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1.
J Biol Chem ; 300(5): 107233, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38552738

RESUMEN

The NACHT, leucine-rich repeat, and pyrin domains-containing protein 3 (collectively known as NLRP3) inflammasome activation plays a critical role in innate immune and pathogenic microorganism infections. However, excessive activation of NLRP3 inflammasome will lead to cellular inflammation and tissue damage, and naturally it must be precisely controlled in the host. Here, we discovered that solute carrier family 25 member 3 (SLC25A3), a mitochondrial phosphate carrier protein, plays an important role in negatively regulating NLRP3 inflammasome activation. We found that SLC25A3 could interact with NLRP3, overexpression of SLC25A3 and knockdown of SLC25A3 could regulate NLRP3 inflammasome activation, and the interaction of NLRP3 and SLC25A3 is significantly boosted in the mitochondria when the NLRP3 inflammasome is activated. Our detailed investigation demonstrated that the interaction between NLRP3 and SLC25A3 disrupted the interaction of NLRP3-NEK7, promoted ubiquitination of NLRP3, and negatively regulated NLRP3 inflammasome activation. Thus, these findings uncovered a new regulatory mechanism of NLRP3 inflammasome activation, which provides a new perspective for the therapy of NLRP3 inflammasome-associated inflammatory diseases.


Asunto(s)
Inflamasomas , Proteínas Mitocondriales , Proteína con Dominio Pirina 3 de la Familia NLR , Proteínas de Transporte de Fosfato , Animales , Humanos , Ratones , Células HEK293 , Inflamasomas/metabolismo , Mitocondrias/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteínas de Transporte de Fosfato/metabolismo , Proteínas de Transporte de Fosfato/genética , Ubiquitinación , Línea Celular , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Técnicas de Silenciamiento del Gen
2.
BMC Geriatr ; 24(1): 139, 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38326792

RESUMEN

BACKGROUND: Arthritis primarily affects older people and is a prominent cause of their activity impairment. This study aimed to examine the mediating role of depressive symptoms in the relationship between social participation and activity impairment, as well as to determine whether sex moderated the mediating effect. METHODS: A total of 2247 older patients with arthritis were included from the China Health and Retirement Longitudinal Study between 2015 and 2018. We first examined a simple mediation model where depressive symptoms were a mediator between social participation and activity impairment. Furthermore, sex was systematically integrated into the model as a moderator. The mediation model and moderated mediation model were analyzed using PROCESS macro. RESULTS: Mediation analysis revealed that the association between social participation and activity impairment was partially mediated by depressive symptoms (B = -0.10, 95% CI = [-0.14, -0.06]) with intermediary effect of 28.6%. Moderated mediation analysis indicated that mediation model was moderated by sex. The indirect effect of social participation on activity impairment among female patients (B = -0.15, 95% CI = [-0.21, -0.09]) was stronger than male patients (B = -0.04, 95% CI = [-0.09, -0.01]). CONCLUSION: Social participation was the key protective factor associated with depressive symptoms and activity impairment among arthritis patients. Encouraging arthritis patients to social participation and improving the depressive symptoms might avoid activity impairment, especially for female patients.


Asunto(s)
Depresión , Participación Social , Humanos , Masculino , Femenino , Anciano , Estudios Longitudinales , Depresión/diagnóstico , Depresión/epidemiología , Análisis de Mediación , Jubilación , China/epidemiología
3.
Nurs Health Sci ; 26(1): e13089, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38356046

RESUMEN

Team cohesion, as a necessary condition for the cooperation and development of a team, has been shown to have a strong association with team performance. However, the mechanism of this internal correlation is unclear and more in-depth studies are lacking. The study aimed to explore the complex links between the dimensions of team cohesion and performance in nurses. A total of 1639 practice nurses from 118 nursing teams were included in this cross-sectional study. Data were collected using the Team Cohesion Scale (including consistency of affection, behavior, and cognition) and the Team Effectiveness Scale (including cooperation satisfaction, and task performance). Using network analysis, the team cohesion and performance network was constructed, and the strength and bridge strength of nodes were calculated. The results showed that the edges between team cohesion and performance dimensions were all positively correlated. Cooperation satisfaction and consistency of affection are the core variables in the network. Interventions targeting cooperation satisfaction and consistency of affection need to be developed at the team level to maximize team cohesion and performance among nurses.


Asunto(s)
Enfermería , Grupo de Atención al Paciente , Humanos , Estudios Transversales , Grupo de Atención al Paciente/organización & administración
4.
Angew Chem Int Ed Engl ; 63(27): e202401373, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38659181

RESUMEN

Inorganic solid-state electrolytes (SSEs) play a vital role in high-energy all-solid-state batteries (ASSBs). However, the current method of SSE preparation usually involves high-energy mechanical ball milling and/or a high-temperature annealing process, which is not suitable for practical application. Here, a facile strategy is developed to realize the scalable synthesis of cost-effective aluminum-based oxyhalide SSEs, which involves a self-propagating method by the exothermic reaction of the raw materials. This strategy enables the synthesis of various aluminum-based oxyhalide SSEs with tunable components and high ionic conductivities (over 10-3 S cm-1 at 25 °C) for different cations (Li+, Na+, Ag+). It is elucidated that the amorphous matrix, which mainly consists of various oxidized chloroaluminate species that provide numerous sites for smooth ion migration, is actually the key factor for the achieved high conductivities. Benefit from their easy synthesis, low cost, and low weight, the aluminum-based oxyhalide SSEs synthesized by our approach could further promote practical application of high-energy-density ASSBs.

5.
BMC Cancer ; 23(1): 1221, 2023 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-38082441

RESUMEN

BACKGROUND: The combinations of PD-1 inhibitors with paclitaxel/cisplatinum (PD-1 + TP) and fluoropyrimidine/cisplatinum (PD-1 + FP) both have been shown to improve overall survival (OS) and progression-free survival (PFS) in patients with previously untreated, advanced esophageal squamous cell carcinoma (ESCC). However, there is no consensus on which chemotherapy regimen combined with PD-1 has better efficacy. To deal with this important issue in the first-line treatment of patients with ESCC, a network meta-analysis (NMA) was performed. METHODS: Data were collected from eligible studies searched in Medline, Web of Science, PubMed, the Cochrane Library and Embase. The pooled hazard ratio (HR) for the OS, and PFS, odds ratio (OR) for the objective response rate (ORR) and ≥ 3 grade treatment-related adverse events (≥ 3TRAEs) were estimated to evaluate the efficacy of PD-1 inhibitors combined with TP or FP. RESULTS: Five RCTs and one retrospective study involving 3685 patients and evaluating four treatments were included in this NMA. Compared to other treatments, PD-1 + TP was better. For the PFS, the HRs for PD-1 + TP compared to PD-1 + FP, TP and FP were 0.59 (0.44, 0.80), 0.56 (0.51, 0.61) and 0.45 (0.37, 0.56) respectively. For the OS, PD-1 + TP was also a better treatment compared to other treatments. The HRs were 0.74 (0.56, 0.96), 0.64 (0.57, 0.71), 0.53 (0.43, 0.67) respectively. For the ORR, there was no significant difference between PD-1 + TP and PD-1 + FP, and the ORs were 1.2 (0.69, 2.11). Compare with TP and FP, PD-1 + TP had an obvious advantage, ORs were 2.5 (2.04, 3.04) and 2.95 (1.91, 4.63). For ≥ 3TRAEs, PD-1 + TP compared to other treatments, ORs were 1.34 (0.74, 2.46) and 1.13 (0.92, 1.38) and 2.23 (1.35, 3.69). CONCLUSION: PD-1 + TP significantly improved both PFS and OS compared to PD-1 + FP. Taking into account both efficacy and safety, PD-1 + TP may be a superior first-line treatment option for ESCC.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Cisplatino , Paclitaxel , Carcinoma de Células Escamosas de Esófago/etiología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Esofágicas/patología , Metaanálisis en Red , Estudios Retrospectivos , Receptor de Muerte Celular Programada 1/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos
6.
Nutr Cancer ; 75(4): 1165-1176, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36892498

RESUMEN

We explored the predictive value of various inflammatory-nutritional indicators for postoperative quality of life (QoL) in gastric cancer (GC) patients undergoing laparoscopic distal gastrectomy (LDG) and developed a novel inflammatory-nutritional score (INS). In this study, 156 GC patients who underwent LDG were included. We used multiple linear regression to analyze the correlation between postoperative QoL and inflammatory-nutritional indicators. Least absolute shrinkage and selection operator (LASSO) regression analysis was performed to construct INS. Hemoglobin was positively correlated with physical functioning (ß =8.5; p = 0.003) and cognitive functioning (ß = 3.5; p = 0.038) 3 mo, after surgery. Prognostic nutritional index (PNI) was positively associated with global health status (ß =5.8; p = 0.043). Albumin-alkaline phosphatase ratio (AAPR) was negatively correlated with emotional functioning 12 mo, after surgery (ß = -5.7; p = 0.024). Neutrophil-lymphocyte ratio (NLR), Lymphocyte- monocyte ratio (LMR), AAPR, hemoglobin and PNI were selected using LASSO regression analysis to construct INS. The C-index values of the model in the training group and the validation group were 0.806 (95% CI, 0.719-0.893) and 0.758 (95% CI: 0.591-0.925), respectively. INS had particular predictive value for postoperative QoL in patients undergoing LDG and provided a reference for risk stratification and clinical practice.


Asunto(s)
Laparoscopía , Neoplasias Gástricas , Humanos , Calidad de Vida , Neoplasias Gástricas/cirugía , Estudios Retrospectivos , Albúminas , Gastrectomía , Pronóstico
7.
Molecules ; 28(20)2023 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-37894615

RESUMEN

Gut microbiota dysbiosis has been reported as a risk factor in the development of type 2 diabetes mellitus (T2DM). Polysaccharides from Phellinus igniarius (P. igniarius) possess various properties that help manage metabolic diseases; however, their underlying mechanism of action remains unclear. Therefore, in this study, we aimed to evaluate the effect of P. igniarius polysaccharides (SH-P) on improving hyperglycemia in mice with T2DM and clarified its association with the modulation of gut microbiota and their metabolites using 16S rDNA sequencing and liquid chromatography-mass spectrometry. Fecal microbiota transplantation (FMT) was used to verify the therapeutic effects of microbial remodeling. SH-P supplementation alleviated hyperglycemia symptoms in T2DM mice, ameliorated gut dysbiosis, and significantly increased the abundance of Lactobacillus in the gut. Pathway enrichment analysis indicated that SH-P treatment altered metabolic pathways associated with the occurrence and development of diabetes. Spearman's correlation analysis revealed that changes in the dominant bacterial genera were significantly correlated with metabolite levels closely associated with hyperglycemia. Additionally, FMT significantly improved insulin sensitivity and antioxidative capacity and reduced inflammation and tissue injuries, indicating improved glucose homeostasis. These results indicate that the ameliorative effects of SH-P on hyperglycemia are associated with the modulation of gut microbiota composition and its metabolites.


Asunto(s)
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Hiperglucemia , Ratones , Animales , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Disbiosis/tratamiento farmacológico , Disbiosis/microbiología , Hiperglucemia/tratamiento farmacológico , Polisacáridos/farmacología , Polisacáridos/uso terapéutico
8.
Geriatr Nurs ; 53: 301-306, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37603965

RESUMEN

OBJECTIVES: To investigate the level of social frailty (SF) in older patients with chronic heart failure (CHF) and examine the mediating role of social support and depressive symptoms between activities of daily living and SF. METHODS: Using a convenience sampling method, 205 older patients with CHF were recruited from China between November 2021 and May 2022. Activities of daily living, social support, depressive symptoms, and SF were assessed using a self-administered questionnaire. Data were analyzed using structural equation modeling. RESULTS: The final model obtained a good fit. Activities of daily living in older patients with CHF were directly related to SF. The multiple mediation analysis revealed that the relationship between activities of daily living and SF was mediated by social support (effect: -0.010, 95% CI [-0.021, -0.003]) and depressive symptoms (effect: -0.011, 95% CI [-0.019, -0.005) separately, and serially (effect: -0.007, 95% CI [-0.012, -0.003). CONCLUSIONS: Social support and depressive symptoms are multiple mediating variables in the relationship between activities of daily living and SF. Activities of daily living can improve patients' SF through social support and depressive symptoms.


Asunto(s)
Fragilidad , Insuficiencia Cardíaca , Humanos , Anciano , Actividades Cotidianas , Depresión , Apoyo Social
9.
Yi Chuan ; 45(3): 212-220, 2023 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-36927647

RESUMEN

Cathepsin B (CatB), a cysteine protease derived from lysosomes, was initially thought to non-selectively degrade proteins from phagocytosis and autophagy in lysosomes. However, CatB has been demonstrated to selectively degrade and specifically activate target proteins, thereby regulating the process of physiological and pathological responses. The expression, enzymatic activity, and cellular localization of CatB are significantly altered in brain aging and age-related neurodegenerative diseases. Therefore, the pathological function of CatB has attracted much attention in neuroscience research. In this review, we systematically summarize the molecular functions of CatB in brain aging and Alzheimer's disease and discuss the current problems in neuropathological studies of CatB, which lay a foundation for a comprehensive understanding of the pathogenesis of aging and Alzheimer's disease.


Asunto(s)
Enfermedad de Alzheimer , Catepsina B , Humanos , Catepsina B/genética , Catepsina B/metabolismo , Enfermedad de Alzheimer/etiología , Encéfalo/metabolismo , Envejecimiento
10.
Angew Chem Int Ed Engl ; 62(48): e202306433, 2023 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-37800699

RESUMEN

As exciting candidates for next-generation energy storage, all-solid-state lithium batteries (ASSLBs) are highly dependent on advanced solid-state electrolytes (SSEs). Here, using cost-effective LaCl3 and CeCl3 lattice (UCl3 -type structure) as the host and further combined with a multiple-cation mixed strategy, we report a series of UCl3 -type SSEs with high room-temperature ionic conductivities over 10-3  S cm-1 and good compatibility with high-voltage oxide cathodes. The intrinsic large-size hexagonal one-dimensional channels and highly disordered amorphous phase induced by multi-metal cation species are believed to trigger fast multiple ionic conductions of Li+ , Na+ , K+ , Cu+ , and Ag+ . The UCl3 -type SSEs enable a stable prototype ASSLB capable of over 3000 cycles and high reversibility at -30 °C. Further exploration of the brand-new multiple-cation mixed chlorides is likely to lead to the development of advanced halide SSEs suitable for ASSLBs with high energy density.

11.
FASEB J ; 35(7): e21709, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34143518

RESUMEN

Tissues undergo a process of degeneration as the body ages. Mesenchymal stem cells (MSCs) have been found to have major potential in delaying the aging process in tissues and organs. However, the mechanism underlying the anti-aging effects of MSC is not clear which limits clinical applications. In this study, we used adipose-derived mesenchymal stem cells (ADSCs) to perform anti-aging treatments on senescent cells and progeroid animal models. Following intervention with ADSCs, replicative senescence was delayed and metabolic homeostasis was transformed from catabolism to anabolism. Metabolomic tests were used to analyze different metabolites. We found that ADSCs acted to accelerate mitophagy which eliminated intracellular ROS and improved the quality of mitochondria. These processes acted to regulate the cellular metabolic homeostasis and ultimately delayed the process of aging. Allogeneic stem cell therapy in a Progeria animal model (DNA polymerase gamma (POLG) knockin, mitochondrial dysfunction) also showed that ADSC therapy can improve alopecia and kyphosis by promoting mitophagy. Our research confirms for the first time that allogeneic stem cell therapy can improve aging-related symbols and phenotypes through mitochondrial quality control. These results are highly significant for the future applications of stem cells in aging-related diseases.


Asunto(s)
Adipocitos/metabolismo , Tejido Adiposo/metabolismo , Envejecimiento/metabolismo , Homeostasis/fisiología , Mitofagia/fisiología , Células Madre/metabolismo , Animales , Diferenciación Celular/fisiología , Proliferación Celular/fisiología , Células Cultivadas , Senescencia Celular/fisiología , Modelos Animales de Enfermedad , Femenino , Masculino , Células Madre Mesenquimatosas/metabolismo , Ratones , Ratones Endogámicos C57BL , Trasplante de Células Madre/métodos
12.
Inorg Chem ; 61(25): 9421-9432, 2022 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-35700095

RESUMEN

Selective oxidation of aryl alkenes is important for chemical synthesis reactions, in which the key lies in the rational design of efficient catalysts. Herein, four polyoxometalate (POM)-incorporated metal-organic networks, with the formulas of [Co(ttb)(H2O)3]2[SiMo12O40]·2H2O (1), [Co(ttb)(H2O)2]2[SiW12O40]·8H2O (2), [Zn(Httb)(H2ttb)][BW12O40]·9H2O (3) and {[Zn(H2O)3(ttb)]4[Zn3(H2O)6]}[H3SiW10.5Zn1.5O40]2·24H2O (4) (ttb = 1,3,5-tri(1,2,4-triazol-1-ylmethyl)-2,4,6-trimethylbenzene), were hydrothermally synthesized and structurally characterized. Structural analysis showed that compound 1 consists of a POM-encapsulated three-dimensional (3-D) supramolecular framework; compound 2 is composed of a POM-supported 3-D coordination network; and compounds 3-4 show POM-incorporated 3-D supramolecular networks. Using selective catalytic oxidation of styrene as the model reaction, compounds 1-4 as heterogeneous catalysts display excellent performance with the double advantages of high styrene conversion and benzaldehyde selectivity owing to the synergistic effect among POM anions and transition metal (TM) centers. Among them, compound 1 exhibits the highest performance with ca. 96% styrene conversion and ca. 99% benzaldehyde selectivity in 3 h. In addition, compound 1 also displays excellent substrate compatibility, good reusability, and structural stability. Thus, a plausible reaction pathway for the selective oxidation of styrene is proposed. This study on the structure-function relationship paves a way for the rational design of POM-based heterogeneous catalysts for important catalysis applications.

13.
Inorg Chem ; 61(50): 20596-20607, 2022 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-36459635

RESUMEN

Photocatalytic organic transformation derived by functionalized polyoxometalate (POM)-based metal-organic frameworks provides a feasible route for fine chemical synthesis. Herein, three kinds of photoactive three-dimensional silver-containing polyoxotungstate frameworks are synthesized with the formulas [Ag3L2(OH)][Na(H2O)0.5][PW12O40]·H2O (1), [Ag4L3][SiW12O40] (2), and [Ag(H2O)][Ag4L3][BW12O40]·9H2O (3) (L = 1,4-di(4H-1,2,4-triazol-4-yl)benzene). In compounds 1-3, the cationic Ag-triazole clusters with diverse nuclei serve as nodes to assemble with rigid bridging ligands (L) and polyoxoanions to extend into stable three-dimensional frameworks, in which Keggin-type anions act as guests or pendants. When using them as heterogeneous photocatalysts, compounds 1-3 show high catalytic activity and selectivity for the photocatalytic aerobic oxidation of benzyl alcohol to benzoic acid under 10 W 365 nm light irradiation. Among them, compound 1 exhibits the highest performance with ca. 99% benzyl alcohol conversion and 99% selectivity of benzoic acid in 9 h. Compounds 2 and 3 show ca. 79 and 88% conversions of benzyl alcohol, respectively, which are higher than those of the individual Keggin-type precursors. Moreover, mechanism investigation suggests that the synergistic cooperation occurring between cationic Ag-triazole clusters and Keggin-type polyoxoanions modulates the energy band structures of compounds 1-3, resulting in the efficient separation of photogenerated carriers and accelerating the aerobic oxidation of benzyl alcohol. This work provides some important guidance for the design and development of efficient POM-based photocatalysts for practical organic transformation.

14.
Nano Lett ; 21(12): 5316-5323, 2021 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-34080870

RESUMEN

Graphitic carbons and their lithium composites have been utilized as lithium deposition substrates to address issues such as the huge volume variation and dendritic growth of lithium. However, new problems have appeared, including the severe exfoliation of the graphite particles and the instability of the solid electrolyte interphase (SEI) film when metallic lithium is plated on the graphite. Herein, we enhance the stability of the SEI film on the graphite substrate for lithium deposition in an electrolyte of lithium bis(fluorosulfonyl)imide (LiFSI) dissolved in the carbonate solvent, thereby improving the lithium plating/stripping cycle on it. The FSI- anion was found to be responsible for the formation of a compact SEI film under the lithium plating potential and could protect the graphite substrate. These findings refresh the understanding of the SEI stability and provide a suggestion on the design and development of electrolytes for the lithium batteries.

15.
Nano Lett ; 21(7): 3310-3317, 2021 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-33797262

RESUMEN

The development of lithium metal batteries is hindered by the low Coulombic efficiency and poor cycling stability of the metallic lithium. The introduction of consumptive LiNO3 as an additive can improve the cycling stability, but its low solubility in the carbonate electrolytes makes this strategy impractical for long-term cycling. Herein we propose LiNO3 as a cosalt in the LiPF6-LiNO3 dual-salt electrolyte to enhance the cycling stability of lithium plating/stripping. Competitions among the components and the resultant substitution of NO3- for PF6- in the solvation shell facilitate the formation of a Li3N-rich solid electrolyte interphase (SEI) film and suppress the LiPF6 decomposition. The highly Li+ conductive and stable SEI film effectively tailors the lithium nucleation, suppresses the formation of lithium dendrites, and improves the cycling performance. The competitive solvation has profound importance for the design of a complex electrolyte to meet the multiple requirements of secondary lithium batteries.

16.
Cancer Cell Int ; 21(1): 619, 2021 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-34819091

RESUMEN

BACKGROUND: Neuroblastoma (NB) is a common solid malignancy in children that is associated with a poor prognosis. Although the novel small molecular compound Dimethylaminomicheliolide (DMAMCL) has been shown to induce cell death in some tumors, little is known about its role in NB. METHODS: We examined the effect of DMAMCL on four NB cell lines (NPG, AS, KCNR, BE2). Cellular confluence, survival, apoptosis, and glycolysis were detected using Incucyte ZOOM, CCK-8 assays, Annexin V-PE/7-AAD flow cytometry, and Seahorse XFe96, respectively. Synergistic effects between agents were evaluated using CompuSyn and the effect of DMAMCL in vivo was evaluated using a xenograft mouse model. Phosphofructokinase-1, liver type (PFKL) expression was up- and down-regulated using overexpression plasmids or siRNA. RESULTS: When administered as a single agent, DMAMCL decreased cell proliferation in a time- and dose-dependent manner, increased the percentage of cells in SubG1 phase, and induced apoptosis in vitro, as well as inhibiting tumor growth and prolonging survival in tumor-bearing mice (NGP, BE2) in vivo. In addition, DMAMCL exerted synergistic effects when combined with etoposide or cisplatin in vitro and displayed increased antitumor effects when combined with etoposide in vivo compared to either agent alone. Mechanistically, DMAMCL suppressed aerobic glycolysis by decreasing glucose consumption, lactate excretion, and ATP production, as well as reducing the expression of PFKL, a key glycolysis enzyme, in vitro and in vivo. Furthermore, PFKL overexpression attenuated DMAMCL-induced cell death, whereas PFKL silencing promoted NB cell death. CONCLUSIONS: The results of this study suggest that DMAMCL exerts antitumor effects on NB both in vitro and in vivo by suppressing aerobic glycolysis and that PFKL could be a potential target of DMAMCL in NB.

17.
BMC Cancer ; 21(1): 1324, 2021 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-34893046

RESUMEN

BACKGROUND: Advanced gastric cancer (AGC) is a disease with poor prognosis due to the current lack of effective therapeutic strategies. Immune checkpoint blockade treatments have shown effective responses in patient subgroups but biomarkers remain challenging. Traditional classification of gastric cancer (GC) is based on genomic profiling and molecular features. Therefore, it is critical to identify the immune-related subtypes and predictive markers by immuno-genomic profiling. METHODS: Single-sample gene-set enrichment analysis (ssGSEA) and ESTIMATE algorithm were used to identify the immue-related subtypes of AGC in two independent GEO datasets. Weighted gene co-expression network analysis (WGCNA) and Molecular Complex Detection (MCODE) algorithm were applied to identify hub-network of immune-related subtypes. Hub genes were confirmed by prognostic data of KMplotter and GEO datasets. The value of hub-gene in predicting immunotherapeutic response was analyzed by IMvigor210 datasets. MTT assay, Transwell migration assay and Western blotting were performed to confirm the cellular function of hub gene in vitro. RESULTS: Three immune-related subtypes (Immunity_H, Immunity_M and Immunity_L) of AGC were identified in two independent GEO datasets. Compared to Immunity_L, the Immuntiy_H subtype showed higher immune cell infiltration and immune activities with favorable prognosis. A weighted gene co-expression network was constructed based on GSE62254 dataset and identified one gene module which was significantly correlated with the Immunity_H subtype. A Hub-network which represented high immune activities was extracted based on topological features and Molecular Complex Detection (MCODE) algorithm. Furthermore, ADAM like decysin 1 (ADAMDEC1) was identified as a seed gene among hub-network genes which is highly associated with favorable prognosis in both GSE62254 and external validation datasets. In addition, high expression of ADAMDEC1 correlated with immunotherapeutic response in IMvigor210 datasets. In vitro, ADAMDEC1 was confirmed as a potential protein in regulating proliferation and migration of gastric cancer cell. Deficiency of ADAMDEC1 of gastric cancer cell also associated with high expression of PD-L1 and Jurkat T cell apoptosis. CONCLUSIONS: We identified immune-related subtypes and key tumor microenvironment marker in AGC which might facilitate the development of novel immune therapeutic targets.


Asunto(s)
Neoplasias Gástricas , Transcriptoma , Microambiente Tumoral , Proteínas ADAM/genética , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Bases de Datos Genéticas , Femenino , Perfilación de la Expresión Génica , Humanos , Inmunoterapia , Células Jurkat , Masculino , Persona de Mediana Edad , Estómago/patología , Transcriptoma/genética , Transcriptoma/inmunología , Microambiente Tumoral/genética , Microambiente Tumoral/inmunología , Adulto Joven
18.
Mol Cell Biochem ; 476(10): 3601-3612, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34024029

RESUMEN

Neuroblastoma (NB) is the most common malignant extra cranial solid tumors in children. It has been well established that retinoic acid (RA) inhibits proliferation of neuroblastoma (NB) by blocking cells at G1 phase of the cell cycle. Clinically, RA has been successfully used to treat NB patients. However, the precise mechanism underlying the potent action of RA-treated NB is not fully explored. In this work, we carried out a gene expression profiling by RNA sequencing on all-trans retinoic acid (ATRA)-treated NB cells. Cancer-related pathway enrichment and subsequent protein-protein interaction (PPI) network analysis identified fibronectin 1 (FN1) as one of the central molecules in the network, which was significantly upregulated during ATRA treatment. In addition, we found that although downregulation of FN1 had no significant effects on either cell proliferation or cell cycle distributions in the presence or absence of ATRA, it increased cell migration and invasion in NB cells and partially blocked ATRA-induced inhibition of cell migration and invasion in SY5Y NB cells. Consistent with this finding, FN1 expression levels in NB patients positively correlate with their overall survivals. Taken together, our data suggest that FN1 is a potential target for effective ATRA treatment on NB patients, likely by facilitating ATRA-induced inhibition of cell migration and invasion.


Asunto(s)
Movimiento Celular/efectos de los fármacos , Fibronectinas/metabolismo , Proteínas de Neoplasias/metabolismo , Neuroblastoma/metabolismo , Tretinoina/farmacología , Línea Celular Tumoral , Movimiento Celular/genética , Fibronectinas/genética , Humanos , Invasividad Neoplásica/genética , Proteínas de Neoplasias/genética , Neuroblastoma/tratamiento farmacológico , Neuroblastoma/genética
19.
Ann Nutr Metab ; 77(3): 159-167, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34082417

RESUMEN

INTRODUCTION: Young and early middle-aged office workers spend most of the day sitting or sleeping. Few studies have used a metabolic chamber to report sitting resting energy expenditure (REE) or sleeping metabolic rate (SMR) estimation equations. This study aimed to develop novel equations for estimating sitting REE and SMR, and previously published equations for SMR were compared against measured values. METHODS: The relationships among sitting REE, SMR, and body composition measured in clinical trials were analyzed. The body composition (fat-free mass [FFM] and fat mass) and energy metabolism of 85 healthy young and early middle-aged Japanese individuals were measured using dual-energy X-ray absorptiometry and a metabolic chamber, respectively. Novel estimate equations were developed using stepwise multiple regression analysis. Estimates of SMR using a new equation and 2 published equations were compared against measured SMR. RESULTS: The sitting mREE and mSMR were highly correlated (r = 0.756, p < 0.01). The new FFM-based estimate accounted for 50.4% of the variance in measured sitting REE (mREE) and 82.3% of the variance in measured SMR (mSMR). The new body weight-based estimate accounted for 49.3% of the variance in sitting mREE and 82.2% of the variance in mSMR. Compared with mSMR, the SMR estimate using an FFM-based published equation was slightly underestimated. CONCLUSION: These novel body weight- and FFM-based equations may help estimate sitting REE and SMR in young and early middle-aged adults. Previous SMR estimated FFM-based equations were slightly underestimated against measured SMR; however, we confirmed the previous SMR estimate equations could be useful. This finding suggests that sitting REE and SMR can be easily estimated from individual characteristics and applied in clinical settings.


Asunto(s)
Metabolismo Energético , Sedestación , Metabolismo Basal , Composición Corporal , Peso Corporal , Calorimetría Indirecta , Humanos , Sueño
20.
Plant Biotechnol J ; 18(2): 581-595, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31368610

RESUMEN

China is the origin and evolutionary centre of Oriental pears. Pyrus betuleafolia is a wild species native to China and distributed in the northern region, and it is widely used as rootstock. Here, we report the de novo assembly of the genome of P. betuleafolia-Shanxi Duli using an integrated strategy that combines PacBio sequencing, BioNano mapping and chromosome conformation capture (Hi-C) sequencing. The genome assembly size was 532.7 Mb, with a contig N50 of 1.57 Mb. A total of 59 552 protein-coding genes and 247.4 Mb of repetitive sequences were annotated for this genome. The expansion genes in P. betuleafolia were significantly enriched in secondary metabolism, which may account for the organism's considerable environmental adaptability. An alignment analysis of orthologous genes showed that fruit size, sugar metabolism and transport, and photosynthetic efficiency were positively selected in Oriental pear during domestication. A total of 573 nucleotide-binding site (NBS)-type resistance gene analogues (RGAs) were identified in the P. betuleafolia genome, 150 of which are TIR-NBS-LRR (TNL)-type genes, which represented the greatest number of TNL-type genes among the published Rosaceae genomes and explained the strong disease resistance of this wild species. The study of flavour metabolism-related genes showed that the anthocyanidin reductase (ANR) metabolic pathway affected the astringency of pear fruit and that sorbitol transporter (SOT) transmembrane transport may be the main factor affecting the accumulation of soluble organic matter. This high-quality P. betuleafolia genome provides a valuable resource for the utilization of wild pear in fundamental pear studies and breeding.


Asunto(s)
Genoma de Planta , Pyrus , China , Frutas , Pyrus/genética , Secuencias Repetitivas de Ácidos Nucleicos/genética
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