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1.
Biol Direct ; 19(1): 95, 2024 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-39425187

RESUMEN

BACKGROUND: MicroRNA host gene (MIRHG) lncRNA is a particular lncRNA subclass that can perform both typical and atypical lncRNA functions. The biological function of MIRHG lncRNA MIR194-2HG in cancer is poorly understood. METHODS: Loss-of-function studies were performed in vivo and in vitro to reveal the biological function of MIR194-2HG in GC. MicroRNA PCR array, northern blotting, RNA sequencing, chromatin immunoprecipitation, and rescue assays were conducted to uncover the molecular mechanism of MIR194-2HG. RESULTS: In this study, we reported an atypical lncRNA function of MIR194-2HG in GC. MIR194-2HG downregulation was clinically associated with malignant progression and poor prognosis in GC. Functional assays confirmed that MIR194-2HG knockdown significantly promoted GC proliferation and metastasis in vitro and in vivo. Mechanismically, MIR194-2HG was required for the biogenesis of miR-194 and miR-192, which were reported to be tumor-suppressor genes in GC. Moreover, hepatocyte nuclear factor HNF4A directly activated the transcription of MIR194-2HG and its derived miR-194 and miR-192. Meanwhile, BTF3L4 was proved to be a common target gene of miR-192 and miR-194. Rescue assay further confirmed that MIR194-2HG knockdown promotes GC progression through maintaining BTF3L4 overexpression in a miR-194/192-dependent manner. CONCLUSION: The dysregulated MIR194-2HG/BTF3L4 axis is responsible for GC progression. Targeting HNF4A to inhibit miR-192/194 expression may be a promising strategy for overcoming GC.


Asunto(s)
Factor Nuclear 4 del Hepatocito , MicroARNs , ARN Largo no Codificante , Neoplasias Gástricas , MicroARNs/genética , MicroARNs/metabolismo , Humanos , Factor Nuclear 4 del Hepatocito/genética , Factor Nuclear 4 del Hepatocito/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Línea Celular Tumoral , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Regulación Neoplásica de la Expresión Génica , Animales , Ratones , Proliferación Celular , Ratones Desnudos , Masculino , Femenino
2.
Chemosphere ; 365: 143394, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39307469

RESUMEN

The discharge of metal nanoparticles into the water inevitably poses a threat to aquatic organisms and the balance of the aquatic ecosystem. Photoperiod is one of the most important ecological factors for the development of cladocerans. In addition, different light conditions can also affect the toxicity of metal nanoparticles. In this study, we studied the effects of four photoperiods (8L/16D, 10L/14D, 14L/10D, and 16L/8D) combined with three concentrations of ZnO NPs (0 mg L-1, 0.05 mg L-1, and 0.10 mg L-1) on the growth and reproduction of Daphnia pulex. With the increase of photoperiod, the maternal body size and growth rate increased first and then decreased; the first time to reproduction was advanced, and broods and the total offspring also increased. Under the influence of ZnO NPs, growth rate and reproductive capacity were inhibited. The photoperiod 8L/16D and 16L/8D interacted with ZnO NPs on the growth of D. pulex, which significantly decreased the growth rate. Besides, the interaction between photoperiod 8L/16D and ZnO NPs decreased the reproduction ability of D. pulex. These results suggest that the effects of zinc oxide nanoparticles on the growth and reproduction of D. pulex is photoperiod dependent, which is useful for assessing the risk of pollutants to cladoceras under different light conditions.


Asunto(s)
Daphnia , Nanopartículas del Metal , Fotoperiodo , Reproducción , Contaminantes Químicos del Agua , Óxido de Zinc , Animales , Daphnia/efectos de los fármacos , Daphnia/crecimiento & desarrollo , Daphnia/fisiología , Óxido de Zinc/toxicidad , Reproducción/efectos de los fármacos , Nanopartículas del Metal/toxicidad , Contaminantes Químicos del Agua/toxicidad , Daphnia pulex
3.
J Allergy Clin Immunol Glob ; 3(4): 100302, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39228895

RESUMEN

Background: Eosinophilic esophagitis (EoE) is a chronic, inflammatory disease of the esophagus leading to symptoms of esophageal dysfunction; dysphagia is the most common symptom experienced by adults and adolescents. Objective: We sought to perform a psychometric evaluation of the Dysphagia Symptom Questionnaire (DSQ), a patient-reported outcome measure for patients with EoE. Methods: Using baseline and week 24 data from the randomized, interventional, multinational phase 3 R668-EE-1774 trial (NCT03633617), the measurement properties of the DSQ-including reliability, construct and known-groups validity, responsiveness, and interpretation of change-were evaluated. Results: The analysis population comprised 239 patients with EoE (age [mean ± SD], 28.1 ± 13.14 years; 63.6% male; 90.4% White). Intraclass correlation coefficients of 0.92 and 0.97 exceeded the acceptable reliability threshold (≥0.70). Construct validity correlations with EoE symptom and impact measures were moderate at baseline (|r| = 0.44-0.55) and week 24 (|r| = 0.55-0.69), and the DSQ biweekly total score discriminated among groups defined by disease severity. Analyses exploring interpretation of change from baseline on the DSQ biweekly total score indicated thresholds for within-patient improvement ranging from 9 to 23 points; a within-patient improvement from baseline of 13 points or greater could be considered clinically meaningful. Conclusions: This analysis confirmed that the DSQ has acceptable distributional properties, test-retest reliability, construct validity, and ability to detect change. Therefore, the DSQ is a valid and reliable measure to assess the patient-reported symptom of dysphagia among adult and adolescent patients with EoE in the context of a clinical trial setting.

4.
Biochem Biophys Res Commun ; 737: 150509, 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39137587

RESUMEN

Salt stress is one of the significant environmental stresses that severely affect plant growth and development. Here, we report quantitative N-glycoproteomics characterization of differential N-glycosylation in Sorghum bicolor under low, median and high salinity stress. 21,621 intact N-glycopeptides coming from the combination of 127 N-glycan structures on 6574 N-glycosites from 5321 proteins were identified; differential N-glycosylation was observed for 682 N-glycoproteins which are mainly involved in the pathways of biosynthesis of secondary metabolites, biosynthesis of amino acids and several metabolic pathways. 41 N-glycan structures modifying on 338 N-glycopeptides from 122 glycoproteins were co-quantified and deregulated under at least one salt stress, including enzymes of energy production and carbohydrate metabolisms, cell wall organization related proteins, glycosyltransferases and so on. Intriguingly, with increasing salt concentration, there was an increase in the percentage of complex N-glycans on the altered N-glycopeptides. Furthermore, the observation of glycoproteins with distinct salt sensitivity is noteworthy, particularly the upregulated hyposensitive glycoproteins that predominantly undergo complex N-glycan modification. This is the first N-glycoproteome description of salt stress response at the intact N-glycopeptide level in sorghum and a further validation of data reported here would likely provide deeper insights into the stress physiology of this important crop plant.

5.
Materials (Basel) ; 17(13)2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38998414

RESUMEN

This paper comprehensively summarizes moisture transport, ion transport, and mechanical damage models applied to concrete under sulfate attack and drying-wetting cycles. It highlights the essential aspects and principles of each model, emphasizing their significance in understanding the movement of moisture and ions, as well as the resulting mechanical damage within the concrete during these degradation processes. The paper critically analyzes the assumptions made in each model, shedding light on their limitations and implications for prediction accuracy. Two primary challenges faced by current models under sulfate attack and drying-wetting cycles are identified: the limited consideration of the coupled effects of chemical and physical attacks from sulfate, and the unclear mechanism of the sulfate attacks. Future research directions are proposed, focusing on exploring the transport mechanism of sulfate ions under various driving forces and further clarifying the crystallization process and expansion damage mechanism in concrete pores. Addressing these research directions will advance our understanding of sulfate attack under drying-wetting cycles, leading to improved models and mitigation strategies for enhancing the durability and performance of concrete structures.

6.
J Exp Clin Cancer Res ; 43(1): 188, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38965605

RESUMEN

BACKGROUND: The vast majority of lncRNAs have low expression abundance, which greatly limits their functional range and impact. As a high expression abundance lncRNA, FGD5-AS1's non-ceRNA biological function in cancer is unclear. METHODS: RNA-seq studies and chromatin immunoprecipitation (Chip) assays were performed to identify ZEB1-regulated lncRNAs. RNA sequencing, RNA pulldown, RNA Immunoprecipitation assays, and rescue assays were conducted to explore the molecular mechanisms of FGD5-AS1 in GC. RESULTS: As one of the most abundant lncRNAs in cells, FGD5-AS1 has been shown to be transcriptionally activated by ZEB1, thus closely related to epithelial-mesenchymal transition (EMT) signaling. Clinical analysis showed that FGD5-AS1 overexpression was clinically associated with lymph node metastasis, and predicted poor survival in GC. Loss-of-function studies confirmed that FGD5-AS1 knockdown inhibited GC proliferation and induced cisplatin chemosensibility, cell senescence, and DNA damage in GC cells. Mechanismically, FGD5-AS1 is a YBX1-binding lncRNA due to its mRNA contains three adjacent structural motifs (UAAUCCCA, ACCAGCCU, and CAGUGAGC) that can be recognized and bound by YBX1. And this RNA-protein interaction prolonged the half-life of the YBX1 protein in GC. Additionally, a rescue assay showed that FGD5-AS1 promotes GC by repressing cell senescence and ROS production via YBX1. CONCLUSION: FGD5-AS1 is a cellular high-abundant lncRNA that is transcriptionally regulated by ZEB1. FGD5-AS1 overexpression promoted GC progression by inhibiting cell senescence and ROS production through binding and stabilizing the YBX1 protein.


Asunto(s)
Proliferación Celular , Senescencia Celular , ARN Largo no Codificante , Especies Reactivas de Oxígeno , Neoplasias Gástricas , Proteína 1 de Unión a la Caja Y , Humanos , Proteína 1 de Unión a la Caja Y/metabolismo , Proteína 1 de Unión a la Caja Y/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Ratones , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Neoplasias Gástricas/metabolismo , Animales , Línea Celular Tumoral , Femenino , Masculino , Regulación Neoplásica de la Expresión Génica , Transición Epitelial-Mesenquimal , Factores de Intercambio de Guanina Nucleótido
7.
Anal Bioanal Chem ; 416(20): 4531-4541, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38922433

RESUMEN

Glycation is a non-enzymatic posttranslational modification coming from the reaction between reducing sugars and free amino groups in proteins, where early glycation products (fructosyl-lysine, FL) and advanced glycation end products (AGEs) are formed. The occurrence of glycation and accumulation of AGEs have been closely associated with hepatocellular carcinoma (HCC). Here, we reported the characterization of differential glycation in HCC using tissue proteomics with stable isotopic labeling; early glycation-modified peptides were enriched with boronate affinity chromatography (BAC), and AGEs-modified peptides were fractionated with basic reversed-phase separation. By this integrated approach, 3717 and 1137 early and advanced glycated peptides corresponding to 4007 sites on 1484 proteins were identified with a false discovery rate (FDR) of no more than 1%. One hundred fifty-five sites were modified with both early and advanced end glycation products. Five early and 7 advanced glycated peptides were quantified to be differentially expressed in HCC tissues relative to paired adjacent tissues. Most (8 out of 10) of the proteins corresponding to the differential glycated peptides have previously been reported with dysregulation in HCC. The results together may deepen our knowledge of glycation as well as provide insights for therapeutics.


Asunto(s)
Carcinoma Hepatocelular , Productos Finales de Glicación Avanzada , Marcaje Isotópico , Neoplasias Hepáticas , Proteómica , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/química , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/química , Humanos , Proteómica/métodos , Glicosilación , Marcaje Isotópico/métodos , Productos Finales de Glicación Avanzada/análisis , Productos Finales de Glicación Avanzada/metabolismo , Productos Finales de Glicación Avanzada/química , Espectrometría de Masas en Tándem/métodos , Masculino , Persona de Mediana Edad
8.
Cell Death Dis ; 15(5): 368, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38806480

RESUMEN

Transforming growth factor beta (TGFß) signaling plays a critical role in tumorigenesis and metastasis. However, little is known about the biological function of TGFbeta-induced lncRNA in cancer. In this study, we discovered a novel TGFbeta-induced lncRNA, termed TGILR, whose function in cancer remains unknown to date. TGILR expression was directly activated by the canonical TGFbeta/SMAD3 signaling axis, and this activation is highly conserved in cancer. Clinical analysis showed that TGILR overexpression showed a significant correlation with lymph node metastasis and poor survival and was an independent prognostic factor in gastric cancer (GC). Depletion of TGILR caused an obvious inhibitory effect on GC cell proliferation, invasion, and epithelial-mesenchymal transition (EMT) in vitro and in vivo. More importantly, we demonstrated that TGFbeta signaling in GC was overactivated due to cancer-associated fibroblast (CAF) infiltration. Mechanistically, increased level of CAF-secreted TGFbeta activates TGFbeta signaling, leading to TGILR overexpression in GC cells. Meanwhile, TGILR overexpression inhibited the microRNA biogenesis of miR-1306 and miR-33a by interacting with TARBP2 and reducing its protein stability, thereby promoting GC progression via TCF4-mediated EMT signaling. In conclusion, CAF infiltration drives GC metastasis and EMT signaling through activating TGFbeta/TGILR axis. Targeted blocking of CAF-derived TGFbeta should be a promising anticancer strategy in GC.


Asunto(s)
Fibroblastos Asociados al Cáncer , Progresión de la Enfermedad , Transición Epitelial-Mesenquimal , MicroARNs , Transducción de Señal , Neoplasias Gástricas , Factor de Crecimiento Transformador beta , Neoplasias Gástricas/patología , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/genética , Humanos , Factor de Crecimiento Transformador beta/metabolismo , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/patología , Línea Celular Tumoral , Animales , MicroARNs/metabolismo , MicroARNs/genética , Proliferación Celular , ARN Largo no Codificante/metabolismo , ARN Largo no Codificante/genética , Regulación Neoplásica de la Expresión Génica , Masculino , Ratones Desnudos , Femenino , Ratones , Ratones Endogámicos BALB C , Proteína smad3/metabolismo
9.
Am J Pathol ; 194(8): 1592-1606, 2024 08.
Artículo en Inglés | MEDLINE | ID: mdl-38705381

RESUMEN

Pulmonary arterial hypertension (PAH) is a sex-biased disease with female sex as a significant risk factor. Increased expression of the long noncoding RNA X-inactive-specific transcript (Xist), as induced by an intersectin-1s protein fragment with proliferative potential (EHITSN), may explain the sexual dimorphism of female pulmonary artery endothelial cells (ECs) and at least in part, the imbalance sex/ratio of PAH. Xist is essential for X-chromosome inactivation and dosage compensation of X-linked genes. Herein, increased Xist expression was detected in a subset of ECs and lung tissue samples of male patients with PAH. The role of different Xist expression levels in ECs of male patients with PAH (ECPAH) was studied in several lines of male ECPAH in conjunction with molecular, biochemical, morphologic, and functional approaches. Male ECPAH showed on average 10.3-fold increase in high Xist versus low Xist, a significant association between Xist levels and their proliferative potential, and a heterogeneous methylation of the Xist/XIST antisense RNA (Tsix) locus. Interestingly, Xist up-regulation in male ECPAH decreased the expression of Krueppel-like factor 2 (Klf2), via EHITSN interaction with enhancer of zeste polycomb repressive complex 2 subunit (EZH2), the catalytic subunit of the polycomb repressive complex 2. Moreover, the studies demonstrate that EHITSN-triggered p38/ETS domain-containing protein Elk1/AP-1 transcription factor subunit (c-Fos) signaling is a pathologic mechanism central to ECPAH proliferation and the dynamic crosstalk with cell cycle regulatory proteins cyclin A1/cyclin D2 and Xist-EZH2-Klf2 interaction participate directly and differentially in establishing the proliferative profile of male ECPAH.


Asunto(s)
Hipertensión Arterial Pulmonar , ARN Largo no Codificante , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Masculino , Humanos , Hipertensión Arterial Pulmonar/genética , Hipertensión Arterial Pulmonar/metabolismo , Hipertensión Arterial Pulmonar/patología , Femenino , Células Endoteliales/metabolismo , Proliferación Celular/genética , Persona de Mediana Edad , Factores de Transcripción de Tipo Kruppel/genética , Factores de Transcripción de Tipo Kruppel/metabolismo , Proteína Elk-1 con Dominio ets/metabolismo , Proteína Elk-1 con Dominio ets/genética , Arteria Pulmonar/metabolismo , Arteria Pulmonar/patología , Regulación de la Expresión Génica , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Proteína Potenciadora del Homólogo Zeste 2/genética , Adulto
10.
ArXiv ; 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38764587

RESUMEN

The integration of neural representations in the two hemispheres is an important problem in neuroscience. Recent experiments revealed that odor responses in cortical neurons driven by separate stimulation of the two nostrils are highly correlated. This bilateral alignment points to structured inter-hemispheric connections, but detailed mechanism remains unclear. Here, we hypothesized that continuous exposure to environmental odors shapes these projections and modeled it as online learning with local Hebbian rule. We found that Hebbian learning with sparse connections achieves bilateral alignment, exhibiting a linear trade-off between speed and accuracy. We identified an inverse scaling relationship between the number of cortical neurons and the inter-hemispheric projection density required for desired alignment accuracy, i.e., more cortical neurons allow sparser inter-hemispheric projections. We next compared the alignment performance of local Hebbian rule and the global stochastic-gradient-descent (SGD) learning for artificial neural networks. We found that although SGD leads to the same alignment accuracy with modestly sparser connectivity, the same inverse scaling relation holds. We showed that their similar performance originates from the fact that the update vectors of the two learning rules align significantly throughout the learning process. This insight may inspire efficient sparse local learning algorithms for more complex problems.

11.
Ann Hematol ; 103(7): 2245-2256, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38644415

RESUMEN

BACKGROUND: Aplastic anemia (AA) is a kind of bone marrow failure (BMF) characterized by pancytopenia with hypoplasia/aplasia of bone marrow. Immunosuppressive therapy and bone marrow transplantation are effective methods to treat severe aplastic anemia. However, the efficacy is limited by complications and the availability of suitable donors. This study aimed to determine whether any circulating druggable protein levels may have causal effects on AA and provide potential novel drug targets for AA. METHODS: Genetic variants strongly associated with circulating druggable protein levels to perform Mendelian randomization (MR) analyses were used. The effect of these druggable protein levels on AA risk was measured using the summary statistics from a large-scale proteomic genome-wide association study (GWAS) and FinnGen database ( https://www.finngen.fi/en/access_results ). Multivariable MR analyses were performed to statistically adjust for potential confounders, including platelet counts, reticulocyte counts, neutrophil counts, and proportions of hematopoietic stem cells. RESULTS: The data showed that higher level of circulating IFN-γ levels was causally associated with AA susceptibility. The causal effects of circulating IFN-γ levels on the AA were broadly consistent, when adjusted for platelet counts, reticulocyte counts, neutrophil counts and proportions of hematopoietic stem cells. CONCLUSIONS: High levels of circulating IFN-γ levels might increase the risk of AA and might provide a potential novel target for AA.


Asunto(s)
Anemia Aplásica , Estudio de Asociación del Genoma Completo , Interferón gamma , Análisis de la Aleatorización Mendeliana , Proteoma , Anemia Aplásica/genética , Anemia Aplásica/sangre , Humanos , Interferón gamma/sangre , Proteoma/análisis , Masculino , Femenino
12.
Comput Methods Programs Biomed ; 250: 108193, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38678957

RESUMEN

BACKGROUND: Cancer/testis antigens (CTAs), also known as tumor-specific antigens (TSAs) are specifically expressed in cancer cells and exhibit high immunogenicity, making them promising targets for immunotherapy and cancer vaccines. METHODS: A new integrated high-throughput screening methodology for CTAs was proposed in this study through combining DNA methylation and RNA sequencing data. Briefly, the genes with increased transcript level and decreased DNA methylation were identified by multi-omics analysis. RNA sequencing studies in cell lines exposed to DNA methyltransferase (DNMT) inhibitors were performed to validate the inherent causal relationship between DNA hypomethylation and gene expression upregulation. RESULTS: We proposed a new integrated high-throughput screening methodology for identification of CTAs using multi-omics analysis. In addition, we tested the feasibility of this method using gastric cancer (GC) as an example. In GC, we identified over 2000 primary candidate CTAs and ultimately identified 20 CTAs with significant tissue-specificity, including a testis-specific serine protease TESSP1/PRSS41. Integrated analysis confirmed that PRSS41 expression was reactivated in gastrointestinal cancers by promoter DNA hypomethylation at the CpG site (cg08104780). Additionally, DNA hypomethylation of PRSS41 predicted a poor prognosis in GC. CONCLUSION: We propose a new high-throughput screening method for the identification of CTAs in cancer and validate its effectiveness. Our work emphasizes that serine protease PRSS41 is a novel TSA that is reactivated in GC due to promoter DNA hypomethylation.


Asunto(s)
Antígenos de Neoplasias , Metilación de ADN , Ensayos Analíticos de Alto Rendimiento , Neoplasias Gástricas , Humanos , Antígenos de Neoplasias/metabolismo , Antígenos de Neoplasias/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Ensayos Analíticos de Alto Rendimiento/métodos , Masculino , Línea Celular Tumoral , Testículo/metabolismo , Regulación Neoplásica de la Expresión Génica , Genómica , Regiones Promotoras Genéticas , Análisis de Secuencia de ARN , Multiómica
13.
Adv Mater ; 36(25): e2400626, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38520245

RESUMEN

The employment of single atoms (SAs), especially Pt SAs, as co-catalysts in photocatalytic H2 generation has gained significant attention due to their exceptional efficiency. However, a major challenge in their application is the light-induced agglomeration of these SAs into less active nanosized particles under photocatalytic conditions. This study addresses the stability and reactivity of Pt SAs on TiO2 surfaces by investigating various post-deposition annealing treatments in air, Ar, and Ar-H2 environments at different temperatures. It is described that annealing in an Ar-H2 atmosphere optimally stabilizes SA configurations, forming stable 2D rafts of assembled SAs ≈0.5-1 nm in diameter. These rafts not only resist light-induced agglomeration but also exhibit significantly enhanced H2 production efficiency. The findings reveal a promising approach to maintaining the high reactivity of Pt SAs while overcoming the critical challenge of their stability under photocatalytic conditions.

14.
Int Immunopharmacol ; 131: 111836, 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38479160

RESUMEN

The cancer-associated fibroblast (CAF)-derived secretome plays critical roles in tumor progression by remodelling tumor microenvironment. Tumorigenesis is accompanied by the transformation of normal fibroblasts (NF) into CAF, leading to significant changes in their secretome. This work aims to identify the differential components of secretome between NFs and CAFs and reveal their functions in gastric cancer (GC). Firstly, our molecular typing studies and immune infiltration analysis showed that CAF infiltration level was increased and showed a significant association with clinical characteristics and poor prognosis of GC patients. Secondly, RNA-seq analysis revealed that a total of 1531 genes showed significant expression changes between NF and CAF. According to the annotation of the Human Protein Atlas (HPA) database, 147 genes encode secreted proteins, including FGF2. Particularly, the cell co-culture and RNA sequencing studies confirmed that exogenous recombinant FGF2 protein treatment promoted GC cell proliferation by enhancing ribosome biogenesis. The rescue assay showed that CAF-secreted FGF2 protein promotes GC cell growth and proliferation in a FGFR1-dependent manner. Our finding provides evidence that targeting blockade of CAF-derived FGF2 protein might be a promising treatment for GC.


Asunto(s)
Fibroblastos Asociados al Cáncer , Factor 2 de Crecimiento de Fibroblastos , Neoplasias Gástricas , Humanos , Fibroblastos Asociados al Cáncer/metabolismo , Línea Celular Tumoral , Proliferación Celular , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Fibroblastos/metabolismo , Ribosomas/metabolismo , Neoplasias Gástricas/genética , Microambiente Tumoral/genética
15.
Sci Total Environ ; 922: 171426, 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38432363

RESUMEN

Climate warming influences the biological activities of aquatic organisms, including feeding, growth, and reproduction, thereby affecting predator-prey interactions. This study explored the variation in thermal sensitivity of anti-predator responses in two cladoceran species with varying body sizes, Daphnia pulex and Ceriodaphnia cornuta. These species were cultured with or without the fish (Rhodeus ocellatus) kairomone at temperatures of 15, 20, 25, and 30 °C for 15 days. Results revealed that cladocerans of different body sizes exhibited varying responses to fish kairomones in aspects such as individual size, first-brood neonate size, total offspring number, average brood size, growth rate, and reproductive effort. Notably, low temperature differently affected defense responses in cladocerans of different body sizes. Both high and low temperatures moderated the intensity of the kairomone-induced response on body size at maturity. Additionally, low temperature reversed the reducing effect of fish kairomone on the total offspring number, average brood size, and reproductive effort in D. pulex. Conversely, it enhanced the increasing effect of fish kairomone on these parameters in C. cornuta. These results suggest that inducible anti-predator responses in cladocerans are modifiable by temperature. The differential effects of fish kairomones on various cladocerans under temperature influence offer crucial insights for predicting changes in predator-prey interactions within freshwater ecosystems under future climate conditions.


Asunto(s)
Cladóceros , Cipriniformes , Animales , Cladóceros/fisiología , Daphnia , Ecosistema , Feromonas/farmacología , Tamaño Corporal , Conducta Predatoria
16.
BMC Cardiovasc Disord ; 24(1): 119, 2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38383333

RESUMEN

INTRODUCTION: This study evaluates the effectiveness of a combined regimen involving injectable hydrogels for the treatment of experimental myocardial infarction. PATIENT CONCERNS: Myocardial infarction is an acute illness that negatively affects quality of life and increases mortality rates. Experimental models of myocardial infarction can aid in disease research by allowing for the development of therapies that effectively manage disease progression and promote tissue repair. DIAGNOSIS: Experimental animal models of myocardial infarction were established using the ligation method on the anterior descending branch of the left coronary artery (LAD). INTERVENTIONS: The efficacy of intracardiac injection of hydrogels, combined with cells, drugs, cytokines, extracellular vesicles, or nucleic acid therapies, was evaluated to assess the functional and morphological improvements in the post-infarction heart achieved through the combined hydrogel regimen. OUTCOMES: A literature review was conducted using PubMed, Web of Science, Scopus, and Cochrane databases. A total of 83 papers, including studies on 1332 experimental animals (rats, mice, rabbits, sheep, and pigs), were included in the meta-analysis based on the inclusion and exclusion criteria. The overall effect size observed in the group receiving combined hydrogel therapy, compared to the group receiving hydrogel treatment alone, resulted in an ejection fraction (EF) improvement of 8.87% [95% confidence interval (CI): 7.53, 10.21] and a fractional shortening (FS) improvement of 6.31% [95% CI: 5.94, 6.67] in rat models, while in mice models, the improvements were 16.45% [95% CI: 11.29, 21.61] for EF and 5.68% [95% CI: 5.15, 6.22] for FS. The most significant improvements in EF (rats: MD = 9.63% [95% CI: 4.02, 15.23]; mice: MD = 23.93% [95% CI: 17.52, 30.84]) and FS (rats: MD = 8.55% [95% CI: 2.54, 14.56]; mice: MD = 5.68% [95% CI: 5.15, 6.22]) were observed when extracellular vesicle therapy was used. Although there have been significant results in large animal experiments, the number of studies conducted in this area is limited. CONCLUSION: The present study demonstrates that combining hydrogel with other therapies effectively improves heart function and morphology. Further preclinical research using large animal models is necessary for additional study and validation.


Asunto(s)
Modelos Animales de Enfermedad , Hidrogeles , Infarto del Miocardio , Recuperación de la Función , Función Ventricular Izquierda , Animales , Infarto del Miocardio/fisiopatología , Infarto del Miocardio/tratamiento farmacológico , Función Ventricular Izquierda/efectos de los fármacos , Miocardio/patología , Inyecciones , Terapia Combinada , Fármacos Cardiovasculares/administración & dosificación , Fármacos Cardiovasculares/efectos adversos , Remodelación Ventricular/efectos de los fármacos , Tratamiento Basado en Trasplante de Células y Tejidos/métodos
17.
Health Qual Life Outcomes ; 22(1): 19, 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38378572

RESUMEN

BACKGROUND: Despite a number of respiratory syncytial virus (RSV) vaccine candidates being tested in clinical trials, disease-specific, self-reported instruments assessing symptom severity of RSV infection from the perspective of adult patients are still needed. The RSV Infection, Intensity and Impact Questionnaire (RSV-iiiQ) was adapted from the Influenza Intensity and Impact Questionnaire (FluiiQ™). This study evaluated some measurement properties of the RSV-iiiQ. METHODS: Data were collected in a web-based survey over two consecutive days. Participants completed the RSV-iiiQ, the Patient Global Impression of Severity, Sheehan Disability Scale, Patient Global Impression of Change, EQ-5D-5L, and a demographic questionnaire. Test-retest reliability, internal consistency, construct validity, and responsiveness of the RSV-iiiQ scales were assessed. RESULTS: 111 adults with RSV were enrolled and self-reported a variety of symptoms across the range of disease severity via a web-based platform. The RSV-iiiQ scales demonstrated satisfactory test-retest reliability, construct validity, and discriminating ability. One-factor confirmatory factor analyses confirmed that each of the four scales was sufficiently unidimensional, and internal consistencies indicated that the computation of RSV-iiiQ scale scores was plausible. Correlation-based analyses provided support for the construct validity of the RSV-iiiQ scores, and known groups analyses supported discriminating ability. Estimates of responsiveness of the scale scores were also satisfactory. CONCLUSIONS: RSV infection is highly symptomatic and causes significant disease burden, and self-report instruments assessing symptom severity and impact are important for evaluation of new treatments. This study describes the preliminary psychometric properties of the RSV-iiiQ and indicates this tool may be useful for the assessment of the severity of symptoms and impact of acute RSV infection in adults. The findings also indicated two items, Runny nose and Ear pain, may be unnecessary and should be revisited using item response theory analysis with a larger sample size.


Asunto(s)
Infecciones por Virus Sincitial Respiratorio , Adulto , Humanos , Infecciones por Virus Sincitial Respiratorio/diagnóstico , Psicometría , Reproducibilidad de los Resultados , Calidad de Vida , Encuestas y Cuestionarios
18.
Digit Health ; 10: 20552076241233244, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38384366

RESUMEN

Purpose: This study aims to evaluate the diagnostic value of texture analysis for lymph node metastasis after thyroid cancer surgery. Methods: We retrospectively analyzed patients who underwent positron emission tomography/computed tomography (PET/CT) examination before 131I treatment at Shanghai Tenth People's Hospital between 2017 and 2020. Clinical follow-up results were used as the criterion for determining the presence of lymph node metastasis. The study included 119 patients, who were then randomly divided into training and test groups in a 7:3 ratio. Regions of interest were identified, and radiomics features were extracted using LIFEx 7.3.0. Mann-Whitney U test and LASSO regression were employed to screen radiomics parameters for modeling. Subsequently, a nomogram model was built by combining radscore and clinical features. SPSS 26.0 software was utilized for statistical analysis, and p < 0.05 was considered statistically significant. Results: Follow-up confirmed 54 patients with thyroid cancer lymph node metastasis and 65 patients in the non-metastasis group. A total of 119 lymph nodes were delineated. For each lesion, 164 CT texture features and 164 PET texture features were extracted, and 107 significant parameters were identified, including 16 CT texture parameters and 91 PET texture parameters. After screening, 3 CT parameters, 4 PET parameters and 12 PET/CT parameters were selected to establish three radiomic models. The AUC values were as follows: AUC (CT) = 0.730, AUC (PET) = 0.759 and AUC (PET/CT) = 0.864. We then combined clinical features and radscore to construct a nomogram, resulting in a C-index of 0.915 in the training group. In the test group, the C-index was confirmed to be 0.868. Conclusions: Radiomics may enhance the diagnostic efficiency of lymph node metastases after thyroid cancer surgery and could potentially assist clinicians in future diagnoses. The developed nomogram, which combines radiomics and clinical features, offers relatively high accuracy in helping clinicians assess the risk of metastasis in thyroid patients after surgery.

19.
Hormones (Athens) ; 23(2): 257-265, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38277093

RESUMEN

PURPOSE: The purposes of this study were to assess the changes in body composition in patients who underwent thyroidectomy due to differentiated thyroid cancer (DTC) after radioactive iodine therapy (RAI) and short-term levothyroxine (LT4) supplementation and to explore the correlations between body composition distribution and corresponding blood indices. METHODS: Fifty-seven thyroidectomized DTC patients were included. Serum was tested for several biochemical indices of thyroid function, lipids, and bone metabolism, and body composition parameters were measured via dual-energy X-ray absorptiometry before and 4-6 weeks after RAI and LT4 supplementation. RESULTS: The body composition of DTC patients changed after RAI. Fat mass in all parts of the body decreased (range of relative change (RRC) -12.97--2.80%). Bone mineral content (BMC) increased throughout the body (relative change (RC) 12.12%), head (RC 36.23%), pelvis (RC 9.00%), and legs (RC 3.15%). Similarly, bone mineral density (BMD) increased in different regions (RRC 3.60-26.43%), except for the arms. Notably, lean mass in the arms (RC 4.30%) and legs (RC 3.67%) increased, while that in the head decreased (RC -2.75%), while total lean mass did not change at 4-6 weeks after LT4 supplementation. Furthermore, changes in fat distribution in the android region were related to the changes in total cholesterol (r = -0.390) and low-density lipoprotein cholesterol (r = -0.354), and changes in the BMC and BMD of the lumbar spine were positively associated with the changes in calcitonin (r = 0.302 and 0.325, respectively). CONCLUSIONS: After RAI and short-term LT4 supplementation in DTC patients, body composition rapidly and positively changed and was characterized by decreased fat mass and increased BMC and BMD.


Asunto(s)
Composición Corporal , Densidad Ósea , Radioisótopos de Yodo , Neoplasias de la Tiroides , Tiroidectomía , Tiroxina , Humanos , Neoplasias de la Tiroides/radioterapia , Neoplasias de la Tiroides/sangre , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/terapia , Femenino , Masculino , Tiroxina/sangre , Persona de Mediana Edad , Composición Corporal/efectos de los fármacos , Adulto , Radioisótopos de Yodo/uso terapéutico , Densidad Ósea/efectos de los fármacos , Terapia de Reemplazo de Hormonas , Anciano
20.
Angew Chem Int Ed Engl ; 63(10): e202316660, 2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38237060

RESUMEN

When using single atoms (SAs) as a co-catalyst in photocatalytic H2 generation, achieving a well-dispersed, evenly distributed and adjustable SA surface density on a semiconductor surface is a challenging task. In the present work we use the planar adsorption of tetrakis-(4-carboxyphenyl)-porphyrin (TCPP) and its platinum coordinated analogue, Pt-TCPP, onto anatase TiO2 surfaces to establish a spatially controlled decoration of SAs. We show that the surface Pt SA density can be very well controlled by co-adsorption of Pt-TCPP and TCPP in the planar monolayer regime, and by adjusting the Pt-TCPP to TCPP ratio a desired well dispersed surface density of SAs up to 2.6×105  atoms µm-2 can be established (which is the most effective Pt SA loading for photocatalysis). This distribution and the SA state are maintained after a thermal treatment in air, and an optimized SA density as well as a most active form of Pt for photocatalytic H2 evolution can be established and maintained.

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