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1.
Front Genet ; 15: 1404215, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39376740

RESUMEN

Introduction: This study aimed to investigate the causal relationship between phosphatidylcholine (PC) levels and dysmenorrhea using Mendelian randomization (MR) analysis. Methods: We conducted a two-sample MR analysis using GWAS data on PC levels and dysmenorrhea. Single nucleotide polymorphisms (SNPs) associated with PC levels were used as instrumental variables. MR-Egger regression and inverse variance weighting (IVW) were used to estimate the causal effect of PC levels on dysmenorrhea. Sensitivity analyses were performed to assess the robustness of the results. Results: The IVW analysis revealed a significant positive association between higher PC levels and dysmenorrhea (OR: 1.533, 95% CI: 1.039-2.262, P = 0.031). The MR-Egger regression did not detect pleiotropy. Sensitivity analyses confirmed the robustness of the results. Conclusion: This study provides evidence suggesting a causal link between increased PC levels and dysmenorrhea. Further research is needed to understand the biological mechanisms underlying this relationship and to explore potential therapeutic implications.

2.
Expert Opin Drug Saf ; 2024 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-39422097

RESUMEN

BACKGROUND: Tezepelumab is the first asthma biologic approved by the FDA that is not restricted by biomarker phenotypes. To date, there have been no studies reporting adverse events (AEs) associated with the real-world use of tezepelumab. RESEARCH DESIGN AND METHODS: This study included a comprehensive evaluation of AE reports related to tezepelumab since its approval (4th quarter of 2021 to 1st quarter of 2024) using the FAERS database, and compared with the currently reported clinical trial results(ClinicalTrials.gov). RESULTS: A total of 2153 reports of tezepelumab-related AEs were extracted. 256 preferred terms (PTs) of adverse reactions involving 27 system organ classes were identified. Significant AEs that were not reported on the drug label, such as 'dyspnea,' 'body temperature,' and 'tongue pruritus,' were reported. The median time to onset (TTO) of tezepelumab-related AEs was 35 days.The most frequent AEs in different sexes were 'arthralgia' and 'dyspnea,' with differences in signal strength ranking between the sexes. CONCLUSIONS: This study represents the largest report to date on tezepelumab-related AEs, providing valuable insights into the potential side effects of tezepelumab. This work is crucial for the broader clinical application of this novel biologic and improving outcomes for patients with severe asthma.

3.
J Cardiothorac Surg ; 19(1): 603, 2024 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-39396001

RESUMEN

BACKGROUND: Pectus excavatum is the most common chest wall deformity, with the Nuss procedure being the preferred surgical approach for correction. However, the decision to use thoracoscopic assistance remains challenging. This study aimed to evaluate the perioperative outcomes of thoracoscopic-assisted versus non-thoracoscopic-assisted minimally invasive repair of pectus excavatum (TA-MIRPE vs. NTA-MIRPE). METHODS: A comprehensive search was conducted across PubMed, Medline, Embase, WOS, and CBM databases for studies published from 2010 to the present related to this topic. Meta-analysis was performed using RevMan 5.0 and STATA 15.0, with primary comparisons focusing on postoperative complications and the incidence of poor incision healing. RESULTS: Eighteen studies involving a total of 5933 patients were included in the analysis, with 1670 undergoing non-thoracoscopic surgery and 4263 receiving thoracoscopic surgery. The meta-analysis revealed that, compared to the NTA-MIRPE group, the TA-MIRPE group had longer operation times [SMD = 1.71, 95% CI (1.14, 2.28), P < 0.001] and extended postoperative hospital stays [SMD = 0.12, 95% CI (0.04, 0.20), P = 0.004]. However, the TA-MIRPE group showed a lower incidence of postoperative complications [OR = 0.48, 95% CI (0.35, 0.65), z = 4.63, P < 0.001] and higher patient satisfaction [OR = 1.88, 95% CI (1.32, 2.67), z = 3.51, P < 0.001]. CONCLUSION: While TA-MIRPE is associated with longer operation times and hospital stays, it offers greater patient satisfaction, reduces postoperative complications, and enhances surgical safety.


Asunto(s)
Tórax en Embudo , Procedimientos Quirúrgicos Mínimamente Invasivos , Complicaciones Posoperatorias , Toracoscopía , Humanos , Tórax en Embudo/cirugía , Toracoscopía/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Complicaciones Posoperatorias/epidemiología , Resultado del Tratamiento , Tempo Operativo
4.
Acta Derm Venereol ; 104: adv40819, 2024 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-39420872

RESUMEN

Recent studies that examined the treatment efficacy of Candida antigen injection for both non-genital and genital warts yield inconsistent results. To address this, a systematic review and meta-analysis was conducted, comparing the treatment response between Candida antigen injection therapy and other intralesional immunotherapies across all types of warts. PubMed, Cochrane Library, and Embase were searched for relevant randomized controlled trials (RCTs) from inception to 16 September 2023, and 24 eligible RCTs were identified. A protocol was developed using the PRISM A-P checklist. In terms of complete clearance, intralesional Candida injection therapy demonstrated a significant improvement compared with saline (risk ratio [RR] 5.39; 95% confidence interval [CI] 3.49-8.33; I2=0%). However, no statistically significant differences were observed when compared with other therapies such as mumps-measles-rubella vaccines, purified protein derivative, vitamin D3, bivalent human papillomavirus vaccine, and zinc sulphate. Adverse effects associated with intralesional Candida therapy were generally reported as mild and manageable. In conclusion, intralesional Candida injection therapy for cutaneous warts may exhibit a superior complete and distant response rate. Nevertheless, owing to a limited sample size and other limitations, future research should aim for larger studies to provide more conclusive evidence.


Asunto(s)
Antígenos Fúngicos , Inyecciones Intralesiones , Verrugas , Humanos , Verrugas/tratamiento farmacológico , Verrugas/terapia , Resultado del Tratamiento , Antígenos Fúngicos/administración & dosificación , Antígenos Fúngicos/inmunología , Candida , Ensayos Clínicos Controlados Aleatorios como Asunto , Femenino , Masculino , Adulto
5.
Transl Lung Cancer Res ; 13(8): 1851-1861, 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39263018

RESUMEN

Background: Family history of cancer (FHC) has been reported to increase mortality of non-small cell lung cancer, mainly comprised of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). However, the impact of FHC on long-term survival remains controversial. This study aims to identify the impact of FHC on postoperative survival in LUAD and LUSC. Methods: Patients underwent lung resection for LUAD or LUSC in West China Hospital from 2009 to 2021 were enrolled. The 5-year overall survival (OS), lung cancer-specific survival (LCSS) and progression-free survival (PFS) were compared between the patients with and without FHC. Multivariable Cox regression was also performed. Results: A total of 6,253 patients were enrolled, including 5,685 LUAD and 568 LUSC. Altogether 18.9% (1,077/5,685) patients had FHC in LUAD, and 12.7% (72/568) patients had FHC in LUSC. In LUAD, the patients with FHC showed comparable survival compared with the patients without FHC regarding 5-year OS (87.9% vs. 86.5%, P=0.49), 5-year PFS (84.8% vs. 80.9%, P=0.06), and 5-year LCSS (89.2% vs. 88.0%, P=0.96). In LUSC, the patients with FHC had poorer survival compared with the patients without FHC according to 5-year OS (40.9% vs. 68.2%, P=0.007), 5-year PFS (42.3% vs. 66.2%, P=0.003), and 5-year LCSS (45.8% vs. 72.7%, P=0.003). Multivariate analyses indicated that FHC was an independent prognostic factor of OS, PFS, and LCSS in the patients with LUSC. Conclusions: FHC was associated with a poor survival after lung resection in LUSC not LUAD patients. More attention should be paid in postoperative monitoring and treatment in LUSC patients with FHC.

6.
R Soc Open Sci ; 11(9): 240459, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39263455

RESUMEN

Fine-grain copper (Cu) films (grain size: 100.36 nm) with a near-atomic-scale surface (0.39 nm) were electroplated. Without advanced post-surface treatment, Cu-Cu direct bonding can be achieved with present-day fine-grain Cu films at 130℃ in air ambient with a minimum pressure of 1 MPa. The instantaneous growth rate on the first day is 164.29 nm d-1. Also, the average growth rate (∆R/∆t) is evaluated by the present experimental results: (i) 218.185 nm d-1 for the first-day period and (ii) 105.58 nm d-1 during the first 14-day period. Ultrafast grain growth and near-atomic-scale surface facilitate grain boundary motion across the bonding interface, which is the key to achieve Cu-Cu direct bonding at 130℃ in air ambient.

7.
Heliyon ; 10(18): e37963, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39323860

RESUMEN

A lack of access to handwashing facilities is a significant risk factor for lower respiratory infections(LRIs). However, no studies have reported epidemiologic changes in the burden of LRIs attributed to the lack of access to handwashing facilities. We conducted an integrated assessment of the burden of LRIs attributable to the lack of handwashing facilities from 1990 to 2019 using data from the Global Burden of Disease Study 2019. In 2019, 270,000 deaths were attributed to LRIs due to a lack of access to handwashing facilities, with DALYs reaching 14.02 million. The age-standardized mortality rate (ASMR) of LRIs caused by a lack of access to handwashing facilities was approximately 3.74, while the age-standardized DALY rate (ASDR) was reported to be 203.55 in 2019. Over the past 30 years, the burden of LRIs attributed to the lack of access to handwashing facilities has shown a global decline. In 2019, this burden was most pronounced in infants under 1 year of age and in those older than 95 years, reflecting the highest DALY (5591.83) and mortality rates (79.43), respectively. The burden of LRIs caused by the lack of access to handwashing facilities was found to be more severe in males and significantly more pronounced in regions with a low sociodemographic index (SDI), such as the Sahara African region. The development of targeted strategies to address the inadequate and unequal distribution of handwashing facilities holds important value in improving the disease burden of LRIs.

8.
Sensors (Basel) ; 24(17)2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39275427

RESUMEN

Industrial Control Systems (ICSs) have faced a significant increase in malware threats since their integration with the Internet. However, existing machine learning-based malware identification methods are not specifically optimized for ICS environments, resulting in suboptimal identification performance. In this work, we propose an innovative method explicitly tailored for ICSs to enhance the performance of malware classifiers within these systems. Our method integrates the opcode2vec method based on preprocessed features with a conditional variational autoencoder-generative adversarial network, enabling classifiers based on Convolutional Neural Networks to identify malware more effectively and with some degree of increased stability and robustness. Extensive experiments validate the efficacy of our method, demonstrating the improved performance of malware classifiers in ICSs. Our method achieved an accuracy of 97.30%, precision of 92.34%, recall of 97.44%, and F1-score of 94.82%, which are the highest reported values in the experiment.

9.
J Headache Pain ; 25(1): 143, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39227797

RESUMEN

BACKGROUND AND OBJECTIVES: About a quarter of migraine cases among women have menstrual migraine (MM), which is usually more severe, longer lasting, and less responsive to treatment than typical migraine. Randomized controlled trials (RCTs) have evaluated the efficacy of several medication in the acute and preventive treatment of MM; this meta-analysis compared the effectiveness of these treatments. METHODS: We conducted systematic searches in the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase databases. The primary outcomes of acute treatment trials were pain relief at 2 and 24 h after treatment compared with placebo or another treatment. The three endpoints we checked for studying MM prevention were: no recurrence of headaches each month, a 50% reduction in monthly migraine days from baseline, and a decrease in the mean number of headache days per month. RESULTS: Out of 342 studies, 26 RCTs met the criteria. Triptans, combined with or without other analgesics, were superior to placebo in providing pain relief in the acute treatment and prevention of MM. Among the treatments, sumatriptan and lasmiditan demonstrated superior pain relief at 2 h (OR: 4.62) and 24 h (OR: 4.81). Frovatriptan exhibited effectiveness in preventing headache recurrence, whereas galcanezumab and erenumab displayed significant preventive benefits in reducing headache days per month. CONCLUSION: Sumatriptan and lasmiditan are effective first-line treatments for acute MM. For prevention, frovatriptan may be the more effective of triptans. Compared with triptans, CGRP monoclonal antibodies, here including erenumab and galcanezumab, are more effective in reducing headache days, and therefore, in preventing MM.


Asunto(s)
Trastornos Migrañosos , Femenino , Humanos , Trastornos Migrañosos/tratamiento farmacológico , Trastornos Migrañosos/fisiopatología , Trastornos Migrañosos/prevención & control , Ensayos Clínicos Controlados Aleatorios como Asunto , Triptaminas/uso terapéutico , Ciclo Menstrual/fisiología
10.
Org Biomol Chem ; 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39315644

RESUMEN

Herein, we present a novel approach for the preparation of alkynyl cyclopropa[c]coumarin derivatives with medium to good yields utilizing propargyl sulfonium salts as C1 synthons. Compared with Br-, using ClO4- as the counter anion significantly enhances the yield due to its lesser nucleophilic ability. This method features mild reaction conditions and a broad substrate scope with good diastereoselectivity when the substituted R1 group is at the 5-position of the coumarin scaffold.

12.
Transl Lung Cancer Res ; 13(7): 1559-1584, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39118883

RESUMEN

Background: Immune checkpoint inhibitors (ICIs) work by activating the immune system, a mechanism that may also cause immune-related adverse events (irAEs). This study seeks to investigate on how different irAEs impact prognosis of advanced lung cancer (LC) patients and identify useful approaches to manage irAEs. Methods: A thorough literature search of PubMed, Embase, the Cochrane Library and manual searches up to January 2024 were undertaken. Treatment outcomes including progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR) were obtained. Meta-analysis was conducted using R software (version 4.3.1). Results: There were 106 studies with 41,050 advanced or recurrent LC patients included. The occurrence of irAEs was correlated with better PFS [hazard ratio (HR) =0.54; 95% confidence interval (CI): 0.49-0.59], OS (HR =0.57; 0.51-0.63), ORR [risk ratio (RR) =2.03; 95% CI: 1.81-2.28] and DCR (RR =1.55; 95% CI: 1.40-1.72) and remained significant after adjusting programmed death-ligand 1 (PD-L1) level. IrAEs affecting skin (OS: HR =0.45; 95% CI: 0.38-0.53) and endocrine system (OS: HR =0.51; 95% CI: 0.41-0.62), of mild severity (OS: HR =0.52; 95% CI: 0.35-0.79), arising in multiple sites (OS: HR =0.47; 95% CI: 0.38-0.59), induced by monotherapy (OS: HR =0.58; 95% CI: 0.52-0.65), with a delayed onset (cutoff: 3 months; OS: HR =0.37; 95% CI: 0.19-0.71) were identified as positive prognostic markers. In contrast, though pulmonary irAEs were found to be corelated with enhanced treatment response (ORR: RR =1.75; 95% CI: 1.37-2.25), they may harm survival, especially those with grade ≥3 (OS: HR =2.40; 95% CI: 1.39-4.14). Treatment resumption tended to improve PFS but might not reduce the risk of death compared to permanent discontinuation. Conclusions: IrAEs suggest better treatment outcomes generally, yet severe pneumonia could increase mortality risk. Close supervision and appropriate handling protocols are warranted to weigh treatment benefit against risk.

13.
Sensors (Basel) ; 24(16)2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39205010

RESUMEN

With the rapid development of industry, the risks factories face are increasing. Therefore, the anomaly detection algorithms deployed in factories need to have high accuracy, and they need to be able to promptly discover and locate the specific equipment causing the anomaly to restore the regular operation of the abnormal equipment. However, the neural network models currently deployed in factories cannot effectively capture both temporal features within dimensions and relationship features between dimensions; some algorithms that consider both types of features lack interpretability. Therefore, we propose a high-precision, interpretable anomaly detection algorithm based on variational autoencoder (VAE). We use a multi-scale local weight-sharing convolutional neural network structure to fully extract the temporal features within each dimension of the multi-dimensional time series. Then, we model the features from various aspects through multiple attention heads, extracting the relationship features between dimensions. We map the attention output results to the latent space distribution of the VAE and propose an optimization method to improve the reconstruction performance of the VAE, detecting anomalies through reconstruction errors. Regarding anomaly interpretability, we utilize the VAE probability distribution characteristics, decompose the obtained joint probability density into conditional probabilities on each dimension, and calculate the anomaly score, which provides helpful value for technicians. Experimental results show that our algorithm performed best in terms of F1 score and AUC value. The AUC value for anomaly detection is 0.982, and the F1 score is 0.905, which is 4% higher than the best-performing baseline algorithm, Transformer with a Discriminator for Anomaly Detection (TDAD). It also provides accurate anomaly interpretation capability.

14.
Clin Transplant ; 38(7): e15410, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39033507

RESUMEN

BACKGROUND: Microvascular inflammation (MVI) can occur in biopsies showing T-cell mediated rejection (TCMR), but it is not well established that T-cells can directly mediate microvascular injury (TCMR-MVI). METHODS: This was a cross sectional RNAseq based Banff Human Organ Transplant (BHOT) gene expression (GE) analysis. The objective of this study was to probe the molecular signature of TCMR-MVI in comparison with C4d+, DSA+ antibody mediated rejection (ABMR), stable renal function (STA), and TCMR without MVI. Transcriptome analysis utilized CLC genomic workbench and R-studio software. RESULTS: No gene set was specific for any diagnostic category, and all were expressed at low levels in STA biopsies. BHOT gene set scores could differentiate ABMR from TCMR and TCMR-MVI, but not TCMR from TCMR-MVI. TCMR-MVI underexpressed several genes associated with ABMR including DSATs, ENDAT, immunoglobulin genes, ADAMDEC1, PECAM1 and NK cell transcripts (MYBL1, GNLY), but overexpressed C3, NKBBIZ, and LTF. On the other hand, there was no significant difference in the expression of these genes in TCMR-MVI versus TCMR. This indicates that the GE profile of TCMR MVI aligns more closely with TCMR than ABMR. The limitations of classifying biopsies using the binary ABMR-TCMR algorithm, and the occurrence of common pathogenesis mechanisms amongst different rejection phenotype was highlighted by the frequent presence of molecular mixed rejection. CONCLUSIONS: T-cell mediated mechanisms play a significant role in the pathogenesis of MVI. GE was broadly different between rejection phenotypes, but molecular scores varied substantially between biopsies with the same Banff grade. It was not always possible to achieve precise molecular score-based diagnostic categorization of individual patients.


Asunto(s)
Rechazo de Injerto , Trasplante de Riñón , Linfocitos T , Humanos , Rechazo de Injerto/etiología , Rechazo de Injerto/patología , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/inmunología , Trasplante de Riñón/efectos adversos , Estudios Transversales , Masculino , Linfocitos T/inmunología , Linfocitos T/metabolismo , Femenino , Supervivencia de Injerto/inmunología , Inflamación/patología , Estudios de Seguimiento , Persona de Mediana Edad , Microvasos/patología , Pronóstico , Biomarcadores/metabolismo , Biomarcadores/análisis , Aloinjertos , Adulto , Perfilación de la Expresión Génica , Tasa de Filtración Glomerular , Factores de Riesgo , Pruebas de Función Renal
15.
Front Immunol ; 15: 1410158, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38873611

RESUMEN

Background: Chronic obstructive pulmonary disease (COPD) is one of the most prevalent chronic respiratory diseases and the fourth cause of mortality globally. Neutrophilic inflammation has a vital role in the occurrence and progression of COPD. This study aimed to identify the novel hub genes involved in neutrophilic inflammation in COPD through bioinformatic prediction and experimental validation. Methods: Both the single-cell RNA sequencing (scRNA-seq) dataset (GSE173896) and the RNA sequencing (RNA-seq) dataset (GSE57148) were downloaded from the Gene Expression Omnibus (GEO) database. The Seurat package was used for quality control, dimensions reduction, and cell identification of scRNA-seq. The irGSEA package was used for scoring individual cells. The Monocle2 package was used for the trajectory analysis of neutrophils. The CIBERSORT algorithm was used for analysis of immune cell infiltration in the lungs of COPD patients and controls in RNA-seq dataset, and weighted gene co-expression network analysis (WGCNA) correlated gene modules with neutrophil infiltration. The Mendelian randomization (MR) analysis explored the causal relationship between feature DEGs and COPD. The protein-protein interaction (PPI) network of novel hub genes was constructed, and real-time quantitative polymerase chain reaction (qRT-PCR) was used to validate novel hub genes in clinical specimens. Results: In scRNA-seq, the gene sets upregulated in COPD samples were related to the neutrophilic inflammatory response and TNF-α activation of the NF-κB signaling pathway. In RNA-seq, immune infiltration analysis showed neutrophils were upregulated in COPD lung tissue. We combined data from differential and modular genes and identified 51 differential genes associated with neutrophilic inflammation. Using MR analysis, 6 genes were explored to be causally associated with COPD. Meanwhile, 11 hub genes were identified by PPI network analysis, and all of them were upregulated. qRT-PCR experiments validated 9 out of 11 genes in peripheral blood leukocytes of COPD patients. Furthermore, 5 genes negatively correlated with lung function in COPD patients. Finally, a network of transcription factors for NAMPT and PTGS2 was constructed. Conclusion: This study identified nine novel hub genes related to the neutrophilic inflammation in COPD, and two genes were risk factors of COPD, which may serve as potential biomarkers for the clinical severity of COPD.


Asunto(s)
Biomarcadores , Neutrófilos , Enfermedad Pulmonar Obstructiva Crónica , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Humanos , Neutrófilos/inmunología , Neutrófilos/metabolismo , Redes Reguladoras de Genes , Mapas de Interacción de Proteínas , Inflamación/genética , Perfilación de la Expresión Génica , Biología Computacional/métodos , Masculino , Transcriptoma , Bases de Datos Genéticas
16.
J Med Chem ; 67(13): 10906-10927, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38913493

RESUMEN

A series of bifunctional compounds have been discovered for their dual functionality as MER/AXL inhibitors and immune modulators. The furanopyrimidine scaffold, renowned for its suitability in kinase inhibitor discovery, offers at least three distinct pharmacophore access points. Insights from molecular modeling studies guided hit-to-lead optimization, which revealed that the 1,3-diketone side chain hybridized with furanopyrimidine scaffold that respectively combined amino-type substituent and 1H-pyrazol-4-yl substituent on the top and bottom of the aryl regions to produce 22 and 33, exhibiting potent antitumor activities in various syngeneic and xenograft models. More importantly, 33 demonstrated remarkable immune-modulating activity by upregulating the expression of total T-cells, cytotoxic CD8+ T-cells, and helper CD4+ T-cells in the spleen. These findings underscored the bifunctional capabilities of 33 (BPR5K230) with excellent oral bioavailability (F = 54.6%), inhibiting both MER and AXL while modulating the tumor microenvironment and highlighting its diverse applicability for further studies to advance its therapeutic potential.


Asunto(s)
Antineoplásicos , Tirosina Quinasa del Receptor Axl , Inhibidores de Proteínas Quinasas , Proteínas Proto-Oncogénicas , Proteínas Tirosina Quinasas Receptoras , Microambiente Tumoral , Tirosina Quinasa c-Mer , Animales , Microambiente Tumoral/efectos de los fármacos , Humanos , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/síntesis química , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Antineoplásicos/uso terapéutico , Proteínas Tirosina Quinasas Receptoras/antagonistas & inhibidores , Proteínas Tirosina Quinasas Receptoras/metabolismo , Proteínas Proto-Oncogénicas/antagonistas & inhibidores , Proteínas Proto-Oncogénicas/metabolismo , Tirosina Quinasa c-Mer/antagonistas & inhibidores , Tirosina Quinasa c-Mer/metabolismo , Ratones , Línea Celular Tumoral , Relación Estructura-Actividad , Descubrimiento de Drogas , Bibliotecas de Moléculas Pequeñas/farmacología , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/síntesis química , Femenino , Ensayos Antitumor por Modelo de Xenoinjerto , Ratones Endogámicos BALB C , Proliferación Celular/efectos de los fármacos
17.
Antioxidants (Basel) ; 13(6)2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38929160

RESUMEN

Djulis (Chenopodium formosanum), a traditional Taiwanese crop enriched with phenolic compounds and betalain pigments, is associated with various health benefits, including antioxidant and hepatoprotective effects. This study analysed the phytochemical content and antioxidant capacity of extracts from both the hull and kernel of Djulis. The hull extract, which contained higher levels of flavonoids and exhibited superior antioxidant activity compared to the kernel extract, was selected for further in vivo studies. These experiments showed that oral administration of the Djulis hull crude extract significantly mitigated lipopolysaccharide (LPS)-induced acute liver injury (ALI) in mice by increasing the activity of the antioxidant enzyme glutathione peroxidase (GPx), reducing plasma levels of pro-inflammatory cytokine interferon gamma (IFN-γ), and enhancing liver levels of the anti-inflammatory cytokine interleukin-4 (IL-4). Additionally, the extract demonstrated potential in inhibiting the TLR4/NF-κB pathway, a critical signalling pathway in inflammation and apoptosis, offering insights into its protective mechanisms. These findings underscore Djulis hull's potential as a functional food ingredient for ALI prevention and propose a valuable application for agricultural by-products.

18.
Mol Diagn Ther ; 28(4): 379-388, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38773009

RESUMEN

BACKGROUND: Psoriasis is a chronic, inflammatory, T-cell-mediated disease with a multifactorial pathogenesis. MicroRNA (miRNA) alteration in psoriasis has been identified within the last few years. In particular, miR-146a levels were altered. However, previous studies have equivocal or even contradictory findings. OBJECTIVE: The current study aimed to perform a systematic review and meta-analysis to evaluate the miRNA expression profile in different tissues in patients with psoriasis. Further, the correlation between miR-146a levels and psoriasis severity as well as the specific expression patterns of the miR-146a profile in patients with psoriasis after treatment were evaluated. METHODS: To retrieve studies investigating the correlation between miRNA and psoriasis, a comprehensive search of databases including PubMed, Cochrane Library, and Embase was performed from inception to 30 June 2023. Relevant journals and references of the included studies were also reviewed. A meta-analysis was conducted using the comprehensive meta-analysis version 3. RESULTS: The correlation between the miR-146a expression levels and psoriasis susceptibility in 14 studies was assessed. Results showed that the miR-146a expression level was upregulated in psoriasis samples [P = 0.001, standardized mean difference (SMD) = 1.489, 95% confidence interval (CI) = 0.618-2.360]. In a subgroup analysis based on sample type, the correlation between the peripheral blood mononuclear cell, blood, and tissue miR-146a expression level and psoriasis was significant (SMD = 1.293, 95% CI 0.310-2.276, P = 0.01; SMD = 2.526, 95% CI 1.710-3.342, P = 0.000; SMD = 3.153, 95% CI 1.432-4.874, P = 0.00, respectively). A positive correlation was observed between the miR-146a expression levels and Psoriasis Area and Severity Index (PASI) score. However, the result was not statistically significant (correlation coefficient = 0.29, 95% CI - 0.038 to 0.575, P = 0.081). Further, the miR-146a levels decreased after treatment (SMD = - 1.592, 95% CI - 2.067 to - 1.117, P = 0.000, I2 = 74.104). CONCLUSIONS: The miR-146a expression level is positively correlated with and can contribute to the pathobiology of psoriasis.


Asunto(s)
MicroARNs , Psoriasis , Psoriasis/genética , Psoriasis/metabolismo , Humanos , MicroARNs/genética , Regulación de la Expresión Génica , Biomarcadores , Perfilación de la Expresión Génica , Índice de Severidad de la Enfermedad
20.
ChemSusChem ; 17(18): e202400197, 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-38629214

RESUMEN

The deep eutectic solvent (DES) has emerged in recent years as a valuable medium for converting CO2 into valuable chemicals because of its easy availability, stability, and safety, and its capability to dissolve carbon dioxide. CO2 valorization in DES has evolved rapidly over the past 20 years. As well as being used as solvents for acid/base-promoted CO2 conversion for the production of cyclic carbonates and carbamates, DESs can be used as reaction media for electrochemical CO2 reduction for formic acid and CO. Among these products, cyclic carbonates can be used as solvents and electrolytes, carbamate derivatives include the core structure of many herbicides and pesticides, and formic acid and carbon monoxide, the C1 electrochemical products, are essential raw materials in the chemical industries. An overview of the application of DESs for CO2 valorization in recent years is presented in this review, followed by a compilation and comparison of product types and reaction mechanisms within the different types of DESs, and an outlook on how CO2 valorization will be developed in the future.

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