Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 12.439
Filtrar
1.
J Environ Sci (China) ; 150: 571-581, 2025 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-39306430

RESUMO

Fifty agricultural soil samples collected from Fuzhou, southeast China, were first investigated for the occurrence, distribution, and potential risks of twelve organophosphate esters (OPEs). The total concentration of OPEs (ΣOPEs) in soil ranged from 1.33 to 96.5 ng/g dry weight (dw), with an average value of 17.1 ng/g dw. Especially, halogenated-OPEs were the predominant group with a mean level of 9.75 ng/g dw, and tris(1-chloro-2-propyl) phosphate (TCIPP) was the most abundant OPEs, accounting for 51.1% of ΣOPEs. The concentrations of TCIPP and ∑OPEs were found to be significantly higher (P < 0.05) in soils of urban areas than those in suburban areas. In addition, the use of agricultural plastic films and total organic carbon had a positive effect on the occurrence of OPE in this study. The positive matrix factorization model suggested complex sources of OPEs in agricultural soils from Fuzhou. The ecological risk assessment demonstrated that tricresyl phosphate presented a medium risk to land-based organisms (0.1 ≤ risk quotient < 1.0). Nevertheless, the carcinogenic and non-carcinogenic risks for human exposure to OPEs through soil ingestion and dermal absorption were negligible. These findings would facilitate further investigations into the pollution management and risk control of OPEs.


Assuntos
Agricultura , Monitoramento Ambiental , Ésteres , Organofosfatos , Poluentes do Solo , Solo , China , Poluentes do Solo/análise , Solo/química , Organofosfatos/análise , Ésteres/análise , Medição de Risco
2.
Ren Fail ; 46(2): 2398826, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39248402

RESUMO

BACKGROUND: During the run-in phase of the TESTING study, approximately half of patients with IgA nephropathy (IgAN) were excluded due to proteinuria below 1 g/24 h after intensive supportive therapy. The long-term prognosis of these patients needs further investigation. METHODS: 112 screening failed patients in the TESTING study from 10 centers in China were enrolled in this retrospective study. The prognosis of 88 patients, who were excluded because of proteinuria below 1 g/24 h, was analyzed by Landmark Kaplan-Meier analysis. The composite kidney endpoint was defined by a ≥ 50% reduction in eGFR, ESKD (eGFR <15 mL/min per 1.73 m2), chronic dialysis for at least 6 months, or renal transplantation. RESULTS: In total, 88 patients were excluded due to proteinuria less than 1 g/24 h. During the follow-up, 73/88 (83.0%) patients received renin-angiotensin system blocker. 72/88 (81.8%) had stable proteinuria remission and did not receive immunosuppressive therapy (IST), and 16/88 (18.2%) received IST because of a relapse of proteinuria. Landmark Kaplan-Meier analysis revealed that, the kidney survival from dialysis or composite kidney outcome of these excluded patients with IST was similar to those without IST during the early stages of follow-up (dialysis, before 60 months, p = 0.778; composite kidney outcome, before 48 months, p = 0.862); whereas the risk for dialysis of patients receiving IST was significantly higher than those without IST after 60 months (OR = 11.3, p = 0.03). Similarly, the risk for the composite kidney outcome of patients receiving IST was also significantly higher than those without IST after 48 months (OR = 5.92, p = 0.029). CONCLUSIONS: IgAN patients who maintained a persistent remission of proteinuria after intensive supportive therapy had a much better long-term kidney outcome than those who experienced a relapse of proteinuria and needed IST.


Assuntos
Taxa de Filtração Glomerular , Glomerulonefrite por IGA , Proteinúria , Humanos , Glomerulonefrite por IGA/complicações , Glomerulonefrite por IGA/terapia , Feminino , Masculino , Proteinúria/etiologia , Estudos Retrospectivos , Adulto , China/epidemiologia , Prognóstico , Pessoa de Meia-Idade , Estimativa de Kaplan-Meier , Indução de Remissão , Imunossupressores/uso terapêutico , Falência Renal Crônica/terapia , Falência Renal Crônica/complicações , Diálise Renal , Adulto Jovem , Transplante de Rim , População do Leste Asiático
3.
Neoplasma ; 71(4): 359-373, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39267543

RESUMO

N6-methyladenosine (m6A) methylation, as a new regulatory mechanism, has been reported to be involved in diverse biological processes in recent years. Wilms tumor 1-associated protein (WTAP), as the key member of m6A methylation, has been proven to participate in tumorigenesis. Here, we studied the expression of WTAP and its potential mechanism involved in the development of esophageal squamous cell carcinoma (ESCC). We detected the expression of WTAP and its correlation with clinicopathological features, and we determined the function of WTAP on ESCC cells by MTS assay, colony formation, scratch wound healing assay, Transwell assay, and subcutaneous xenograft assay. We used mRNA sequencing technology to screen candidate downstream targets for WTAP and investigated the underlying mechanism of CCND1 in ESCC promotion through a series of rescue assays. An elevated expression of WTAP in ESCC malignancy indicated a worse prognosis. WTAP promoted the proliferation and metastasis of ESCC cells, and CCND1 was identified as the potential downstream effecter of WTAP. Moreover, WTAP modulated ESCC progression through a MAPK pathway-dependent pattern. Our research suggested that WTAP promoted both proliferation and metastasis of ESCC by accelerating the expression of CCND1 via the MAPK signaling pathway, indicating that WTAP may be a candidate prognostic biomarker for ESCC and also will be a promising strategy for ESCC cancer therapy.


Assuntos
Proliferação de Células , Ciclina D1 , Progressão da Doença , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Sistema de Sinalização das MAP Quinases , Humanos , Ciclina D1/metabolismo , Ciclina D1/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/metabolismo , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Animais , Linhagem Celular Tumoral , Camundongos , Masculino , Regulação Neoplásica da Expressão Gênica , Prognóstico , Feminino , Fatores de Processamento de RNA/genética , Fatores de Processamento de RNA/metabolismo , Movimento Celular , Camundongos Nus , Pessoa de Meia-Idade , Proteínas de Ciclo Celular
4.
Materials (Basel) ; 17(17)2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39274719

RESUMO

This study focuses on investigating the strength recovery of fire-damaged fly ash concrete (FAC) with a low substitution rate of 10% through post-fire curing. The chemical and microstructural changes were analyzed using X-ray diffraction (XRD), derivative thermogravimetry (DTG), scanning electron microscopy (SEM), energy dispersive X-ray spectrometry (EDS), and nitrogen adsorption. The findings indicate that the incorporation of fly ash slightly enhanced the strength after exposure to 400 °C; this was attributed to improved pozzolanic reactions, which were not observed at higher temperatures of 600 °C and 800 °C. Moreover, a positive effect on the recovery of compressive strength was observed due to the pozzolanic reaction. However, due to the relatively low fly ash content, depletion occurred at a later age, resulting in the inability to inhibit microstructural damage caused by the production of portlandite, thereby weakening the compressive strength. Interestingly, fly ash influenced the morphology of calcium carbonate and calcium silicate hydrate crystals, which is potentially ascribed to the role of high aluminum content acting as a crystallization-guiding agent.

5.
J Med Chem ; 2024 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-39305244

RESUMO

The fluorescence high-throughput screening method is of importance for new antioxidant drug candidate discovery for the treatment of serious hepatorenal syndrome, which displayed an obvious upregulated peroxynitrite level. However, most of the current ONOO- probes possessed incomplete fluorescence quenching efficiency, which can result in non-negligible probe inherent fluorescence. Hence, we utilized the probe conjugated structure disruption strategy to construct hydrogenation phosphorus-substituted rhodamine (H-PRh) with "zero" probe inherent fluorescence character. Based on the precursor, a series of natural products were screened for identifying antioxidant drug candidates. Luteolin was screened out by activating the Sirt1-Nrf2-HO-1 signaling pathway to regulate the accumulation of ONOO- in the hepatorenal syndrome. Overall, the "zero" probe inherent fluorescence ONOO- sensor constructed here applies for a promising and versatile toolbox for illuminating the ONOO--related pathological process in the hepatorenal syndrome. Besides, this strategy of constructing highly sensitive sensors could serve as a valuable reference for further fluorescent probes.

6.
Geriatr Nurs ; 60: 241-248, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39305546

RESUMO

OBJECTIVE: Baduanjin is a traditional Chinese regimen involving flowing movements, breath control, and strengthening to benefit health and well-being. We investigated the effectiveness of Baduanjin for older adults with insomnia. METHODS: We assessed eight databases for methodological quality according to the Cochrane Handbook for Evaluation of Interventions, and analyzed by Stata 16.0 software. RESULTS: Participants (N = 789) of ten studies were included. The meta-analysis showed that Baduanjin was effective for older adults with insomnia as measured by the Pittsburgh Sleep Quality Index (PSQI)[WMD =-2.20, 95 %CI (-2.87, -1.74), P = 0.000], and 12 weeks or more of treatment effect was superior to <12 weeks. Moreover, there were significant differences in all dimensions of the PSQI between experimental and control groups. CONCLUSIONS: Baduanjin is a complementary therapy option for older adults with insomnia. However, high-quality research is still needed to investigate the optimal exercise intensity, duration and frequency for older adults with insomnia.

7.
J Ethnopharmacol ; : 118833, 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39306212

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Chronic pancreatitis (CP), a syndrome characterized by inflammatory fibrosis, can impair both the internal and external secretory functions of the pancreas. The global incidence of this disease is gradually increasing. However, the exact pathogenesis remains unclear, resulting in a lack of targeted clinical therapies. According to the principles of traditional Chinese medicine, CP can be attributed to Shaoyang and Yangming syndromes, which manifest as abdominal pain and hypochondriac distension. Dachaihu Decoction (DCHD) is a classic formula from the "Treatise on Febrile and Miscellaneous Disease." It is frequently prescribed for conditions associated with combined Shaoyang and Yangming syndromes. However, the specific mechanisms by which DCHD prevents and treats CP remain unclear and require further investigation. AIM OF THE STUDY: Using a holistic methodology, including network pharmacology, molecular docking, transcriptomic profiling, and animal experimentation, we explored the potential therapeutic mechanisms of DCHD in CP. MATERIALS AND METHODS: In a mouse model, caerulein was used to induce CP, and DCHD was administered via gastric lavage to assess its therapeutic effect on pancreatic injury caused by caerulein-induced CP. Subsequently, pancreatic tissues were collected for transcriptomic analysis. Screening of DCHD-active ingredient-target pathways for CP treatment was conducted using network pharmacology and further preliminary validation was performed using molecular docking techniques. Additionally, in vivo and in vitro validation was conducted using animal and cells experiments based on the predicted results. RESULTS: Our findings suggest that DCHD ameliorates pancreatic acinar cell injury, pancreatic inflammation, and fibrosis in mice with CP. Network pharmacology identified 385 potential targets of DCHD associated with CP. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the therapeutic effect of DCHD on CP may be linked to the mitogen-activated protein kinase (MAPK) signaling pathway. Transcriptomic data supported this finding, as it confirmed that DCHD inhibited the pancreatic MAPK signaling pathway in CP. Molecular docking studies further revealed that the top ten active components of DCHD exhibited strong docking activity with key molecules within the MAPK signaling pathway. Finally, animal experiments confirmed that DCHD effectively reduced the phosphorylation of P38, Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) in pancreatic tissues. In addition, the expression of p-P38, p-JNK, and p-ERK was reduced in pancreatic stellate cells and macrophages in the DCHD group. We further treated CP mice, pancreatic stellate cell line hPSCs, and macrophage cell line RAW264.7 with the active component baicalin from DCHD, and found that baicalin effectively reduced pancreatic damage in CP. Additionally, the expression of key proteins in the MAPK signaling pathway was significantly decreased in both hPSCs and RAW264.7. CONCLUSION: In summary, DCHD plays an important role in the treatment of chronic pancreatitis, and it may become a promising drug against the progression of CP. The role of DCHD in alleviating pancreatic inflammatory cell infiltration and fibrosis may be related to the regulation of the MAPK signaling pathway.

8.
Mol Med Rep ; 30(5)2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39301660

RESUMO

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that, concerning the Transwell cell migration and invasion assays shown in Fig. 4Ba and 4Ca on p. 215, quite a large number of the data panels contained overlapping sections, such that data panels which were intended to show the results from differently performed experiments had been derived from a smaller number of original sources. After having considered this matter, in view of the number of overlapping data panels that were identified, the Editor of Molecular Medicine Reports has decided that this paper should be retracted from the Journal on account of a lack of confidence in the presented data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 21: 209-219, 2020; DOI: 10.3892/mmr.2019.10809].

9.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 42(5): 581-592, 2024 Oct 01.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-39304502

RESUMO

OBJECTIVES: This study aimed to identifyPAX9variants in non-syndromic tooth agenesis families of China, as well as to analyze the genotype⁃phenotype of non-syndromic tooth agenesis caused by PAX9variants, which can provide a basis for the genetic diagnosis of tooth agenesis. METHODS: We collected the data of 44 patients with non-syndromic oligodontia who underwent treatment at Stomatological Hospital of Hebei Medical University between 2018 and 2023. Whole-exome sequencing was performed on the peripheral blood of the proband and its core family members, and the variants were verified by Sanger sequencing. Pathogenicity analysis and function prediction of the variants were performed using bioinformatics tools. The correlation between the genotype of PAX9 variant and its corresponding phenotype was examined by reviewing 55 publications retrieved from PubMed. The studies involved 232 tooth agenesis patients with PAX9 variants. RESULTS: A novel PAX9 c.447delG (p.Pro150Argfs*62) and a reported PAX9 c.406C>T (p.Gln136*) were identified in two Chinese families. Through bioinformatics analysis and three-dimensional structural modeling, we postulated that the frameshift variant was pathogenic. The outcome was the premature cessation of PAX9 protein, which caused severe structural and functional deficiencies. Summarizing the PAX9 genotype-phenotype relationship revealed that patients carrying the PAX9 variant commonly led to loss of the second molars. CONCLUSIONS: We identified the novel PAX9 c.447delG (p.Pro150Argfs*62) in a Chinese family of non-syndromic oligodontia, expanding the known variant spectrum of PAX9. The most susceptible tooth position for PAX9 variants of tooth agenesis was the second molars and the deciduous molars during the deciduous dentition.


Assuntos
Anodontia , Povo Asiático , Sequenciamento do Exoma , Genótipo , Fator de Transcrição PAX9 , Fenótipo , Humanos , Fator de Transcrição PAX9/genética , Anodontia/genética , China , Estudos de Associação Genética , Linhagem , População do Leste Asiático
10.
Chin Med Sci J ; 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39297281

RESUMO

The growing utilization of critical care echocardiography (CCE) by clinicians necessitates a meticulous review of clinical conditions in critically ill patients, both before and during the examination. The reviewing process of clinical conditions minimizes the risk of overlooking or misinterpreting crucial findings. This article proposes a comprehensive strategy, namely BILL strategy to integrated into the CCE protocol, where "B" represents baseline respiratory and hemodynamic support, "I" signifies information gleaned from invasive monitoring, including central venous pressure and thermodilution-derived cardiac output, the first "L" denotes laboratory results such as central venous oxygen saturation, troponin, and brain natriuretic peptide, and the second "L" refers to lung ultrasound data. xx Combining the BILL strategy with CCE enhances a more comprehensive understanding of critical illness, potentially leading to improved diagnostic accuracy and patient outcomes.

11.
Discov Oncol ; 15(1): 456, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39292372

RESUMO

OBJECTIVE: High-risk neuroblastoma patients often have poor outcomes despite multi-treatment options. The risk stratification of high-risk MYCN-not-amplified (HR-MYCN-NA) patients remains difficult. This study aims to identify a gene set signature that can help further stratify HR-MYCN-NA patients for a potential personalized therapeutic strategy. METHODS: Three microarrays and one single-cell RNA sequence dataset were acquired and analyzed. Firstly, the prognostic-related genes (PRGs) in HR-MYCN-NA tumor cells were identified using TARGET-NB and GSE137804 datasets. Then, the prognostic model was established by LASSO-Cox regression, and verified in external cohort (GSE49710, GSE45547). Moreover, a time-dependent receiver operating characteristic curve (ROC) and area under the ROC (AUC) was used to assess survival prediction. A nomogram was established to predict the 1-, 3- and 5-year overall survival (OS) of HR-MYCN-NA patients. RESULTS: In the training set, a five-PRGs signature, which include GAL, GFRA3, MARCKS, PSMD13, and ZNHIT3 genes, was identified and successfully stratified HR-MYCN-NA patients into ultra-high risk (UHR) and high-risk (HR) subtypes (HR = 4.29, P < 0.001). ROC curve analysis confirmed its predictive power (AUC = 0.74-0.82), suggesting a good predictive efficacy. Consistently, high-risk scores also predicted worse OS (HR = 2, P = 0.033) in the external validation dataset (AUC = 0.67-0.71). Moreover, the overall C-index of the nomogram was 0.75 (P < 0.001), which indicated good agreement between the observed and predicted survival rates. Further integrating the five PRGs signature with clinical factors, these 5 gene signature (HR = 4.45, P < 0.001) and tumor grade (HR = 4.15, P = 0.02) were found to be independent prognostic factors for HR-MYCN-NA patients. CONCLUSION: The novel five PRGs signature could well predict the survival of HR-MYCN-NA patients, which may provide constructive information for these subsets.

13.
Adv Mater ; : e2409592, 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39308199

RESUMO

The fabrication of stable perovskite nanofilm patterns is important for the development of functional optical devices. However, current production approaches are limited by the requirement for strict inert gas protection and long processing times. Here, a confined flash printing synthesis method is presented to generate perovskite nanofilms under ambient conditions, combining precursor transfer, perovskite synthesis, crystallization, and polymer protection in a single step within milliseconds. A laser simultaneously prints and induces the flash synthesis, confined in a polymer nanofilm, under normal ambient conditions. Due to its simplicity and flexibility, the method enables the combination and screening of many different perovskite precursor materials on various substrates. Besides for the development of novel perovskite materials and devices, the nanofilms can be applied for biodetection. The unique H2O2-responsive property of the ultrathin perovskite quantum dot film is applied for biomolecule detection based on oxidase-catalyzed enzymatic reactions.

14.
Oncol Lett ; 28(5): 545, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39310026

RESUMO

Endometrial carcinoma (EC) is one of the most common gynecological malignant neoplasms, the prognosis of which is strongly related to the time of diagnosis, with an earlier diagnosis leading to a better prognosis. Therefore, effective diagnostic indicators and methods are needed to ensure early detection. The present study explored the following in EC: Circulating tumor cells (CTCs); the long noncoding RNAs (lncRNAs) RP4-616B8.5, RP11-389G6.3 and carboxy-terminal domain (CTD)-2377D24.6; and the methylation of cysteine dioxygenase type 1 (CDO1) and CUGBP Elav-like family member 4 (CELF4). In total, 85 patients, including 71 with EC, and 14 without EC (NO-EC) but with uterine fibroids or polyps, were included in the present study. In total, 46 patients with EC and 8 NO-EC patients underwent CTC detection. In the evaluation of the EC vs. NO-EC groups, the results showed that the CTC-positive rate of the EC group was 80.43% and that the area under the curve (AUC) value of CTCs was 0.8872 (P=0.0098). A total of 35 patients with EC and 14 NO-EC patients underwent detection of the RP4-616B8.5, RP11-389G6.3 and CTD-2377D24.6 lncRNAs. When the levels of the three lncRNAs RP4-616B8.5, RP11-389G6.3 and CTD-2377D24.6 were compared between the EC and NO-EC groups, they were higher in the EC group; the P-values were 0.0002, 0.0001 and <0.0001, respectively, and the AUC values were 0.8184, 0.8347 and 0.8265, respectively. In addition, a total of 35 patients with EC and 8 NO-EC patients underwent CDO1 and CELF4 DNA methylation analysis. The positive rates of the methylated genes CDO1 and CELF4 were 20% (7/35) and 5.71% (2/35), and the P-values of the comparisons between the EC and NO-EC groups were 0.1748 and 0.5004, respectively; the AUC values were 0.6000 and 0.5286. Furthermore, the combination of CTCs, and lncRNAs RP4-616B8.5, RP11-389G6.3 and CTD-2377D24.6 exhibited high performance in the detection of EC (AUC=0.9375).

15.
Comput Struct Biotechnol J ; 23: 3315-3326, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39310280

RESUMO

Prostate cancer (PCa) is a multifocal disease characterized by genomic and phenotypic heterogeneity within a single gland. In this study, Visium spatial transcriptomics (ST) analysis was applied to PCa tissues with different histological structures to infer the molecular events involved in Gleason score (GS) progression. The spots in tissue sections were classified into various groups using Principal Component Analysis (PCA) and Louvain clustering analysis based on transcriptome data. Anotation of the spots according to GS revealed notable similarities between transcriptomic profiles and histologically identifiable structures. The accuracy of macroscopic GS determination was bioinformatically verified through malignancy-related feature analysis, specifically inferred copy number variation (inferCNV), as well as developmental trajectory analyses, such as diffusion pseudotime (DPT) and partition-based graph abstraction (PAGA). Genes related to GS progression were identified from the differentially expressed genes (DEGs) through pairwise comparisons of groups along a GS gradient. The proteins encoded by the representative oncogenes UQCRB and LBH were found to be highly expressed in advanced-stage PCa tissues. Knockdown of their mRNAs significantly suppressed PCa cell proliferation and invasion. These findings were validated using The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) dataset, as well as through histological and cytological experiments. The results presented here establish a foundation for ST-based evaluation of GS progression and provide valuable insights into the GS progression-related genes UQCRB and LBH.

16.
Nat Commun ; 15(1): 8243, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39304651

RESUMO

Both plastics and CO2 are waste carbon resources, and their accumulation in nature has led to severe environmental pollution. However, simultaneously converting plastic waste and CO2 into value-added chemicals remains a challenge. Here we demonstrate a catalytic reforming process that converts plastics and CO2 into syngas over an electrified FeCrAl heating wire. The temperature of the electrified heating wire can quickly exceed 800 °C, facilitating the decomposition of polyethylene into gaseous hydrocarbons. The high-temperature heating wire promote the CO2 deoxygenation, resulting in the generation of CO, as well as the dehydrogenation of gaseous hydrocarbons. Significantly, the additional O species from CO2 and the carbon species from hydrocarbons can react to form CO, maintaining the high catalytic activity of the electrified heating wire. This novel approach is of paramount to achieving a circular economy in addressing the ongoing environmental crisis caused by the accumulation of plastic waste and excessive CO2 emissions.

17.
Eur J Pharmacol ; : 177007, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39307335

RESUMO

BACKGROUND: Autophagy plays an important role in the pathogenesis of focal segmental glomerulosclerosis (FSGS). Podocyte-specific Yes-associated protein (YAP) deletion mice, referred to as YAP-KO mice, is considered a new animal model to study the underlying mechanism of FSGS. ROC-325 is a novel small-molecule lysosomal autophagy inhibitor that is more effective than chloroquine (CQ) and hydroxychloroquine (HCQ) in suppressing autophagy. In this study, we sought to determine the therapeutic benefit and mechanism of action of ROC-325 in YAP-KO mice, an experimental FSGS model. METHODS AND RESULTS: YAP-KO mice were treated with ROC-325 (50 mg/kg, p.o.) daily for one month. Our results revealed that albuminuria, mesangial matrix expension, and focal segmental glomerulosclerosis in YAP-KO mice were significantly attenuated by ROC-325 administration. Transmission electron microscopy and immunofluorescence staining showed that ROC-325 treatment significantly inhibited YAP-KO-induced autophagy activation by decreasing autophagosome-lysosome fusion and increasing LC3A/B and p62/SQSTM. Meanwhile, Immunofluorescence staining revealed that preapplication of ROC-325 in podocyte with YAP-targeted siRNA and mRFP-GFP-LC3 adenovirus markedly suppressed autophagic flux in vitro, suggesting that autophagy intervention may serve as a target for FSGS. CONCLUSIONS: These results showed that the role of autophagic activity in FSGS mice model and ROC-325 could be a novel and promising agent for the treatment of FSGS.

18.
Mater Today Bio ; 28: 101191, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39221221

RESUMO

Contemporary progress in tumor immunotherapy has solidified its role as an effective approach in combating cancer. Nonetheless, the prevalent "immune cold" state within the tumor microenvironment poses a substantial barrier to its efficacy. Addressing this, pyroptosis-a gasdermin-mediated programmed cell death characterized by its inflammatory profile-emerges as a crucial mechanism. It catalyzes the release of vast quantities of pro-inflammatory cytokines and immunogens, potentially transforming immunosuppressive "cold" tumors into reactive "hot" ones. Herein, we will initially present an overview of pyroptosis as a distinct form of cell death, along with its molecular mechanisms. Subsequently, we will focus on introducing how pyroptosis activators are utilized in the field of tumor immunotherapy. Insights gained from applications of pyroptosis activators in tumor immunotherapy could lead to the development of safe and efficient pyroptosis activators, significantly enriching the arsenal for tumor immunotherapy.

19.
Artigo em Inglês | MEDLINE | ID: mdl-39223992

RESUMO

BACKGROUND: Rotational atherectomy (RA) remains an integral tool for the treatment of severe coronary calcified lesions despite emergence of newer techniques. We aimed to evaluate the contemporary clinical practices and outcomes of RA in China. METHODS: The Rota China Registry (NCT03806621) was an investigator-initiated, prospective, multicenter registry based on China Rota Elite Group. Consecutive patients treated with RA were recruited. A pre-designed, standardized protocol was recommended for the RA procedure. The primary safety endpoint was major adverse cardiovascular events (MACE: composite of cardiac death, myocardial infarction, or ischemia-driven target lesion revascularization) at 30 days. The primary efficacy endpoint was procedural success. RESULTS: Between July 2018 and December 2020, 980 patients were enrolled at 19 sites in China. Mean patient age was 68.4 years, and 61.4% were men. Radial access was used in 79.1% patients, and 32.7% procedures were guided by intravascular imaging. A total of 22.6% procedures used more than 1 burr, and the maximal burr size was ≥1.75 mm in 24.4% cases, with burr upsizing in 19.3% cases, achieving a final burr-to-artery ratio of 0.52. Procedural success was achieved in 91.1% of patients, and the rate of 30-day and 1-year MACE was 4.9% and 8.2%, respectively. Multivariable analysis identified the total lesion length (HR 1.014, 95% CI: 1.002-1.027; p = 0.021) as predictor of 30-day MACE, and renal insufficiency (HR 1.916, 95% CI: 1.073-3.420; p = 0.028) as predictor of 1-year MACE. CONCLUSIONS: In this contemporary prospective registry in China, the use of RA was effective in achieving high procedural success rate with good short- and long-term outcomes in patients with severely calcified lesions.

20.
J Neurooncol ; 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39225955

RESUMO

OBJECTIVE: This study aimed to develop a predictive model for cerebellar mutism syndrome (CMS) in pediatric patients with posterior fossa tumors, integrating lesion-symptom mapping (LSM) data with clinical factors, and to assess the model's performance. METHODS: A cohort of pediatric patients diagnosed with posterior fossa tumors and undergoing surgery at Beijing Children's Hospital from July 2013 to December 2023 was analyzed. Clinical variables gender, age at surgery, tumor characteristics, hydrocephalus, surgical route and pathology were collected. LSM was used to link tumor locations with CMS outcomes. Lasso regression and logistic regression were employed for feature selection and model construction, respectively. Model performance was assessed using area under the curve (AUC) and accuracy metrics. RESULTS: The study included 197 patients in total, with CMS rates consistent across training, validation, and prospective groups. Significant associations were found between CMS and gender, tumor type, hydrocephalus, paraventricular edema, surgical route, and pathology. A predictive model combining voxel location data from LSM with clinical factors achieved high predictive performance (C-index: training 0.956, validation 0.933, prospective 0.892). Gender, pathology, and voxel location were identified as key predictors for CMS. CONCLUSION: The study established an effective predictive model for CMS in pediatric posterior fossa tumor patients, leveraging LSM data and clinical factors. The model's accuracy and robustness suggest its potential utility in clinical practice for early CMS risk assessment and intervention planning.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...