Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.278
Filtrar
1.
CNS Neurosci Ther ; 30(7): e14829, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38961264

RESUMEN

AIMS: Paclitaxel (PTX) is extensively utilized in the management of diverse solid tumors, frequently resulting in paclitaxel-induced peripheral neuropathy (PIPN). The present study aimed to investigate sex differences in the behavioral manifestations and underlying pathogenesis of PIPN and search for clinically efficacious interventions. METHODS: Male and female C57BL/6 mice (5-6 weeks and 12 months, weighing 18-30 g) were intraperitoneally (i.p.) administered paclitaxel diluted in saline (NaCl 0.9%) at a dose of 2 mg/kg every other day for a total of 4 injections. Von Frey and hot plate tests were performed before and after administration to confirm the successful establishment of the PIPN model and also to evaluate the pain of PIPN and the analgesic effect of PD-L1. On day 14 after PTX administration, PD-L1 protein (10 ng/pc) was injected into the PIPN via the intrathecal (i.t.) route. To knock down TRPV1 in the spinal cord, adeno-associated virus 9 (AAV9)-Trpv1-RNAi (5 µL, 1 × 1013 vg/mL) was slowly injected via the i.t. route. Four weeks after AAV9 delivery, the downregulation of TRPV1 expression was verified by immunofluorescence staining and Western blotting. The levels of PD-L1, TRPV1 and CGRP were measured via Western blotting, RT-PCR, and immunofluorescence staining. The levels of TNF-α and IL-1ß were measured via RT-PCR. RESULTS: TRPV1 and CGRP protein and mRNA levels were higher in the spinal cords of control female mice than in those of control male mice. PTX-induced nociceptive behaviors in female PIPN mice were greater than those in male PIPN mice, as indicated by increased expression of TRPV1 and CGRP. The analgesic effects of PD-L1 on mechanical hyperalgesia and thermal sensitivity were significantly greater in female mice than in male mice, with calculated relative therapeutic levels increasing by approximately 2.717-fold and 2.303-fold, respectively. PD-L1 and CGRP were partly co-localized with TRPV1 in the dorsal horn of the mouse spinal cord. The analgesic effect of PD-L1 in PIPN mice was observed to be mediated through the downregulation of TRPV1 and CGRP expression following AAV9-mediated spinal cord specific decreased TRPV1 expression. CONCLUSIONS: PTX-induced nociceptive behaviors and the analgesic effect of PD-L1 in PIPN mice were sexually dimorphic, highlighting the significance of incorporating sex as a crucial biological factor in forthcoming mechanistic studies of PIPN and providing insights for potential sex-specific therapeutic approaches.


Asunto(s)
Antígeno B7-H1 , Péptido Relacionado con Gen de Calcitonina , Ratones Endogámicos C57BL , Paclitaxel , Enfermedades del Sistema Nervioso Periférico , Caracteres Sexuales , Canales Catiónicos TRPV , Animales , Paclitaxel/toxicidad , Masculino , Femenino , Ratones , Péptido Relacionado con Gen de Calcitonina/metabolismo , Canales Catiónicos TRPV/metabolismo , Canales Catiónicos TRPV/antagonistas & inhibidores , Antígeno B7-H1/metabolismo , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Antineoplásicos Fitogénicos/toxicidad , Médula Espinal/efectos de los fármacos , Médula Espinal/metabolismo , Hiperalgesia/inducido químicamente , Hiperalgesia/tratamiento farmacológico , Hiperalgesia/metabolismo
2.
Chem Sci ; 15(26): 10214-10220, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38966364

RESUMEN

Selective recognition and enrichment of fullerenes (e.g., C60 and C70) remains challenging due to the same diameter and geometrical similarity. Herein, we report a hexagonal anthracene-based nanotube (1) through a one-pot Suzuki-Miyaura cross-coupling reaction. With anthracene-based side walls and pyridine linkers, 1 features a nano-scale tubular cavity measuring 1.2 nm in diameter and 0.9 nm in depth, along with pH-responsive properties. Interestingly, the electron-rich 1 shows high binding affinity (K a ≈ 106 M-1) and selectivity (K s ≈ 140) to C70 over C60 in toluene, resulting from their different contribution of π-π interactions with the host. The protonation of 1 simultaneously alters the electronic properties within the nanotube, resulting in the release of the fullerene guests. Lastly, the selective recognition and pH stimuli-responsive properties of the nanotube have been utilized to enrich C70 from its low-content mixtures of fullerenes in chloroform.

3.
Chem Commun (Camb) ; 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38979947

RESUMEN

This report describes a copper-catalyzed, photoinduced N-to-alkyl radical relay Sonogashira-type reactions at benzylic sites in o-alkylbenzamides with alkynes. The process employs an N-to-alkyl radical mechanism, initiated through the copper-catalyzed reductive generation of nitrogen radicals. Radical translocation is facilitated by a 1,5-hydrogen atom transfer (1,5-HAT), leading to the formation of translocated carbon radicals. These radicals are then subjected to copper-catalyzed alkynylation. The methodology exhibits broad sub-strate scope and applicability to the synthesis of complex natural products.

4.
Toxicol Rep ; 13: 101682, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39006370

RESUMEN

A traditional Chinese herbal medicine formula named Huang-Lian-Jie-Du Decoction (HLJDD) has been used to cure various inflammatory diseases with a long history. However, one component of HLJDD Gardeniae fructus has remarkable liver and kidney toxicities. Therefore, it was altered with Dictamni cortex to form a modified HLJDD (MHLJDD). In this study, we aimed to evaluate the sub-chronic toxicity of the active fraction of MHLJDD (MHLJDD-F) in rats. Adult rats of both sexes were intragastrically administered with vehicle or MHLJDD-F (at the dose of 170, 340, and 680 mg/kg/day) once daily for 90 days. Half of the rats from each group were kept for an additional 30-day period to observe the drug withdrawal effect. The signs of toxicity and mortality of the rats were observed, and the body weight and food consumption were recorded. Blood was collected for hematological and biochemical analyses and major organs were weighed and harvested for histopathological examinations. The results revealed that no systemic toxicity of MHLJDD-F was found during the experiments. Organ coefficients and pathological alterations of major organs were comparable to the control rats. The no-observed adverse effect level (NOAEL) of MHLJDD-F was found up to 680 mg/kg/day. All these results demonstrated that long-term oral administration of MHLJDD-F did not cause significant toxicity, which is worthy to be widely applied as a new herbal medicine in pre-clinical and clinical studies.

5.
Mil Med Res ; 11(1): 46, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38992778

RESUMEN

BACKGROUND: Subarachnoid hemorrhage (SAH) is a subtype of hemorrhagic stroke characterized by high mortality and low rates of full recovery. This study aimed to investigate the epidemiological characteristics of SAH between 1990 and 2021. METHODS: Data on SAH incidence, mortality, and disability-adjusted life-years (DALYs) from 1990 to 2021 were obtained from the Global Burden of Disease Study (GBD) 2021. Estimated annual percentage changes (EAPCs) were calculated to evaluate changes in the age-standardized rate (ASR) of incidence and mortality, as well as trends in SAH burden. The relationship between disease burden and sociodemographic index (SDI) was also analyzed. RESULTS: In 2021, the incidence of SAH was found to be 37.09% higher than that in 1990; however, the age-standardized incidence rates (ASIRs) showed a decreased [EAPC: -1.52; 95% uncertainty interval (UI) -1.66 to -1.37]. Furthermore, both the number and rates of deaths and DALYs decreased over time. It was observed that females had lower rates compared to males. Among all regions, the high-income Asia Pacific region exhibited the highest ASIR (14.09/100,000; 95% UI 12.30/100,000 - 16.39/100,000) in 2021, with an EPAC for ASIR < 0 indicating decreasing trend over time for SAH ASIR. Oceania recorded the highest age-standardized mortality rates (ASMRs) and age-standardized DALYs rates among all regions in 2021 at values of respectively 8.61 (95% UI 6.03 - 11.95) and 285.62 (95% UI 209.42 - 379.65). The burden associated with SAH primarily affected individuals aged between 50 - 69 years old. Metabolic risks particularly elevated systolic blood pressure were identified as the main risk factors contributing towards increased disease burden associated with SAH when compared against environmental or occupational behavioral risks evaluated within the GBD framework. CONCLUSIONS: The burden of SAH varies by gender, age group, and geographical region. Although the ASRs have shown a decline over time, the burden of SAH remains significant, especially in regions with middle and low-middle SDI levels. High systolic blood pressure stands out as a key risk factor for SAH. More specific supportive measures are necessary to alleviate the global burden of SAH.


Asunto(s)
Carga Global de Enfermedades , Hemorragia Subaracnoidea , Humanos , Hemorragia Subaracnoidea/epidemiología , Masculino , Femenino , Incidencia , Persona de Mediana Edad , Anciano , Adulto , Carga Global de Enfermedades/tendencias , Años de Vida Ajustados por Discapacidad/tendencias , Salud Global/estadística & datos numéricos , Anciano de 80 o más Años
6.
J Am Chem Soc ; 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39020477

RESUMEN

Realizating of a low work function (WF) and room-temperature stability in electrides is highly desired for various applications, such as electron emitters, catalysts, and ion batteries. Herein, a criterion based on the electron localization function (ELF) and projected density of states (PDOS) in the vacancy of the oxide electride [Ca24Al28O64]4+(4e-) (C12A7) was adopted to screen out 13 electrides in single-metal oxides. By creating oxygen vacancies in nonelectride oxides, we find out 9 of them showed vacancy-induced anionic electrons. Considering the thermodynamic stability, two electrides with ordered vacancies, Nb3O3 and Ce4O3, stand out and show vacancy-induced zero-dimensional anionic electrons. Both exhibit low WFs, namely 3.1 and 2.3 eV for Nb3O3 and Ce4O3, respectively. In the case of Nb3O3, the ELF at oxygen vacancies decreases first and then increases during the decrease in the total number of electrons in self-consistent calculations due to Nb's multivalent state. Meanwhile, Ce4O3 displays promise for ammonia synthesis due to its low hydrogen diffusion barrier and low activation energy. Further calculations revealed that CeO with disordered vacancies at low concentrations also exhibits electride-like properties, suggesting its potential as a substitute for Ce4O3.

7.
Mol Nutr Food Res ; : e2400010, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38958100

RESUMEN

SCOPE: Celiac disease (CD) is an allergic intestinal disease caused mainly by gliadin in wheat, which is widespread in the population and currently lacks effective treatment. α-Gliadin peptides cause cellular damage by substantially increasing cellular reactive oxygen species (ROS) levels. METHODS AND RESULTS: This study investigates the protective effect of 11 pea-derived peptides (PPs) on ɑ-gliadin peptide (P31-43) treated Caco-2 cells. Results show that cells treated with PP2, PP5, and PP6 peptides significantly reduce the cell mortality caused by P31-43. Three PPs significantly reduce the P31-43-induced decrease in ROS levels to control levels, and there is no difference between them and the vitamin C (Vc) group. The results in terms of antioxidant-related enzymes show that PPs significantly decrease superoxide dismutase activity (SOD), glutathione reductases (GR), and glutathione (GSH)/oxidized glutathione (GSSG) levels, thus significantly enhancing the antioxidant level of cells. By studying the key proteins of the Kelch-like ECH-associated protein 1 (Keap1)/NF-E2-related factor 2 (Nrf2) pathway, it is found that PPs activate the Keap1/Nrf2 signaling pathway. CONCLUSION: The study finds that peptides from peas can effectively alleviate ɑ-gliadin peptide-induced cell damage. The discovery of these food-derived peptides provides novel potential solutions for the prevention and treatment of CD.

8.
J Affect Disord ; 362: 308-316, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38971193

RESUMEN

BACKGROUND: The bidirectional relationships between metabolic syndrome (MetS) and major depressive disorder (MDD) were discovered, but the influencing factors of the comorbidity were barely investigated. We aimed to fully explore the factors and their associations with MetS in MDD patients. METHODS: The data were retrieved from the electronic medical records of a tertiary psychiatric hospital in Beijing from 2016 to 2021. The influencing factors were firstly explored by univariate analysis and multivariate logistic regressions. The propensity score matching was used to reduce the selection bias of participants. Then, the Bayesian networks (BNs) with hill-climbing algorithm and maximum likelihood estimation were preformed to explore the relationships between influencing factors with MetS in MDD patients. RESULTS: Totally, 4126 eligible subjects were included in the data analysis. The proportion rate of MetS was 32.6 % (95 % CI: 31.2 %-34.1 %). The multivariate logistic regression suggested that recurrent depression, uric acid, duration of depression, marriage, education, number of hospitalizations were significantly associated with MetS. In the BNs, number of hospitalizations and uric acid were directly connected with MetS. Recurrent depression and family history psychiatric diseases were indirectly connected with MetS. The conditional probability of MetS in MDD patients with family history of psychiatric diseases, recurrent depression and two or more times of hospitalizations was 37.6 %. CONCLUSION: Using the BNs, we found that number of hospitalizations, recurrent depression and family history of psychiatric diseases contributed to the probability of MetS, which could help to make health strategies for specific MDD patients.

9.
World J Clin Cases ; 12(20): 4419-4426, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39015931

RESUMEN

BACKGROUND: On June 30, 2021, China received certification from the World Health Organization for malaria elimination. However, this certification does not signify the absence of malaria within China. Due to the increasing frequency of international exchanges and collaborations, the threat of imported malaria persists in China. Consequently, the prevention and control of imported malaria have become a primary focus for our country to maintain its malaria elimination status. CASE SUMMARY: Herein, we present a case report of a 53-year-old Chinese man who worked in Africa for nearly two years. He was diagnosed with malaria in the Democratic Republic of the Congo between November 19 and November 23, 2022. After receiving effective treatment with oral antimalarial drugs, his condition improved, allowing him to return to China. He was later admitted to our hospital on January 12, 2023, during the coronavirus disease 2019 pandemic in Huangshi, China. Through a thorough evaluation of the patient's symptoms, clinical signs, imaging and laboratory test results, and epidemiological data, he was rapidly diagnosed with severe cerebral malaria. The patient underwent successful treatment through a series of intensive care unit interventions. CONCLUSION: The successful treatment of this imported case of severe cerebral malaria provides a valuable reference for managing patients with similar malaria infections and has significant clinical implications.

10.
BMJ ; 385: e077890, 2024 06 19.
Artículo en Inglés | MEDLINE | ID: mdl-38897625

RESUMEN

OBJECTIVE: To compare the effectiveness and safety of nab-paclitaxel, cisplatin, and capecitabine (nab-TPC) with gemcitabine and cisplatin as an alternative first line treatment option for recurrent or metastatic nasopharyngeal carcinoma. DESIGN: Phase 3, open label, multicentre, randomised trial. SETTING: Four hospitals located in China between September 2019 and August 2022. PARTICIPANTS: Adults (≥18 years) with recurrent or metastatic nasopharyngeal carcinoma. INTERVENTIONS: Patients were randomised in a 1:1 ratio to treatment with either nab-paclitaxel (200 g/m2 on day 1), cisplatin (60 mg/m2 on day 1), and capecitabine (1000 mg/m2 twice on days 1-14) or gemcitabine (1 g/m2 on days 1 and 8) and cisplatin (80 mg/m2 on day 1). MAIN OUTCOME MEASURES: Progression-free survival was evaluated by the independent review committee as the primary endpoint in the intention-to-treat population. RESULTS: The median follow-up was 15.8 months in the prespecified interim analysis (31 October 2022). As assessed by the independent review committee, the median progression-free survival was 11.3 (95% confidence interval 9.7 to 12.9) months in the nab-TPC cohort compared with 7.7 (6.5 to 9.0) months in the gemcitabine and cisplatin cohort. The hazard ratio was 0.43 (95% confidence interval 0.25 to 0.73; P=0.002). The objective response rate in the nab-TPC cohort was 83% (34/41) versus 63% (25/40) in the gemcitabine and cisplatin cohort (P=0.05), and the duration of response was 10.8 months in the nab-TPC cohort compared with 6.9 months in the gemcitabine and cisplatin cohort (P=0.009). Treatment related grade 3 or 4 adverse events, including leukopenia (4/41 (10%) v 13/40 (33%); P=0.02), neutropenia (6/41 (15%) v 16/40 (40%); P=0.01), and anaemia (1/41 (2%) v 8/40 (20%); P=0.01), were higher in the gemcitabine and cisplatin cohort than in the nab-TPC cohort. No deaths related to treatment occurred in either treatment group. Survival and long term toxicity are still being evaluated with longer follow-up. CONCLUSION: The nab-TPC regimen showed a superior antitumoural efficacy and favourable safety profile compared with gemcitabine and cisplatin for recurrent or metastatic nasopharyngeal carcinoma. Nab-TPC should be considered the standard first line treatment for recurrent or metastatic nasopharyngeal carcinoma. Longer follow-up is needed to confirm the benefits for overall survival. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900027112.


Asunto(s)
Albúminas , Protocolos de Quimioterapia Combinada Antineoplásica , Capecitabina , Cisplatino , Desoxicitidina , Gemcitabina , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Recurrencia Local de Neoplasia , Paclitaxel , Humanos , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Cisplatino/efectos adversos , Masculino , Persona de Mediana Edad , Femenino , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/mortalidad , Desoxicitidina/análogos & derivados , Desoxicitidina/administración & dosificación , Desoxicitidina/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Capecitabina/uso terapéutico , Capecitabina/administración & dosificación , Adulto , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/mortalidad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico , Paclitaxel/efectos adversos , Albúminas/administración & dosificación , Albúminas/efectos adversos , Albúminas/uso terapéutico , Anciano , Supervivencia sin Progresión , China , Metástasis de la Neoplasia
11.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(3): 693-701, 2024 Jun.
Artículo en Chino | MEDLINE | ID: mdl-38926955

RESUMEN

OBJECTIVE: To analyze the factors affecting overall survival (OS) of adult patients with core-binding factor acute myeloid leukemia (CBF-AML) and establish a prediction model. METHODS: A total of 216 newly diagnosed patients with CBF-AML in the First Affiliated Hospital of Zhengzhou University from May 2015 to July 2021 were retrospectively analyzed. The 216 CBF-AML patients were divided into the training and the validation cohort at 7∶3 ratio. The Cox regression model was used to analyze the clinical factors affecting OS. Stepwise regression was used to establish the optimal model and the nomogram. Receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) were used to evaluate the model performance. RESULTS: Age(≥55 years old), peripheral blood blast(≥80%), fusion gene (AML1-ETO), KIT mutations were identified as independent adverse factors for OS. The area under the ROC curve at 3-year was 0.772 and 0.722 in the training cohort and validation cohort, respectively. The predicted value of the calibration curve is in good agreement with the measured value. DCA shows that this model performs better than a single factor. CONCLUSION: This prediction model is simple and feasible, and can effectively predict the OS of CBF-AML, and provide a basis for treatment decision.


Asunto(s)
Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/diagnóstico , Pronóstico , Estudios Retrospectivos , Persona de Mediana Edad , Femenino , Masculino , Mutación , Curva ROC , Factores de Unión al Sitio Principal/genética , Nomogramas , Adulto , Proteína 1 Compañera de Translocación de RUNX1/genética , Proteínas Proto-Oncogénicas c-kit/genética , Modelos de Riesgos Proporcionales , Proteínas de Fusión Oncogénica/genética , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética
12.
Biomed Chromatogr ; 38(8): e5922, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38867488

RESUMEN

This study aims to explore the pharmacological substance basis of Qi Ge Decoction (QG) in antihyperlipidemia through a combination of metabolomics and serum pharmacochemistry. We used ultra-performance liquid chromatography quadrupole-time-of-flight/MS (UPLC Q-TOF/MS) to analyze and identify the chemical constituents of QG in vitro and in blood chemical components. The metabolomics technology was used to analyze serum biomarkers of QG in preventing and treating hyperlipidemia. We constructed a mathematical model of the relationship between constituents absorbed into the blood and endogenous biomarkers and explored the potential therapeutic application of QG for the prevention and treatment of hyperlipidemia. Compared with the model group, the levels of total cholesterol and triglyceride in the QG group were significantly decreased (P < 0.01). A total of 12 chemical components absorbed into the blood were identified, and 48 biomarkers of the hyperlipidemia model were obtained from serum metabolomic analysis, of which 15 metabolites were backregulated after QG intervention. Puerarin, hesperetin, puerarin xyloside, calycosin, and monohydroxy-tetramethoxyflavone had a high correlation with the biomarkers regulated by QG. This study elucidated the material basis of QG in the intervention of hyperlipidemia, thereby facilitating future research aimed at further revealing the pharmacodynamic material basis of QG's antihyperlipidemic effects.


Asunto(s)
Medicamentos Herbarios Chinos , Hiperlipidemias , Hipolipemiantes , Metabolómica , Metabolómica/métodos , Hipolipemiantes/sangre , Hipolipemiantes/farmacocinética , Hipolipemiantes/química , Cromatografía Líquida de Alta Presión/métodos , Animales , Hiperlipidemias/tratamiento farmacológico , Hiperlipidemias/sangre , Masculino , Biomarcadores/sangre , Ratas , Metaboloma/efectos de los fármacos , Ratas Sprague-Dawley , Espectrometría de Masas/métodos
13.
J Autoimmun ; 147: 103278, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38943864

RESUMEN

Immune checkpoints are essential regulators of immune responses, either by activating or suppressing them. Consequently, they are regarded as pivotal elements in the management of infections, cancer, and autoimmune disorders. In recent years, researchers have identified numerous soluble immune checkpoints that are produced through various mechanisms and demonstrated biological activity. These soluble immune checkpoints can be produced and distributed in the bloodstream and various tissues, with their roles in immune response dysregulation and autoimmunity extensively documented. This review aims to provide a thorough overview of the generation of various soluble immune checkpoints, such as sPD-1, sCTLA-4, sTim-3, s4-1BB, sBTLA, sLAG-3, sCD200, and the B7 family, and their importance as indicators for the diagnosis and prediction of autoimmune conditions. Furthermore, the review will investigate the potential pathological mechanisms of soluble immune checkpoints in autoimmune diseases, emphasizing their association with autoimmune diseases development, prognosis, and treatment.


Asunto(s)
Enfermedades Autoinmunes , Proteínas de Punto de Control Inmunitario , Humanos , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/diagnóstico , Proteínas de Punto de Control Inmunitario/metabolismo , Proteínas de Punto de Control Inmunitario/genética , Biomarcadores , Animales , Autoinmunidad , Pronóstico , Susceptibilidad a Enfermedades/inmunología
15.
Neuro Oncol ; 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38864832

RESUMEN

BACKGROUND: Super-enhancers (SEs) typically govern the expression of critical oncogenes and play a fundamental role in the initiation and progression of cancer. Focusing on genes that are abnormally regulated by SE in cancer may be a new strategy for understanding pathogenesis. In the context of this investigation, we have identified a previously unreported SE-driven gene IRF2BP2 in neuroblastoma (NB). METHODS: The expression and prognostic value of IRF2BP2 were detected in public databases and clinical samples. The effect of IRF2BP2 on NB cell growth and apoptosis was evaluated through in vivo and in vitro functional loss experiments. The molecular mechanism of IRF2BP2 was investigated by the study of chromatin regulatory regions and transcriptome sequencing. RESULTS: The sustained high expression of IRF2BP2 results from the activation of a novel SE established by NB master transcription factors MYCN, MEIS2 and HAND2, and they form a new complex that regulates the gene network associated with the proliferation of NB cell populations. We also observed a significant enrichment of the AP-1 family at the binding sites of IRF2BP2. Remarkably, within NB cells, AP-1 plays a pivotal role in shaping the chromatin accessibility landscape, thereby exposing the binding site for IRF2BP2. This orchestrated action enables AP-1 and IRF2BP2 to collaboratively stimulate the expression of the NB susceptibility gene ALK, thereby upholding the highly proliferative phenotype characteristic of NB. CONCLUSION: Our findings indicate that SE-driven IRF2BP2 can bind to AP-1 to maintain the survival of tumor cells via regulating chromatin accessibility of NB susceptibility gene ALK.

17.
Acta Diabetol ; 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38888635

RESUMEN

AIMS: To offer a holistic view of the personal, external, and psychological factors influencing adherence to nutrition and diet in patients undergoing metabolic/bariatric surgery. METHODS: This systematic synthesis of mixed methods research involved a comprehensive search for articles in English databases, including PubMed, Cochrane Library, Web of Science, EBSCO, Scopus, and Embase, as well as Chinese databases. The search encompassed articles published from the inception of the database up to June 2023. Following the evaluation of literature quality and extraction of relevant information from the selected studies, data from both quantitative and qualitative studies were integrated. The extracted data were analyzed separately, and themes were identified and summarized to elucidate the factors influencing adherence to nutritional and dietary guidelines. The methodology adhered to the guidelines recommended by the Joanna Briggs Institute (JBI) for mixed methods systematic evaluations. RESULTS: Three themes and their corresponding descriptive elements were identified, including: (1) Personal factors: subjective factors (attitude, capability, awareness, behaviors), objective factors (age, sex, work status, economic level, physical activity, dietary habits, weight change); (2) External factors: medication (quantity of pills, complexity of intake times, side effects, unpleasant smell or taste), surgery factor, social influences (family members, dietitians, and peers); (3) Psychological factors: self-efficacy, attachment anxiety, and mental health problems. CONCLUSIONS: The synthesis provided a comprehensive overview of the factors influencing postoperative compliance of nutrition and diet among patients undergoing metabolic and bariatric surgery. It emphasizes the necessity for clinical staff to tailor interventions based on these diverse factors, as well as to attach importance to patients' mental health, giving multidimensional dietary guidance and health care.

18.
Org Lett ; 26(24): 5087-5091, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38864522

RESUMEN

Presented herein are two distinct regiodivergent [3+2] cyclization reactions between N-CF3 imidoyl chlorides and N-isocyaniminotriphenylphosphorane (NIITP) that include flexible modulation of the electronic properties of NIITP. The regioselectivity of reactions was different in the absence and presence of the Mo catalyst. The approach provides alternative efficient and scalable routes for N-CF3 triazole synthesis, demonstrating a broad substrate scope, excellent functional group tolerance, and practical advantages.

19.
Biomed Pharmacother ; 177: 116977, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38901203

RESUMEN

BACKGROUND: Pancreatic cancer (PanCa), ranked as the 4th leading cause of cancer-related death worldwide, exhibits an dismal 5-year survival rate of less than 5 %. Chronic pancreatitis (CP) is a known major risk factor for PanCa. Brusatol (BRT) possesses a wide range of biological functions, including the inhibition of PanCa proliferation. However, its efficacy in halting the progression from CP to pancreatic carcinogenesis remains unexplored. METHODS: We assess the effects of BRT against pancreatic carcinogenesis from CP using an experimentally induced CP model with cerulein, and further evaluate the therapeutic efficacy of BRT on PanCa by employing Krastm4TyjTrp53tm1BrnTg (Pdx1-cre/Esr1*) #Dam/J (KPC) mouse model. RESULTS: Our finding demonstrated that BRT mitigated the severity of cerulein-induced pancreatitis, reduced pancreatic fibrosis and decreased the expression of α-smooth muscle actin (α-SMA), which is a biomarker for pancreatic fibrosis. In addition, BRT exerted effects against cerulein-induced pancreatitis via inactivation of NLRP3 inflammasome. Moreover, BRT significantly inhibited tumor growth and impeded cancer progression. CONCLUSIONS: The observed effect of BRT on impeding pancreatic carcinogenesis through targeting NLRP3 inflammasome suggests its good potential as a potential agent for treatment of PanCa.

20.
Foods ; 13(11)2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38890863

RESUMEN

The adsorption characteristics of ß-glucooligosaccharides on activated carbon and the purification were systematically investigated. The maximum adsorption capacity of activated carbon reached 0.419 g/g in the optimal conditions. The adsorption behavior was described to be monolayer, spontaneous, and exothermic based on several models' fitting results. Five fractions with different degrees of polymerization (DPs) and structures of ß-glucooligosaccharides were obtained by gradient ethanol elution. 10E mainly contained disaccharides with dp2a (G1→6G) and dp2b (G1→3G). 20E possessed trisaccharides with dp3a (G1→6G1→3G) and dp3b (G1→3G1→3G). 30E mainly consisted of dp3a and dp4a (G1→3G1→3(G1→6)G), dp4b (G1→6G1→3G1→3G), and dp4c (G1→3G1→3G1→3G). In addition to tetrasaccharides, 40E and 50E also contained pentasaccharides and hexasaccharides with ß-(1→3)-linked or ß-(1→6)-linked glucose residues. All fractions could inhibit the accumulation of intracellular reactive oxygen species (ROS) in H2O2-induced Caco-2 cells, and they could improve oxidative stress damage by increasing the activity of superoxide dismutase (SOD) and reduced glutathione (GSH), which were related to their DPs and structures. 50E with high DPs showed better anti-oxidative stress activity.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...