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1.
Artículo en Inglés | MEDLINE | ID: mdl-39303063

RESUMEN

The synthetical methodology for the [Cu(dmp)2]2+/1+ (dmp = 2,9-dimethyl-1,10-phenanthroline; neocuproine) complexes has been systematically investigated by using various copper precursors, including CuCl2, Cu(NO3)2, and Cu(ClO4)2. After an anion exchange to trifluoromethanesulfonimide (TFSI), the tetra-coordinated CuII(dmp)2(TFSI)2-Cu(ClO4)2 (7.43%) outperformed the penta-coordinated CuII(dmp)2(TFSI)(NO3)-Cu(NO3)2 (4.30%) and CuII(dmp)2(TFSI)(Cl)-CuCl2. Polymeric chalcogenides, including a conducting copolymeric electrode of PEDOT-PEDTT [PEDOT = poly(3,4-ethylenedioxythiophene); PEDTT = poly(3,4-ethylenedithiothiophene)] and a coordination polymeric electrode of silver bezeneselenolate ([Ag2(SePh)2]n; mithrene), are introduced as the electrocatalysts for [Cu(dmp)2]2+/1+ for the first time. After optimization, dye-sensitized solar cells (DSSCs) based on carbon cloth (CC)/AgSePh-30 (10.18%) showed superior electrocatalytic ability compared to the benchmark CC/Pt (7.43%) due to numerous active sites provided by electron-donating Se atoms, high film roughness, and bottom-up 2D charge transfer routes. The DSSC based on CC/PEDTT-50 (10.38%) also outperformed CC/Pt due to numerous active sites provided by electron-donating S atoms and proper energy band structure. This work sheds light on the future design and synthesis in Cu-complex mediators and functional polymeric chalcogenides for high-performance DSSCs.

2.
Eur J Med Chem ; 279: 116810, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39243456

RESUMEN

Alzheimer's disease (AD) is the most common form of dementia among the elderly, accounting for 60 %-70 % of cases. At present, the pathogenesis of this condition remains unclear, but the hydrolysis of acetylcholine (ACh) is thought to play a role. Acetylcholinesterase (AChE) can break down ACh transmission from the presynaptic membrane and stop neurotransmitters' excitatory effect on the postsynaptic membrane, which plays a key role in nerve conduction. Acetylcholinesterase inhibitors (AChEIs) can delay the hydrolysis of acetylcholine (ACh), which represents a key strategy for treating AD. Due to its complex etiology, AD has proven challenging to treat. Various inhibitors and antagonists targeting key enzymes and proteins implicated in the disease's pathogenesis have been explored as potential therapeutic agents. These include Glycogen Synthase Kinase 3ß (GSK-3ß) inhibitors, ß-site APP Cleaving Enzyme (BACE-1) inhibitors, Monoamine Oxidase (MAO) inhibitors, Phosphodiesterase inhibitors (PDEs), N-methyl--aspartic Acid (NMDA) antagonists, Histamine 3 receptor antagonists (H3R), Serotonin receptor subtype 4 (5-HT4R) antagonists, Sigma1 receptor antagonists (S1R) and soluble Epoxide Hydrolase (sEH) inhibitors. The drug development strategy of multi-target-directed ligands (MTDLs) offers unique advantages in the treatment of complex diseases. On the one hand, it can synergistically enhance the therapeutic efficacy of single-target drugs. On the other hand, it can also reduce the side effects. In this review, we discuss the design strategy of dual inhibitors based on acetylcholinesterase and the structure-activity relationship of these drugs.

3.
MedComm (2020) ; 5(7): e640, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39006762

RESUMEN

Liquid-liquid phase separation (LLPS), an emerging biophysical phenomenon, can sequester molecules to implement physiological and pathological functions. LLPS implements the assembly of numerous membraneless chambers, including stress granules and P-bodies, containing RNA and protein. RNA-RNA and RNA-protein interactions play a critical role in LLPS. Scaffolding proteins, through multivalent interactions and external factors, support protein-RNA interaction networks to form condensates involved in a variety of diseases, particularly neurodegenerative diseases and cancer. Modulating LLPS phenomenon in multiple pathogenic proteins for the treatment of neurodegenerative diseases and cancer could present a promising direction, though recent advances in this area are limited. Here, we summarize in detail the complexity of LLPS in constructing signaling pathways and highlight the role of LLPS in neurodegenerative diseases and cancers. We also explore RNA modifications on LLPS to alter diseases progression because these modifications can influence LLPS of certain proteins or the formation of stress granules, and discuss the possibility of proper manipulation of LLPS process to restore cellular homeostasis or develop therapeutic drugs for the eradication of diseases. This review attempts to discuss potential therapeutic opportunities by elaborating on the connection between LLPS, RNA modification, and their roles in diseases.

4.
Bioorg Chem ; 148: 107454, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38795581

RESUMEN

HPK1 also referred to as MAP4K1, belongs to the category of mammalian STE20-like protein serine/threonine kinases. Its physiological function involves the down-regulation of T cell signals, and it is regarded as a new immune checkpoint of tumor immunology. In this study, we commenced our investigation with the hit compounds, focusing the efforts on structural optimization and SAR exploration to identify a novel class of 2,4-diaminopyrimidine HPK1 inhibitors. Notably, compound 14g exhibited a remarkable inhibitory effect on HPK1 kinase (IC50 = 0.15 nM), significantly suppressed the phosphorylation of the downstream adaptor protein SLP76 (pSLP76 IC50 = 27.92 nM), and effectively stimulated the secretion of the T cell activation marker IL-2 (EC50 = 46.64 nM). In vitro microsomal stability assay, compound 14g showed moderate stability in HLMs with T1/2 = 38.2 min and CLint = 36.4 µL·min-1·mg-1 proteins. In vivo pharmacokinetic studies, compound 14g demonstrated heightened plasma exposure (AUC0-inf = 644 ng·h·mL-1), extended half-life (T1/2 = 9.98 h), and reduced plasma clearance (CL = 52.3 mL·min-1·kg-1) compared to the reference compound after a single intravenous dose of 2 mg/kg in rats. These results indicated that compound 14g emerged as a promising inhibitor of HPK1.


Asunto(s)
Diseño de Fármacos , Inhibidores de Proteínas Quinasas , Proteínas Serina-Treonina Quinasas , Pirimidinas , Pirimidinas/farmacología , Pirimidinas/química , Pirimidinas/síntesis química , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/química , Humanos , Relación Estructura-Actividad , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Serina-Treonina Quinasas/metabolismo , Animales , Estructura Molecular , Ratas , Relación Dosis-Respuesta a Droga , Masculino , Simulación del Acoplamiento Molecular , Ratas Sprague-Dawley
5.
Diabetol Metab Syndr ; 16(1): 91, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38659035

RESUMEN

OBJECTIVE: Asprosin, a newly identified adipokine, is pathologically increased in type 2 diabetes. The aim of this study is to see whether serum asprosin concentrations are linked to diabetes mellitus-induced erectile dysfunction (DMED). METHODS: 90 male patients with type 2 diabetes were included. According to the International Index of Erectile Function (IIEF-5) score, they were classified into two groups: 45 type 2 diabetes patients without erectile dysfunction (DM group) (IIEF-5 > 21),45 patients with diabetes induced erectile dysfunction (DMED group) (IIEF-5 ≤ 21)0.45 healthy male volunteers with normal blood glucose, IIEF-5 score > 21 points, and age matched with the DMED group were included as the control group. Anthropometric and biochemical variables were determined in all participants. RESULTS: When compared to the controls, T2DM ( Type 2 Diabetes Mellitus)patients had higher serum asprosin levels. The DMED group had significantly higher serum asprosin than the T2DM groups(p < 0.001). After adjusting for multiple variables considered traditional risk factors for ED(erectile dysfunction), Asprosin can still be used as an independent risk factor for ED; The ROC(Receive Operating Characteristic Curve) indicates that asprosin has good sensitivity (97.8%) and specificity (62.2%) in predicting ED, with an area under the curve of 0.843.Correlation analysis shows that asprosin is negatively correlated with SOD(superoxide dismutase ) and positively correlated with MDA (malondialdehyde). CONCLUSION: Serum asprosin concentrations are increased in patients with DMED. Also, asprosin is correlated with oxidative stress indexes (MDA, SOD).

6.
Bioorg Med Chem ; 101: 117609, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38364599

RESUMEN

In this study, we have designed, synthesized and tested three series of novel dihydropteridone derivatives possessing isoindolin-1-one or isoindoline moieties as potent inhibitors of PLK1/BRD4. Remarkably, most of the compounds showed preferable inhibitory activity against PLK1 and BRD4. Compound SC10 exhibited excellent inhibitory activity with IC50 values of 0.3 nM and 60.8 nM against PLK1 and BRD4, respectively. Meanwhile, it demonstrated significant anti-proliferative activities against three tumor-derived cell lines (MDA-MB-231 IC50 = 17.3 nM, MDA-MB-361 IC50 = 8.4 nM, and MV4-11 IC50 = 5.4 nM). Moreover, SC10 exhibited moderate rat liver microsomal stability (CLint = 21.3 µL·min-1·mg-1), acceptable pharmacokinetic profile (AUC0-t = 657 ng·h·mL-1, oral bioavailability of 21.4 %) in Sprague-Dawley rats, reduced hERG toxicity, acceptable PPB and CYP450 inhibition. Further research indicated that SC10 could induce MV4-11 cell arrest at the S phase and apoptosis in a dose-dependent manner. This investigation provided us with an initial point for developing novel anticancer agents as dual inhibitors of PLK1 and BRD4.


Asunto(s)
Antineoplásicos , Neoplasias , Inhibidores de Proteínas Quinasas , Animales , Ratas , Antineoplásicos/farmacología , Antineoplásicos/metabolismo , Proteínas de Ciclo Celular , Línea Celular Tumoral , Proliferación Celular , Diseño de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Neoplasias/tratamiento farmacológico , Proteínas Nucleares/metabolismo , Ratas Sprague-Dawley , Relación Estructura-Actividad , Factores de Transcripción , Proteínas que Contienen Bromodominio/antagonistas & inhibidores , Indoles/química , Indoles/farmacología , Quinasa Tipo Polo 1/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/farmacología
7.
ACS Med Chem Lett ; 14(9): 1266-1274, 2023 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-37736169

RESUMEN

Recent studies have shown that phosphoinositide 3-kinase (PI3K) plays a vital role in cell division, and it has become a therapeutic target for many cancers. In this paper, some new 1,3,5-triazine or pyrimidine skeleton derivatives containing dithiocarbamate were designed and synthesized based on the reasonable drug design strategy from the previously effective compound 2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (ZSTK-474), in order to get effective selective PI3Kα inhibitors that have not been reported in the literature. In addition, the inhibitory activities of these compounds on PI3Kα and two tumor cell lines in vitro (HCT-116, U87-MG) were evaluated. The representative compound 13 showed a half-maximal inhibitory concentration (IC50) value of 1.2 nM for PI3Kα and an exciting kinase selectivity. Compound 13 displayed strong efficacy in HCT-116 and U87-MG cell lines with IC50 values of 0.83 and 1.25 µM, respectively. In addition, compound 13 induced obvious tumor regression in the U87-MG cell line xenografts mouse model, with no obvious signs of toxicity after intraperitoneal injection at a dose of 40 mg/kg. Compound 13 can be an effective selective inhibitor of PI3Kα, and it provides patients with an opportunity to avoid the side effects related to the wider inhibition of the class I PI3K family.

8.
Bioorg Chem ; 140: 106738, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37562315

RESUMEN

Phosphoinositide 3-kinase (PI3K) was an important cellular signal transducer, while PI3Kα was the most mutated family member in cancer. Selective PI3Kα inhibitors have become the frequent research in recent years because of their excellent curative effect and reduced side effects. Here, we described a series of PI3Kα inhibitors with 1,3,5-triazine or pyrimidine skeleton containing benzoyl hydrazine based on the pan-PI3K inhibitor ZSTK474 relying on the strategies of structure-based drug discovery (SBDD) and computer-aided drug design (CADD). Among them, compound F8 exhibited improved selective PI3Kα inhibition with an IC50 value of 0.14 nM and more significant anti-proliferative activities against three tumor-derived cell lines (PC-3 IC50 = 0.28 µM, HCT-116 IC50 = 0.57 µM, and U87-MG IC50 = 1.37 µM) than ZSTK-474. Compound F-8 induced a great decrease in mitochondrial membrane which caused cell cycle arrest at G1 phase and apoptosis in U87-MG cells in a dose-dependent manner. Furthermore, compound F8 induced significant tumor regressions in a xenograft mouse model of U87-MG cell line with no clear evidence of toxicity following intraperitoneal injection of 40 mg/kg. Compound F8 may serve as a PI3Kα-selective inhibitor and provided the opportunity to spare patients the side effects associated with broader inhibition of the class I PI3K family.


Asunto(s)
Antineoplásicos , Fosfatidilinositol 3-Quinasas , Humanos , Ratones , Animales , Fosfatidilinositol 3-Quinasas/metabolismo , Antineoplásicos/farmacología , Proliferación Celular , Línea Celular Tumoral , Fosfatidilinositol 3-Quinasa , Diseño de Fármacos , Hidrazinas/farmacología , Pirimidinas/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Relación Estructura-Actividad
9.
J Cell Mol Med ; 27(15): 2215-2227, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37307404

RESUMEN

Melatonin, a lipophilic hormone released from the pineal gland, has oncostatic effects on various types of cancers. However, its cancer treatment potential needs to be improved by deciphering its corresponding mechanisms of action and optimising therapeutic strategy. In the present study, melatonin inhibited gastric cancer cell migration and soft agar colony formation. Magnetic-activated cell sorting was applied to isolate CD133+ cancer stem cells. Gene expression analysis showed that melatonin lowered the upregulation of LC3-II expression in CD133+ cells compared to CD133- cells. Several long non-coding RNAs and many components in the canonical Wnt signalling pathway were altered in melatonin-treated cells. In addition, knockdown of long non-coding RNA H19 enhanced the expression of pro-apoptotic genes, Bax and Bak, induced by melatonin treatment. Combinatorial treatment with melatonin and cisplatin was investigated to improve the applicability of melatonin as an anticancer therapy. Combinatorial treatment increased the apoptosis rate and induced G0/G1 cell cycle arrest. Melatonin can regulate migration and stemness in gastric cancer cells by modifying many signalling pathways. Combinatorial treatment with melatonin and cisplatin has the potential to improve the therapeutic efficacy of both.


Asunto(s)
Melatonina , Neoplasias Gástricas , Humanos , Cisplatino/farmacología , Cisplatino/uso terapéutico , Melatonina/farmacología , Melatonina/uso terapéutico , Neoplasias Gástricas/patología , Línea Celular Tumoral , Transducción de Señal , Apoptosis , Proliferación Celular
11.
Dalton Trans ; 52(18): 5956-5968, 2023 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-37039287

RESUMEN

Electrochemically durable perovskite electrodes of nickel foam/TiO2/FA(Pb1-xGex)I3, passivated using various surfactants of tetra-n-alkyl ammonium halides (alkyl = ethyl, butyl, hexyl, or octyl; halide = I, I0.5Br0.5, Br, Br0.5Cl0.5, or Cl), were successfully applied as good electro-catalysts on the counter electrodes in dye-sensitized solar cells (DSSCs). The longer alkyl chain of a surfactant resulted in a higher water contact angle, but poorer film conductivity. Based on the optimal tetra-n-hexyl ammonium (THA) cation, shrinking the halide radius of THA from I to I0.5Br0.5 formed an appropriate amount of FAPbBr3 nano-crystals covering on the FA(Pb1-xGex)I3 grain surface. This phenomenon not only suppressed the perovskite decomposition under electrochemical measurements, but also created additional electro-catalytic active sites for triggering the iodide/triiodide redox reaction. Further shrinking the halide radius of THA from I0.5Br0.5 to Cl resulted in a severe self-aggregation of THACl, leading to an insufficient passivation and thereby poor electrochemical performance. In an ambient environment with a relative humidity higher than 75%, the optimal perovskite electrode of nickel foam/TiO2/FA(Pb1-xGex)I3-THAI0.5Br0.5 maintained the good crystallinity of α-FAPbI3 at least for 6 months, without obvious decomposition. Compared to the DSSC couple with a common counter electrode of nickel foam/Pt (8.74%), a better cell performance of 8.87% was achieved using the counter electrode of nickel foam/TiO2/FA(Pb1-xGex)I3-THAI0.5Br0.5, which was attributed to its good intrinsic electro-catalytic activity, large surface area, multiple active sites, and decent thermodynamic stability. Under room light illumination, higher cell efficiencies were obtained at 1 klux (21.5% for an office), 3 klux (22.9% for a shopping window), and 6 klux (22.3% for a lampshade). There is no doubt that air-stable perovskites have great potential in showing high performance for various electrochemical devices.

12.
Front Public Health ; 11: 1063694, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36923041

RESUMEN

Introduction: Cervical cancer is still one of the cancers threatening the health of Chinese women with high morbidity and mortality. However, the participation rate of cervical cancer screening (CCS) among women is low due to various reasons, so it is crucial to understand the factors that influence women's willingness to be screened for cervical cancer. This study's goal was to understand the intention of cervical cancer screening in Chinese women using the theory of planned behavior (TPB). Methods: An online questionnaire was administered to 286 women using a cross-sectional design. The questionnaire was created using the theory of planned behavior and included demographic characteristics as well as the basic structure of TPB. Results: Descriptive, correlation, and multiple linear regression models were performed to identify factors associated with cervical cancer screening behavior. 286 respondents completed the survey (95.3%). The mean scores for behavioral attitude, subjective norm and perceived behavioral control (PBC) were 32.50 (SD = 3.30), 22.59 (SD = 2.80) and 29.57 (SD = 3.37). From the regression analysis, behavioral attitude (B = 0.110, p = 0.001), subjective norm (B = 0.234, p = 0.000) and perceived behavioral control (B = 0.171, p = 0.000) were statistically significant in terms of intention. Discussion: This study provided a reference for improving the intention of cervical cancer screening in women.


Asunto(s)
Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/diagnóstico , Detección Precoz del Cáncer , Intención , Estudios Transversales , Pueblos del Este de Asia , Teoría del Comportamiento Planificado
13.
J Orthop Surg Res ; 18(1): 5, 2023 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-36593454

RESUMEN

BACKGROUND: A minimally invasive technique with various screw configurations without open surgery is currently used for the fixation of transverse patellar fractures. Percutaneous crossing screw configuration has been reported to have a good bone union rate in patellar fractures. However, the difference in mechanical stability of the fractured patella between different screw-included angles has not been fully investigated. Hence, this study aims to compare the mechanical stability of parallel and crossing screw fixations with different screw-included angles for the fixation of transverse patellar fractures during level walking. METHODS: A finite element knee model containing a patella with a transverse fracture is created. Two headless compression screws with different angles (0°, 30°, 60°, and 90°) are used to fix the fracture. The loading conditions of the knee joint during level walking are used to compare the stability of the fractured patella with different fixation screw configurations. RESULTS: The results indicate that the maximum fracture gap opening distance increased with an increase in the included angle. Two parallel screws yield the smallest gap distance among all screw configurations. The maximum gap opening distances at the anterior leading edge of the fractured patella with two parallel screws and two screws having an included angle of 90° are 0.73 mm and 1.31 mm, respectively, at 15% walking cycle. CONCLUSIONS: Based on these results, the superior performance of two parallel screws over crossing screw fixations in the fixation of transverse patellar fractures is established. Furthermore, the smaller the angle between the crossing screws, the better is the stability of the fractured patella.


Asunto(s)
Fracturas Óseas , Traumatismos de la Rodilla , Humanos , Fijación Interna de Fracturas/métodos , Análisis de Elementos Finitos , Tornillos Óseos , Fracturas Óseas/cirugía , Rótula/cirugía , Fenómenos Biomecánicos
14.
Poult Sci ; 102(1): 102286, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36436372

RESUMEN

Aflatoxin B1 (AFB1) is the most toxic subtype of aflatoxin in feed. Poultry is sensitive to AFB1, and the liver is the main target organ of AFB1. Our previous studies have shown that taraxasterol isolated from the traditional Chinese medicinal herb Taraxacum has protective effects against immune-mediated and alcoholic-induced liver injuries. This study aimed to investigate whether taraxasterol has the protective effect and its mechanism against AFB1-induced injury in chicken primary hepatocytes in vitro. The chicken primary hepatocytes were induced with AFB1 (0.05 µg/mL), and treated with taraxasterol (5, 10, and 20 µg/mL). The results showed that taraxasterol increased superoxide dismutase (SOD) and glutathione (GSH) activity and decreased malondialdehyde (MDA) and reactive oxygen species (ROS) production in AFB1-induced hepatocytes. Moreover, taraxasterol up-regulated the mRNA and protein expression of antioxidant-related factors heme oxygenase-1 (HO-1), NADPH quinone oxidoreductase 1 (NQO1) and nuclear factor erythroid E2-related factor 2 (Nrf2), while down-regulated the expression of oxidant-related factor Kelch-like ECH-associated protein 1 (Keap1) in Nrf2/Keap1 signaling pathway. In addition, taraxasterol effectively reduced AFB1-induced hepatocyte autophagy and inhibited the mRNA expression of autophagy-related genes Beclin-2, LC3-I, LC3-II, and ATG-5. Taraxasterol also inhibited AFB1-induced hepatocyte apoptosis and decreased the mRNA expression of apoptosis-related genes Caspase3 and Caspase9. These findings indicates taraxasterol alleviates oxidative stress in AFB1-induced chicken hepatocytes by activating Nrf2/Keap1 signaling pathway, and regulating the cell autophagy and apoptosis.


Asunto(s)
Aflatoxina B1 , Pollos , Animales , Aflatoxina B1/toxicidad , Aflatoxina B1/metabolismo , Pollos/genética , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Hepatocitos , Estrés Oxidativo , Apoptosis , Glutatión/metabolismo , ARN Mensajero/metabolismo
15.
Melanoma Res ; 33(1): 27-37, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-36545920

RESUMEN

Malignant melanoma is the most aggressive form of skin cancer, and it is characterized by poor prognosis in patients with metastatic diseases. Accurate prediction of prognosis is crucial for therapeutic decisions. In this study, bioinformatics analysis was used to explore the prognostic value of growth factor receptor-bound protein 2-associated binding protein 3 (GAB3) mRNA. RNA transcriptome sequencing data and clinical data from The Cancer Genome Atlas and genotype-tissue expression (GTEx) were analyzed for differentially expressed genes in high and low GAB3 mRNA expression groups in melanoma. Performing gene enrichment analysis and constructing protein-protein interaction networks. High expression of GAB3 was significantly correlated with a lower T stage, melanoma Clark level, Breslow depth, and melanoma ulceration. And high GAB3 expression was also associated with better progression-free interval in T1 and T2 stages and N0 stage and longer overall survival in T1 and T2 stages, N0 stage, and N1 stage. GAB3 promoted high levels of infiltration of macrophages and activated natural killer cells in melanoma. High expression of GAB3 predicted a positive prognosis in early-stage melanoma that may be mediated by the anticancer immune response.


Asunto(s)
Melanoma , Neoplasias Cutáneas , Humanos , Melanoma/patología , Neoplasias Cutáneas/patología , ARN Mensajero/genética , Pronóstico , Transcriptoma , Proteína Adaptadora GRB2/genética , Proteína Adaptadora GRB2/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo
16.
BMC Womens Health ; 22(1): 512, 2022 12 10.
Artículo en Inglés | MEDLINE | ID: mdl-36496376

RESUMEN

BACKGROUND: Cervical cancer is the most common malignant tumor in women with a high mortality rate. However, the awareness and participation of women in cervical cancer screening were not high, and rare attention was paid to cervical cancer screening. The extensive promotion and execution of cervical cancer screening in China are still facing difficulties. In order to fully comprehend and evaluate the barriers and promote factors of cervical cancer screening in women, the objective of this study was to develop a scientifically sound and clinically useful Chinese cervical cancer screening intention scale. This study would allow for the development of targeted interventions which may contribute to the increase of individual participation in cervical cancer screening going forward. METHODS: This study used the Delphi method to construct a Chinese cervical cancer screening intention scale based on the theory of planned behavior (TPB) and evaluate its validity. The study was based on the overview of the TPB questionnaire proposed by Ajzen, and was conducted through the literature search and two rounds of the Delphi expert consultation. According to the literature search published from 2012 to 2022, the scale item pool was established and a questionnaire was designed. A survey of 16 experts from 6 different provinces, cities and regions in China was conducted, and the Delphi technique was used to collect and analyze expert opinions data. RESULTS: The final scale consisted of 4 dimensions and 23 items. The response rates in two rounds of expert consultation were 80% and 93.75%, respectively, with authority coefficients of 0.928 and 0.930. Variation coefficients varied from 0.07 to 0.21. Dimensions included "attitude towards behavior", "subjective norm", "perceived behavioral control" and "behavioral intention". CONCLUSIONS: Women's cervical cancer screening intentions could be assessed with the scale, since it had high validity and reliability, as well as high authority and coordination, meanwhile affording explanations and improving the efficiency of interventions.


Asunto(s)
Detección Precoz del Cáncer , Neoplasias del Cuello Uterino , Femenino , Humanos , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/prevención & control , Teoría del Comportamiento Planificado , Técnica Delphi , Pueblos del Este de Asia , Reproducibilidad de los Resultados , Teoría Psicológica , Intención , Encuestas y Cuestionarios
17.
Front Immunol ; 13: 1051998, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36439106

RESUMEN

With cancer incidence rates continuing to increase and occurrence of resistance in drug treatment, there is a pressing demand to find safer and more effective anticancer strategy for cancer patients. Natural products, have the advantage of low toxicity and multiple action targets, are always used in the treatment of cancer prevention in early stage and cancer supplement in late stage. Tumor microenvironment is necessary for cancer cells to survive and progression, and immune activation is a vital means for the tumor microenvironment to eliminate cancer cells. A number of studies have found that various natural products could target and regulate immune cells such as T cells, macrophages, mast cells as well as inflammatory cytokines in the tumor microenvironment. Natural products tuning the tumor microenvironment via various mechanisms to activate the immune response have immeasurable potential for cancer immunotherapy. In this review, it highlights the research findings related to natural products regulating immune responses against cancer, especially reveals the possibility of utilizing natural products to remodel the tumor microenvironment to overcome drug resistance.


Asunto(s)
Productos Biológicos , Neoplasias , Humanos , Microambiente Tumoral , Productos Biológicos/farmacología , Productos Biológicos/uso terapéutico , Inmunoterapia , Resistencia a Medicamentos
18.
Clin Cosmet Investig Dermatol ; 15: 1979-1990, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36159202

RESUMEN

Objective: To summarise the clinical characteristics of patients with Stevens-Johnson syndrome/toxic epidermal necrolysis syndrome (SJS/TEN) and analyse the efficacy and safety of systemic glucocorticoid therapy. Methods: This study was a retrospective study of 56 patients with SJS/TEN who had been systematically treated with glucocorticoids in the dermatology ward of Peking University Third Hospital from 2010 to 2020. The clinical characteristics, treatment regimen, effects on underlying diseases, incidence and outcome of hormone-related adverse reactions and skin lesion prognosis were summarised and analysed for each patient. Results: ① The allergenic drugs were found to be antibiotics (31.51%), antipyretic and analgesics (21.92%), traditional Chinese medicines and health products (15.07%) and neuropsychiatric drugs (13.70%). ② Based on the 56 patients' scores of toxic epidermal necrosis at admission, the actual mortality rate was 1.8% (1/56), which was significantly lower than the average expected mortality rate of 15.0% (P = 0.032; standardised mortality ratio = 0.13; 95% confidence interval: 0.00-0.53). ③ A total of 33 patients (58.9%) had underlying diseases, of which 10 patients (30.3%) had underlying diseases that fluctuated during treatment but stabilised after symptomatic treatment. ④ During treatment, 73.2% (41/56) of patients had complications that may have been related to systemic glucocorticoids; 97.6% (40/41) had mild symptoms, and 92.7% (38/41) had improved/recovered complications at the time of discharge. Conclusion: ① Antibiotics are still the most common sensitising drugs, and traditional Chinese medicine and health products are also common sensitising drugs. ② Early systemic application of medium- to high-dose glucocorticoids is effective in the treatment of SJS/TEN, and it is beneficial in reducing mortality. ③ The short-term application of medium- to high-dose hormone therapy for SJS/TEN has little effect on underlying diseases. The related complications are mostly mild, and the treatment is safe.

19.
Molecules ; 27(11)2022 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-35684574

RESUMEN

This work aimed to develop and evaluate a post-acquisition data processing strategy, referred to as a mass defect filter (MDF), for rapid target the resin glycosides in root of Convolvulus scammonia by setting mass rang and mass defect range from high-resolution MS data. The full-scan mass data were acquired by high-performance liquid chromatography coupled with Q Exactive Plus hybrid quadrupole-orbitrap mass spectrometer that featured high resolution, mass accuracy, and sensitivity. To screen resin glycosides, three parent filter m/z 871, m/z 853, and m/z 869 combined with diagnostic fragment ions (DFIs) approach were applied to remove the interference from complex herbal extract. The targeted components were characterized based on detailed fragment ions. Using this approach, 80 targeted components, including 22 glycosidic acids and 58 resin glycosides were tentatively identified. The present results suggested that the proposed MDF strategy would be adaptable to the analysis of complex system in relevant filed.


Asunto(s)
Convolvulus , Glicósidos , Cromatografía Líquida de Alta Presión/métodos , Glicósidos/química , Iones , Espectrometría de Masas/métodos , Resinas de Plantas
20.
Sci Total Environ ; 836: 155670, 2022 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-35523353

RESUMEN

Hierarchically porous iron/nitrogen-doped carbons (Fe-N-PC) were developed for the oxidation of ibuprofen (IBP) with peroxymonosulfate (PMS). The incorporation of trace-level iron and nitrogen dopants promoted the catalytic performance remarkably, leading to 4.8, 16.4 and 22.9-fold enhancement over N-doped carbon (N-PC), porous carbon (PC), and Fe-doped carbon (Fe-PC), respectively. Fe(III) was anchored in nitrogen-coordinated pots (Fe-Nx) in the sp2-hybridized carbon network, and graphitic-N could synergistically boost the catalysis. Notably, methyl phenyl sulfoxide (PMSO) transformation, quenching tests, in situ electrochemical analysis and Raman spectroscopy verified high-valent iron-oxo species and direct electron transfer pathway accounted for pollutant oxidation. The relationship between the kinetic constants (lnkobs) and the oxidation peak potential (Eop) of pollutants was established with good correlation, manifesting particular selectivity toward oxidizing electron-rich pollutants and great immunity to background inorganic ions and natural organic matters (NOMs) for real wastewater treatment. The deactivation mechanisms of Fe-N-PC were revealed via surface oxidation and dopant refabrication. This work delicates to deepen the understanding of the nonradical mechanisms and structure-oriented PMS activation by engineered carbonaceous materials.


Asunto(s)
Contaminantes Ambientales , Hierro , Carbono , Nitrógeno , Oxidación-Reducción , Peróxidos , Porosidad
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