Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 916
Filtrar
1.
Quant Imaging Med Surg ; 14(5): 3302-3311, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38720836

RESUMEN

Background: The parietal pleural adhesion/invasion of lung cancer can contribute substantially to poor prognosis and difficulty in surgery. The value of ultrasound in evaluating the parietal pleural adhesion or invasion (pleural adhesion/invasion) of lung cancer remains uncertain. This study investigated the value of B-mode ultrasound and contrast-enhanced ultrasound (CEUS) in diagnosing parietal pleural adhesion/invasion of subpleural lung cancer. Methods: The study animals included 40 male New Zealand white rabbits. A rabbit subpleural lung cancer model was constructed by injecting VX2 tumor tissue under ultrasound guidance. In the 1-3 weeks after subpleural lesion formation, parietal pleural adhesion/invasion of the largest subpleural lesion was evaluated with B-mode ultrasound and CEUS by two sonographers. The parietal pleural adhesion/invasion was also determined using the gold standard method of findings from anatomical and pathological examination. Results: Ultimately, 34 rabbits were subjected to complete ultrasonic evaluation. There were 20 and 14 cases with and without parietal pleural adhesion/invasion, respectively, as confirmed by anatomical and pathological evaluations. The diagnostic sensitivity, specificity, and accuracy of sonographer 1 using B-mode ultrasound were 50.0% [95% confidence interval (CI): 26.0-74.0%], 100%, and 70.6% (95% CI: 54.5-86.7%), respectively; for CEUS, they were 90.0% (95% CI: 75.6-100.0%), 100.0%, and 94.1% (95% CI: 85.8-100.0%), respectively. The diagnostic sensitivity, specificity, and accuracy of sonographer 2 using B-mode ultrasound were 45.0% (95% CI: 21.1-68.9%), 92.9% (95% CI: 77.5-100.0%), and 64.7% (95% CI: 47.8-81.6%), respectively; for CEUS, they were 85.0% (95% CI: 67.9-100.0%), 100.0%, and 91.2% (95% CI: 81.1-100.0%), respectively. The diagnostic accuracy of sonographer 1 was higher with CEUS than with B-mode ultrasound, but not significantly so (94.1% vs. 70.6%; P=0.08). The diagnostic accuracy of sonographer 2 was significantly higher with CEUS than with B-mode ultrasound (91.2% vs. 64.7%; P=0.03). The interrater reliability was higher for CEUS than for B-mode ultrasound (κ=0.941 vs. κ =0.717). Conclusions: Based on an animal model, B-mode ultrasound and CEUS both exhibited good diagnostic efficacy and interrater reliability in evaluating parietal pleural adhesion/invasion of subpleural lung cancer although CEUS outperformed B-mode ultrasound for both measures.

2.
BMC Biol ; 22(1): 104, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38702712

RESUMEN

BACKGROUND: Gonadotropin precisely controls mammalian reproductive activities. Systematic analysis of the mechanisms by which epigenetic modifications regulate the synthesis and secretion of gonadotropin can be useful for more precise regulation of the animal reproductive process. Previous studies have identified many differential m6A modifications in the GnRH-treated adenohypophysis. However, the molecular mechanism by which m6A modification regulates gonadotropin synthesis and secretion remains unclear. RESULTS: Herein, it was found that GnRH can promote gonadotropin synthesis and secretion by promoting the expression of FTO. Highly expressed FTO binds to Foxp2 mRNA in the nucleus, exerting a demethylation function and reducing m6A modification. After Foxp2 mRNA exits the nucleus, the lack of m6A modification prevents YTHDF3 from binding to it, resulting in increased stability and upregulation of Foxp2 mRNA expression, which activates the cAMP/PKA signaling pathway to promote gonadotropin synthesis and secretion. CONCLUSIONS: Overall, the study reveals the molecular mechanism of GnRH regulating the gonadotropin synthesis and secretion through FTO-mediated m6A modification. The results of this study allow systematic interpretation of the regulatory mechanism of gonadotropin synthesis and secretion in the pituitary at the epigenetic level and provide a theoretical basis for the application of reproductive hormones in the regulation of animal artificial reproduction.


Asunto(s)
Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato , Hormona Liberadora de Gonadotropina , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/metabolismo , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética , Hormona Liberadora de Gonadotropina/metabolismo , Hormona Liberadora de Gonadotropina/genética , Animales , Gonadotropinas/metabolismo , Ratones , ARN Mensajero/metabolismo , ARN Mensajero/genética , Metilación de ARN
3.
Heliyon ; 10(9): e30336, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38707272

RESUMEN

Adults with spinal cord injury (SCI), a destructive neurological injury, have a significantly higher incidence of osteoarthritis (OA), a highly prevalent chronic joint disorder. This study aimed to dissect the neuroimmune-related regulatory mechanisms of SCI and OA using bioinformatics analysis. Using microarray data from the Gene Expression Omnibus database, differentially expressed genes (DEGs) were screened between SCI and sham samples and between OA and control samples. Common DEGs were used to construct a protein-protein interaction (PPI) network. Weighted gene co-expression network analysis (WGCNA) was used to mine SCI- and OA-related modules. Shared miRNAs were identified, and target genes were predicted using the Human MicroRNA Disease Database (HMDD) database. A miRNA-gene-pathway regulatory network was constructed with overlapping genes, miRNAs, and significantly enriched pathways. Finally, the expression of the identified genes and miRNAs was verified using RT-qPCR. In both the SCI and OA groups, 185 common DEGs were identified, and three hub clusters were obtained from the PPI network. WGCNA revealed three SCI-related modules and two OA-related modules. There were 43 overlapping genes between the PPI network clusters and the WGCNA network modules. Seventeen miRNAs shared between patients with SCI and OA were identified. A regulatory network consisting of five genes, six miRNAs, and six signaling pathways was constructed. Upregulation of CD44, TGFBR1, CCR5, and IGF1, while lower levels of miR-125b-5p, miR-130a-3p, miR-16-5p, miR-204-5p, and miR-204-3p in both SCI and OA were successfully verified using RT-qPCR. Our study suggests that a miRNA-gene-pathway network is implicated in the neuroimmune-related regulatory mechanisms of SCI and OA. CD44, TGFBR1, CCR5, and IGF1, and their related miRNAs (miR-125b-5p, miR-130a-3p, miR-16-5p, miR-204-5p, and miR-204-3p) may serve as promising biomarkers and candidate therapeutic targets for SCI and OA.

4.
J Med Chem ; 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38717088

RESUMEN

A series of heterocyclic ring-fused derivatives of bisnoralcohol (BA) were synthesized and evaluated for their inhibitory effects on RANKL-induced osteoclastogenesis. Most of these derivatives possessed potent antiosteoporosis activities in a dose-dependent manner. Among these compounds, 31 (SH442, IC50 = 0.052 µM) exhibited the highest potency, displaying 100% inhibition at 1.0 µM and 82.8% inhibition at an even lower concentration of 0.1 µM, which was much more potent than the lead compound BA (IC50 = 2.325 µM). Cytotoxicity tests suggested that the inhibitory effect of these compounds on RANKL-induced osteoclast differentiation did not result from their cytotoxicity. Mechanistic studies revealed that SH442 inhibited the expression of osteoclastogenesis-related marker genes and proteins, including TRAP, TRAF6, c-Fos, CTSK, and MMP9. Especially, SH442 could significantly attenuate bone loss of ovariectomy mouse in vivo. Therefore, these BA derivatives could be used as promising leads for the development of a new type of antiosteoporosis agent.

5.
Artículo en Inglés | MEDLINE | ID: mdl-38708876

RESUMEN

BACKGROUND: High perforation risk hinders the widespread adoption of ESD for colorectal neoplasms. This study was performed to determine the risk factors of colorectal endoscopic submucosal dissection (ESD)-induced perforation and develop a predictive model. METHODS: A total of 1046 colorectal neoplasms in 1011 patients were retrospectively enrolled from January 2011 to December 2021, in a single tertiary center as the derivation cohort. We identified independent risk factors for perforation using univariate analysis and multi-variate logistic regression. A nomogram was developed based on the logistic regression model and prospectively applied to 266 colorectal neoplasms as the validation cohort. The performance of the predictive model was evaluated with the receiver operating characteristic curve, calibration plot, and decision curve analysis. RESULTS: Independent pre-operative factors for colorectal ESD-induced perforation were tumor located in the left colon [odds ratio (OR) 2.39, P = 0.040], size ≥ 40 mm (OR 3.36, P < 0.001), ≥2/3 circumference (OR 7.55, P = 0.004), located across folds (OR 6.26, P < 0.001), and laterally spreading tumor (non-granular type, OR 2.34, P = 0.029; granular type, OR 2.46, P = 0.021). The nomogram model incorporating the pre-operative factors performed well in both the derivation and validation cohorts (areas under the curve of 0.750 and 0.806, respectively). Decision curve analysis demonstrated that the clinical benefit of the nomogram was favorable. CONCLUSIONS: The novel nomogram, developed and prospectively validated, incorporating tumor size, location, and morphology can successfully predict perforation during ESD for colorectal neoplasms.

6.
Sci Rep ; 14(1): 10286, 2024 05 04.
Artículo en Inglés | MEDLINE | ID: mdl-38704482

RESUMEN

Jinlida granule (JLD) is a Traditional Chinese Medicine (TCM) formula used for the treatment of type 2 diabetes mellitus (T2DM). However, the mechanism of JLD treatment for T2DM is not fully revealed. In this study, we explored the mechanism of JLD against T2DM by an integrative pharmacology strategy. Active components and corresponding targets were retrieved from Traditional Chinese Medicine System Pharmacology (TCMSP), SwissADME and Bioinformatics Analysis Tool for Molecular Mechanisms of Traditional Chinese Medicine Database (BATMAN-TCM) database. T2DM-related targets were obtained from Drugbank and Genecards databases. The protein-protein interaction (PPI) network was constructed and analyzed with STRING (Search Toll for the Retrieval of Interacting Genes/proteins) and Cytoscape to get the key targets. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genomes (KEGG) enrichment analyses were performed with the Database for Annotation, Visualization and Integrated Discovery (DAVID). Lastly, the binding capacities and reliability between potential active components and the targets were verified with molecular docking and molecular dynamics simulation. In total, 185 active components and 337 targets of JLD were obtained. 317 targets overlapped with T2DM-related targets. RAC-alpha serine/threonine-protein kinase (AKT1), tumor necrosis factor (TNF), interleukin-6 (IL-6), cellular tumor antigen p53 (TP53), prostaglandin G/H synthase 2 (PTGS2), Caspase-3 (CASP3) and signal transducer and activator of transcription 3 (STAT3) were identified as seven key targets by the topological analysis of the PPI network. GO and KEGG enrichment analyses showed that the effects were primarily associated with gene expression, signal transduction, apoptosis and inflammation. The pathways were mainly enriched in PI3K-AKT signaling pathway and AGE-RAGE signaling pathway in diabetic complications. Molecular docking and molecular dynamics simulation verified the good binding affinity between the key components and targets. The predicted results may provide a theoretical basis for drug screening of JLD and a new insight for the therapeutic effect of JLD on T2DM.


Asunto(s)
Diabetes Mellitus Tipo 2 , Medicamentos Herbarios Chinos , Simulación del Acoplamiento Molecular , Mapas de Interacción de Proteínas , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Humanos , Mapas de Interacción de Proteínas/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Medicina Tradicional China/métodos , Simulación de Dinámica Molecular , Biología Computacional/métodos , Ontología de Genes , Hipoglucemiantes/farmacología , Hipoglucemiantes/química
7.
Methods ; 2024 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-38768930

RESUMEN

With the recent advanced direct RNA sequencing technique that proposed by the Oxford Nanopore Technologies, RNA modifications can be detected and profiled in a simple and straightforward manner. Majority nanopore-based modification studies were devoted to those popular types such as m6A and pseudouridine. To address current limitations on studying the crucial regulator, m1A modification, we conceived this study. We have developed an integrated computational workflow designed for the detection of m1A modifications from direct RNA sequencing data. This workflow comprises a feature extractor responsible for capturing signal characteristics (such as mean, standard deviations, and length of electric signals), a single molecule-level m1A predictor trained with features extracted from the IVT dataset using classical machine learning algorithms, a confident m1A site selector employing the binomial test to identify statistically significant m1A sites, and an m1A modification rate estimator. Our model achieved accurate molecule-level prediction (Average AUC = 0.9689) and reliable m1A site detection and quantification. To show the feasibility of our workflow, we conducted a study on in vivo transcribed human HEK293 cell line, and the results were carefully annotated and compared with other techniques (i.e., Illumina sequencing-based techniques). We believed that this tool will enabling a comprehensive understanding of the m1A modification and its functional mechanisms within cells and organisms.

8.
Int J Biol Macromol ; 270(Pt 2): 132433, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38759861

RESUMEN

Nanopore direct RNA sequencing provided a promising solution for unraveling the landscapes of modifications on single RNA molecules. Here, we proposed NanoMUD, a computational framework for predicting the RNA pseudouridine modification (Ψ) and its methylated analog N1-methylpseudouridine (m1Ψ), which have critical application in mRNA vaccination, at single-base and single-molecule resolution from direct RNA sequencing data. Electric signal features were fed into a bidirectional LSTM neural network to achieve improved accuracy and predictive capabilities. Motif-specific models (NNUNN, N = A, C, U or G) were trained based on features extracted from designed dataset and achieved superior performance on molecule-level modification prediction (Ψ models: min AUC = 0.86, max AUC = 0.99; m1Ψ models: min AUC = 0.87, max AUC = 0.99). We then aggregated read-level predictions for site stoichiometry estimation. Given the observed sequence-dependent bias in model performance, we trained regression models based on the distribution of modification probabilities for sites with known stoichiometry. The distribution-based site stoichiometry estimation method allows unbiased comparison between different contexts. To demonstrate the feasibility of our work, three case studies on both in vitro and in vivo transcribed RNAs were presented. NanoMUD will make a powerful tool to facilitate the research on modified therapeutic IVT RNAs and provides useful insight to the landscape and stoichiometry of pseudouridine and N1-pseudouridine on in vivo transcribed RNA species.

9.
Front Endocrinol (Lausanne) ; 15: 1325434, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38742201

RESUMEN

Background: Diabetic foot complications impose a significant strain on healthcare systems worldwide, acting as a principal cause of morbidity and mortality in individuals with diabetes mellitus. While traditional methods in diagnosing and treating these conditions have faced limitations, the emergence of Machine Learning (ML) technologies heralds a new era, offering the promise of revolutionizing diabetic foot care through enhanced precision and tailored treatment strategies. Objective: This review aims to explore the transformative impact of ML on managing diabetic foot complications, highlighting its potential to advance diagnostic accuracy and therapeutic approaches by leveraging developments in medical imaging, biomarker detection, and clinical biomechanics. Methods: A meticulous literature search was executed across PubMed, Scopus, and Google Scholar databases to identify pertinent articles published up to March 2024. The search strategy was carefully crafted, employing a combination of keywords such as "Machine Learning," "Diabetic Foot," "Diabetic Foot Ulcers," "Diabetic Foot Care," "Artificial Intelligence," and "Predictive Modeling." This review offers an in-depth analysis of the foundational principles and algorithms that constitute ML, placing a special emphasis on their relevance to the medical sciences, particularly within the specialized domain of diabetic foot pathology. Through the incorporation of illustrative case studies and schematic diagrams, the review endeavors to elucidate the intricate computational methodologies involved. Results: ML has proven to be invaluable in deriving critical insights from complex datasets, enhancing both the diagnostic precision and therapeutic planning for diabetic foot management. This review highlights the efficacy of ML in clinical decision-making, underscored by comparative analyses of ML algorithms in prognostic assessments and diagnostic applications within diabetic foot care. Conclusion: The review culminates in a prospective assessment of the trajectory of ML applications in the realm of diabetic foot care. We believe that despite challenges such as computational limitations and ethical considerations, ML remains at the forefront of revolutionizing treatment paradigms for the management of diabetic foot complications that are globally applicable and precision-oriented. This technological evolution heralds unprecedented possibilities for treatment and opportunities for enhancing patient care.


Asunto(s)
Pie Diabético , Aprendizaje Automático , Pie Diabético/terapia , Humanos
10.
Environ Pollut ; 352: 124114, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38718965

RESUMEN

Lead (Pb) is a heavy metal that has been recognized as a neurotoxin, meaning it can cause harmful effects on the nervous system. However, the neurotoxicology of Pb to birds still needs further study. In this study, we examined the neurotoxic effects of Pb exposure on avian cerebellum by using an animal model-Japanese quail (Coturnix japonica). The one-week old male chicks were exposed to 50, 200 and 500 mg/kg Pb of environmental relevance in the feed for five weeks. The results showed Pb caused cerebellar microstructural damages charactered by deformation of neuroglia cells, granule cells and Purkinje cells with Nissl body changes. Moreover, cerebellar neurotransmission was disturbed by Pb with increasing acetylcholine (ACh) and decreasing acetylcholinesterase (AChE), dopamine (DA), γ-Aminobutyric Acid (GABA) and Na+/K+ ATPase. Meanwhile, cerebellar oxidative stress was caused by Pb exposure represented by increasing reactive oxygen species (ROS) and malondialdehyde (MDA) as well as decreasing catalase (CAT), glutathione peroxidase (GPX), glutathione (GSH) and superoxide dismutase (SOD). Moreover, RNA-Seq analysis showed that molecular signaling pathways in the cerebellum were disrupted by Pb exposure. In particular, the disruption of nuclear factor erythroid-2-related factor 2 (Nfr2)/kelch-like ECH-associated protein 1 (Keap1) pathway and glutathione metabolism pathway indicated increasing cell apoptosis and functional disorder in the cerebellum. The present study revealed that Pb induced cerebellar toxicology through structural injury, oxidative stress, neurotransmission interference and abnormal apoptosis.

11.
Small ; : e2311725, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38558506

RESUMEN

Photocatalytic hydrogen production is a prevalent method for hydrogen synthesis. However, high recombination rate of photogenerated carriers and high activation energy barrier of H remain persistent challenge. Here, the two-step hydrothermal method is utilized to prepare dual S-defect mediated catalyst molybdenum sulfide/zinc indium sulfide (MSv/ZISv), which has high hydrogen production rate of 8.83 mmol g-1h-1 under simulated sunlight. The achieved rate is 21.91 times higher than pure ZnIn2S4 substrate. Defects in ZIS within MSv/ZISv modify the primitive electronic structure by creating defect state that retaining good reducing power, leading to the rapid separation of electron-hole pairs and the generation of additional photogenerated carriers. The internal electric field further enhances the migration toward to cocatalyst. Simultaneously, the defects introduced on the MoS2 cause electron rearrangement, leading to electron clustering on both S vacancies and edge S. Thereby MSv/ZISv exhibits the lowest activation energy barrier and |ΔGH*|. This work explores the division of synergies between different types of S defects, providing new insights into the coupling of defect engineering.

12.
Midwifery ; 133: 103994, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38608543

RESUMEN

BACKGROUND: Women undergoing caesarean section (CS) experience difficulties when preparing for discharge, and readiness for hospital discharge (RHD) may depend on individual characteristics. OBJECTIVE: To explore the status of RHD in women with CS, identify the latent classes of RHD, and analyse predictors from a bio-psycho-social perspective. METHODS: A sample of 410 women with CS completed the following questionnaires on demographic and obstetric characteristics: Readiness for Hospital Discharge Study-New Mother Form (RHDS-NMF), Parents' Postnatal Sense of Security (PPSS), Quality of Discharge Teaching Scale (OB-QDTS), and Postpartum Support Questionnaire (PSQ). Latent profile analysis was used to identify the latent classes of RHD. Multiple logistic regression analysis was used to analyse the predictors. RESULTS: In total, 96.6 % of women with CS reported discharge ready, and the score of RHDS-NMF was 136.09 ± 25.59. Three latent classes were identified as Low RHD (16.1 %), Moderate RHD (41.7 %), and High RHD (42.2 %). Primiparas (OR = 2.867 / 1.773; P = 0.012 / 0.033), emergency CS (OR = 3.134 / 2.470; P = 0.006 / 0.002), lower levels of PPSS (OR = 0.909 / 0.942; P = 0.009 / 0.013) and OB-ODTS (OR = 0.948 / 0.975; P < 0.001) were associated with Moderate and Low RHD. Lower PSQ predicted a higher probability of Low RHD (OR = 0.955; P = 0.038). CONCLUSIONS: The perception of RHD by women in the study was inaccurate, with more than half not being classified as High RHD. Healthcare professionals can anticipate interventions for maternal well-being based on the characteristics of the different RHD classes.

13.
Sci Rep ; 14(1): 8630, 2024 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-38622211

RESUMEN

Glycogen storage disease type Ib (GSD-Ib) is a rare inborn error of glycogen metabolism caused by mutations in SLC37A4. Patients with GSD-Ib are at high risk of developing inflammatory bowel disease (IBD). We evaluated the efficacy of empagliflozin, a renal sodium‒glucose cotransporter protein 2 (SGLT2) inhibitor, on colonic mucosal healing in patients with GSD-associated IBD. A prospective, single-arm, open-label clinical trial enrolled eight patients with GSD-associated IBD from Guangdong Provincial People's Hospital in China from July 1, 2022 through December 31, 2023. Eight patients were enrolled with a mean age of 10.34 ± 2.61 years. Four male and four female. The endoscopic features included deep and large circular ulcers, inflammatory hyperplasia, obstruction and stenosis. The SES-CD score significantly decreased at week 48 compared with before empagliflozin. Six patients completed 48 weeks of empagliflozin therapy and endoscopy showed significant improvement or healing of mucosal ulcers, inflammatory hyperplasia, stenosis, and obstruction. One patient had severe sweating that required rehydration and developed a urinary tract infection. No serious or life-threatening adverse events. This study suggested that empagliflozin may promote colonic mucosal healing and reduce hyperplasia, stenosis, and obstruction in children with GSD-associated IBD.


Asunto(s)
Compuestos de Bencidrilo , Glucósidos , Enfermedad del Almacenamiento de Glucógeno Tipo I , Enfermedades Inflamatorias del Intestino , Niño , Humanos , Masculino , Femenino , Adolescente , Constricción Patológica/complicaciones , Úlcera , Hiperplasia , Estudios Prospectivos , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/genética , Enfermedad del Almacenamiento de Glucógeno Tipo I/complicaciones , Enfermedad del Almacenamiento de Glucógeno Tipo I/tratamiento farmacológico , Enfermedad del Almacenamiento de Glucógeno Tipo I/genética , Proteínas de Transporte de Monosacáridos/genética , Antiportadores/genética
14.
Curr Pharm Des ; 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38616754

RESUMEN

BACKGROUND: Traditional Chinese medicine Scutellaria Baicalensis (SB), one of the clinical firstline heat-clearing drugs, has obvious symptomatic advantages for hepatic fibrosis with dampness-heat stasis as its syndrome. We aim to predict and validate the potential mechanism of Scutellaria baicalensis active ingredients against liver fibrosis more scientifically and effectively. METHODS: The underlying mechanism of Scutellaria baicalensis in inhibiting hepatic fibrosis was studied by applying network pharmacology, molecular docking and molecular dynamics simulation. Expression levels of markers in activated Hepatic Stellate Cells (HSC) after administration of three Scutellaria baicalensis extracts were determined by Western blot and Real-time PCR, respectively, in order to verify the anti-fibrosis effect of the active ingredients Results: There are 164 common targets of drugs and diseases screened and 115 signaling pathways obtained, which were mainly associated with protein phosphorylation, senescence and negative regulation of the apoptotic process. Western blot and Real-time PCR showed that Scutellaria baicalensis extracts could reduce the expression of HSC activation markers, and Oroxylin A had the strongest inhibitory effect on it. Molecular docking results showed that Oroxylin A had high binding activity to target proteins. Molecular dynamics simulation demonstrates promising stability of the Oroxylin A-AKT1 complex over the simulated MD time of 200 ns. CONCLUSION: Scutellaria baicalensis active ingredients may inhibit HSC proliferation, reduce the generation of pro-inflammatory factors and block the anti-inflammatory effect of inflammatory signal transduction by inducing HSC apoptosis and senescence, thus achieving the effect of anti-fibrosis.

15.
Bioorg Chem ; 146: 107320, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38569323

RESUMEN

Spleen tyrosine kinase (Syk) plays a crucial role as a target for allergy treatment due to its involvement in immunoreceptor signaling. The purpose of this study was to identify natural inhibitors of Syk and assess their effects on the IgE-mediated allergic response in mast cells and ICR mice. A list of eight compounds was selected based on pharmacophore and molecular docking, showing potential inhibitory effects through virtual screening. Among these compounds, sophoraflavanone G (SFG) was found to inhibit Syk activity in an enzymatic assay, with an IC50 value of 2.2 µM. To investigate the conformational dynamics of the SYK-SFG system, we performed molecular dynamics simulations. The stability of the binding between SFG and Syk was evaluated using root mean square deviation (RMSD) and root mean square fluctuation (RMSF). In RBL-2H3 cells, SFG demonstrated a dose-dependent suppression of IgE/BSA-induced mast cell degranulation, with no significant cytotoxicity observed at concentrations below 10.0 µM within 24 h. Furthermore, SFG reduced the production of TNF-α and IL-4 in RBL-2H3 cells. Mechanistic investigations revealed that SFG inhibited downstream signaling proteins, including phospholipase Cγ1 (PLCγ1), as well as mitogen-activated protein kinases (AKT, Erk1/2, p38, and JNK), in mast cells in a dose-dependent manner. Passive cutaneous anaphylaxis (PCA) experiments demonstrated that SFG could reduce ear swelling, mast cell degranulation, and the expression of COX-2 and IL-4. Overall, our findings identify naturally occurring SFG as a direct inhibitor of Syk that effectively suppresses mast cell degranulation both in vitro and in vivo.


Asunto(s)
Interleucina-4 , Mastocitos , Ratones , Animales , Interleucina-4/metabolismo , Interleucina-4/farmacología , Mastocitos/metabolismo , Anafilaxis Cutánea Pasiva , Simulación del Acoplamiento Molecular , Inmunoglobulina E/metabolismo , Inmunoglobulina E/farmacología , Ratones Endogámicos ICR , Ratones Endogámicos BALB C
16.
Langmuir ; 40(16): 8427-8439, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38607689

RESUMEN

This work aims to enhance the adsorption performance of Laponite @diatomite for organic pollutants by modifying it with cetyltrimethylammonium bromide (CTAB). The microstructure and morphology of the CTAB-modified Laponite @diatomite material were characterized using SEM, XRD, FTIR, BET, and TG. Furthermore, the influences of key parameters, containing pH, adsorbent dosage, reaction time, and reaction temperature, on the adsorption process were investigated. The kinetics, thermodynamics, and isotherm models of the adsorption process were analyzed. Finally, potential adsorption mechanisms were given based on the characterization. The research findings indicate that CTAB-La@D exhibits good adsorption performance toward Congo red (CR) over a broad pH range. The maximum adsorption capacity of CR was 451.1 mg/g under the optimum conditions (dosage = 10 mg, contact time = 240 min, initial CR concentration = 100 mg/L, temperature = 25 °C, and pH = 7). The adsorption process conformed to the pseudo-second-order kinetic model, and the adsorption isotherms indicated that the adsorption process of CR was more in line with the Langmuir model, and it was physical adsorption. Thermodynamic analysis illustrates that the adsorption process is exothermic and spontaneous. Additionally, the mechanisms of electrostatic adsorption and hydrophobic effect adsorption of CR were investigated through XPS and FTIR analysis. This work provides an effective pathway for designing high-performance adsorbents for the removal of organic dye, and the synthesized materials hold great capability for practical utilization in the treatment of wastewater.

17.
Heliyon ; 10(8): e28787, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38628705

RESUMEN

Genetic diseases are currently diagnosed by functional mutations. However, only some mutations are associated with disease. It is necessary to establish a quick prediction model for clinical screening. Pathogenic mutations in NGLY1 cause a rare autosomal recessive disease known as congenital disorder of deglycosylation (NGLY1-CDDG). Although NGLY1-CDDG can be diagnosed through gene sequencing, clinical relevance of a detected mutation in NGLY1 needs to be further confirmed. In this study, taken NGLY1-CDDG as an example, a comprehensive and practical predictive model for pathogenic mutations on NGLY1 through an NGLY1/Glycopeptide complex model was constructed, the binding sites of NGLY1 and glycopeptides were simulated, and an in vitro enzymatic assay system was established to facilitate quick clinical decisions for NGLY1-CDDG patients. The docking model covers 42 % of reported NGLY1-CDDG missense mutations (5/12). All reported mutations were subjected to in vitro enzymatic assay in which 18 mutations were dysfunctional (18/30). In addition, a full spectrum of functional R328 mutations was assayed and 11 mutations were dysfunctional (11/19). In this study, a model of NGLY1 and glycopeptides was built for potential functional mutations in NGLY1. In addition, the effect of potential regulatory compounds, including N-acetyl-l-cysteine and dithiothreitol, on NGLY1 was examined. The established in vitro assay may serve as a standard protocol to facilitate rapid diagnosis of all mutations in NGLY1-CDDG. This method could also be applied as a comprehensive and practical predictive model for the other rare genetic diseases.

18.
J Fungi (Basel) ; 10(4)2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38667943

RESUMEN

In this study, five new species from China, Hymenogaster latisporus, H. minisporus, H. papilliformis, H. perisporius, and H. variabilis, are described and illustrated based on morphological and molecular evidence. Hymenogaster latisporus was distinguished from other species of the genus by the subglobose, broad ellipsoidal, ovoid basidiospores (average = 13.7 µm × 11.6 µm) with sparse verrucose and ridge-like ornamentation (1-1.2 µm high); H. minisporus by the ellipsoidal to broadly ellipsoidal and small basidiospores (average = 11.7 µm × 9.5 µm); H. papilliformis was characterized by the whitish to cream-colored basidiomes, and broadly fusiform to citriform basidiospores with a pronounced apex (2-3 µm, occasionally up to 4 µm high), papillary, distinct warts and ridges, and pronounced appendix (2-3 µm long); H. perisporius by the dirty white to pale yellow basidiomes, broad ellipsoidal to ellipsoidal, and yellow-brown to dark-brown basidiospores with warts and gelatinous perisporium; H. variabilis by the peridium with significant changes in thickness (167-351 µm), and broad ellipsoidal to subglobose basidiospores ornamented with sparse warts and ridges. An ITS/LSU-based phylogenetic analysis supported the erection of the five new species. A key for Hymenogaster species from northern China is provided.

19.
J Neurogastroenterol Motil ; 30(2): 143-155, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38576367

RESUMEN

Diabetic gastroparesis (DGP) is a common complication of diabetes mellitus, marked by gastrointestinal motility disorder, a delayed gastric emptying present in the absence of mechanical obstruction. Clinical manifestations include postprandial fullness and epigastric discomfort, bloating, nausea, and vomiting. DGP may significantly affect the quality of life and productivity of patients. Research on the relationship between gastrointestinal dynamics and DGP has received much attention because of the increasing prevalence of DGP. Gastrointestinal motility disorders are closely related to a variety of factors including the absence and destruction of interstitial cells of Cajal, abnormalities in the neuro-endocrine system and hormone levels. Therefore, this study will review recent literature on the mechanisms of DGP and gastrointestinal motility disorders as well as the development of prokinetic treatment of gastrointestinal motility disorders in order to give future research directions and identify treatment strategies for DGP.

20.
Plant Dis ; 108(4): 996-1004, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38613135

RESUMEN

Bacterial wilt caused by Ralstonia solanacearum (RS) is one of the most devastating diseases in patchouli (Pogostemon cablin [Blanco] Benth.), which results in low yield and quality of patchouli. However, no stable and effective control methods have been developed yet. To evaluate the potential of dominant bacterial endophytes in biocontrol, the endophytic bacterial diversity of patchouli was investigated based on Illumina sequencing analysis, and the ability of isolates belonging to the dominant bacterial genera to control RS wilt of patchouli was explored in pot experiments. A total of 245 bacterial genera were detected in patchouli plants, with the highest relative abundance of operational taxonomic units belonging to the genus Pseudomonas detected in roots, leaves, and stems. The Pseudomonas isolates S02, S09, and S26 showed antagonistic activity against RS in vitro and displayed many plant growth-promoting characteristics, including production of indole-3-acetic acid, siderophores, and 1-aminocyclopropane-1-carboxylic acid deaminase and phosphate- and potassium-solubilizing capability. Inoculation of patchouli plants with the isolates S02, S09, and S26 significantly improved shoot growth and decreased the incidence of bacterial wilt caused by RS. The results suggest that screening of dominant bacterial endophytes for effective biocontrol agents based on Illumina sequencing analysis is more efficient than random isolation and screening procedures.


Asunto(s)
Endófitos , Enfermedades de las Plantas , Ralstonia solanacearum , Ralstonia solanacearum/fisiología , Ralstonia solanacearum/genética , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/prevención & control , Endófitos/genética , Endófitos/fisiología , Endófitos/aislamiento & purificación , Pseudomonas/genética , Pseudomonas/fisiología , Secuenciación de Nucleótidos de Alto Rendimiento , Filogenia , Agentes de Control Biológico
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA