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1.
Front Immunol ; 15: 1439033, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39234244

RESUMEN

Transformation from non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) is rare and is associated with poor prognosis. However, the standard treatment protocols for patients with SCLC transformation remain unknown. Here, we report the case of a patient with advanced EGFR exon 19 deletion (19del) NSCLC who underwent SCLC transformation during targeted therapy. Biopsies and genetic testing were performed to adjust treatment regimens accordingly. The patient responded favorably to a combined treatment regimen comprising etoposide plus cisplatin chemotherapy and adebrelimab plus osimertinib. This case highlights the critical importance of acknowledging tumor heterogeneity in clinical decision-making and identifying potentially effective treatment options for patients with SCLC transformation. Additionally, we reviewed cases of the transformation of NSCLC to SCLC from 2017 to 2023.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Receptores ErbB , Neoplasias Pulmonares , Mutación , Carcinoma Pulmonar de Células Pequeñas , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/genética , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/patología , Receptores ErbB/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Masculino , Transformación Celular Neoplásica/genética , Persona de Mediana Edad , Etopósido/uso terapéutico , Etopósido/administración & dosificación , Anciano , Acrilamidas , Compuestos de Anilina , Indoles , Pirimidinas
2.
Psychother Psychosom ; : 1-12, 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39312891

RESUMEN

INTRODUCTION: Stress may lead to allostatic overload. Well-being therapy (WBT) might mitigate it by enhancing psychological well-being and protecting from psychological symptoms. Since no reports are available on the use of WBT in allostatic overload, we evaluated online WBT effects in reducing allostatic overload in medical workers during the coronavirus pandemic. METHODS: Sixty-six participants with allostatic overload were enrolled and randomly assigned to eight sessions of online WBT (n = 32) or eight sessions of an online psychoeducation program on healthy lifestyle (CON) (n = 34). The primary outcome was the prevalence rate of allostatic overload in the two groups at session 8 (T2). Secondary analyses were performed on changes in the PsychoSocial Index (PSI) and Psychological Well-Being (PWB) scales scores at the same time points. Generalized estimating equation models were employed. RESULTS: The WBT group showed a significantly lower rate of allostatic overload at T2 than the CON group (28.13% vs. 70.59%, p < 0.001); similar results were found at T1, T3, and T4 (p < 0.001). Compared to CON, WBT produced a significant decrease in psychological distress (p < 0.001) and abnormal illness behavior (p = 0.031), as well as a significant improvement in PWB autonomy, environmental mastery, personal growth, positive relations with others, purpose in life, and self-acceptance (p < 0.001). CONCLUSION: Online WBT may be an effective non-pharmacological therapeutic strategy for individuals with allostatic overload. These findings need to be further validated in different clinical populations.

3.
Artículo en Inglés | MEDLINE | ID: mdl-39325344

RESUMEN

Early embryonic arrest (EEA) is a critical impediment in assisted reproductive technology (ART), affecting 40% of infertile patients by halting the development of early embryos from the zygote to blastocyst stage, resulting in a lack of viable embryos for successful pregnancy. Despite its prevalence, the molecular mechanism underlying EEA remains elusive. This review synthesizes the latest research on the genetic and molecular factors contributing to EEA, with a focus on maternal, paternal, and embryonic factors. Maternal factors such as irregularities in follicular development and endometrial environment, along with mutations in genes like NLRP5, PADI6, KPNA7, IGF2, and TUBB8, have been implicated in EEA. Specifically, PATL2 mutations are hypothesized to disrupt the maternal-zygotic transition, impairing embryo development. Paternal contributions to EEA are linked to chromosomal variations, epigenetic modifications, and mutations in genes such as CFAP69, ACTL7A, and M1AP, which interfere with sperm development and lead to infertility. Aneuploidy may disrupt spindle assembly checkpoints and pathways including Wnt, MAPK, and Hippo signaling, thereby contributing to EEA. Additionally, key genes involved in embryonic genome activation-such as ZSCAN4, DUXB, DUXA, NANOGNB, DPPA4, GATA6, ARGFX, RBP7, and KLF5-alongside functional disruptions in epigenetic modifications, mitochondrial DNA, and small non-coding RNAs, play critical roles in the onset of EEA. This review provides a comprehensive understanding of the genetic and molecular underpinnings of EEA, offering a theoretical foundation for the diagnosis and potential therapeutic strategies aimed at improving pregnancy outcomes.

4.
Artículo en Inglés | MEDLINE | ID: mdl-39167530

RESUMEN

Venous malformation is acongenital vascular system structure malformation caused by abnormal vascular endothelial cell morphology, which can occur in any tissue or organ of the oral and maxillofacial region. Laser treatment is currently a commonly used minimally invasive treatment. In this case, the patient with congenital multiple venous malformation was treated with Nd:YAG laser for the visible submucosal part, and the subcutaneous part under the chin tip was treated with ultrasound. The chin tip was treated with ultrasound guided by the chair to achieve the purpose of minimally invasive laser treatment. In this case's diagnosis and treatment process, we hope to provide a new idea for laser treatment of oromaxillofacial vein malformations.

5.
Front Public Health ; 12: 1450935, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39171313

RESUMEN

Background: Recent years have seen an increase in school refusal behavior among adolescents, potentially due to factors like excessive short-form video viewing, bullying, and school anxiety. Limited research has investigated how these factors contribute to school refusal behavior. This study used random forest regression, path analysis, and network analysis to identify key variables and pathways leading to school refusal behavior. Methods: In this cross-sectional questionnaire-based study, 2,056 (996 male, 1,060 female, mean age: 14.79 ± 1.24 years) middle and senior high school students were asked to complete the School Refusal Behavior Assessment questionnaire to assess school refusal behavior features, the Excessive Short-Form Video Viewing Scale as well as self-reported viewing times during leisure days to assess excessive short-form video viewing, the SNAP-IV Rating Scale to assess the severity of inattention symptoms, and the self-administered questionnaires to assess experiences of being bullied and school anxiety. Results: The prevalence of school refusal behavior in the surveyed adolescents was found to be 31.9% [95% confidence interval (CI): 29.8-33.9%]. In terms of significance, the severity of inattention symptoms exhibited the greatest predictive power, while excessive short-form video viewing accounted for the most variance. Path analysis revealed that excessive short-form video viewing not only directly affects school refusal behavior features but also does so indirectly through severity of inattention symptoms and school anxiety. Key bridge factors in this pathway include intense fear and anxiety associated with school attendance, manifesting as somatic symptoms and avoidance behaviors. Conclusion: The findings indicate that not only does excessive short-form video viewing directly influence school refusal behavior features in adolescents, but it also indirectly impacts these features through mechanisms involving severity of inattention symptoms and school anxiety. The bridge factors highlight potential targets for interventions among the SRB features and predictors.


Asunto(s)
Conducta del Adolescente , Ansiedad , Acoso Escolar , Instituciones Académicas , Estudiantes , Humanos , Adolescente , Femenino , Masculino , Estudios Transversales , Acoso Escolar/psicología , Acoso Escolar/estadística & datos numéricos , Encuestas y Cuestionarios , Ansiedad/psicología , Conducta del Adolescente/psicología , Estudiantes/psicología , Estudiantes/estadística & datos numéricos
6.
Molecules ; 29(16)2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39202815

RESUMEN

Sonosensitizers play a crucial role in the efficacy of sonodynamic antitumor therapy (SDT) and sonodynamic antimicrobial chemotherapy (SACT), highlighting the necessity for the development of new compounds with good sonodynamic activity. In this study, three novel 3-substituted ciprofloxacin derivatives (CIPD1, CIPD2, and CIPD3) were designed and synthesized. Their sonodynamic activities were evaluated by assessing the damage to bovine serum albumin (BSA) and Escherichia coli (E. coli). Furthermore, the potential mechanism underlying their sonodynamic damage activities was investigated by detecting reactive oxygen species (ROS) under ultrasound irradiation (US). The results demonstrated that all three derivatives exhibited enhanced sonodynamic damage to BSA and E. coli under US, with CIPD1 and CIPD2 showing superior effectiveness compared to CIP. Both the concentrations of derivatives and the duration of ultrasound irradiation were found to significantly impact their sonodynamic effects. All three CIP derivates could be activated to produce ROS following ultrasound irradiation, primarily consisting of 1O2 and ·OH. The levels of ROS production were positively correlated with their sonodynamic activities, potentially explaining the mechanism underlying their sonodynamic damage activities.


Asunto(s)
Ciprofloxacina , Escherichia coli , Especies Reactivas de Oxígeno , Albúmina Sérica Bovina , Ciprofloxacina/farmacología , Ciprofloxacina/química , Especies Reactivas de Oxígeno/metabolismo , Escherichia coli/efectos de los fármacos , Albúmina Sérica Bovina/química , Ondas Ultrasónicas , Animales , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química
8.
Funct Integr Genomics ; 24(4): 135, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39117866

RESUMEN

Gene co-expression networks may encode hitherto inadequately recognized vulnerabilities for adult gliomas. By identifying evolutionally conserved gene co-expression modules around EGFR (EM) or PDGFRA (PM), we recently proposed an EM/PM classification scheme, which assigns IDH-wildtype glioblastomas (GBM) into the EM subtype committed in neural stem cell compartment, IDH-mutant astrocytomas and oligodendrogliomas into the PM subtype committed in early oligodendrocyte lineage. Here, we report the identification of EM/PM subtype-specific gene co-expression networks and the characterization of hub gene polypyrimidine tract-binding protein 1 (PTBP1) as a genomic alteration-independent vulnerability in IDH-wildtype GBM. Supervised by the EM/PM classification scheme, we applied weighted gene co-expression network analysis to identify subtype-specific global gene co-expression modules. These gene co-expression modules were characterized for their clinical relevance, cellular origin and conserved expression pattern during brain development. Using lentiviral vector-mediated constitutive or inducible knockdown, we characterized the effects of PTBP1 on the survival of IDH-wildtype GBM cells, which was complemented with the analysis of PTBP1-depedent splicing pattern and overexpression of splicing target neuron-specific CDC42 (CDC42-N) isoform.  Transcriptomes of adult gliomas can be robustly assigned into 4 large gene co-expression modules that are prognostically relevant and are derived from either malignant cells of the EM/PM subtypes or tumor microenvironment. The EM subtype is associated with a malignant cell-intrinsic gene module involved in pre-mRNA splicing, DNA replication and damage response, and chromosome segregation, and a microenvironment-derived gene module predominantly involved in extracellular matrix organization and infiltrating immune cells. The PM subtype is associated with two malignant cell-intrinsic gene modules predominantly involved in transcriptional regulation and mRNA translation, respectively. Expression levels of these gene modules are independent prognostic factors and malignant cell-intrinsic gene modules are conserved during brain development. Focusing on the EM subtype, we identified PTBP1 as the most significant hub for the malignant cell-intrinsic gene module. PTBP1 is not altered in most glioma genomes. PTBP1 represses the conserved splicing of CDC42-N. PTBP1 knockdown or CDC42-N overexpression disrupts actin cytoskeleton dynamics, causing accumulation of reactive oxygen species and cell apoptosis. PTBP1-mediated repression of CDC42-N splicing represents a potential genomic alteration-independent, developmentally conserved vulnerability in IDH-wildtype GBM.


Asunto(s)
Glioblastoma , Ribonucleoproteínas Nucleares Heterogéneas , Proteína de Unión al Tracto de Polipirimidina , Proteína de Unión al GTP cdc42 , Proteína de Unión al Tracto de Polipirimidina/genética , Proteína de Unión al Tracto de Polipirimidina/metabolismo , Humanos , Ribonucleoproteínas Nucleares Heterogéneas/genética , Ribonucleoproteínas Nucleares Heterogéneas/metabolismo , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/patología , Proteína de Unión al GTP cdc42/genética , Proteína de Unión al GTP cdc42/metabolismo , Línea Celular Tumoral , Isocitrato Deshidrogenasa/genética , Isocitrato Deshidrogenasa/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Redes Reguladoras de Genes , Regulación Neoplásica de la Expresión Génica , Empalme del ARN , Neuronas/metabolismo , Neuronas/patología
9.
Neural Netw ; 179: 106515, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39032393

RESUMEN

Accurate image reconstruction is crucial for photoacoustic (PA) computed tomography (PACT). Recently, deep learning has been used to reconstruct PA images with a supervised scheme, which requires high-quality images as ground truth labels. However, practical implementations encounter inevitable trade-offs between cost and performance due to the expensive nature of employing additional channels for accessing more measurements. Here, we propose a masked cross-domain self-supervised (CDSS) reconstruction strategy to overcome the lack of ground truth labels from limited PA measurements. We implement the self-supervised reconstruction in a model-based form. Simultaneously, we take advantage of self-supervision to enforce the consistency of measurements and images across three partitions of the measured PA data, achieved by randomly masking different channels. Our findings indicate that dynamically masking a substantial proportion of channels, such as 80%, yields meaningful self-supervisors in both the image and signal domains. Consequently, this approach reduces the multiplicity of pseudo solutions and enables efficient image reconstruction using fewer PA measurements, ultimately minimizing reconstruction error. Experimental results on in-vivo PACT dataset of mice demonstrate the potential of our self-supervised framework. Moreover, our method exhibits impressive performance, achieving a structural similarity index (SSIM) of 0.87 in an extreme sparse case utilizing only 13 channels, which outperforms the performance of the supervised scheme with 16 channels (0.77 SSIM). Adding to its advantages, our method can be deployed on different trainable models in an end-to-end manner, further enhancing its versatility and applicability.


Asunto(s)
Aprendizaje Profundo , Procesamiento de Imagen Asistido por Computador , Técnicas Fotoacústicas , Tomografía Computarizada por Rayos X , Técnicas Fotoacústicas/métodos , Animales , Procesamiento de Imagen Asistido por Computador/métodos , Ratones , Tomografía Computarizada por Rayos X/métodos , Aprendizaje Automático Supervisado , Redes Neurales de la Computación , Algoritmos
10.
Clin Mol Hepatol ; 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38988296

RESUMEN

Background & Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvedilol-treating cohort. Results: In the meta-analysis with six studies (n = 819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new "CSPH risk" model. In the HVPG cohort (n = 151), the new model accurately predicted CSPH with cutoff values of 0 and -0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n = 1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <-0.68 (low-risk), -0.68 to 0 (medium-risk), and >0 (high-risk). In the carvedilol-treated cohort, patients with high-risk CSPH treated with carvedilol (n = 81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n = 613 before propensity score matching [PSM], n = 162 after PSM). Conclusions: Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

11.
J Nanobiotechnology ; 22(1): 390, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38961442

RESUMEN

BACKGROUND: Zinc oxide nanoparticle (ZnO NP) is one of the metal nanomaterials with extensive use in many fields such as feed additive and textile, which is an emerging threat to human health due to widely distributed in the environment. Thus, there is an urgent need to understand the toxic effects associated with ZnO NPs. Although previous studies have found accumulation of ZnO NPs in testis, the molecular mechanism of ZnO NPs dominated a decline in male fertility have not been elucidated. RESULTS: We reported that ZnO NPs exposure caused testicular dysfunction and identified spermatocytes as the primary damaged site induced by ZnO NPs. ZnO NPs led to the dysfunction of spermatocytes, including impaired cell proliferation and mitochondrial damage. In addition, we found that ZnO NPs induced ferroptosis of spermatocytes through the increase of intracellular chelatable iron content and lipid peroxidation level. Moreover, the transcriptome analysis of testis indicated that ZnO NPs weakened the expression of miR-342-5p, which can target Erc1 to block the NF-κB pathway. Eventually, ferroptosis of spermatocytes was ameliorated by suppressing the expression of Erc1. CONCLUSIONS: The present study reveals a novel mechanism in that miR-342-5p targeted Erc1 to activate NF-κB signaling pathway is required for ZnO NPs-induced ferroptosis, and provide potential targets for further research on the prevention and treatment of male reproductive disorders related to ZnO NPs.


Asunto(s)
Ferroptosis , MicroARNs , FN-kappa B , Transducción de Señal , Espermatocitos , Testículo , Óxido de Zinc , Animales , Masculino , Ratones , Proliferación Celular/efectos de los fármacos , Ferroptosis/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Nanopartículas del Metal/química , MicroARNs/metabolismo , MicroARNs/genética , FN-kappa B/metabolismo , Transducción de Señal/efectos de los fármacos , Espermatocitos/metabolismo , Espermatocitos/efectos de los fármacos , Testículo/metabolismo , Testículo/efectos de los fármacos , Óxido de Zinc/farmacología , Óxido de Zinc/química
12.
Wideochir Inne Tech Maloinwazyjne ; 19(1): 91-99, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38974766

RESUMEN

Introduction: Both hook-wire (HW) and anchored needle (AN) techniques can be used for preoperative computed tomography (CT)-guided localization for pulmonary nodules (PNs). But the outcomes associated with these two materials remain unclear. Aim: To assess the relative safety and efficacy of preoperative CT-guided HW and AN localization for PNs. Material and methods: This was a retrospective analysis of data collected from two institutions. Consecutive patients with PNs between January 2020 and December 2021 who underwent preoperative CT-guided HW or AN localization followed by video-assisted thoracoscopic surgery (VATS) procedures were included in these analyses, which compared the safety and clinical efficiency of these two localization strategies. Results: In total, 98 patients (105 PNs) and 93 patients (107 PNs) underwent CT-guided HW and AN localization procedures, respectively. The HW and AN groups exhibited similar rates of successful PN localization (95.2% vs. 99.1%, p = 0.117), but the dislodgement rate in the HW group was significantly higher than that for the AN group (4.8% vs. 0.0%, p = 0.029). The mean pain score of patients in the HW group was significantly higher than that for the AN group (p = 0.001). HW and AN localization strategies were associated with comparable pneumothorax (21.4% vs. 16.1%, p = 0.349) and pulmonary hemorrhage (29.6% vs. 23.7%, p = 0.354) rates. All patients other than 1 individual in the HW group successfully underwent VATS-guided limited resection. Conclusions: These data suggest that AN represents a safe, well-tolerated, feasible preoperative localization strategy for PNs that may offer value as a replacement for HW localization.

14.
Gut Pathog ; 16(1): 35, 2024 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-38972976

RESUMEN

An increasing number of studies have shown that the consumption of soybeans and soybeans products is beneficial to human health, and the biological activity of soy products may be attributed to the presence of Soy Isoflavones (SI) in soybeans. In the intestinal tracts of humans and animals, certain specific bacteria can metabolize soy isoflavones into equol. Equol has a similar chemical structure to endogenous estradiol in the human body, which can bind with estrogen receptors and exert weak estrogen effects. Therefore, equol plays an important role in the occurrence and development of a variety of hormone-dependent malignancies such as breast cancer and prostate cancer. Despite the numerous health benefits of equol for humans, only 30-50% of the population can metabolize soy isoflavones into equol, with individual variation in gut microbiota being the main reason. This article provides an overview of the relevant gut microbiota involved in the synthesis of equol and its anti-tumor effects in various types of cancer. It also summarizes the molecular mechanisms underlying its anti-tumor properties, aiming to provide a more reliable theoretical basis for the rational utilization of equol in the field of cancer treatment.

15.
Angew Chem Int Ed Engl ; : e202411166, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39008335

RESUMEN

Molecular editing promises to facilitate the rapid diversification of complex molecular architectures by rapidly and conveniently altering core frameworks. This approach has the potential to accelerate both drug discovery and total synthesis. In this study, we present a novel protocol for the molecular editing of pyrroles. Initially, N-Boc pyrroles and alkynes are converted into N-bridged compounds through a Diels-Alder reaction. These compounds then undergo deprotection of the Boc group, nitrosylation, and cheletropic N2O extrusion to yield benzene or naphthalene products. By using benzyne as a substrate, this method can be conceptually viewed as a fusion of skeletal editing of the pyrrole ring and site-selective peripheral editing of the benzene ring. Furthermore, this proof-of-concept protocol has demonstrated its potential to transform the (hetero)arene motif from commercially available drugs, offering the possibility of generating new biologically active compounds.

16.
Arch Oral Biol ; 167: 106055, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39067325

RESUMEN

OBJECTIVE: The molecular regulation of odontoblasts in dentin formation remains largely uncharacterized. Using neohesperidin (NEO), a well-documented osteoblast regulator, we investigated whether and how NEO participates in odontoblast regulation through longitudinal treatments using various doses of NEO. DESIGN: Mouse dental papilla cell-23 (MDPC-23) served as a model for odontoblasts. MDPC-23 were treated with various doses of NEO (0, 1, 5, 10, 15, 20 µmol/L). Proliferation was assessed using the Cell counting kit-8 assay. Survival/apoptosis was assayed by live/dead ratio. Migration capability was assessed using scratch healing and Transwell migration assays. Mineralization was assessed using alkaline phosphatase staining and alizarin red staining. The expression levels of four key genes (Runx2, osteocalcin [OCN], ß-catenin, and bone morphogenetic protein [BMP]-2) representing NEO-induced differentiation of MDPC-23 were measured by quantitative reverse transcription polymerase chain reaction. RESULTS: The proliferation trajectories of MDPC-23 treated with the five doses of NEO demonstrated similar curves, with a rapid increase in the 10 µmol/L NEO condition after 48 h of treatment. Similar dose-dependent trajectories were observed for survival/apoptosis. All four key genes representing odontogenic differentiation were upregulated in MDPC-23 induced by NEO treatments at two optimal doses (5 µmol/L and 10 µmol/L). Optimal migration and mobility trajectories were observed in MDPC-23 treated with 10 µmol/L NEO. Optimal mineralization was observed in MDPC-23 treated with 5 µmol/L NEO. CONCLUSION: NEO can subtly regulate odontoblast proliferation, differentiation, migration, and mineralization in vitro. NEO at 5-10 µmol/L offers a safe and effective perspective for clinical promotion of dentin bridge formation in teenagers.


Asunto(s)
Apoptosis , Diferenciación Celular , Movimiento Celular , Proliferación Celular , Papila Dental , Hesperidina , Odontoblastos , Animales , Ratones , Proliferación Celular/efectos de los fármacos , Hesperidina/farmacología , Hesperidina/análogos & derivados , Diferenciación Celular/efectos de los fármacos , Odontoblastos/efectos de los fármacos , Papila Dental/citología , Papila Dental/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Osteocalcina/metabolismo , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Técnicas In Vitro , Proteína Morfogenética Ósea 2/farmacología , Supervivencia Celular/efectos de los fármacos , beta Catenina/metabolismo , Fosfatasa Alcalina/metabolismo , Células Cultivadas , Reacción en Cadena en Tiempo Real de la Polimerasa
17.
Aging (Albany NY) ; 16(14): 11318-11338, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-39028290

RESUMEN

BACKGROUND: The aim of this study was to investigate the correlation between m6A methylation regulators and cell infiltration characteristics in tumor immune microenvironment (TIME), so as to help understand the immune mechanism of early-stage lung adenocarcinoma (LUAD). METHODS: The expression and consensus cluster analyses of m6A methylation regulators in early-stage LUAD were performed. The clinicopathological features, immune cell infiltration, survival and functional enrichment in different subtypes were analyzed. We also constructed a prognostic model. Clinical tissue samples were used to validate the expression of model genes through real-time polymerase chain reaction (RT-PCR). In addition, cell scratch assay and Transwell assay were also performed. RESULTS: Expression of m6A methylation regulators was abnormal in early-stage LUAD. According to the consensus clustering of m6A methylation regulators, patients with early-stage LUAD were divided into two subtypes. Two subtypes showed different infiltration levels of immune cell and survival time. A prognostic model consisting of HNRNPC, IGF2BP1 and IGF2BP3 could be used to predict the survival of early-stage LUAD. RT-PCR results showed that HNRNPC, IGF2BP1 and IGF2BP3 were significantly up-regulated in early-stage LUAD tissues. The results of cell scratch assay and Transwell assay showed that overexpression of HNRNPC promotes the migration and invasion of NCI-H1299 cells, while knockdown HNRNPC inhibits the migration and invasion of NCI-H1299 cells. CONCLUSIONS: This work reveals that m6A methylation regulators may be potential biomarkers for prognosis in patients with early-stage LUAD. Our prognostic model may be of great value in predicting the prognosis of early-stage LUAD.


Asunto(s)
Adenocarcinoma del Pulmón , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares , Microambiente Tumoral , Humanos , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/inmunología , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/mortalidad , Pronóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/mortalidad , Ribonucleoproteína Heterogénea-Nuclear Grupo C/genética , Ribonucleoproteína Heterogénea-Nuclear Grupo C/metabolismo , Femenino , Masculino , Análisis por Conglomerados , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Metilación , Línea Celular Tumoral , Estadificación de Neoplasias , Adenosina/análogos & derivados , Adenosina/metabolismo , Adenosina/genética , Persona de Mediana Edad , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo
18.
Blood Purif ; 53(9): 755-767, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38901418

RESUMEN

INTRODUCTION: Chronic kidney disease-associated pruritus (CKD-aP) frequently occurs in patients with end-stage renal disease (ESRD) undergoing peritoneal dialysis (PD) and presents a therapeutic challenge to physicians owing to the diversity of its pathogenesis. Herein, we developed and validated a nomogram model for individualized risk estimation of CKD-aP and investigated the possible causes of CKD-aP in PD patients. METHODS: We retrospectively screened patients with CKD-aP who underwent PD between 2021 and 2023 at the First Affiliated Hospital of Xi'an Jiaotong University Peritoneal Dialysis Center. Nomograms for each outcome were computed from multivariate logistic regression models with the least absolute shrinkage and selection operator regression and univariate logistic regression for variable selection. The discriminative ability was estimated by Harrell's C-index, and the accuracy was assessed graphically with a calibration curve plot. Models were validated internally using bootstrapping and externally by calculating their performance on a validation cohort. Decision curve analysis was used to assess the model's clinical usefulness. RESULTS: In all, a total of 487 patients were entered in the analysis, including 325 in the development cohort and 162 in the validation cohort. The final nomogram incorporated five variables: age, interleukin-6, hemoglobin, residual urine volume, and renal Kt/V. The C-index of the model was 0.733 (95% CI: 0.679-0.787), and the calibration curve was a straight line with a slope close to 1. Both internal and external validations confirmed the model's good performance, with C-index of 0.725 (95% CI: 0.662-0.774) and 0.706 (95% CI: 0.623-0.789), respectively. Decision curve analysis showed that the nomogram had good clinical benefits. CONCLUSION: Our study proposes a nomogram model for CKD-aP risk assessment in ESRD patients with PD. This nomogram might help in clinical decision-making and evidence-based selection of therapy.


Asunto(s)
Fallo Renal Crónico , Nomogramas , Diálisis Peritoneal , Prurito , Humanos , Diálisis Peritoneal/efectos adversos , Fallo Renal Crónico/terapia , Fallo Renal Crónico/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Prurito/etiología , Prurito/epidemiología , Estudios Retrospectivos , Anciano , Adulto , Insuficiencia Renal Crónica/terapia , Insuficiencia Renal Crónica/complicaciones , Medición de Riesgo , Factores de Riesgo
19.
Org Lett ; 26(24): 5115-5119, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38862412

RESUMEN

An ammonium ylide-based relay annulation was disclosed, which uses DABCO as the catalyst and oxindole-derived α,ß-unsaturated ketimines and γ-bromo-crotonates as the starting materials. This method enables the rapid assembly of a series of structurally novel spiro-polycyclic oxindoles containing a bicyclo[4.1.0]heptane moiety through simultaneous generation of three new bonds and two rings in one step under mild reaction conditions.

20.
Front Microbiol ; 15: 1391553, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38841075

RESUMEN

Introduction: The composition and structure of natural soil are very complex, leading to the difficult contact between hydrophobic organic compounds and degrading-bacteria in contaminated soil, making pollutants hard to be removed from the soil. Several researches have reported the bacterial migration in unsaturated soil mediated by fungal hyphae, but bacterial movement in soil of different particle sizes or in heterogeneous soil was unclear. The remediation of contaminated soil enhanced by hyphae still needs further research. Methods: In this case, the migration and biodegradation of Diaphorobacter sp. LW2 in soil was investigated in presence of Pythium ultimum. Results: Hyphae could promote the growth and migration of LW2 in culture medium. It was also confirmed that LW2 was able to migrate in the growth direction and against the growth direction along hyphae. Mediated by hyphae, motile strain LW2 translocated over 3 cm in soil with different particle size (CS1, 1.0-2.0 mm; CS2, 0.5-1.0mm; MS, 0.25-0.5 mm and FS, <0.25 mm), and it need shorter time in bigger particle soils. In inhomogeneous soil, hyphae participated in the distribution of introduced bacteria, and the total number of bacteria increased. Pythium ultimum enhanced the migration and survival of LW2 in soil, improving the bioremediation of polluted soil. Discussion: The results of this study indicate that the mobilization of degrading bacteria mediated by Pythium ultimum in soil has great potential for application in bioremediation of contaminated soil.

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