Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.137
Filtrar
1.
Clin Exp Med ; 24(1): 100, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38758217

RESUMEN

BACKGROUND: The incidence of malignant tumors has increased in patients with non-paraneoplastic pemphigus, although there has been no systematic analysis of global epidemiology. OBJECTIVE: To explore the epidemiology of various types of non-paraneoplastic pemphigus associated with malignant tumors. METHODS: Five databases from establishment through October 20, 2023, were searched. STATA SE 17 was used for the data analysis. Subgroup, meta-regression, and sensitivity analyses were used to evaluate the heterogeneity of pooled studies. RESULTS: A total of 6679 participants were included in our meta-analysis from 16 studies. The aggregated prevalence of tumors in patients diagnosed with pemphigus was 8%. The prevalence was 7% in patients with pemphigus vulgaris, 10% in those with pemphigus foliaceus, and 12% in individuals diagnosed with other types of pemphigus. The prevalence was 8% in Asia, 11% in Europe, and 8% in North America. From a country-specific perspective, patients with pemphigus from Israel, Greece, and Germany exhibited a higher prevalence of tumors at 11%. Furthermore, when categorized by the duration of the study period, the highest prevalence was observed in studies spanning 10 to 20 years, at 11%. CONCLUSION: These findings demonstrate the incidence and prevalence of malignant tumors in patients with non-paraneoplastic pemphigus, which may achieve early detection and intervention, and then reduce mortality rates.


Asunto(s)
Neoplasias , Pénfigo , Pénfigo/epidemiología , Humanos , Prevalencia , Incidencia , Neoplasias/epidemiología , Neoplasias/complicaciones , Europa (Continente)/epidemiología , América del Norte/epidemiología , Asia/epidemiología
2.
Front Immunol ; 15: 1287415, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38707899

RESUMEN

Background: The dysregulated immune response to sepsis still remains unclear. Stratification of sepsis patients into endotypes based on immune indicators is important for the future development of personalized therapies. We aimed to evaluate the immune landscape of sepsis and the use of immune clusters for identifying sepsis endotypes. Methods: The indicators involved in innate, cellular, and humoral immune cells, inhibitory immune cells, and cytokines were simultaneously assessed in 90 sepsis patients and 40 healthy controls. Unsupervised k-means cluster analysis of immune indicator data were used to identify patient clusters, and a random forest approach was used to build a prediction model for classifying sepsis endotypes. Results: We depicted that the impairment of innate and adaptive immunity accompanying increased inflammation was the most prominent feature in patients with sepsis. However, using immune indicators for distinguishing sepsis from bacteremia was difficult, most likely due to the considerable heterogeneity in sepsis patients. Cluster analysis of sepsis patients identified three immune clusters with different survival rates. Cluster 1 (36.7%) could be distinguished from the other clusters as being an "effector-type" cluster, whereas cluster 2 (34.4%) was a "potential-type" cluster, and cluster 3 (28.9%) was a "dysregulation-type" cluster, which showed the lowest survival rate. In addition, we established a prediction model based on immune indicator data, which accurately classified sepsis patients into three immune endotypes. Conclusion: We depicted the immune landscape of patients with sepsis and identified three distinct immune endotypes with different survival rates. Cluster membership could be predicted with a model based on immune data.


Asunto(s)
Sepsis , Humanos , Sepsis/inmunología , Sepsis/diagnóstico , Sepsis/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Anciano , Análisis por Conglomerados , Adulto , Citocinas/inmunología , Citocinas/metabolismo , Biomarcadores , Inmunidad Innata , Inmunidad Adaptativa
3.
Digit Health ; 10: 20552076241253079, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38715974

RESUMEN

Background: Digital health technologies are progressively assuming significant roles in aspects encompassing in-hospital management, patient-centered design, and tiered referral systems. Nevertheless, current studies do not involve exploration into the potential value and mechanisms of digital health in a patient-centered context. This study aimed to explore the development of a framework of comprehensive, evidence-based digital health technologies for the construction of welfare-oriented healthcare. Methods: From March to June 2023, a cross-sectional online study was performed, involving 335 respondents with prior referral experiences hailing from the Central China region. Data on welfare-oriented healthcare factors (clinical pathway management, medical structure configuration, healthcare service accessibility, two-way referrals) underwent factor analysis in advance, and correlation between these factors and their association with two-way referrals was evaluated by testing for direct and indirect (mediating) effects. Results: Firstly, there existed a significant positive correlation between integrative medical indicators and welfare-centered healthcare (ß = 0.02-0.16, p < 0.05). Furthermore, two-way referral had an direct association with integrative medical parameters and the welfare healthcare service system (ß = 0.15-0.31, p < 0.05), but exerted a partial mediatory function in the welfare healthcare service system (ß = 0.005-0.021, α < 0.05). Two-way referrals partially mediate the integrated medical indicators, mainly through direct effects, while also providing complementary support. Clinical pathways, medical structure, and accessibility are closely linked to welfare healthcare and significantly influence healthcare quality. Thus, improving these factors should be prioritized. Conclusion: This study proposes a method combining integrated evaluation indicators with pathway mechanism design. This pathway mechanism design includes key steps such as patient registration, information extraction, hospital allocation or referral, diagnosis and treatment, rehabilitation plan monitoring, service feedback, and demand resolution. This design aims to change patients' intentions in seeking healthcare, thereby increasing their acceptance of bidirectional referrals, and ultimately enhancing the effectiveness and realization of welfare healthcare.

4.
Infect Agent Cancer ; 19(1): 20, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38693593

RESUMEN

BACKGROUND: Cytokines/chemokines play essential roles in the occurrence and progression of hepatitis B virus (HBV) infection. This study aimed to observe the expression patterns of 10 related cytokines/chemokines in the serum of healthy individuals, self-limited patients and HBV-infected patients at different stages of disease (chronic hepatitis B (CHB), liver cirrhosis (LC), hepatocellular dysplastic nodules (DNs) and hepatocellular carcinoma (HCC)) and to analyze the relationships of these cytokines/chemokines with disease progression. METHODS: The levels of six cytokines (FGF-2, IFN-α2, IL-4, IL-6, IL-10 and VEGF-A) and four chemokines (GRO-α, IL-8, IP-10 and MCP-1) were quantified using Luminex multiplex technology. RESULTS: There were no significant differences in the expression of the 10 cytokines/chemokines between healthy individuals and self-limited patients. The levels of IL-4, IL-6, and IL-8 increased significantly in the CHB and LC groups. IL-10 was highly expressed in the HCC group. The level of IP-10 was significantly greater in all liver disease groups (CHB, LC, DN and HCC) than in the HI and SL-HBV groups, while the level of GRO was significantly lower in all liver disease groups than in the HI and SL-HBV groups. The levels of the 10 cytokines/chemokines were not significantly different between the preoperative group and the two-day postoperative group. Significant increases in the levels of IL-4, VEGF-A and IL-8 and significant decreases in those of IL-10 and GRO-α were observed 3 months after surgery. Correlation analysis revealed that most of the cytokines/chemokines with significant correlation differences were positively correlated before and after HCC surgery. CONCLUSION: Our results highlight the fluctuating status of specific cytokines in HBV infection-related disease progression. It is speculated that these cytokines may be used as serum markers to monitor dynamic changes during the progression of HBV-related liver disease and to predict patient prognosis.

5.
Int Immunopharmacol ; 135: 112244, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38776847

RESUMEN

Psoriasis is a common and prevalent chronic papulosquamous cutaneous disorder characterized by sustained inflammation, uncontrolled keratinocyte proliferation, dysfunctional differentiation, and angiogenesis. Autophagy, an intracellular catabolic process, can be induced in response to nutrient stress. It entails the degradation of cellular constituents through the lysosomal machinery, and its association with psoriasis has been well-documented. Nevertheless, there remains a notable dearth of research concerning the involvement of autophagy in the pathogenesis of psoriasis within human skin. This review provides a comprehensive overview of autophagy in psoriasis pathogenesis, focusing on its involvement in two key pathological manifestations: sustained inflammation and uncontrolled keratinocyte proliferation and differentiation. Additionally, it discusses potential avenues for disease management.

6.
J Gen Appl Microbiol ; 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38763756

RESUMEN

In cyanobacteria that perform oxygenic photosynthesis, alternative sigma factors can play critical roles in environmental acclimation at the transcriptional initiation step. Here, we found in Synechococcus elongatus PCC 7942 that transcription of the pilA1 gene, encoding the type IV pilin, is dependent on one of the group 3 sigma factors, SigF1. We analyzed the promoter sequence determinants and proposed herein that the -10 and -35 boxes upstream of the transcriptional start site are critical for transcription. Interestingly, while the pilA1 promoter is activated by illumination, RNA polymerase containing SigF1 is already located on the promoter region under dark conditions, prior to illumination. This strongly suggests that promoter activation by light follows the recruitment of RNA polymerase during transcriptional initiation.

7.
Front Microbiol ; 15: 1256814, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38746752

RESUMEN

Cobalt pollution is harmful to both the aquatic ecosystem and human health. As the primary producer of aquatic ecosystems in hypersaline environments, unicellular planktonic Dunaliella microalgae is considered to be a low-energy and eco-friendly biosorbent that removes excess cobalt and enhances the vitality of coastal and marine ecosystems. In this study, we found that the halotolerant microalga named Dunaliella sp. FACHB-558 could grow under a salinity condition with 0.5-4.5 M NaCl. A phylogenetic analysis based on the rbcL gene revealed that Dunaliella sp. FACHB-558 is a close relative of Dunaliella primolecta TS-3. At lab-scale culture, Dunaliella sp. FACHB-558 exhibited high tolerance to heavy metal stresses, including cobalt, nickel, and cadmium. Treatment with 60 µM cobalt delayed its stationary phase but ultimately led to a higher population density. Furthermore, Dunaliella sp. FACHB-558 has the ability to adsorb the cobalt ions in the aquatic environment, which was evidenced by the decreased amount of cobalt in the culture medium. In addition, the tolerance of Dunaliella sp. FACHB-558 to cobalt stress was correlated with enhanced nitric oxide content and peroxidase activity. The autophagy inhibitor 3-MA enhanced nitric oxide burst, increased peroxidase activity, and accelerated the bioremoval of cobalt, suggesting that the autophagy pathway played a negative role in response to cobalt stress in Dunaliella sp. FACHB-558. In summary, our study identified a novel microalga possessing high cobalt tolerance and provided a promising natural biosorbent for the research and application of heavy metal bioremediation technology.

8.
Pediatr Res ; 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38760472

RESUMEN

BACKGROUND: The risk factors for central venous access device-related thrombosis (CRT) in children are not fully understood. We used evidence-based medicine to find the risk factors for CRT by pooling current studies reporting risk factors of CRT, aiming to guide clinical diagnosis and treatment. METHODS: A systematic search of PubMed, Web of Science, Embase, Cochrane Library, Scopus, CNKI, Sinomed, and Wanfang databases was conducted. RevMan 5.4 was employed for data analysis. RESULTS: The review included 47 studies evaluating 262,587 children with CVAD placement. Qualitative synthesis and quantitative meta-analysis identified D-dimer, location of insertion, type of catheter, number of lumens, catheter indwelling time, and central line-associated bloodstream infection as the most critical risk factors for CRT. Primarily due to observational design, the quality of evidence was regarded as low certainty for these risk factors according to the GRADE approach. CONCLUSION: Because fewer high-quality studies are available, larger sample sizes and well-designed prospective studies are still needed to clarify the risk factors affecting CRT. In the future, developing pediatric-specific CRT risk assessment tools is important. Appropriate stratified preventive strategies for CRT according to risk assessment level will help improve clinical efficiency, avoid the occurrence of CRT, and alleviate unnecessary suffering of children. IMPACT: This is the latest systematic review of risk factors and incidence of CRT in children. A total of 47 studies involving 262,587 patients were included in our meta-analysis, according to which the pooled prevalence of CRT was 9.1%. This study identified several of the most critical risk factors affecting CRT in children, including D-dimer, insertion location, type of catheter, number of lumens, catheter indwelling time, and central line-associated bloodstream infection (CLABSI).

9.
J Hazard Mater ; 472: 134519, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38733790

RESUMEN

Emerging contaminants (ECs) are increasingly recognized as a global threat to biodiversity and ecosystem health. However, the cumulative risks posed by ECs to aquatic organisms and ecosystems, as well as the influence of anthropogenic activities and natural factors on these risks, remain poorly understood. This study assessed the mixed risks of ECs in Dongting Lake, a Ramsar Convention-classified Typically Changing Wetland, to elucidate the major EC classes, key risk drivers, and magnitude of anthropogenic and natural impacts. Results revealed that ECs pose non-negligible acute (30% probability) and chronic (70% probability) mixed risks to aquatic organisms in the freshwater lake ecosystem, with imidacloprid identified as the primary pollutant stressor. Redundancy analysis (RDA) and structural equation modeling (SEM) indicated that cropland and precipitation were major drivers of EC contamination levels and ecological risk. Cropland was positively associated with EC concentrations, while precipitation exhibited a dilution effect. These findings provide critical insights into the ecological risk status and key risk drivers in a typical freshwater lake ecosystem, offering data-driven support for the control and management of ECs in China.

10.
Inflammation ; 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38739343

RESUMEN

Acacetin, a flavonoid derived compound has been recognized for its diverse biological activities, such as anti-oxidative and anti-inflammatory effects. Acute lung injury (ALI) is a severe condition characterized by respiratory insufficiency and tissue damage, commonly triggered by pneumonia and severe sepsis. These conditions induce an inflammatory response via Toll-like receptor 4 (TLR4) signaling activation. This study explored acacetin's therapeutic potential against lipopolysaccharide (LPS) induced ALI in mice, focusing on its ability to modulate the NF-κB pathway via regulation of the Nod-like receptor family CARD domain containing 3 (NLRC3), a signal sensor that plays an important role in the regulation of inflammation and the maintenance of homeostasis. Our findings revealed that high-dose acacetin reduced the mortality rate of ALI mice, significantly ameliorated LPS-induced lung pathological changes, reduced lung edema, and decreased the expression of inflammatory mediators in lung tissues. This protective impact of acacetin appears to stem form its capacity to enhance NLRC3 expression, which, intern, can inhibit the activation of NF-κB and subsequently inhibit the production of inflammatory mediators. NLRC3 deficiency inhibits the protective effect of acacetin on ALI mice. Molecular docking also verified that acacetin tightly bound acacetin to NLRC3. Additionally, acacetin was found to influence macrophage recruitment dynamics via NLRC3, inhibiting the overactivation of NLRC3-NF-κB related pathways. Taken together, our results indicate that acacetin inhibited LPS-induced acute lung injury and macrophage overrecruitment to the lungs in mice by upregulating NLRC3.

11.
Environ Pollut ; 350: 124034, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38663507

RESUMEN

Metconazole (MEZ), a chiral triazole fungicide, produces enantioselective adverse effects in non-target organisms. Among MEZ's isomers, cis-MEZ displays robust antimicrobial properties. Evaluating MEZ and cis-MEZ's toxicity may mitigate fungicide usage and safeguard non-target organisms. Our study evaluated the toxicity of MEZ and its cis-isomers at concentrations of 0.02, 0.2, 2, and 4 mg L-1. We report stereoselectivity and severe cardiovascular defects in zebrafish, including pericardial oedema, decreased heart rate, increased sinus venous and bulbous arteries distances, intersegmental vessel defects, and altered cardiovascular development genes (hand2, gata4, nkx2.5, tbx5, vmhc, amhc, dll4, vegfaa, and vegfc). Further, MEZ significantly increased oxidative stress and apoptosis in zebrafish, primarily in the cardiac region. Isoquercetin, an antioxidant found in plants, partially mitigates MEZ-induced cardiac defects. Furthermore, MEZ upregulated the Wnt/ß-catenin pathway genes (wnt3, ß-catenin, axin2, and gsk-3ß) and ß-catenin protein expression. Inhibitor of Wnt Response-1 (IWR-1) rescued MEZ-induced cardiotoxicity. Our findings highlight oxidative stress, altered cardiovascular development genes, and upregulated Wnt/ß-catenin signaling as contributors to cardiovascular toxicity in response to MEZ and cis-MEZ treatments. Importantly, 1R,5S-MEZ exhibited greater cardiotoxicity than 1S,5R-MEZ. Thus, our study provides a comprehensive understanding of cis-MEZ's cardiovascular toxicity in aquatic life.


Asunto(s)
Embrión no Mamífero , Estrés Oxidativo , Vía de Señalización Wnt , Pez Cebra , Animales , Estrés Oxidativo/efectos de los fármacos , Vía de Señalización Wnt/efectos de los fármacos , Embrión no Mamífero/efectos de los fármacos , Triazoles/toxicidad , Fungicidas Industriales/toxicidad , Corazón/efectos de los fármacos , Cardiotoxicidad/etiología , Contaminantes Químicos del Agua/toxicidad
12.
Sci Rep ; 14(1): 7730, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38565602

RESUMEN

Meandering flow can be formed during the advance of natural rivers by the scouring of river banks. However, this phenomenon is not common in artificial cement channels. This study used experimental scouring terrain data for a numerical simulation to study the meandering flow pattern formed between double alternating deflectors in a straight channel. The numerical results showed that the path of the accelerated flow generated by the upstream deflector was changed by installing a downstream deflector while the flow rate remained unchanged. Thus, a meandering flow formed, and a stable, narrow, high-speed zone formed in the downstream area. The accelerated flow between the two deflectors hit the channel bank soon after its direction changed. Then, a strong downward flow formed in this area, which may have produced an elliptical scour hole. A large-scale vortex structure was formed in the elliptical scour hole, which was influenced by the horseshoe vortex system before the downstream deflector.

13.
ACS Omega ; 9(12): 14604-14612, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38559966

RESUMEN

Early detection and viral concentration monitoring of human immunodeficiency virus in resource-poor settings are important to control disease spread and reduce mortality. Nucleic acid amplification tests are expensive for low-resource settings. Lateral flow antibody tests are not sensitive if testing is performed within 7-10 days, and these tests are not quantitative. We describe a signal enhancement technique based on fluorescent silica nanoparticles and bioorthogonal chemistries for the femtomolar detection of the HIV-1 p24 antigen. We developed a magnetic bead-based assay, wherein we used fluorescent-dye-encapsulated silica nanoparticles as reporters. The number of reporters was increased by using bioorthogonal chemistry to provide signal enhancement. The limit and range of detection of the sandwich immunoassay using alternating multiple layers for p24 in human serum were found to be 46 fg/mL (1.84 fM) and 46 fg/mL to 10 ng/mL, respectively. This simple assay was 217-fold higher in sensitivity compared to that of commercial enzyme-linked immunoassays (limit of detection of 10 pg/mL).

14.
Front Microbiol ; 15: 1352531, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38591036

RESUMEN

Objective: The limited existing knowledge regarding resistance to antimicrobial peptides (AMPs) is hindering their broad utilization. The aim of this study is to enhance the understanding of AMP resistance, a pivotal factor in the exploration of alternative drug development in response to the escalating challenge of antibiotic resistance. Methods: We utilized metagenomic functional selection to analyze genes resistant to AMPs, with a specific focus on the microbiota in soil and the human gut. Through a combination of experimental methods and bioinformatics analyses, our investigation delved into the possibilities of the evolution of resistance to AMPs, as well as the transfer or interchange of resistance genes among the environment, the human body, and pathogens. Additionally, we examined the cross-resistance between AMPs and evaluated interactions among AMPs and conventional antibiotics. Results: The presence of AMP resistance, including various resistance mechanisms, was observed in both soil and the human gut microbiota, as indicated by our findings. Significantly, the study underscored the facile evolution of AMP resistance and the potential for gene sharing or exchange among different environments. Notably, cross-resistance among AMPs was identified as a phenomenon, while cross-resistance between AMPs and antibiotics was found to be relatively infrequent. Conclusion: The results of our study highlight the significance of taking a cautious stance when considering the extensive application of AMPs. It is imperative to thoroughly assess potential resistance risks, with a particular focus on the development of resistance to AMPs across diverse domains. A comprehensive grasp of these aspects is essential for making well-informed decisions and ensuring the responsible utilization of AMPs in the ongoing fight against antibiotic resistance.

15.
Small ; : e2401024, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38597755

RESUMEN

Exposing different facets on metal-organic frameworks (MOFs) is highly desirable to enhance the performance for various applications, however, exploiting a concise and effective approach to achieve facet-controlled synthesis of MOFs remains challenging. Here, by modulating the ratio of metal precursors to ligands, the facet-engineered iron-based MOFs (Fe-MOFs) exhibits enhanced catalytic activity for Fenton reaction are explored, and the mechanism of facet-dependent performance is revealed in detail. Fully exposed (101) and (100) facets on spindle-shaped Fe-MOFs enable rapid oxidation of colorless o-phenylenediamine (OPD) to colored products, thereby establishing a dual-mode platform for the detection of hydrogen peroxide (H2O2) and triacetone triperoxide (TATP). Thus, a detection limit as low as 2.06 nm is achieved, and robust selectivity against a wide range of common substances (>16 types) is obtained, which is further improved by incorporating a deep learning architecture with an SE-VGG16 network model, enabling precise differentiation of oxidizing agents from captured images. The present strategy is expected will shine light on both the rational synthesis of nanomaterials with modulated morphologies and the exploitation of high-performance trace chemical sensors.

16.
Int Wound J ; 21(4): e14837, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38629613

RESUMEN

The accurate assessment of wound healing post-caesarean section, especially in twin pregnancies, remains a pivotal concern in obstetrics, given its implications for maternal health and recovery. Traditional methods, including conventional abdominal ultrasonography (CU), have been challenged by the advent of transvaginal ultrasonography (TU), offering potentially enhanced sensitivity and specificity. This meta-analysis directly compares the efficacy of TU and CU in evaluating wound healing and scar formation, crucial for optimizing postoperative care. Results indicate that TU is associated with significantly better outcomes in wound healing, demonstrated by lower REEDA scores (SMD = -20.56, 95% CI: [-27.34.20, -13.77], p < 0.01), and in scar formation reduction, evidenced by lower Manchester Scar Scale scores (SMD = -25.18, 95% CI: [-29.98, -20.39], p < 0.01). These findings underscore the potential of integrating TU into routine post-caesarean evaluation protocols to enhance care quality and patient recovery.


Asunto(s)
Cesárea , Cicatriz , Embarazo , Humanos , Femenino , Cicatriz/diagnóstico por imagen , Cicatriz/etiología , Cicatriz/cirugía , Cesárea/efectos adversos , Cicatrización de Heridas , Ultrasonografía , Sensibilidad y Especificidad
17.
Molecules ; 29(7)2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-38611695

RESUMEN

Oxidative stress plays a crucial role in the pathogenesis of many diseases. Esculetin is a natural coumarin compound with good antioxidant and anti-inflammatory properties. However, whether esculetin can protect HepG2 cells through inhibiting H2O2-induced apoptosis and pyroptosis is still ambiguous. Therefore, this study aimed to investigate the protective effects and mechanisms of esculetin against oxidative stress-induced cell damage in HepG2 cells. The results of this study demonstrate that pretreatment with esculetin could significantly improve the decrease in cell viability induced by H2O2 and reduce intracellular ROS levels. Esculetin not only apparently reduced the apoptotic rates and prevented MMP loss, but also markedly decreased cleaved-Caspase-3, cleaved-PARP, pro-apoptotic protein (Bax), and MMP-related protein (Cyt-c) expression, and increased anti-apoptotic protein (Bcl-2) expression in H2O2-induced HepG2 cells. Meanwhile, esculetin also remarkably reduced the level of LDH and decreased the expression of the pyroptosis-related proteins NLRP3, cleaved-Caspase-1, Il-1ß, and GSDMD-N. Furthermore, esculetin pretreatment evidently downregulated the protein expression of p-JNK, p-c-Fos, and p-c-Jun. Additionally, anisomycin, a specific activator of JNK, blocked the protection of esculetin against H2O2-induced HepG2 cells apoptosis and pyroptosis. In conclusion, esculetin can protect HepG2 cells against H2O2-induced oxidative stress, apoptosis, and pyroptosis via inhibiting the JNK signaling pathway. These findings indicate that esculetin has the potential to be used as an antioxidant that improves oxidative stress-related diseases.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Umbeliferonas , Humanos , Piroptosis , Peróxido de Hidrógeno/toxicidad , Antioxidantes/farmacología , Células Hep G2 , Neoplasias Hepáticas/tratamiento farmacológico , Apoptosis , Estrés Oxidativo
18.
Int J Biol Macromol ; 267(Pt 2): 131514, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38608986

RESUMEN

The cell nucleus serves as the pivotal command center of living cells, and delivering therapeutic agents directly into the nucleus can result in highly efficient anti-tumor eradication of cancer cells. However, nucleus-targeting drug delivery is very difficult due to the presence of numerous biological barriers. Here, three antitumor drugs (DNase I, ICG: indocyanine green, and THP: pirarubicin) were sequentially triggered protein self-assembly to produce a nucleus-targeting and programmed responsive multi-drugs delivery system (DIT). DIT consisted of uniform spherical particles with a size of 282 ± 7.7 nm. The acidic microenvironment of tumors and near-infrared light could successively trigger DIT for the programmed release of three drugs, enabling targeted delivery to the tumor. THP served as a nucleus-guiding molecule and a chemotherapy drug. Through THP-guided DIT, DNase I was successfully delivered to the nucleus of tumor cells and killed them by degrading their DNA. Tumor acidic microenvironment had the ability to induce DIT, leading to the aggregation of sufficient ICG in the tumor tissues. This provided an opportunity for the photothermal therapy of ICG. Hence, three drugs were cleverly combined using a simple method to achieve multi-drugs targeted delivery and highly effective combined anticancer therapy.


Asunto(s)
Antineoplásicos , Núcleo Celular , Desoxirribonucleasa I , Doxorrubicina , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Animales , Ratones , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/administración & dosificación , Línea Celular Tumoral , Núcleo Celular/metabolismo , Desoxirribonucleasa I/metabolismo , Doxorrubicina/farmacología , Doxorrubicina/química , Doxorrubicina/administración & dosificación , Doxorrubicina/análogos & derivados , Portadores de Fármacos/química , Verde de Indocianina/química , Microambiente Tumoral/efectos de los fármacos , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos
19.
Toxins (Basel) ; 16(4)2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38668602

RESUMEN

Patulin contamination has become a bottleneck problem in the safe production of fruit products, although biodegradation technology shows potential application value in patulin control. In the present study, the patulin biodegradation mechanism in a probiotic yeast, Pichia guilliermondii S15-8, was investigated. Firstly, the short-chain dehydrogenase PgSDR encoded by gene A5D9S1 was identified as a patulin degradation enzyme, through RNA sequencing and verification by qRT-PCR. Subsequently, the exogenous expression system of the degradation protein PgSDR-A5D9S1 in E. coli was successfully constructed and demonstrated a more significant patulin tolerance and degradation ability. Furthermore, the structure of PgSDR-A5D9S1 and its active binding sites with patulin were predicted via molecular docking analysis. In addition, the heat-excited protein HSF1 was predicted as the transcription factor regulating the patulin degradation protein PgSDR-A5D9S1, which may provide clues for the further analysis of the molecular regulation mechanism of patulin degradation. This study provides a theoretical basis and technical support for the industrial application of biodegradable functional strains.


Asunto(s)
Biodegradación Ambiental , Patulina , Pichia , Patulina/metabolismo , Pichia/metabolismo , Pichia/genética , Simulación del Acoplamiento Molecular , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo
20.
Medicine (Baltimore) ; 103(14): e37707, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38579033

RESUMEN

BACKGROUND: This meta-analysis aimed to systematically summarize the association between cancer risks and glutathione s-transferases (GSTs) among smokers and drinkers. METHODS: Literature was searched through PubMed, Web of Science, CNKI, and WANFANG published from 2001 to 2022. Stata was used with fixed-effect model or random-effect model to calculate pooled odds ratios (ORs) and the 95% confidence interval (95% CI). Sensitivity and heterogeneity calculations were performed, and publication bias was analyzed by Begg and Egger's test. Regression analysis was performed on the correlated variables about heterogeneity, and the false-positive report probabilities (FPRP) and the Bayesian False Discovery Probability (BFDP) were calculated to assess the confidence of a statistically significant association. RESULTS: A total of 85 studies were eligible for GSTs and cancer with smoking status (19,604 cases and 23,710 controls), including 14 articles referring to drinking status (4409 cases and 5645 controls). GSTM1-null had significant associations with cancer risks (for smokers: OR = 1.347, 95% CI: 1.196-1.516, P < .001; for nonsmokers: OR = 1.423, 95% CI: 1.270-1.594, P < .001; for drinkers: OR = 1.748, 95% CI: 1.093-2.797, P = .02). GSTT1-null had significant associations with cancer risks (for smokers: OR = 1.356, 95% CI: 1.114-1.651, P = .002; for nonsmokers: OR = 1.103, 95% CI: 1.011-1.204, P = .028; for drinkers: OR = 1.423, 95% CI: 1.042-1.942, P = .026; for nondrinkers: OR = 1.458, 95% CI: 1.014-2.098, P = .042). Negative associations were found between GSTP1rs1695(AG + GG/AA) and cancer risks among nondrinkers (OR = 0.840, 95% CI: 0.711-0.985, P = .032). CONCLUSIONS: GSTM1-null and GSTT1-null might be related cancers in combination with smoking or drinking, and GSTP1rs1695 might be associated with cancers among drinkers.


Asunto(s)
Gutatión-S-Transferasa pi , Neoplasias , Humanos , Gutatión-S-Transferasa pi/genética , Teorema de Bayes , Predisposición Genética a la Enfermedad , Glutatión Transferasa/genética , Fumar/efectos adversos , Neoplasias/etiología , Neoplasias/genética , Glutatión , Factores de Riesgo , Genotipo , Estudios de Casos y Controles
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA