solution and to guide the growth of the nanowires along the prescribed direction with good crystallinity. The further constructed photodetectors based on the obtained MAPbI3 TNWs exhibit superior photoresponse properties with a responsivity of (125.2 ± 2.5) A W-1 and detectivity of (2.8 ± 0.8) × 1013 Jones at the wavelength of 650 nm. This excellent performance is attributed to the highly crystalline TNW with optical anisotropy and a small asymptotic height, which reduces the probability of the photon reflection and promotes the carrier transport. More interestingly, the increased surface area of the triangular device can present superior flexibility after a couple of thousands of bending cycles. Furthermore, by fabricating 7 × 7 photodetector arrays, the potential image sensor application is demonstrated. The perovskite nanowire fabrication approach is scalable and compatible with current semiconductor manufacturing, which indicates their great potential in broad applications.

10.
Heliyon ; 9(10): e20850, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37867830

RESUMEN

Background and aims: Hepatitis B virus (HBV) is a common cause of hepatocellular carcinoma (HCC) in China, and this study aimed to identify high-risk factors for overall survival and develop a nomogram prediction model. Methods: In the present retrospective cohort study, patients with HBV-associated HCC diagnosed from January 2009 to December 2018 were enrolled. Their clinical characteristics and time-to-event information were retrieved from electronic medical records. The zero time was the date of HCC diagnosis, and the endpoint was death or liver transplantation. Multivariable COX proportional hazard regression was used to screen independent risk factors for overall survival; then a nomogram model was developed to predict the survival probability of HCC patients. Results: A total of 1723 patients were enrolled, with 82.7 % male and a median age of 54.0 years. During a median follow-up time of 41.3 months, 672 cases (39.0 %) died. Age ≥60 years (HR = 1.209), Male (HR = 1.293), ALB <35 g/L (HR = 1.491), AST ≥80 U/L (HR = 1.818); AFP 20-400 ng/mL (HR = 2.284), AFP ≥400 ng/mL (HR = 2.746); LSM 9-22 kPa (HR = 2.266), LSM ≥22 kPa (HR = 4.326); BCLC stage B/C (HR = 4.079) and BCLC stage D (HR = 16.830) were the independent high-risk factors associated with HCC survival. A prognostic nomogram with a consistency index of 0.842 (95 % CI: 0.827-0.858) was developed. The calibration curve for long-term survival rate fitted well. Conclusions: This study identified independent risk factors affecting the survival of patients with HBV-associated HCC and constructed a predictive nomogram model, which can individually predict the overall survival and has good clinical application value.

11.
Front Genet ; 14: 1224015, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37680198

RESUMEN

The dirigent (DIR) gene is a key player in environmental stress response and has been identified in many multidimensional tube plant species. However, there are few studies on the StDIR gene in potato. In this study, we used genome-wide identification to identify 31 StDIR genes in potato. Among the 12 potato chromosomes, the StDIR gene was distributed on 11 chromosomes, among which the third chromosome did not have a family member, while the tenth chromosome had the most members with 11 members. 22 of the 31 StDIRs had a classical DIR gene structure, with one exon and no intron. The conserved DIR domain accounts for most of the proteins in the 27 StDIRs. The structure of the StDIR gene was analyzed and ten different motifs were detected. The StDIR gene was divided into three groups according to its phylogenetic relationship, and 22 duplicate genes were identified. In addition, four kinds of cis-acting elements were detected in all 31 StDIR promoter regions, most of which were associated with biotic and abiotic stress. The findings demonstrated that the StDIR gene exhibited specific responses to cold stress, salt stress, ABA, and drought stress. This study provides new candidate genes for improving potato's resistance to stress.

13.
Artículo en Inglés | MEDLINE | ID: mdl-37548549

RESUMEN

Aims: Myocardial ischemia-reperfusion (I/R) injury facilitates cardiomyocyte death and endangers human health. N6-methyladenosine (m6A) methylation plays a critical role in cardiovascular diseases. The m6A reader YTHDF2 identifies m6A-modified RNA and promotes target RNA degradation. Hence, we hypothesized that YTHDF2 affects I/R injury by regulating RNA stability. Results: Both messenger RNA (mRNA) and protein levels of YTHDF2 were upregulated in I/R mice and hypoxia-reoxygenation (H/R)-induced cardiomyocytes. Silencing endogenous YTHDF2 abrogated cardiac dysfunction and lowered the infarct size in I/R mice, and the forced expression of YTHDF2 aggravated these adverse pathological processes. Consistently, the protective effect of silencing YTHDF2 occurred in cardiomyocytes exposed to H/R and erastin. Further, RNA-Seq and RNA-binding protein immunoprecipitation (RIP) revealed that YTHDF2 recognized the m6A modification sites of the ferroptosis-related gene solute carrier family 7 member 11 (SLC7A11) mRNA to promote its degradation both in vivo and in vitro. Inhibition of SLC7A11 impaired cardiac function, increased infarct size, and the release of lactate dehydrogenase (LDH) in I/R mice after silencing YTHDF2. The beneficial effects of si-YTHDF2 on H/R injury were reversed by co-transfection with SLC7A11-specific siRNA (si-SLC7A11), which substantially exacerbated ferroptosis and the production of reactive oxygen species. Innovation and Conclusion: The cardioprotective effects of silencing YTHDF2 are accomplished by increasing SLC7A11 stability and expression, reducing ferroptosis, and providing novel potential therapeutic targets for treating ischemic cardiac diseases.

14.
Anal Chem ; 95(19): 7761-7769, 2023 05 16.
Artículo en Inglés | MEDLINE | ID: mdl-37140051

RESUMEN

Protein methylation is the smallest possible yet vitally important post-translational modification (PTM). This small and chemically inert addition in proteins makes the analysis of methylation more challenging, thus calling for an efficient tool for the sake of recognition and detection. Herein, we present a nanofluidic electric sensing device based on a functionalized nanochannel that was constructed by introducing monotriazole-containing p-sulfonatocalix[4]arene (TSC) into a single asymmetric polymeric nanochannel via click chemistry. The device can selectively detect lysine methylpeptides with subpicomole sensitivity, distinguish between different lysine methylation states, and monitor the lysine methylation process by methyltransferase at the peptide level in real time. The introduced TSC molecule, with its confined asymmetric configuration, presents the remarkable ability to selectively bind to lysine methylpeptides, which, coupled with the release of the complexed Cu ions, allows the device to transform the molecular-level recognition to the discernible change in ionic current of the nanofluidic electric device, thus enabling detection. This work could serve as a stepping stone to the development of a new methyltransferase assay and the chemical that specifically targets lysine methylation in PTM proteomics.


Asunto(s)
Lisina , Proteínas , Metilación , Lisina/metabolismo , Proteínas/metabolismo , Procesamiento Proteico-Postraduccional , Metiltransferasas/metabolismo
15.
Nat Commun ; 14(1): 1737, 2023 03 28.
Artículo en Inglés | MEDLINE | ID: mdl-36977665

RESUMEN

Structural complexity of glycans derived from the diversities in composition, linage, configuration, and branching considerably complicates structural analysis. Nanopore-based single-molecule sensing offers the potential to elucidate glycan structure and even sequence glycan. However, the small molecular size and low charge density of glycans have restricted direct nanopore detection of glycan. Here we show that glycan sensing can be achieved using a wild-type aerolysin nanopore by introducing a facile glycan derivatization strategy. The glycan molecule can induce impressive current blockages when moving through the nanopore after being connected with an aromatic group-containing tag (plus a carrier group for the neutral glycan). The obtained nanopore data permit the identification of glycan regio- and stereoisomers, glycans with variable monosaccharide numbers, and distinct branched glycans, either independently or with the use of machine learning methods. The presented nanopore sensing strategy for glycans paves the way towards nanopore glycan profiling and potentially sequencing.


Asunto(s)
Nanoporos , Polisacáridos/química
16.
Front Pharmacol ; 14: 1071709, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36874016

RESUMEN

Background: Drug-induced liver injury (DILI) is a potentially serious adverse drug reaction. Due to the lack of definite etiology, specific clinical manifestations, and diagnostic methods, its prediction and diagnosis are challenging. Elderly individuals are deemed to be at high risk for DILI due to abnormal pharmacokinetics, aging tissue repair function, comorbidities, and taking multiple drugs. This study aimed to identify the clinical characteristics and explore the risk factors associated with the severity of illness in elderly patients with DILI. Methods: In the present study, the clinical characteristics at the time of liver biopsy of consecutive patients with biopsy-proven DILI who presented at our hospital from June 2005 to September 2022 were evaluated. Hepatic inflammation and fibrosis were assessed according to the Scheuer scoring system. The presence of autoimmunity was considered if IgG level >1.1 × ULN (1826 mg/dL), or high titer (>1:80) of ANA, or SMA. Results: In total, 441 patients were enrolled, and the median age was 63.3 years (IQR, 61.0-66.0); 122 (27.7%), 195 (44.2%), or 124 (28.1%) were classified as having minor, moderate, or severe hepatic inflammation, respectively; and 188 (42.6%), 210 (47.6%) or 43 (9.8%) patients presented minor, significant fibrosis or cirrhosis, respectively. Female sex (73.5%) and the cholestatic pattern (47.6%) were dominant in elderly DILI patients. Autoimmunity existed in 201 patients (45.6%). Comorbidities were not directly associated with the severity of DILI. PLT (OR: 0.994, 95% CI: 0.991-0.997; p < 0.001), AST (OR: 1.001, 95% CI: 1.000-1.003, p = 0.012), TBIL (OR: 1.006, 95% CI: 1.003-1.010, p < 0.001), and autoimmunity (OR: 1.831, 95% CI: 1.258-2.672, p = 0.002) were associated with the degree of hepatic inflammation. Meanwhile, PLT (OR: 0.990, 95% CI: 0.986-0.993, p < 0.001), TBIL (OR: 1.004, 95% CI: 1.000-1.007, p = 0.028), age (OR: 1.123, 95% CI: 1.067-1.183, p < 0.001), and autoimmunity (OR: 1.760, 95% CI: 1.191-2.608, p = 0.005) were associated with the stage of hepatic fibrosis. Conclusion: This study revealed that the presence of autoimmunity represents a more serious illness state of DILI, deserving more intensive monitoring and progressive treatment.

17.
Mol Nutr Food Res ; 67(7): e2101052, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36738079

RESUMEN

OBJECTIVE: To determine the mechanism of oxidative stress mediated by N6-methyladenosine (m6A) methylation contributing to high fat diet-induced reproductive dysfunction. RESULTS: In vivo, compared with those in the Control group, the sperm count and sperm motility decrease significantly; the testosterone, luteinizing hormone levels, hyaluronidase, acrosomal enzyme levels, and total antioxidant capacity decrease significantly; malondialdehyde increases significantly in the DIO and DIO-R groups. The expression of nuclear factor erythroid 2-related factor 2 (Nrf2), superoxide dismutase 1 (SOD1), and NAD(P)H quinone dehydrogenase 1 (NQO1) decreases significantly in the DIO and DIO-R groups; m6A levels in testis tissue in the DIO and DIO-R groups increase; the enrichment of m6A-modified Nrf2 mRNA in testis in the DIO group and DIO-R group increases significantly. Also the m6A regulatory proteins increase significantly in the DIO group and DIO-R group. In vitro, compared to palmitic acid treated cells, the reactive oxygen species (ROS) level significantly decreases in STM2457, S-Adenosylhomocysteine treated cells and YTHDC2, YTHDF2 gene silence cells; however, Nrf2 expression increases in all treated cells. In addition, m6A expression decreases. CONCLUSIONS: Oxidative stress mediates by methylation of m6A may contribute to high fat diet-induced male reproductive dysfunction.


Asunto(s)
Dieta Alta en Grasa , Factor 2 Relacionado con NF-E2 , Masculino , Humanos , Dieta Alta en Grasa/efectos adversos , Metilación , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Motilidad Espermática , Semen/metabolismo , Estrés Oxidativo
18.
Transl Res ; 257: 30-42, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36775059

RESUMEN

Cardiac fibrosis is a common pathological change in the development of heart disease. Circular RNA (circRNA) has been shown to be related to the occurrence and development of various cardiovascular diseases. This study aimed to evaluate the effects and potential mechanisms of circHelz in cardiac fibrosis. Knockdown of circHelz alleviated cardiac fibrosis and myocardial fibroblast activation induced by myocardial infarction (MI) or angiotensin II (AngII) in vivo and transforming growth factor-ß (TGF-ß) in vitro. Overexpression of circHelz exacerbated cell proliferation and differentiation. Mechanistically, nuclear factor of activated T cells, cytoplasmic 2 (NFATc2) was found to act as a transcriptional activator to upregulate the expression of circHelz. The increased circHelz was demonstrated to bind to Yes-associated protein (YAP) and facilitate its localization in the nucleus to promote cell proliferation and growth. Moreover, silencing YAP1 reversed the detrimental effects caused by circHelz in vitro, as indicated by the observed decreases in cell viability, fibrotic marker expression levels, proliferation and migration. Collectively, the protective effect of circHelz knockdown against cardiac fibrosis injury is accomplished by inhibiting the nuclear translocation of YAP1. Thus, circHelz may be a novel target for the prevention and treatment of cardiovascular disease.


Asunto(s)
Infarto del Miocardio , ARN Circular , Humanos , ARN Circular/genética , ARN Circular/metabolismo , Miocardio/patología , Infarto del Miocardio/genética , Infarto del Miocardio/patología , Fibrosis , Diferenciación Celular , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Fibroblastos/patología , Factor de Crecimiento Transformador beta1/metabolismo
19.
RSC Adv ; 12(54): 34892-34903, 2022 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-36540264

RESUMEN

Circulating tumor cells (CTCs) released from the primary tumor to peripheral blood are promising targets for liquid biopsies. Their biological information is vital for early cancer detection, efficacy assessment, and prognostic monitoring. Despite the tremendous clinical applications of CTCs, development of effective separation techniques are still demanding. Traditional separation methods usually use batch processing for enrichment, which inevitably destroy cell integrity and affect the complete information acquisition. Considering the rarity and heterogeneity of CTCs, it is urgent to develop effective separation methods. Microfluidic chips with precise fluid control at the micron level are promising devices for CTC separation. Their further combination with micro-/nanostructure arrays adds more biomolecule binding sites and exhibit unique fluid barrier effect, which significantly improve the CTC capture efficiency, purity, and sensitivity. This review summarized the recent advances in micro-/nanostructure array integrated microfluidic devices for CTC separation, including microrods, nanowires, and 3D micro-/nanostructures. The mechanisms by which these structures contribute to improved capture efficiency are discussed. Two major categories of separation methods, based on the physical and biological properties of CTCs, are discussed separately. Physical separation includes the design and preparation of micro-/nanostructure arrays, while chemical separation additionally involves the selection and modification of specific capture probes. These emerging technologies are expected to become powerful tools for disease diagnosis in the future.

20.
Molecules ; 27(13)2022 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-35807363

RESUMEN

With the rapid development of communication technology in civil and military fields, the problem of electromagnetic radiation pollution caused by the electromagnetic wave becomes particularly prominent and brings great harm. It is urgent to explore efficient electromagnetic wave absorption materials to solve the problem of electromagnetic radiation pollution. Therefore, various absorbing materials have developed rapidly. Among them, iron (Fe) magnetic absorbent particle material with superior magnetic properties, high Snoek's cut-off frequency, saturation magnetization and Curie temperature, which shows excellent electromagnetic wave loss ability, are kinds of promising absorbing material. However, ferromagnetic particles have the disadvantages of poor impedance matching, easy oxidation, high density, and strong skin effect. In general, the two strategies of morphological structure design and multi-component material composite are utilized to improve the microwave absorption performance of Fe-based magnetic absorbent. Therefore, Fe-based microwave absorbing materials have been widely studied in microwave absorption. In this review, through the summary of the reports on Fe-based electromagnetic absorbing materials in recent years, the research progress of Fe-based absorbing materials is reviewed, and the preparation methods, absorbing properties and absorbing mechanisms of iron-based absorbing materials are discussed in detail from the aspects of different morphologies of Fe and Fe-based composite absorbers. Meanwhile, the future development direction of Fe-based absorbing materials is also prospected, providing a reference for the research and development of efficient electromagnetic wave absorbing materials with strong absorption performance, frequency bandwidth, light weight and thin thickness.

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