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1.
Int J Biol Macromol ; 279(Pt 2): 135169, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39218172

RESUMEN

Replacing fossil resource with biomass is one of the promising approaches to reduce our carbon footprint. Lignin is one of the three major components of lignocellulosic biomass, accounting for 10-35 wt% of dried weight of the biomass. Hydrogenolytic depolymerization of lignin is attracting increasing attention because of its capacity of utilizing lignin in its uncondensed form and compatibility with the biomass fractionation processes. Lignin is a natural aromatic polymer composed of a variety of monolignols associated with a series of lignin linkage motifs. Hydrogenolysis cleaves various ether bonds in lignin and releases phenolic monomers which can be further upgraded into valuable products, i.e., drugs, terephthalic acid, phenol. This review provides an overview of the state-of-the-art advances of the reagent (lignin), products (hydrol lignin), mass balance, and mechanism of the lignin hydrogenolysis reaction. The chemical structure of lignin is reviewed associated with the free radical coupling of monolignols and the chemical reactions of lignin upon isolation processes. The reactions of lignin linkages upon hydrogenolysis are discussed. The components of hydrol lignin and the selectivity production of phenolic monomers are reviewed. Future challenges on hydrogenolysis of lignin are proposed. This article provides an overview of lignin hydrogenolysis reaction which shows light on the generation of optimized lignin ready for hydrogenolytic depolymerization.

2.
Dalton Trans ; 53(36): 15048-15058, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39206556

RESUMEN

Exploring charge transfer channels in the Z-scheme heterojunction is an essential challenge. A strategy to precisely connect g-C3N4 with SrTiO3 through sharing N atoms was developed to create a chemically bonded Z-scheme heterojunction photocatalyst (STON/CNx). By sharing the N atoms, not only was the activity of the photocatalytic reduction of CO2 greatly improved, but the selectivity of the product was also changed. The CH4 product rate over optimal STON/CNx was 102.4 µmol g-1 h-1, with a 98.9% product selectivity. Both characterization and theoretical calculations indicate that N atoms tightly connect the heterostructures and serve as a channel for electron transport, facilitating the transfer of photogenerated electrons. This research lays a way for creating a sharing atoms' Z-scheme interface, providing the potential for exciting future photocatalytic applications.

3.
Biomed Chromatogr ; : e5989, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39171645

RESUMEN

Epilepsy (EP) is one of the most common neurological diseases in the world. Anemarrhena asphodeloides Bunge. (AA), as a typical heat-cleaning medicine, has been proven to possess the antiepileptic effect in clinical and experimental studies. Anemarrhena asphodeloides steroidal saponins (AAS) are main components. However, the therapeutic effects and underlying mechanisms of AAS against EP are not been fully elucidated. In this study, 63 steroidal saponins were discovered in AAS by UPLC-Q-TOF/MS analysis. Pharmacological and behavioral analysis demonstrated that AAS could significantly lower the Racine classification and reduce the frequency of generalized spike rhythm the rate of tetanic seizures in kainic acid-induced epileptic rats. Hematoxylin and eosin and Nissl staining-indicated AAS could significantly improve hippocampal injury and neuron loss in epileptic rats. TMT proteomic analysis discovered 26 different expressed proteins (DEPs), which were identified as the rescue proteins. After bioinformatic analysis, Heat Shock Protein 90 Alpha Family Class B Member 1 (Hsp90ab1) and Tyrosine 3-Monooxygenase (Ywhab) were screened as key DEPs and verified by western blotting. AAS could significantly inhibited the up-regulation of Hsp90ab1 and Ywhab in EP rats; these two proteins might be the key targets of AAS in treating EP.

4.
Fundam Res ; 4(4): 951-960, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39156576

RESUMEN

We consider the scheduling of battery charging of electric vehicles (EVs) integrated with renewable power generation. The increasing adoption of EVs and the development of renewable energies contribute importance to this research. The optimization of charging scheduling is challenging because of the large action space, the multi-stage decision making, and the high uncertainty. To solve this problem is time-consuming when the scale of the system is large. It is urgent to develop a practical and efficient method to properly schedule the charging of EVs. The contribution of this work is threefold. First, we provide a sufficient condition on which the charging of EVs can be completely self-sustained by distributed generation. An algorithm is proposed to obtain the optimal charging policy when the sufficient condition holds. Second, the scenario when the supply of the renewable power generation is deficient is investigated. We prove that when the renewable generation is deterministic there exists an optimal policy which follows the modified least laxity and longer remaining processing time first (mLLLP) rule. Third, we provide an adaptive rule-based algorithm which obtains a near-optimal charging policy efficiently in general situations. We test the proposed algorithm by numerical experiments. The results show that it performs better than the other existing rule-based methods.

5.
World J Clin Cases ; 12(24): 5542-5548, 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39188610

RESUMEN

BACKGROUND: Tooth defects can cause elongation of occlusal teeth, leading to insufficient repair space. The combination of dental implant restoration and orthodontic treatment of oblique adjacent teeth has a significant therapeutic effect. AIM: To explore clinical efficacy, bone density, and follow-up of implant and orthodontic treatment for patients with inclined adjacent teeth. METHODS: In total, 98 patients with oblique adjacent teeth were randomly assigned to implant restoration combined with orthodontic treatment (group A, n = 49) or to receive implant restoration alone (group B, n = 49). Changes in alveolar ridge bone density and apical bone density were observed before and after treatment in the two groups. Changes in chewing function and language function were compared between the two groups of patients. Follow-up lasted for 12 mo after repair to observe any adverse reactions in the oral cavity. RESULTS: The clinical effective rates of group A and group B were 97.96% and 85.71%, respectively, with group A having a higher clinical effective rate than group B. After treatment, the bone density of the alveolar ridge and apical bone in both groups decreased compared to before treatment, while the chewing and language functions improved. The changes in various indicators in group A were more significant. After treatment, the satisfaction rate of group A (97.96%) was higher than that of group B (79.59%). The incidence of adverse reactions in group A (2.04%) was lower than that in group B (24.49%). CONCLUSION: The amalgamation of implant restoration and orthodontic treatment for adjacent tilted teeth demonstrates notable clinical efficacy, diminishes alveolar bone resorption, and fosters patient functional rehabilitation while exhibiting negligible adverse reactions.

6.
Acta Histochem ; 126(5-7): 152184, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39053176

RESUMEN

BACKGROUND: There is an urgent need for new treatments to solve hair loss problem. As mesenchymal stem cells were proved to have effects on promoting tissue repair and regeneration, in which the exosome plays a vital role, we aim to investigate the influence of umbilical cord mesenchymal stem cells exosome (UCMSC-Exos) on hair growth and its mechanism. METHODS: The hUCMSC-Exos were extracted by ultracentrifugation. Primary fibroblasts were cultured with or without hUCMSC-Exos and cell proliferation was evaluated by CCK-8 assay. C57BL/6 mice model of depilation-induced hair regrowth was treated with either hUCMSC-Exos (200 µg/mL) or PBS on one side of the dorsal back. Real time quantitative PCR, flow cytometry analysis, immunohistochemistry and Immunofluorescent staining were used to analyze the regulative effect of hUCMSC-Exos on hair follicle stem/progenitor cells and Wnt/ß-catenin pathway. RESULTS: The proliferation of fibroblasts incubated with hUCMSC-Exos at the concentration of 200 µg/mL was greater than other groups. Treatment with hUCMSC-Exos resulted in rapid reentry into anagen. Hair follicle stem/progenitor cell markers (K15, Lgr5, Lgr6, CD34 and Lrig1) and Wnt/ß-catenin pathway related factors (Wnt5, Lef1, Lrp5 and ß-catenin) were increased in hUCMSC-Exos-injected region. CONCLUSION: hUCMSC-Exos promote fibroblasts proliferation and accelerate mouse hair regrowth by upregulating hair follicle stem/progenitor cell and Wnt/ß-catenin pathway, which suggests potential therapeutic approaches for hair loss disorders.


Asunto(s)
Exosomas , Folículo Piloso , Células Madre Mesenquimatosas , Ratones Endogámicos C57BL , Cordón Umbilical , Animales , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Exosomas/metabolismo , Cordón Umbilical/citología , Humanos , Ratones , Folículo Piloso/citología , Folículo Piloso/metabolismo , Folículo Piloso/crecimiento & desarrollo , Proliferación Celular , Vía de Señalización Wnt , Cabello/crecimiento & desarrollo , Fibroblastos/metabolismo
7.
Adv Sci (Weinh) ; : e2403592, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39023171

RESUMEN

Endocrine-resistant ER+HER2- breast cancer (BC) is particularly aggressive and leads to poor clinical outcomes. Effective therapeutic strategies against endocrine-resistant BC remain elusive. Here, analysis of the RNA-sequencing data from ER+HER2- BC patients receiving neoadjuvant endocrine therapy and spatial transcriptomics analysis both show the downregulation of innate immune signaling sensing cytosolic DNA, which primarily occurs in endocrine-resistant BC cells, not immune cells. Indeed, compared with endocrine-sensitive BC cells, the activity of sensing cytosolic DNA through the cGAS-STING pathway is attenuated in endocrine-resistant BC cells. Screening of kinase inhibitor library show that this effect is mainly mediated by hyperactivation of AKT1 kinase, which binds to kinase domain of TBK1, preventing the formation of a trimeric complex TBK1/STING/IRF3. Notably, inactivation of cGAS-STING signaling forms a positive feedback loop with hyperactivated AKT1 to promote endocrine resistance, which is physiologically important and clinically relevant in patients with ER+HER2- BC. Blocking the positive feedback loop using the combination of an AKT1 inhibitor with a STING agonist results in the engagement of innate and adaptive immune signaling and impairs the growth of endocrine-resistant tumors in humanized mice models, providing a potential strategy for treating patients with endocrine-resistant BC.

8.
Ecol Evol ; 14(7): e11653, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38983705

RESUMEN

Cirsium japonicum contains a variety of medicinal components with good clinical efficacy. With the rapid changes in global climate, it is increasingly important to study the distribution of species habitats and the factors influencing their adaptability. Utilizing the MaxEnt model, we forecasted the present and future distribution regions of suitable habitats for C. japonicum under various climate scenarios. The outcome showed that under the current climate, the total suitable area of C. japonicum is 2,303,624 km2 and the highly suitable area is 79,117 km2. The distribution of C. japonicum is significantly influenced by key environmental factors such as temperature annual range, precipitation of the driest month, and precipitation of the wettest month. In light of future climate change, the suitable habitat for C. japonicum is anticipated to progressively relocate toward the western and northern regions, leading to an expansion in the total suitable area. These findings offer valuable insights into the conservation, sustainable utilization, and standardized cultivation of wild C. japonicum resources.

9.
Small ; : e2402141, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38953313

RESUMEN

Abdominal aortic aneurysm (AAA) represents a critical cardiovascular condition characterized by localized dilation of the abdominal aorta, carrying a significant risk of rupture and mortality. Current treatment options are limited, necessitating novel therapeutic approaches. This study investigates the potential of a pioneering nanodrug delivery system, RAP@PFB, in mitigating AAA progression. RAP@PFB integrates pentagalloyl glucose (PGG) and rapamycin (RAP) within a metal-organic-framework (MOF) structure through a facile assembly process, ensuring remarkable drug loading capacity and colloidal stability. The synergistic effects of PGG, a polyphenolic antioxidant, and RAP, an mTOR inhibitor, collectively regulate key players in AAA pathogenesis, such as macrophages and smooth muscle cells (SMCs). In macrophages, RAP@PFB efficiently scavenges various free radicals, suppresses inflammation, and promotes M1-to-M2 phenotype repolarization. In SMCs, it inhibits apoptosis and calcification, thereby stabilizing the extracellular matrix and reducing the risk of AAA rupture. Administered intravenously, RAP@PFB exhibits effective accumulation at the AAA site, demonstrating robust efficacy in reducing AAA progression through multiple mechanisms. Moreover, RAP@PFB demonstrates favorable biosafety profiles, supporting its potential translation into clinical applications for AAA therapy.

10.
J Intensive Care Med ; : 8850666241264231, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39043369

RESUMEN

BACKGROUND: Bicaval dual lumen cannula (DLC) is gaining popularity in veno-venous extracorporeal membrane oxygenation (V-V ECMO) for having less recirculation and facilitating mobilization. It is usually inserted under fluoroscopic or transesophageal echocardiographic guidance to prevent potentially fatal complications. Thus, their utilization was limited during the COVID-19 outbreak due to stringent quarantine policy and manpower shortage, especially when emergency insertion was required. PURPOSE: To describe our experience on DLC insertion using transthoracic echocardiography alone during the pandemic, with a focus on safety considerations by using detail step-by-step procedural guide. OUTCOME: Four patients were performed V-V ECMO using the transthoracic echocardiographic-guided DLC cannulation technique during the fifth wave of the COVID-19 outbreak, with no cannulation-related complications. CONCLUSION: Transthoracic echocardiographic guidance for DLC insertion is feasible and probably safe with a detailed guide, which can be adopted as a supplementary tool during future endemic outbreaks.

11.
Redox Biol ; 75: 103268, 2024 09.
Artículo en Inglés | MEDLINE | ID: mdl-39032396

RESUMEN

Intracerebral hemorrhage (ICH) is a prevalent hemorrhagic cerebrovascular emergency. Alleviating neurological damage in the early stages of ICH is critical for enhancing patient prognosis and survival rate. A novel form of cell death called ferroptosis is intimately linked to hemorrhage-induced brain tissue injury. Although studies have demonstrated the significant preventive impact of bovine serum albumin-stabilized selenium nanoparticles (BSA-SeNPs) against disorders connected to the neurological system, the neuroprotective effect on the hemorrhage stroke and the mechanism remain unknown. Therefore, based on the favorable biocompatibility of BSA-SeNPs, h-ICH (hippocampus-intracerebral hemorrhage) model was constructed to perform BSA-SeNPs therapy. As expected, these BSA-SeNPs could effectively improve the cognitive deficits and ameliorate the damage of hippocampal neuron. Furthermore, BSA-SeNPs reverse the morphology of mitochondria and enhanced the mitochondrial function, evidenced by mitochondrial respiration function (OCR) and mitochondrial membrane potential (MMP). Mechanistically, BSA-SeNPs could efficiently activate the Nrf2 to enhance the expression of antioxidant GPX4 at mRNA and protein levels, and further inhibit lipid peroxidation production in erastin-induced ferroptotic damages. Taken together, this study not only sheds light on the clinical application of BSA-SeNPs, but also provides its newly theoretical support for the strategy of the intervention and treatment of neurological impairment following ICH.


Asunto(s)
Hemorragia Cerebral , Ferroptosis , Factor 2 Relacionado con NF-E2 , Nanopartículas , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Selenio , Animales , Humanos , Masculino , Ratones , Hemorragia Cerebral/tratamiento farmacológico , Hemorragia Cerebral/metabolismo , Modelos Animales de Enfermedad , Ferroptosis/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Nanopartículas/química , Neuronas/metabolismo , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Fármacos Neuroprotectores/administración & dosificación , Factor 2 Relacionado con NF-E2/metabolismo , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Selenio/química , Selenio/farmacología , Albúmina Sérica Bovina/química
12.
Animal Model Exp Med ; 7(3): 234-258, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38863309

RESUMEN

BACKGROUND: According to traditional Chinese medicine (TCM), drugs supplementing the vital energy, Qi, can eliminate tumors by restoring host immunity. The objective of this study is to investigate the underlying immune mechanisms of anti-tumor activity associated with Qi-supplementing herbs, specifically the paired use of Huangqi and Danggui. METHODS: Analysis of compatibility regularity was conducted to screen the combination of Qi-supplementing TCMs. Using the MTT assay and a transplanted tumor mice model, the anti-tumor effects of combination TCMs were investigated in vitro and in vivo. High content analysis and flow cytometry were then used to evaluate cellular immunity, followed by network pharmacology and molecular docking to dissect the significant active compounds and potential mechanisms. Finally, the anti-tumor activity and the mechanism of the active ingredients were verified by molecular experiments. RESULTS: There is an optimal combination of Huangqi and Danggui that, administered as an aqueous extract, can activate immunity to suppress tumor and is more effective than each drug on its own in vitro and in vivo. Based on network pharmacology analysis, PIK3R1 is the core target for the anti-tumor immunity activity of combined Huangqi and Danggui. Molecular docking analysis shows 6 components of the combined Danggui and Huangqi extract (quercetin, jaranol, isorhamnetin, kaempferol, calycosin, and suchilactone) that bind to PIK3R1. Jaranol is the most important component against breast cancer. The suchilactone/jaranol combination and, especially, the suchilactone/kaempferol combination are key for immunity enhancement and the anti-tumor effects of the extract. CONCLUSIONS: The combination of Huangqi and Danggui can activate immunity to suppress breast cancer and is more effective than the individual drugs alone.


Asunto(s)
Neoplasias de la Mama , Medicamentos Herbarios Chinos , Ratones Endogámicos BALB C , Simulación del Acoplamiento Molecular , Medicamentos Herbarios Chinos/farmacología , Animales , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/inmunología , Ratones , Humanos , Astragalus propinquus , Línea Celular Tumoral , Regulación hacia Arriba/efectos de los fármacos
13.
Ecol Evol ; 14(6): e11629, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38919643

RESUMEN

Many species of Salvia have excellent ornamental, culinary, and medicinal values. Salvia daiguii, is an ornamental and highly medicinal perennial herb endemic to the prefecture-level city of Zhangjiajie in Hunan Province, China, with a narrow geographical distribution. However, currently, it has only been assessed as a Critically Endangered species according to the IUCN classification criteria, but its conservation has not yet been studied. This study investigated the distribution and niche characteristics of S. daiguii, and compared the differences in growth, flowering characteristics, and soil nutrients between the wild and ex situ populations. We also analyzed the effects of soil nutrients on plant growth and flowering characteristics. During the survey, we found 274 individuals on a rock approximately 200 m from ZEFR1. Nevertheless, S. daiguii were still restricted in three populations, TNFP, TGM, and ZEFR in Zhangjiajie City, with a total of about 500 plants and less than 250 mature individuals. Our results show that aspects such as adverse environmental conditions, low seedling renewal rate, a lack of soil nutrients, and competition for the characteristic niche of this and other dominant plants in the natural community are the main ecological factors affecting the growth, flowering, and geographic distribution of S. daiguii. Based on the results of field surveys, we recommend that (1) S. daiguii be classified as Critically Endangered C2b and China's List of Plant Species with Extremely Small Populations. (2) Comprehensive conservation strategies were developed, such as the establishment of nature reserves, reintroduction, public education, and institutional development to provide management recommendations related to the conservation of S. daiguii and other endangered plants.

14.
PLoS One ; 19(6): e0306470, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38924028

RESUMEN

[This corrects the article DOI: 10.1371/journal.pone.0268007.].

15.
Bioorg Chem ; 148: 107467, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38772290

RESUMEN

KRAS-G12C inhibitors has been made significant progress in the treatment of KRAS-G12C mutant cancers, but their clinical application is limited due to the adaptive resistance, motivating development of novel structural inhibitors. Herein, series of coumarin derivatives as KRAS-G12C inhibitors were found through virtual screening and rational structural optimization. Especially, K45 exhibited strong antiproliferative potency on NCI-H23 and NCI-H358 cancer cells harboring KRAS-G12C with the IC50 values of 0.77 µM and 1.50 µM, which was 15 and 11 times as potent as positive drug ARS1620, respectively. Furthermore, K45 reduced the phosphorylation of KRAS downstream effectors ERK and AKT by reducing the active form of KRAS (KRAS GTP) in NCI-H23 cells. In addition, K45 induced cell apoptosis by increasing the expression of anti-apoptotic protein BAD and BAX in NCI-H23 cells. Docking studies displayed that the 3-naphthylmethoxy moiety of K45 extended into the cryptic pocket formed by the residues Gln99 and Val9, which enhanced the interaction with the KRAS-G12C protein. These results indicated that K45 was a potent KRAS-G12C inhibitor worthy of further study.


Asunto(s)
Antineoplásicos , Proliferación Celular , Cumarinas , Ensayos de Selección de Medicamentos Antitumorales , Proteínas Proto-Oncogénicas p21(ras) , Humanos , Proteínas Proto-Oncogénicas p21(ras)/antagonistas & inhibidores , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Cumarinas/química , Cumarinas/farmacología , Cumarinas/síntesis química , Relación Estructura-Actividad , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Proliferación Celular/efectos de los fármacos , Estructura Molecular , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Descubrimiento de Drogas , Apoptosis/efectos de los fármacos , Simulación del Acoplamiento Molecular , Evaluación Preclínica de Medicamentos
16.
J Clin Hypertens (Greenwich) ; 26(7): 789-796, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38715256

RESUMEN

An increased risk of target organ damage (TOD) has been reported in patients with primary aldosteronism (PA). However, there is relatively little related research on the correlation between the degree of TOD and those with and without PA in newly diagnosed hypertensive patients. The aim of this study was to assess the association between PA and TOD among patients with newly diagnosed hypertension. Newly diagnosed hypertensive patients were consecutively recruited from January 2015 to June 2020 at the University of Hong Kong-Shenzhen Hospital. Patients were stratified into those with and without PA. Data for left ventricular mass index (LVMI), carotid intima-media thickness (CIMT) and plaque, and microalbuminuria were systematically collected. A total of 1044 patients with newly diagnosed hypertension were recruited, 57 (5.5%) of whom were diagnosed with PA. Patients with PA had lower blood pressure, serum lipids, body mass index, and plasma renin activity and a higher incidence of hypokalemia than those without PA. In contrast, the prevalence of left ventricular hypertrophy, increased CIMT, and microalbuminuria was higher in patients with PA than in those without PA. Multivariable regression analysis demonstrated that PA was independently associated with increased LVMI, CIMT and microalbuminuria. Among patients with newly diagnosed hypertension, those with PA had more severe TOD, including a higher LVMI, CIMT and microalbuminuria, than those without PA. These findings emphasize the need for screening TOD in newly diagnosed hypertension due to underlying PA.


Asunto(s)
Albuminuria , Grosor Intima-Media Carotídeo , Hiperaldosteronismo , Hipertensión , Hipertrofia Ventricular Izquierda , Humanos , Hiperaldosteronismo/complicaciones , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/epidemiología , Femenino , Masculino , Hipertensión/epidemiología , Hipertensión/complicaciones , Persona de Mediana Edad , Hipertrofia Ventricular Izquierda/epidemiología , Hipertrofia Ventricular Izquierda/etiología , Hipertrofia Ventricular Izquierda/diagnóstico , Hipertrofia Ventricular Izquierda/fisiopatología , Albuminuria/epidemiología , Albuminuria/etiología , Albuminuria/diagnóstico , Prevalencia , Adulto , Factores de Riesgo , Presión Sanguínea/fisiología , Hong Kong/epidemiología , Anciano , Hipopotasemia/epidemiología , Hipopotasemia/etiología , Hipopotasemia/diagnóstico
17.
World J Clin Oncol ; 15(4): 531-539, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38689626

RESUMEN

Metastasis remains a major challenge in the successful management of malignant diseases. The liver is a major site of metastatic disease and a leading cause of death from gastrointestinal malignancies such as colon, stomach, and pancreatic cancers, as well as melanoma, breast cancer, and sarcoma. As an important factor that influences the development of metastatic liver cancer, alternative splicing drives the diversity of RNA transcripts and protein subtypes, which may provide potential to broaden the target space. In particular, the dysfunction of splicing factors and abnormal expression of splicing variants are associated with the occurrence, progression, aggressiveness, and drug resistance of cancers caused by the selective splicing of specific genes. This review is the first to provide a detailed summary of the normal splicing process and alterations that occur during metastatic liver cancer. It will cover the role of alternative splicing in the mechanisms of metastatic liver cancer by examining splicing factor changes, abnormal splicing, and the contribution of hypoxia to these changes during metastasis.

18.
Viruses ; 16(5)2024 05 06.
Artículo en Inglés | MEDLINE | ID: mdl-38793618

RESUMEN

Viral infection can regulate the cell cycle, thereby promoting viral replication. Hijacking and altering the cell cycle are important for the virus to establish and maintain a latent infection. Previously, Spodoptera exigua multiple nucleopolyhedrovirus (SeMNPV)-latently infected P8-Se301-C1 cells, which grew more slowly than Se301 cells and interfered with homologous SeMNNPV superinfection, were established. However, the effects of latent and superinfection with baculoviruses on cell cycle progression remain unknown. In this study, the cell cycle profiles of P8-Se301-C1 cells and SeMNPV or Autographa californica multiple nucleopolyhedrovirus (AcMNPV)-infected P8-Se301-C1 cells were characterized by flow cytometry. The results showed that replication-related genes MCM4, PCNA, and BAF were down-regulated (p < 0.05) in P8-Se301-C1 cells, and the S phase of P8-Se301-C1 cells was longer than that of Se301 cells. P8-Se301-C1 cells infected with SeMNPV did not arrest in the G2/M phase or affect the expression of Cyclin B and cyclin-dependent kinase 1 (CDK1). Furthermore, when P8-Se301-C1 cells were infected with SeMNPV after synchronized treatment with hydroxyurea and nocodazole, light microscopy and qRT-PCR analysis showed that, compared with unsynchronized cells and S and G2/M phase cells, SeMNPV-infected P8-Se301-C1 cells in G1 phase induced G2/M phase arrest, and the amount of virus adsorption and intracellular viral DNA replication were significantly increased (p < 0.05). In addition, budded virus (BV) production and occlusion body (OB)-containing cells were both increased at 120 h post-infection (p < 0.05). The expression of Cyclin B and CDK1 was significantly down-regulated at 48 h post-infection (p < 0.05). Finally, the arrest of SeMNPV-infected G1 phase cells in the G2/M phase increased BV production (p < 0.05) and the number of OB-containing cells. In conclusion, G1 phase infection and G2/M arrest are favorable to SeMNPV proliferation in P8-Se301-C1 cells, thereby alleviating the homologous superinfection exclusion. The results contribute to a better understanding of the relationship between baculoviruses and insect cell cycle progression and regulation.


Asunto(s)
Puntos de Control de la Fase G2 del Ciclo Celular , Nucleopoliedrovirus , Spodoptera , Sobreinfección , Replicación Viral , Animales , Nucleopoliedrovirus/fisiología , Línea Celular , Spodoptera/virología , Sobreinfección/virología , Fase G1
19.
Bioorg Med Chem ; 106: 117752, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38749341

RESUMEN

Bromodomain protein 4 (BRD4) is a member of the BET family, and its overexpression is closely associated with the development of many tumors. Inhibition of BRD4 shows great therapeutic potential in anti-tumor, and pan-BRD4 inhibitors show adverse effects of dose limiting toxicity and thrombocytopenia in clinical trials. To improve clinical effects and reduce side effects, more efforts have focused on seeking selective inhibitors of BD1 or BD2. Herein, a series of indole-2-one derivatives were designed and synthesized through docking-guided optimization to find BRD4-BD1 selective inhibitors, and their BRD4 inhibitory and antiproliferation activities were evaluated. Among them, compound 21r had potent BRD4 inhibitory activity (the IC50 values of 41 nM and 313 nM in BD1 and BD2 domain), excellent anti-proliferation (the IC50 values of 4.64 ± 0.30 µM, 0.78 ± 0.03 µM, 5.57 ± 1.03 µM against HL-60, MV-4-11 and HT-29 cells), and displayed low toxicity against normal cell GES-1 cells. Further studies revealed that 21r inhibited proliferation by decreasing the expression of proto-oncogene c-Myc, blocking cell cycle in G0/G1 phase, and inducing apoptosis in MV-4-11 cells in a dose-dependent manner. All the results showed that compound 21r was a potent BRD4 inhibitor with BD1 selectivity, which had potential in treatment of leukemia.


Asunto(s)
Antineoplásicos , Proteínas de Ciclo Celular , Proliferación Celular , Ensayos de Selección de Medicamentos Antitumorales , Indoles , Factores de Transcripción , Humanos , Factores de Transcripción/antagonistas & inhibidores , Factores de Transcripción/metabolismo , Proteínas de Ciclo Celular/antagonistas & inhibidores , Proteínas de Ciclo Celular/metabolismo , Indoles/química , Indoles/farmacología , Indoles/síntesis química , Proliferación Celular/efectos de los fármacos , Relación Estructura-Actividad , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Estructura Molecular , Descubrimiento de Drogas , Relación Dosis-Respuesta a Droga , Proto-Oncogenes Mas , Apoptosis/efectos de los fármacos , Simulación del Acoplamiento Molecular , Línea Celular Tumoral , Proteínas que Contienen Bromodominio
20.
Chin J Traumatol ; 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38762418

RESUMEN

PURPOSE: Intertrochanteric fracture (ITF) classification is crucial for surgical decision-making. However, orthopedic trauma surgeons have shown lower accuracy in ITF classification than expected. The objective of this study was to utilize an artificial intelligence (AI) method to improve the accuracy of ITF classification. METHODS: We trained a network called YOLOX-SwinT, which is based on the You Only Look Once X (YOLOX) object detection network with Swin Transformer (SwinT) as the backbone architecture, using 762 radiographic ITF examinations as the training set. Subsequently, we recruited 5 senior orthopedic trauma surgeons (SOTS) and 5 junior orthopedic trauma surgeons (JOTS) to classify the 85 original images in the test set, as well as the images with the prediction results of the network model in sequence. Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS) 20.0 (IBM Corp., Armonk, NY, USA) to compare the differences among the SOTS, JOTS, SOTS + AI, JOTS + AI, SOTS + JOTS, and SOTS + JOTS + AI groups. All images were classified according to the AO/OTA 2018 classification system by 2 experienced trauma surgeons and verified by another expert in this field. Based on the actual clinical needs, after discussion, we integrated 8 subgroups into 5 new subgroups, and the dataset was divided into training, validation, and test sets by the ratio of 8:1:1. RESULTS: The mean average precision at the intersection over union (IoU) of 0.5 (mAP50) for subgroup detection reached 90.29%. The classification accuracy values of SOTS, JOTS, SOTS + AI, and JOTS + AI groups were 56.24% ± 4.02%, 35.29% ± 18.07%, 79.53% ± 7.14%, and 71.53% ± 5.22%, respectively. The paired t-test results showed that the difference between the SOTS and SOTS + AI groups was statistically significant, as well as the difference between the JOTS and JOTS + AI groups, and the SOTS + JOTS and SOTS + JOTS + AI groups. Moreover, the difference between the SOTS + JOTS and SOTS + JOTS + AI groups in each subgroup was statistically significant, with all p < 0.05. The independent samples t-test results showed that the difference between the SOTS and JOTS groups was statistically significant, while the difference between the SOTS + AI and JOTS + AI groups was not statistically significant. With the assistance of AI, the subgroup classification accuracy of both SOTS and JOTS was significantly improved, and JOTS achieved the same level as SOTS. CONCLUSION: In conclusion, the YOLOX-SwinT network algorithm enhances the accuracy of AO/OTA subgroups classification of ITF by orthopedic trauma surgeons.

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