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T follicular helper (Tfh) cells provide essential help to B cells in germinal center (GC) reactions. Bcl6 is the obligatory lineage transcription factor in Tfh cells. Here, we examined the molecular pathways that induce Bcl6 gene expression and underscore Bcl6-dependent function during Tfh cell commitment. Integration of genome-wide Bcl6 occupancy in Tfh cells and differential gene expression analyses suggested an important role for the transcription factor Tox2 in Tfh cell differentiation. Ectopic expression of Tox2 was sufficient to drive Bcl6 expression and Tfh development. In genome-wide ChIP-seq analyses, Tox2-bound loci associated with Tfh cell differentiation and function, including Bcl6. Tox2 binding was associated with increased chromatin accessibility at these sites, as measured by ATAC-seq. Tox2-/- mice exhibited defective Tfh differentiation, and inhibition of both Tox2 and the related transcription factor Tox abolished Tfh differentiation. Thus, a Tox2-Bcl6 axis establishes a transcriptional feed-forward loop that promotes the Tfh program.
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Ensamble y Desensamble de Cromatina , Cromatina/genética , Cromatina/metabolismo , Proteínas de Homeodominio/metabolismo , Linfocitos T Colaboradores-Inductores/metabolismo , Animales , Diferenciación Celular/genética , Regulación de la Expresión Génica , Técnicas de Silenciamiento del Gen , Proteínas de Homeodominio/genética , Ratones , Ratones Noqueados , Proteínas Proto-Oncogénicas c-bcl-6/metabolismo , Linfocitos T Colaboradores-Inductores/citología , Linfocitos T Colaboradores-Inductores/inmunología , Factores de Transcripción/metabolismoRESUMEN
The regulatory circuitry underlying embryonic stem (ES) cell self-renewal is well defined, but how this circuitry is disintegrated to enable lineage specification is unclear. RNA-binding proteins (RBPs) have essential roles in RNA-mediated gene regulation, and preliminary data suggest that they might regulate ES cell fate. By combining bioinformatic analyses with functional screening, we identified seven RBPs played important roles for the exit from pluripotency of ES cells. We characterized hnRNPLL, which mainly functions as a global regulator of alternative splicing in ES cells. Specifically, hnRNPLL promotes multiple ES cell-preferred exon skipping events during the onset of ES cell differentiation. hnRNPLL depletion thus leads to sustained expression of ES cell-preferred isoforms, resulting in a differentiation deficiency that causes developmental defects and growth impairment in hnRNPLL-KO mice. In particular, hnRNPLL-mediated alternative splicing of two transcription factors, Bptf and Tbx3, is important for pluripotency exit. These data uncover the critical role of RBPs in pluripotency exit and suggest the application of targeting RBPs in controlling ES cell fate.
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Empalme Alternativo , Antígenos Nucleares/metabolismo , Diferenciación Celular , Células Madre Embrionarias/citología , Ribonucleoproteínas Nucleares Heterogéneas/fisiología , Proteínas del Tejido Nervioso/metabolismo , Células Madre Pluripotentes/citología , Proteínas de Dominio T Box/metabolismo , Factores de Transcripción/metabolismo , Animales , Antígenos Nucleares/genética , Células Madre Embrionarias/metabolismo , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas del Tejido Nervioso/genética , Células Madre Pluripotentes/metabolismo , Isoformas de Proteínas , Proteínas de Dominio T Box/genética , Factores de Transcripción/genéticaRESUMEN
OBJECTIVE: To investigate the efficacy of roxadustat in hemodialysis patients with erythropoietin (EPO) hypo-responsive anemia. MATERIALS AND METHODS: This retrospective study included 55 hemodialysis patients with erythropoietin hypo-responsive anemia at the First Affiliated Hospital of Chongqing Medical University from January to December 2020. We observed their hemoglobin (Hb) changes, inflammatory factors, and adverse reactions before and after 12 weeks of roxadustat treatment. RESULTS: Among the 55 patients, the average age was 60.75 ± 13.96 years old, and the median dialysis age was 48 months. All patients were taken off EPO and switched to roxadustat during the follow-up period. Compared with baseline, patients' Hb was significantly increased (90.64 ± 20.01 g/L, 98.52 ± 15.89 g/L, 104.34 ± 19.15 g/L, and 107.02 ± 20.54 g/L, respectively) (p < 0.05). At 12 weeks of roxadustat treatment, 34 patients (61.82%) met the target Hb levels (100 - 130 g/L). The multivariate logistic analysis showed that Hb response positively correlated with the Hb level before roxadustat treatment (p = 0.046), while responding well to roxadustat negatively correlated with blood platelet-to-lymphocyte ratio (PLR) and duration of dialysis (p = 0.029 and p = 0.046) in patients with EPO hypo-responsive anemia. CONCLUSION: Roxadustat could effectively improve anemia; the PLR and dialysis age were independent predictors of roxadustat efficacy in dialysis patients with EPO hypo-responsive anemia.
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Anemia , Eritropoyetina , Humanos , Persona de Mediana Edad , Anemia/tratamiento farmacológico , Anemia/etiología , Epoetina alfa , Eritropoyetina/uso terapéutico , Glicina/efectos adversos , Hemoglobinas/análisis , Isoquinolinas/efectos adversos , Diálisis Renal/efectos adversos , Estudios RetrospectivosRESUMEN
A novel portable cotton swab based on nitrogen-doped carbon dots (NCDs) for Al3+ detection was constructed for the first time. NCDs with bright green fluorescence were prepared by hydrothermal method with phenylhydrazine hydrochloride and 3-hydroxy-2-naphthoic acid hydrazide as precursors. The surface of NCDs was exposed to abundant functional groups (such as amino, carboxyl, hydroxyl, etc.), which was helpful for the formation of complexes between NCDs and Al3+. In the presence of Al3+, the aggregation of NCDs obviously induced their fluorescence enhancement due to the aggregation-induced emission (AIE) of NCDs. Furthermore, the quantum yield (QY) of NCDs was enhanced by 12 times with Al3+, and the fluorescence lifetime was increased by 7.54 ns. The fluorescence intensity was linearly correlated with the concentration of Al3+ (2.5-300 µM), and the limit of detection was 0.76 µM. Moreover, for the portable way, cotton swabs were successfully employed to construct the sensors for the detection of Al3+ in food samples. This proposal has potential for the application in food analysis.
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Aluminio , Carbono , Límite de Detección , Puntos Cuánticos , Espectrometría de Fluorescencia , Aluminio/química , Aluminio/análisis , Carbono/química , Puntos Cuánticos/química , Espectrometría de Fluorescencia/métodos , Colorantes Fluorescentes/química , Análisis de los Alimentos/métodos , Análisis de los Alimentos/instrumentación , Contaminación de Alimentos/análisis , FluorescenciaRESUMEN
New portable hydrogel sensors for Al3+ and Fe3+ detection were designed based on the aggregation-induced emission (AIE) and color change of N-doped carbon dots (N-CDs). N-CDs with yellow fluorescence were prepared by a one-pot hydrothermal method from 2,5-dihydroxyterephthalic acid and acrylamide. The fluorescence of N-CDs was enhanced by Al3+ about 20 times and quenched by Fe3+. It was interesting that although Fe3+ showed obvious quenching on the fluorescence of N-CDs it did not cause a noticeable change in the fluorescence of N-CDs + Al3+. The colorless solution of N-CDs appeared blue in the presence of Fe3+ without the influence of Al3+. Therefore, the turn-on fluorometry and colorimetry systems based on N-CDs were constructed for the simultaneous detection of Al3+ and Fe3+. Furthermore, the portable sensing of Al3+ and Fe3+ was realized with the assistance of hydrogel, filter paper, cellulose acetate, and cellulose nitrate film. The proposed approach was successfully applied to the detection of Al3+ and Fe3+ in food samples and cell imaging.
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An event camera is a neuromimetic sensor inspired by the human retinal imaging principle, which has the advantages of high dynamic range, high temporal resolution, and low power consumption. Due to the interference of hardware and software and other factors, the event stream output from the event camera usually contains a large amount of noise, and traditional denoising algorithms cannot be applied to the event stream. To better deal with different kinds of noise and enhance the robustness of the denoising algorithm, based on the spatio-temporal distribution characteristics of effective events and noise, an event stream noise reduction and visualization algorithm is proposed. The event stream enters fine filtering after filtering the BA noise based on spatio-temporal density. The fine filtering performs time sequence analysis on the event pixels and the neighboring pixels to filter out hot noise. The proposed visualization algorithm adaptively overlaps the events of the previous frame according to the event density difference to obtain clear and coherent event frames. We conducted denoising and visualization experiments on real scenes and public datasets, respectively, and the experiments show that our algorithm is effective in filtering noise and obtaining clear and coherent event frames under different event stream densities and noise backgrounds.
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Time-varying characteristics of particulate matter (PM) pollution play a crucial role in shaping atmospheric dynamics, which impact the health and welfare of urban commuters. Previously published studies on the diurnal patterns of PMs are not consistent, especially in the context of field experiments in central China, and most field studies have only focused on particles with a single particle size. This study conducted regional-scale studies across 72 street canyon sets in Wuhan, China, investigated diurnal and seasonal PM concentration variations while also evaluating various PM size and the key driving factors. During summer (July, August, and September), evergreen tree-lined street canyons maintained a stable linear trend for smaller dp particulates (i.e., PM1, PM2.5, and PM4), while deciduous street canyons exhibited a bimodal distribution. In winter (January and February), fine particulates (i.e., PM1 and PM2.5) remained a linear trend in evergreen street canyons, while deciduous street canyons show a slightly wavy fluctuating pattern. Meanwhile, it exhibited quadrimodal-peak and triple-trough patterns in both PM7, PM10, and TSP concentrations. The lowest PM concentrations were observed between 14:00 and 16:00 for all particle sizes, with decreased summer pollution (7.81% lower in PM2.5, 53.47% lower in PM10, and 50.3% lower in TSP) noted in our seasonal analysis. Among the various meteorological factors, relative humidity (RH) was identified as the dominant influencing PM factor in both summer and winter. Results from this study will help us better understand field-based air pollutant dispersion processes within pedestrian spaces while laying the groundwork for future research into street PM experiments.
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Contaminantes Atmosféricos , Contaminación del Aire , Ciudades , Monitoreo del Ambiente , Tamaño de la Partícula , Material Particulado , Estaciones del Año , Material Particulado/análisis , Contaminantes Atmosféricos/análisis , China , Contaminación del Aire/estadística & datos numéricosRESUMEN
Microdosing can facilitate better accommodation to the training stimulus while aligning with the scheduling needs of teams. In this study, the effectiveness of microdosing exposure was investigated by comparing the effects of microdosing plyometric jump training (microPJT) with those of regular plyometric jump training (regPJT) and a control group not exposed to plyometric training. The comparison focused on the effects on jumping performance, reactive strength index (RSI), and acceleration over a 10-meter distance. Fifty-two male youth soccer players (16.3 ± 0.6 years old) from under-17 teams participated in a randomized controlled study, with interventions lasting 8 weeks. Assessments were conducted twice, before and after the intervention, measuring squat jump (SJ), countermovement jump (CMJ), RSI during drop jumps, and acceleration in a 10-meter sprint test. The regPJT group completed 34 bilateral jumps and 48 unilateral jumps per week over two weekly sessions, totaling 82 jumps. Conversely, the microPJT group performed 17 bilateral jumps and 24 unilateral jumps weekly over 4 sessions week, totaling 41 jumps. Significant interactions between groups and time were observed concerning SJ (p < 0.001; η2= 0.282), CMJ (p < 0.001; η2= 0.368), RSI (p < 0.001; η2= 0.400) and 10-m sprint time (p < 0.001; η2 = 0.317). Between-group analysis indicated that both the microPJT (p < 0.001) and regPJT (p < 0.001) groups exhibited significant better results compared to the control group in post-intervention evaluation of SJ, CMJ, RSI and 10-m sprint time, while no significant differences were found between experimental groups (p > 0.050). In conclusion, this study has revealed that both microPJT and regPJT are equally effective in enhancing jumping performance and acceleration time in soccer players. This suggests that a smaller training volume, distributed more frequently across the week, can effectively induce improvements in soccer players.
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Aceleración , Rendimiento Atlético , Fuerza Muscular , Ejercicio Pliométrico , Fútbol , Humanos , Fútbol/fisiología , Adolescente , Masculino , Rendimiento Atlético/fisiología , Fuerza Muscular/fisiologíaRESUMEN
This study aimed to analyze the effects of three off-season training programs on the aerobic capacity, countermovement jump (CMJ), and linear sprint performance of young male soccer players. The study employed a randomized multi-arm design, consisting of three experimental groups: i) a high-intensity interval training (HIIT) group; (ii) a plyometric jump training (PJT) group; and (iii) a HIIT+PJT group; and an inactive control group. Fifty-eight under-19 male soccer players (aged 17.6 ±0.6 years) were randomly assigned to participate in a 3-week offseason training program exclusively performing HIIT, PJT, or a combination of both, while the fourth group remained inactive. Players underwent assessments twice, using the Yo-Yo Intermittent Recovery Test - Level 1 (YYIRT), CMJ, and 30-meter linear sprint. Significant interactions between time and groups were found in CMJ (p<0.001), YYIRT (p<0.001), and 30-m sprint (p<0.001). Group*time interaction revealed that the control group was significantly different from HIIT (p<0.001), PJT (p<0.001), and HIIT+PJT (p<0.001) considering the CMJ. Moreover, the control group was significantly different from HIIT (p=0.037) in YYIRT. Finally, the control group was significantly different from HIIT (p=0.024), PJT (p<0.001), and HIIT+PJT (p=0.021) considering the 30-m sprint. In conclusion, off-season training programs are effective in significantly reducing declines in CMJ and sprint performance compared to maintaining training cessation. However, in the YYIRT, only HIIT seems to be significantly superior to maintaining inactivity. To mitigate aerobic performance declines, incorporating HIIT sessions twice weekly during the offseason is advisable. To enhance or maintain jump performance, integrating at least one session of PJT weekly is beneficial.
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Rendimiento Atlético , Entrenamiento de Intervalos de Alta Intensidad , Ejercicio Pliométrico , Fútbol , Humanos , Masculino , Adolescente , Aptitud FísicaRESUMEN
Enhancing peak landing forces and ensuring faster stabilization in the lower limbs during jumping activities can significantly improve performance and decrease the risk of injury among basketball players. This study aimed to compare the effects of unilateral (uPJT) and bilateral plyometric jump training (bPJT) programs on various performance measures, including countermovement jump (CMJ), squat jump (SJ), and single-leg land and hold (SLLH) test outcomes, assessed using force plates. A randomized multi-arm study design was employed, comprising two experimental groups (n = 25; uPJT and n = 25; bPJT) and one control group (n = 25), conducted with youth male regional-level basketball players (16.3 ± 0.6 years old). Participants underwent assessment twice, both before and after an 8-week intervention training period. The uPJT program exclusively involved plyometric drills (e.g., vertical jump exercises; horizontal jump exercises) focusing on single-leg exercises, whereas the bPJT program utilized drills involving both legs simultaneously. The outcomes analyzed included CMJ peak landing force, CMJ peak power, SJ peak force, SJ maximum negative displacement, SLLH time to stabilization, and SLLH peak landing force. The control group exhibited significantly greater SLLH time to stabilization compared to both the uPJT (p < 0.001) and bPJT (p < 0.030) groups. Additionally, time to stabilization was also significantly higher in bPJT than in uPJT (p = 0.042). Comparisons between groups in regards SLLH peak landing force after intervention revealed that the value was significantly smaller in uPJT than in bPJT (p = 0.043) and control (p < 0.001). In the remaining outcomes of CMJ and SJ, both uPJT and bPJT showed significant improvement compared to the control group (p > 0.05), although there was no significant difference between them. In conclusion, our study suggests that utilizing uPJT is equally effective as bPJT in enhancing performance in bilateral jump tests. However, it significantly outperforms bPJT in improving time to stabilization and peak landing forces during single-leg land and hold test. uPJT could be advantageous not for maximizing performance but also for potentially decreasing injury risk by enhancing control and balance during single-leg actions, which are common in basketball.
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Rendimiento Atlético , Baloncesto , Ejercicio Pliométrico , Humanos , Baloncesto/fisiología , Masculino , Ejercicio Pliométrico/métodos , Adolescente , Rendimiento Atlético/fisiología , Extremidad Inferior/fisiología , Prueba de Esfuerzo/métodos , Fenómenos Biomecánicos , Fuerza Muscular/fisiología , Pierna/fisiología , Acondicionamiento Físico Humano/métodos , Acondicionamiento Físico Humano/fisiologíaRESUMEN
Cervical cancer (CC) is a gynecological malignant tumor worldwide. Astragaloside IV (AS-IV) has been found to exert antitumor effects on CC. In addition, M2-polarized macrophages, known as tumor-associated macrophages (TAMs), play an important role in promoting cancer cell growth and angiogenesis. Thus, we explored the association between the antitumor effect of AS-IV and macrophage polarization in CC. Flow cytometry, ELISA, and RTâqPCR assays were applied to detect the levels of CD163, IL-10, TGFß, and CD206 in M2 macrophages with or without AS-IV treatment. In addition, conditioned medium (CM) was collected from these M2 macrophages, and CC cells were then cultured in various CMs. Wound healing and transwell assays were used to assess the migratory ability of CC cells. In this study, we found that AS-IV significantly inhibited M2 polarization of macrophages, as shown by decreased CD163, IL-10, TGFß, and CD206 expression. In addition, compared with CM from M2 macrophages, CM from AS-IV-treated M2 macrophages notably inhibited angiogenesis, migration, and epithelial-mesenchymal transition (EMT) in CC cells. Furthermore, compared with CM from M2 macrophages, CM from AS-IV-treated M2 macrophages markedly reduced p-Smad2 and p-Smad3 protein expression in CC cells, and these changes were reversed by TGF-ß treatment. Collectively, suppression of M2-like polarization of macrophages by AS-IV could prevent the migration and EMT of CC cells by inactivating TGF-ß/Smad2/3 signaling. These findings might provide some theoretical support for exploring novel treatments for CC.
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Transición Epitelial-Mesenquimal , Neoplasias del Cuello Uterino , Femenino , Humanos , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-10/farmacología , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/genética , Macrófagos/metabolismo , Línea Celular Tumoral , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/metabolismo , Proteína Smad2/genética , Proteína Smad2/metabolismo , Proteína Smad2/farmacologíaRESUMEN
Adenosine-to-inosine RNA editing and the catalyzing enzyme adenosine deaminase are both essential for hematopoietic development and differentiation. However, the RNA editome during hematopoiesis and the underlying mechanisms are poorly defined. Here, we sorted 12 murine adult hematopoietic cell populations at different stages and identified 30 796 editing sites through RNA sequencing. The dynamic landscape of the RNA editome comprises stage- and group-specific and stable editing patterns, but undergoes significant changes during lineage commitment. Notably, we found that antizyme inhibitor 1 (Azin1) was highly edited in hematopoietic stem and progenitor cells (HSPCs). Azin1 editing results in an amino acid change to induce Azin1 protein (AZI) translocation to the nucleus, enhanced AZI binding affinity for DEAD box polypeptide 1 to alter the chromatin distribution of the latter, and altered expression of multiple hematopoietic regulators that ultimately promote HSPC differentiation. Our findings have delineated an essential role for Azin1 RNA editing in hematopoietic cells, and our data set is a valuable resource for studying RNA editing on a more general basis.
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Proteínas Portadoras/genética , ARN Helicasas DEAD-box/metabolismo , Hematopoyesis , Células Madre Hematopoyéticas/citología , Edición de ARN , Animales , Proteínas Portadoras/metabolismo , Diferenciación Celular , Células Cultivadas , Femenino , Células Madre Hematopoyéticas/metabolismo , Ratones Endogámicos C57BL , ARN/genéticaRESUMEN
Metabolic reprogramming to fulfill the biosynthetic and bioenergetic demands of cancer cells has aroused great interest in recent years. However, metabolic reprogramming for cancer metastasis has not been well elucidated. Here, we screened a subpopulation of breast cancer cells with highly metastatic capacity to the lung in mice and investigated the metabolic alternations by analyzing the metabolome and the transcriptome, which were confirmed in breast cancer cells, mouse models, and patients' tissues. The effects and the mechanisms of nucleotide de novo synthesis in cancer metastasis were further evaluated in vitro and in vivo. In our study, we report an increased nucleotide de novo synthesis as a key metabolic hallmark in metastatic breast cancer cells and revealed that enforced nucleotide de novo synthesis was enough to drive the metastasis of breast cancer cells. An increased key metabolite of de novo synthesis, guanosine-5'-triphosphate (GTP), is able to generate more cyclic guanosine monophosphate (cGMP) to activate cGMP-dependent protein kinases PKG and downstream MAPK pathway, resulting in the increased tumor cell stemness and metastasis. Blocking de novo synthesis by silencing phosphoribosylpyrophosphate synthetase 2 (PRPS2) can effectively decrease the stemness of breast cancer cells and reduce the lung metastasis. More interestingly, in breast cancer patients, the level of plasma uric acid (UA), a downstream metabolite of purine, is tightly correlated with patient's survival. Our study uncovered that increased de novo synthesis is a metabolic hallmark of metastatic breast cancer cells and its metabolites can regulate the signaling pathway to promote the stemness and metastasis of breast cancer.
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Neoplasias de la Mama/metabolismo , Células Madre Neoplásicas/metabolismo , Nucleótidos/metabolismo , Adulto , Animales , Neoplasias de la Mama/genética , Línea Celular Tumoral , China , GMP Cíclico/metabolismo , Proteínas Quinasas Dependientes de GMP Cíclico/metabolismo , Femenino , Perfilación de la Expresión Génica/métodos , Humanos , Sistema de Señalización de MAP Quinasas/fisiología , Metabolómica/métodos , Ratones , Ratones Endogámicos BALB C , Nucleótidos/biosíntesis , Purinas , Ribosa-Fosfato Pirofosfoquinasa/metabolismo , Transducción de SeñalRESUMEN
The hematopoietic stem cells (HSCs) have the ability to differentiate and give rise to all mature blood cells. Commitment to differentiation progressively limits the self-renewal potential of the original HSCs by regulating the level of lineage-specific gene expression. In this review, we will summarize the current understanding of the molecular mechanisms underlying HSC differentiation toward erythroid, myeloid, and lymphocyte lineages. Moreover, we will decipher how the single-cell technologies advance the lineage-biased HSC subpopulations and their differentiation potential.
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Células Madre Hematopoyéticas , Diferenciación Celular/fisiología , Linaje de la Célula/genéticaRESUMEN
Multiple sclerosis (MS) was once considered an untreatable disease. Through years of research, many drugs have been discovered and are widely used for the treatment of MS. However, the current treatment can only alleviate the clinical symptoms of MS and has serious side effects. Mesenchymal stem cells (MSCs) provide neuroprotection by migrating to injured tissues, suppressing inflammation, and fostering neuronal repair. Therefore, MSCs therapy holds great promise for MS treatment. This review aimed to assess the feasibility and safety of use of MSCs in MS treatment as well as its development prospect in clinical treatment by analysing the existing clinical studies.
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Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Esclerosis Múltiple , Humanos , Esclerosis Múltiple/terapia , Esclerosis Múltiple/etiología , Trasplante de Células Madre Mesenquimatosas/métodos , Células Madre Mesenquimatosas/fisiología , NeuroprotecciónRESUMEN
CONTEXT: Polycystic ovary syndrome (PCOS) is a common and complex disease caused by endocrine and metabolic dysfunction in women of reproductive age. Baicalin is reported to ameliorate PCOS. OBJECTIVE: This study determines whether baicalin could affect the progression of PCOS. MATERIALS AND METHODS: To establish an animal model of PCOS, female Sprague-Dawley (SD) rats were subcutaneously injected with dehydroepiandrosterone (DHEA, 60 mg/kg) for 20 days. Next, normal and PCOS mice were divided into 3 groups: control, PCOS, PCOS + Baicalin (20 mg/kg) groups. In addition, the levels of microRNA-874-3p (miR-874-3p) and microRNA-144 (miR-144) in ovarian tissues were assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). RESULTS: Compared to the PCOS group, baicalin treatment significantly declined free testosterone (33.71 pg/mL vs. 56.05 pg/mL) and luteinizing hormone (LH; 3971.73 pg/mL vs. 5201.50 pg/mL) levels in rats with PCOS. Additionally, compared to the control group, 100 µM baicalin lessened miR-874-3p and miR-144 levels in human ovarian granulosa cells (KGN cells) by 36.87% and 32.57%, respectively. Furthermore, forkhead box O (FOXO) proteins FOXO1 and FOXO3 are the direct targets of miR-144 and miR-874-3p, respectively. Meanwhile, baicalin induced G0-G1 phase arrest (69.56 ± 3.7% at baicalin with 100 µM vs. 51.24 ± 3.2%, control) in KGN cells correlating with decreased p27 Kip1 (FOXO proteins downstream effector gene) expression by 55.5%; however, miR-874-3p or miR-144 overexpression could abolish this effect. CONCLUSIONS: Baicalin could alleviate the symptoms of PCOS via regulating miR-874-3p/FOXO3 and miR-144/FOXO1 axis, demonstrating its potential utility in PCOS treatment.
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MicroARNs , Síndrome del Ovario Poliquístico , Humanos , Femenino , Ratas , Ratones , Animales , Síndrome del Ovario Poliquístico/inducido químicamente , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Síndrome del Ovario Poliquístico/genética , Ratas Sprague-Dawley , MicroARNs/genética , MicroARNs/metabolismo , Apoptosis , Proliferación Celular/genética , Proteína Forkhead Box O1 , Proteína Forkhead Box O3/genéticaRESUMEN
It remains challenging to excite traditional photocatalysts through near-infrared (NIR) light. Attempts to use NIR-light-response materials for photochemical reduction usually suffer from inapposite band position due to extremely narrow band gaps. Here, we report that large π-conjugated organic semiconductor engineered metal-organic framework (MOF) can result in NIR-light-driven CO2 reduction catalyst with high photocatalytic activity. A series of mesoporous MOFs, with progressively increased macrocyclic π-conjugated units, were synthesized for tuning the light adsorption range and catalytic performance. Attainment of these MOFs in single-crystal form revealed the identical topology and precise spatial arrangements of constituent organic semiconductor units and metal clusters. Furthermore, the ultrafast spectroscopic studies confirmed the formation of charge separation state and the mechanism underlying photoexcited dynamics. This combined with X-ray photoelectron spectroscopy and in situ electron paramagnetic resonance studies verified the photoinduced electron transfer pathway within MOFs for NIR-light-driven CO2 reduction. Specifically, tetrakis(4-carboxybiphenyl)naphthoporphyrin) MOF (TNP-MOF) photocatalyst displayed an unprecedentedly high CO2 reduction rate of over 6630 µmol h-1 g-1 under NIR light irradiation, and apparent quantum efficiencies (AQE) at 760 and 808 nm were over 2.03% and 1.11%, respectively. The photocatalytic performance outperformed all the other MOF-based photocatalysts, even visible-light-driven MOF-based catalysts.
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Volatile oils from several Bupleuri radix (BR) are reported as potential sources of drugs. To provide evidence for the application of BR, the volatile oils from 19 batches of different species and habitats of BR including Bupleurum chinese DC. (BCD), Bupleurum scorzonerifolium Willd. (BSW), Bupleurum bicaule Helm (BBH), Bupleurum marginatum var. stenophyllum (Wolff) Shan et Y.Li (BMS), Bupleurum marginatum Wall.ex DC. (BMW) and Bupleurum falcatum L. (BFL) were investigated. The composition of BR volatile oils was determined by GC/MS. Samples were clustered by hierarchical cluster analysis (HCA). Fever was induced by Lipopolysaccharide (LPS), and antipyretic activities of BR volatile oils were evaluated with Chaihu injection (CI) as the positive control. The yields of volatile oils were among 360-5320â ppm. A total of 229 components were identified by GC/MS. Samples could be divided into 4 clusters by HCA. 4 representative samples, one for each cluster, were selected to further compare their antipyretic activities. For the highest content of volatile oil (5320â ppm) and the best activity, BSW has great potential for utilization.
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Antipiréticos , Medicamentos Herbarios Chinos , Aceites Volátiles , Aceites Volátiles/farmacología , Aceites Volátiles/química , Antipiréticos/farmacología , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , EcosistemaRESUMEN
For hundreds of years, Atractylodes chinensis (DC.) Koidz. (AK) has been widely used as a treatment for spleen and stomach diseases in China. The AK polysaccharides (AKPs) have been thought to be the important bioactive components. In this stud, the impacts of different extraction methods were analyzed. The differences between AKPs extracted by hot water extraction (HWE), AKPs extracted by ultrasonic extraction (UAE), and AKPs extracted by enzyme extraction (EAE) were compared in terms of yield, total carbohydrate content, molecular weight distribution, monosaccharide composition, and synergistic activity of the AKPs with apatinib were determined. The results indicated that the yield of the polysaccharide obtained from HWE was higher than that of UAE and EAE. However, activity assays indicated that UAE-AKPs and HWE-AKPs enhanced apoptosis of human gastric cancer cells (SGC-7901) treated with apatinib and UAE-AKPs showed the strongest synergistic activities. This is also in agreement with the fact that UAE-AKPs have a smaller molecular weight, ß-configuration, and higher galactose content. These findings suggested that UAE is an efficient and environmentally friendly method for producing new polysaccharides from Atractylodes chinensis (DC.) Koidz. for the development of natural synergist and for the treatment of gastric cancer.
Asunto(s)
Atractylodes , Neoplasias Gástricas , Atractylodes/química , Humanos , Polisacáridos/química , Polisacáridos/farmacología , Piridinas/farmacología , AguaRESUMEN
Platycodon grandiflorum is an edible and medicinal plant, and polysaccharides are one of its important components. To further improve the utilization rate of P. grandiflorum, we investigated the effects of four different extraction methods, including hot water, ultrasonic-assisted, acid-assisted, and alkali-assisted extractions, on the polysaccharides, which were named PG-H, PG-U, PG-C, and PG-A. The findings indicated that the extraction method had a significant impact on the yield, characteristics, and immunoregulatory activity. We observed that the yields decreased in the following order: PG-H, PG-U, PG-C, and PG-A. Galacturonic acid, glucose, galactose, and arabinose were the most prevalent monosaccharides in the four PGs. However, their proportions varied. In addition, the difference between the content of glucose and galacturonic acid was more significant. PG-U had the highest glucose content, whereas PG-C had the lowest. Galacturonic acid content was highest in PG-A, while the lowest in PG-U. The molecular weight decreased in the order of PG-U, PG-H, PG-C, and PG-A; the particle size was in the order of PG-U, PG-A, PG-H, and PG-C. Moreover, the extraction method had a great impact on immunoregulatory activity. The ability to stimulate the immune function of macrophages was as follows: PG-A > PG-C > PG-U > PG-H. The results indicated that PGs, with lower molecular weights and higher GalA content, exhibited better immune-stimulating activity. And more important the AAE method was a good way to extract polysaccharides from Platycodon grandiflorum for use as a functional product and immunological adjuvant.