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Soil (or plant) water deficit accelerates plant reproduction. However, the underpinning molecular mechanisms remain unknown. By modulating cell division/number, ABSCISIC ACID-INSENSITIVE 5 (ABI5), a key bZIP (basic (region) leucine zippers) transcription factor, regulates both seed development and abiotic stress responses. The KIP-RELATED PROTEIN (KRP) cyclin-dependent kinases (CDKs) play an essential role in controlling cell division, and SHOOT MERISTEMLESS (STM) plays a key role in the specification of flower meristem identity. Here, our findings show that abscisic acid (ABA) signaling and/or metabolism in adjust reproductive outputs (such as rosette leaf number and open flower number) under water-deficient conditions in Arabidopsis (Arabidopsis thaliana) plants. Reproductive outputs increased under water-sufficient conditions but decreased under water-deficient conditions in the ABA signaling/metabolism mutants abscisic acid2-1 (aba2-1), aba2-11, abscisic acid insensitive3-1 (abi3-1), abi4-1, abi5-7, and abi5-8. Further, under water-deficient conditions, ABA induced-ABI5 directly bound to the promoter of KRP1, which encodes a CDK that plays an essential role in controlling cell division, and this binding subsequently activated KRP1 expression. In turn, KRP1 physically interacted with STM, which functions in the specification of flower meristem identity, promoting STM degradation. We further demonstrate that reproductive outputs are adjusted by the ABI5-KRP1-STM molecular module under water-deficient conditions. Together, our findings reveal the molecular mechanism by which ABA signaling and/or metabolism regulate reproductive development under water-deficient conditions. These findings provide insights that may help guide crop yield improvement under water deficiency.
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Ácido Abscísico , Proteínas de Arabidopsis , Arabidopsis , Flores , Regulación de la Expresión Génica de las Plantas , Arabidopsis/genética , Arabidopsis/crecimiento & desarrollo , Arabidopsis/metabolismo , Arabidopsis/fisiología , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Ácido Abscísico/metabolismo , Flores/genética , Flores/crecimiento & desarrollo , Flores/fisiología , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Transducción de Señal , Meristema/genética , Meristema/crecimiento & desarrollo , Meristema/metabolismo , Reproducción , Mutación/genética , Quinasas Ciclina-Dependientes/metabolismo , Quinasas Ciclina-Dependientes/genética , Proteínas de HomeodominioRESUMEN
Diabetic kidney disease (DKD) is one of the severe complications of diabetes mellitus, yet there is no effective treatment. Exploring the development of DKD is essential to treatment. Podocyte injury and inflammation are closely related to the development of DKD. However, the mechanism of podocyte injury and progression in DKD remains largely unclear. Here, we observed that FTO expression was significantly upregulated in high glucose-induced podocytes and that overexpression of FTO promoted podocyte injury and inflammation. By performing RNA-seq and MeRIP-seq with control podocytes and high glucose-induced podocytes with or without FTO knockdown, we revealed that serum amyloid A2 (SAA2) is a target of FTO-mediated m6A modification. Knockdown of FTO markedly increased SAA2 mRNA m6A modification and decreased SAA2 mRNA expression. Mechanistically, we demonstrated that SAA2 might participate in podocyte injury and inflammation through activation of the NF-κB signaling pathway. Furthermore, by generating podocyte-specific adeno-associated virus 9 (AAV9) to knockdown SAA2 in mice, we discovered that the depletion of SAA2 significantly restored podocyte injury and inflammation. Together, our results suggested that upregulation of SAA2 promoted podocyte injury through m6A-dependent regulation, thus suggesting that SAA2 may be a therapeutic target for diabetic kidney disease.
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Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato , Nefropatías Diabéticas , Podocitos , Proteína Amiloide A Sérica , Animales , Ratones , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética , Nefropatías Diabéticas/genética , Glucosa , Inflamación/genética , FN-kappa B , ARN Mensajero/genética , Transducción de Señal , Proteína Amiloide A Sérica/genéticaRESUMEN
In recent years, the impact of age-related diseases on human health has become increasingly severe, and developing effective drugs to deal with these diseases has become an urgent task. Considering the essential regulatory role of hydrogen sulfide (H2S) in these diseases, it is regarded as a promising target for treatment. H2S is a novel gaseous transmitter involved in many critical physiological activities, including anti-oxidation, anti-inflammation, and angiogenesis. H2S also regulates cell activities such as cell proliferation, migration, invasion, apoptosis, and autophagy. These regulatory effects of H2S contribute to relieving and treating age-related diseases. In this review, we mainly focus on the pathogenesis and treatment prospects of H2S in regulating age-related diseases.
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Envejecimiento , Sulfuro de Hidrógeno , Sulfuro de Hidrógeno/metabolismo , Sulfuro de Hidrógeno/farmacología , Humanos , Envejecimiento/metabolismo , Animales , Autofagia/efectos de los fármacos , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacosRESUMEN
Accurate analysis of microRNAs (miRNAs) at the single-cell level is extremely important for deeply understanding their multiple and intricate biological functions. Despite some advancements in analyzing single-cell miRNAs, challenges such as intracellular interferences and insufficient detection limits still remain. In this work, an ultrasensitive nanopore sensor for quantitative single-cell miRNA-155 detection is constructed based on ionic current rectification (ICR) coupled with enzyme-free catalytic hairpin assembly (CHA). Benefiting from the enzyme-free CHA amplification strategy, the detection limit of the nanopore sensor for miRNA-155 reaches 10 fM and the nanopore sensor is more adaptable to complex intracellular environments. With the nanopore sensor, the concentration of miRNA-155 in living single cells is quantified to realize the early diagnosis of triple-negative breast cancer (TNBC). Furthermore, the nanopore sensor can be applied in screening anticancer drugs by tracking the expression level of miRNA-155. This work provides an adaptive and universal method for quantitatively analyzing intracellular miRNAs, which will greatly improve our understanding of cell heterogeneity and provide a more reliable scientific basis for exploring major diseases at the single-cell level.
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MicroARNs , Nanoporos , Análisis de la Célula Individual , Neoplasias de la Mama Triple Negativas , MicroARNs/análisis , Neoplasias de la Mama Triple Negativas/diagnóstico , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patología , Humanos , Femenino , Línea Celular Tumoral , Límite de DetecciónRESUMEN
Exposure of dark-grown etiolated seedlings to light triggers the transition from skotomorphogenesis/etiolation to photomorphogenesis/de-etiolation. In the life cycle of plants, de-etiolation is essential for seedling development and plant survival. The mobilization of soluble sugars (glucose [Glc], sucrose, and fructose) derived from stored carbohydrates and lipids to target organs, including cotyledons, hypocotyls, and radicles, underpins de-etiolation. Therefore, dynamic carbohydrate biochemistry is a key feature of this phase transition. However, the molecular mechanisms coordinating carbohydrate status with the cellular machinery orchestrating de-etiolation remain largely opaque. Here, we show that the Glc sensor HEXOKINASE 1 (HXK1) interacts with GROWTH REGULATOR FACTOR5 (GRF5), a transcriptional activator and key plant growth regulator, in Arabidopsis (Arabidopsis thaliana). Subsequently, GRF5 directly binds to the promoter of phytochrome A (phyA), encoding a far-red light (FR) sensor/cotyledon greening inhibitor. We demonstrate that the status of Glc within dark-grown etiolated cotyledons determines the de-etiolation of seedlings when exposed to light irradiation by the HXK1-GRF5-phyA molecular module. Thus, following seed germination, accumulating Glc within dark-grown etiolated cotyledons stimulates a HXK1-dependent increase of GRF5 and an associated decrease of phyA, triggering the perception, amplification, and relay of HXK1-dependent Glc signaling, thereby facilitating the de-etiolation of seedlings following light irradiation. Our findings, therefore, establish how cotyledon carbohydrate signaling under subterranean darkness is sensed, amplified, and relayed, determining the phase transition from skotomorphogenesis to photomorphogenesis on exposure to light irradiation.
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Proteínas de Arabidopsis , Arabidopsis , Plantones/metabolismo , Cotiledón/metabolismo , Etiolado , Glucosa/metabolismo , Luz , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Fitocromo A/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
Acetaminophen (APAP) overdose is the most common cause for acute liver failure (ALF) in the developed countries, with limited treatment options. Piezo1 is a mechanosensitive cation channel. We found that APAP caused upregulation of Piezo1 in both an APAP-induced acute liver injury (ALI) animal model and a mouse hepatocyte cell line AML12. Activation of Piezo1 by its activator Yoda1 reduced APAP-induced hepatotoxicity and ROS level. Mechanistically, activation of Piezo1 led to accumulation of the antioxidant regulator Nrf2 and upregulation of its target genes Nqo1 and Gsta1, while knockdown of Piezo1 downregulated this pathway. Finally, injection of Yoda1 decreased serum AST and ALT levels, reduced cell death and rescued liver injury in the APAP-induced ALI mouse model. Our findings suggested a previously undiscovered protective role of Piezo1 in APAP-induced ALI, which might shed light on a new therapeutic target for this disease.
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Acetaminofén , Enfermedad Hepática Inducida por Sustancias y Drogas , Animales , Ratones , Especies Reactivas de Oxígeno/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Hígado/metabolismo , Hepatocitos/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Estrés Oxidativo , Ratones Endogámicos C57BL , Canales Iónicos/metabolismoRESUMEN
In this paper, we implement integrated magnetic flux concentrators (MFCs) combined with a multi-frequency modulation method to achieve high-magnetic-detection sensitivity using a nuclear spin on the solid nuclear spin in diamonds. First, we excited the nuclear spin in diamonds using a continuous-wave technique, and a linewidth of 1.37 MHz and frequency resolution of 79 Hz were successfully obtained, which is reduced by one order of the linewidth, and increased by 56 times in frequency resolution compared to that excited by an electron spin. The integrated high-permeability MFC was designed to magnify the magnetic field near the diamond, with a magnification of 9.63 times. Then, the multi-frequency modulation technique was used to fully excite the hyperfine energy level of Nitrogen Vacancy (NV) centers along the four axes on the diamond with MFC, and magnetic detection sensitivity of 250p T/H z 1/2 was realized. These techniques should allow designing an integrated NV magnetometer with high sensitivity in a small volume.
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Objectives: To investigate the influence of helper T cell type 1 (Th1)/Th2 cytokines and Treg cells on the pregnancy outcome of patients with recurrent pregnancy loss (RPL) and to reveal the predictive value of their combination on the pregnancy outcome. Methods: The 165 RPL patients admitted to the Reproductive Medicine Department of the Second Hospital of Lanzhou University from September 2019 to June 2021 served as the research subjects for the study. The subjects comprised a live birth group (102 patients) or a non-live birth group (63 patients) based on their pregnancy outcomes. All patients were tracked through the end of pregnancy. Flow cytometry was applied to determine Treg and Th1/Th2 cytokine levels in the peripheral blood of patients without pregnancy. Results: The levels of interleukin-6 (IL-6), IL-2, IL-10, and Treg in the RPL live birth group were significantly higher than those in the non-live birth group. The ratio of TNF - α/ IL-6, NF-α/ IL-10, IFN- γ/ IL-6, IFN- γ/ IL-10 in the non-live birth group increased significantly. The area under the curve (AUC) of Th1/Th2 cytokines combined with Treg cells was 0.786 (95% CI: 0.712-0.860), the specificity was 76.2%, and the sensitivity was 74.5%. Conclusion: Treg and Th1/Th2 cytokines showed a predictive ability for the pregnancy outcome of patients with recurrent pregnancy loss and their higher combined predictive efficacy. Meanwhile, in the Th1/Th2 immune response, its ratio was more important than the expression of a single cytokine.
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Aborto Habitual , Citocinas , Femenino , Embarazo , Humanos , Citocinas/metabolismo , Resultado del Embarazo , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Linfocitos T Reguladores/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Aborto Habitual/metabolismoRESUMEN
Double cross-linked dynamic hydrogels, dynagels, have been prepared through reversible imine bonds and supramolecular interactions, which showed good pH responsiveness, injectability, self-healing property and biocompatibility. With the further encapsulation of heparin, the obtained hydrogels exhibited good anti-bacterial activity and promotion effects for 3D cell culture.
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Heparina , Hidrogeles , Técnicas de Cultivo de CélulaRESUMEN
OBJECTIVE: To investigate the correlation of intravoxel incoherent motion (IVIM) and diffusion kurtosis imaging (DKI) parameters with the expression of HIF-1α in soft tissue sarcoma (STS). METHODS: This prospective study was approved by the institutional ethics committee. Written informed consent was obtained from all patients. Forty patients with STS who underwent 3.0 T MRI, including IVIM and DKI, were included in the study. Standard apparent diffusion coefficient (ADC), true ADC (Dslow), pseudo ADC (Dfast), perfusion fraction (f), mean kurtosis (MK), and mean diffusivity (MD) of each lesion were independently analyzed by two observers. An MRI-pathology control method was used to ensure correspondence between the MRI slices and the pathological sections. Spearman analysis, independent sample t test, Mann-Whitney U test, chi-squared test, and receiver operating characteristic (ROC) curve analysis were performed. RESULTS: Dslow and MD values showed a negative correlation with HIF-1α expression (r = - 0.469, - 0.588). MK and f values showed a positive correlation with HIF-1α expression (r = 0.779, 0.572). Dslow, MD, MK, and f values showed significant differences between the high- and low-expression groups. The MK value showed the best diagnostic ability. The optimal cut-off MK value of 0.604 was associated with 78.3% sensitivity and 88.2% specificity (area under the curve, 0.867). CONCLUSIONS: This preliminary study demonstrated the association of IVIM and DKI parameters with the expression of HIF-1α in STS. KEY POINTS: ⢠IVIM and DKI parameters are correlated with the expression of HIF-1α in STS. ⢠The MRI-pathology control method can be used in clinical studies to ensure correspondence between MRI slices and pathology sections.
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Imagen de Difusión Tensora , Sarcoma , Imagen de Difusión por Resonancia Magnética , Humanos , Imagen por Resonancia Magnética , Movimiento (Física) , Estudios Prospectivos , Sarcoma/diagnóstico por imagen , Sensibilidad y EspecificidadRESUMEN
Microplastics (MPs) considered as a new persistent environmental pollutant could enter into the circulatory system and result in decrease of sperm quantity and quality in mice. However, the effects of Polystyrene MPs (PS MPs) on the ovary and its mechanism in rats remained unclear. In this present study, thirty-two healthy female Wistar rats were exposed to different concentrations of 0.5 µm PS MPs dispersed in deionized water for 90 days. Using hematoxylin-eosin (HE) staining, the number of growing follicles was decreased compared to the control group. In addition, the activity of glutathione peroxidase (GSH-Px), catalase (CAT) and superoxide dismutase (SOD) were decreased while the expression level of malondialdehyde (MDA) was increased in ovary tissue. Confirmed by immunohistochemistry, the integrated optical density of NLRP3 and Cleaved-Caspase-1 had been elevated by 13.9 and 14 in granulosa cells in the 1.5 mg/kg/d group. Furthermore, compared to the control group, the level of AMH had been decreased by 23.3 pg/ml while IL-1ß and IL-18 had been increased by 32 and 18.5 pg/ml in the 1.5 mg/kg/d group using the enzyme-linked immune sorbent assay (ELISA). Besides, the apoptosis of granulosa cells was elevated measured by terminal deoxyribonucleotide transferase-mediated nick end labeling (TUNEL) staining and flow cytometry. Moreover, western blot assays showed that the expressions of NLRP3/Caspase-1 signaling pathway related factors and Cleaved-Caspase-3 were increased. These results demonstrated that PS MPs could induce pyroptosis and apoptosis of ovarian granulosa cells via the NLRP3/Caspase-1 signaling pathway maybe triggered by oxidative stress. The present study suggested that exposure to microplastics had adverse effects on ovary and could be a potential risk factor for female infertility, which provided new insights into the toxicity of MPs on female reproduction.
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Apoptosis/efectos de los fármacos , Caspasa 1/metabolismo , Microplásticos/toxicidad , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Ovario/efectos de los fármacos , Poliestirenos/toxicidad , Piroptosis/efectos de los fármacos , Animales , Femenino , Células de la Granulosa/efectos de los fármacos , Células de la Granulosa/metabolismo , Células de la Granulosa/patología , Interleucina-18/metabolismo , Interleucina-1beta/metabolismo , Malondialdehído/metabolismo , Ovario/metabolismo , Ovario/patología , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar , Transducción de SeñalRESUMEN
Autophagy is a highly conserved process of the eukaryotic cell cycle. It plays an important role in the survival and maintenance of cells by degrading organelles, proteins, and macromolecules in the cytoplasm and the circulation of degraded products. The dysfunction of autophagy can lead to the pathology of many human diseases. The nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome belongs to the family of nucleotide-binding and oligomerization domain-like receptors (NLRs) and can induce caspase-1 activation, thus leading to the maturation and secretion of interleukin-1beta (IL-1ß) and IL-18. It has been reported that the interplay between autophagy and NLRP3 inflammasome is involved in many diseases, including renal diseases. In this review, the interplay between autophagy and the NLRP3 inflammasome and the mechanisms in renal diseases are explored to provide ideas for relevant basic research in the future.
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Autofagia , Inflamasomas/metabolismo , Enfermedades Renales/patología , Animales , Humanos , Enfermedades Renales/etiología , Enfermedades Renales/metabolismoRESUMEN
An important goal in designing a head-mounted display device is to improve its exit pupils' output light areal uniformity. The goal cannot be reached by using an output grating coupler of uniform surface profile depth. To solve this problem, we propose a method to fabricate 2D and continuously variable depth gratings by using a specially modified reactive ion-beam etching system, which features variable speed scanning etching and ion beam cross-sectional shaping in two orthogonal dimensions. We experimentally verified that the uniformity of the light outcoupled from the coupler fabricated by using the proposed method was 52% better than that of a uniform-depth output grating coupler.
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OBJECTIVE: To determine if dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) parameters reflect histological grade of soft tissue sarcoma (STS) MATERIALS AND METHODS: The medical records of 50 patients diagnosed with pathologically confirmed STS were retrospectively reviewed. Each STS was assessed with conventional contrast-enhanced MRI and DCE-MRI using a 3.0-T MRI system. The conventional MRI characteristics of low-grade (grade 1) and high-grade (grade 2 and grade 3) tumors were analyzed. Semi-quantitative parameters, including iAUC and TTP, and quantitative parameters, including Ktrans, Kep, and Ve, were derived from DCE-MRI. The diagnostic performances and optimal thresholds of various combinations of DCE-MRI parameters for predicting histological grades of STS were investigated using receiver operator characteristic (ROC) curves. RESULTS: On conventional MRI, high-grade STSs were significantly larger (≥ 5 cm) and more likely to show a heterogeneous signal intensity on T2WI (> 75%), peritumoral hyperintensity on T2WI, or tumor necrosis (> 50%) compared with low-grade STS. On DCE-MRI, iAUC, TTP, Ktrans, and Kep were significant predictors of STS histological grade. Ktrans had a high diagnostic value for differentiating between high-grade and low-grade STSs. The combination of iAUC, TTP, and Ktrans yielded a higher AUC value (0.841) than the other models. CONCLUSION: High-grade STSs were usually larger than low-grade STSs, had unclear boundaries, a heterogeneous signal intensity on T2-weighted image (T2WI), and extensive necrosis. On DCE-MRI, iAUC, TTP, Ktrans, and Kep could differentiate between high-grade and low-grade STSs. The combination of iAUC, TTP, and Ktrans had a high diagnostic performance for differentiating between STS histological grades.
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Imagen por Resonancia Magnética , Sarcoma , Neoplasias de los Tejidos Blandos , Medios de Contraste , Humanos , Estudios Retrospectivos , Sarcoma/diagnóstico por imagen , Neoplasias de los Tejidos Blandos/diagnóstico por imagenRESUMEN
Some ingredients in foods can activate the aryl hydrocarbon receptor (AhR) and arrest cell proliferation. In this study, we hypothesized that 6-formylindolo [3, 2-b] carbazole (FICZ) arrests the cell cycle in LoVo cells (a colon cancer line) through the AhR. The AhR agonist FICZ and the AhR antagonist CH223191 were used to treat LoVo cells. Real-time PCR and Western blot analyses were performed to detect the expression of the AhR, CYP1A1, CDK4, cyclinD1, cyclin E, CDK2, P27, and pRb. The distribution and activation of the AhR were detected with immunofluorescence. A 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and flow cytometric analysis were performed to measure cell viability, cell cycle stage, and apoptosis. Our results show that FICZ inhibited LoVo cell proliferation by inducing G1 cell cycle arrest but had no effect on epithelial apoptosis. Further analysis found that FICZ downregulated cyclinD1 and upregulated p27 expression to arrest Rb phosphorylation. The downregulation of cyclinD1 and upregulation of p27 were abolished by co-treatment with CH223191. We conclude that the AhR, when activated by FICZ (an endogenous AhR ligand), can arrest the cell cycle and block LoVo cell proliferation.
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Carbazoles/farmacología , Puntos de Control de la Fase G1 del Ciclo Celular/efectos de los fármacos , Receptores de Hidrocarburo de Aril/metabolismo , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Ciclina D1/efectos de los fármacos , Ciclina D1/genética , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Humanos , Proteínas de la Membrana/metabolismo , Fosforilación , Receptores de Hidrocarburo de Aril/agonistas , Receptores de Hidrocarburo de Aril/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: Keratinocyte growth factor (KGF) stimulates normal growth, development and intestinal epithelial cell proliferation. Cyclin D1 promotes the cell cycle by inhibiting retinoblastoma protein (RB1). The activated aryl hydrocarbon receptor (AhR) has an important influence on the development of tumors through its interactions with the cell cycle. AIM: The aim of the present study was to explore a new role for AhR in KGF-induced colon cancer cell growth. MATERIALS AND METHODS: Real-time PCR, western blot or immunofluorescence analysis were used to detect the expression of KGF, AhR, cyclin D1 and CYP1A1. Immunohistochemistry was used to observe the localization of AhR. MTT assay and flow cytometric analyses were performed to measure cell viability and the cell cycle. RESULTS: Real-time PCR analysis revealed that KGF, AhR, and CYP1A1 mRNAs were overexpressed in colorectal cancer tissues. Meanwhile, overexpression of AhR was primarily observed in epithelial cells. In in vitro assay, KGF promoted colon cancer cell growth, as well as up-regulated and activated AhR. At the same time, AhR-knockdown colon cancer cells were less responsive to KGF. Western blot analysis, real-time PCR, or immunofluorescence data indicated that cyclin D1 expression was up-regulated by KGF but this up-regulation was compromised when AhR was silenced, and the cell cycle was arrested in the G0/G1 stage in these cells. CONCLUSIONS: Our study suggests that KGF, AhR, and CYP1A1 are overexpressed in colorectal cancer tissues. Moreover, we reveal a new mechanism by which KGF promotes cell proliferation through the AhR-cyclin D1 pathway in colon cancer cells.
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Neoplasias Colorrectales/metabolismo , Citocromo P-450 CYP1A1/metabolismo , Factor 7 de Crecimiento de Fibroblastos/metabolismo , Receptores de Hidrocarburo de Aril/metabolismo , Puntos de Control del Ciclo Celular , Línea Celular Tumoral , Proliferación Celular , Neoplasias Colorrectales/genética , Ciclina D1 , Citocromo P-450 CYP1A1/genética , Factor 7 de Crecimiento de Fibroblastos/genética , Regulación Neoplásica de la Expresión Génica/fisiología , Técnicas de Silenciamiento del Gen , Humanos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores de Hidrocarburo de Aril/genéticaRESUMEN
Aqueous zinc-ion batteries (AZIBs) are considered as attractive energy storage systems with great promise owing to their low cost, environmental friendliness and high safety. Nevertheless, cathode materials with stable structure and rapid diffusion of zinc ions are in great demand for AZIBs. In this work, a new kind of potassium vanadate compound (KV3 O8 ) is synthesized with fibrous morphology as an excellent cathode material for AZIBs, which shows outstanding electrochemical performance. KV3 O8 exhibits a high discharge capacity of 556.4 mAh g-1 at 0.8 A g-1 , and the capacity retention is 81.3% at 6 A g-1 even after a long cycle life of 5000 cycles. The excellent performance of the KV3 O8 cathode is benefited from the structural stability, sufficient active sites, and high conductivity, which is revealed by in situ X-ray diffraction and various other characterizations. This work offers a new design strategy into fabricating high efficiency cathode materials for AZIBs and beyond.
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Ghrelin, produced mainly by gastric X/A-like cells, triggers a hunger signal to the central nervous system to stimulate appetite. It remains unclear whether X/A-like cells sense gastric distention and thus regulate ghrelin production. Here we show that PIEZO1 expression in X/A-like cells decreases in patients with obesity when compared to controls, whereas it increases after sleeve gastrectomy. Male and female mice with specific loss of Piezo1 in X/A-like cells exhibit hyperghrelinaemia and hyperphagia and are more susceptible to overweight. These phenotypes are associated with impairment of the gastric CaMKKII/CaMKIV-mTOR signalling pathway. Activation of PIEZO1 by Yoda1 or gastric bead implantation inhibits ghrelin production, decreases energy intake and induces weight loss in mice. Inhibition of ghrelin production by Piezo1 through the CaMKKII/CaMKIV-mTOR pathway can be recapitulated in a ghrelin-producing cell line mHypoE-42. Our study reveals a mechanical regulation of ghrelin production and appetite by PIEZO1 of X/A-like cells, which suggests a promising target for anti-obesity therapy.
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Ghrelina , Serina-Treonina Quinasas TOR , Humanos , Masculino , Femenino , Ratones , Animales , Ghrelina/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Obesidad/metabolismo , Apetito/fisiología , Ingestión de Alimentos , Canales Iónicos/genéticaRESUMEN
AIMS: Although radiotherapy is a core treatment modality for various human cancers, including glioblastoma multiforme (GBM), its clinical effects are often limited by radioresistance. The specific molecular mechanisms underlying radioresistance are largely unknown, and the reduction of radioresistance is an unresolved challenge in GBM research. METHODS: We analyzed and verified the expression of nuclear autoantigenic sperm protein (NASP) in gliomas and its relationship with patient prognosis. We also explored the function of NASP in GBM cell lines. We performed further mechanistic experiments to investigate the mechanisms by which NASP facilitates GBM progression and radioresistance. An intracranial mouse model was used to verify the effectiveness of combination therapy. RESULTS: NASP was highly expressed in gliomas, and its expression was negatively correlated with the prognosis of glioma. Functionally, NASP facilitated GBM cell proliferation, migration, invasion, and radioresistance. Mechanistically, NASP interacted directly with annexin A2 (ANXA2) and promoted its nuclear localization, which may have been mediated by phospho-annexin A2 (Tyr23). The NASP/ANXA2 axis was involved in DNA damage repair after radiotherapy, which explains the radioresistance of GBM cells that highly express NASP. NASP overexpression significantly activated the signal transducer and activator of transcription 3 (STAT3) signaling pathway. The combination of WP1066 (a STAT3 pathway inhibitor) and radiotherapy significantly inhibited GBM growth in vitro and in vivo. CONCLUSION: Our findings indicate that NASP may serve as a potential biomarker of GBM radioresistance and has important implications for improving clinical radiotherapy.
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Anexina A2 , Neoplasias Encefálicas , Glioblastoma , Factor de Transcripción STAT3 , Animales , Humanos , Ratones , Anexina A2/genética , Anexina A2/metabolismo , Anexina A2/uso terapéutico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/metabolismo , Proliferación Celular/genética , Glioblastoma/genética , Factor de Transcripción STAT3/genética , Línea Celular TumoralRESUMEN
OBJECTIVE: To compare the characteristics of lesions with consistent and inconsistent judgments of coronary stenosis on 320-slice dynamic volume computed tomography (DVCT) versus coronary angiography (CAG). METHODS: Ninety-two patients (265 lesions) with CAG and DVCT within 2 weeks from January 2011 to May 2012 were enrolled. According to the matching degree of stenotic judgment, all lesions were divided into consistent and inconsistent groups. The position of lesions, degree of bending, plaque morphology and calcification proportion were analyzed. RESULTS: There were 236 lesions in consistent group versus 29 lesions in inconsistent group.In inconsistent group, there were more left circumflex artery, distal, ostial and tortuous lesions than that in consistent group (P < 0.05). At the same time, the proportion of nubbly type plaque, calcified plaque, nubbly and nodular type calcification in the main plaque in inconsistent group was higher than those in consistent group (P < 0.05).Segmental coronary calcium score (250 ± 210 vs 82 ± 66, P < 0.05), number of calcifications and calcification proportion in main plaque (55% ± 28% vs 43% ± 30%, P < 0.05) in inconsistent group were higher than those in consistent group (P < 0.05). CONCLUSION: When coronary lesion occurs in ostial, distal or tortuous position or its main plaque is of nubbly type with a heavy calcification load, the judgment of stenosis by CTA and CAG is more likely to be inconsistent.