RESUMEN
Plants undergo extended morphogenesis. The shoot apical meristem (SAM) allows for reiterative development and the formation of new structures throughout the life of the plant. Intriguingly, the SAM produces morphologically different leaves in an age-dependent manner, a phenomenon known as heteroblasty. In Arabidopsis thaliana, the SAM produces small orbicular leaves in the juvenile phase, but gives rise to large elliptical leaves in the adult phase. Previous studies have established that a developmental decline of microRNA156 (miR156) is necessary and sufficient to trigger this leaf shape switch, although the underlying mechanism is poorly understood. Here we show that the gradual increase in miR156-targeted SQUAMOSA PROMOTER BINDING PROTEIN-LIKE transcription factors with age promotes cell growth anisotropy in the abaxial epidermis at the base of the leaf blade, evident by the formation of elongated giant cells. Time-lapse imaging and developmental genetics further revealed that the establishment of adult leaf shape is tightly associated with the longitudinal cell expansion of giant cells, accompanied by a prolonged cell proliferation phase in their vicinity. Our results thus provide a plausible cellular mechanism for heteroblasty in Arabidopsis, and contribute to our understanding of anisotropic growth in plants.
Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , MicroARNs , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Factores de Transcripción/metabolismo , Hojas de la Planta/metabolismo , Meristema/genética , Meristema/metabolismo , Proliferación Celular/genética , Regulación de la Expresión Génica de las Plantas/genética , MicroARNs/genética , MicroARNs/metabolismoRESUMEN
Heteroblasty refers to a phenomenon that a plant produces morphologically or functionally different lateral organs in an age-dependent manner. In the model plant Arabidopsis thaliana, the production of trichomes (epidermal leaf hairs) on the abaxial (lower) side of leaves is a heteroblastic mark for the juvenile-to-adult transition. Here, we show that the heteroblastic development of abaxial trichomes is regulated by a spatiotemporally regulated complex comprising the leaf abaxial fate determinant (KAN1) and the developmental timer (miR172-targeted AP2-like proteins). We provide evidence that a short-distance chromatin loop brings the downstream enhancer element into close association with the promoter elements of GL1, which encodes a MYB transcription factor essential for trichome initiation. During juvenile phase, the KAN1-AP2 repressive complex binds to the downstream sequence of GL1 and represses its expression through chromatin looping. As plants age, the gradual reduction in AP2-like protein levels leads to decreased amount of the KAN1-AP2 complex, thereby licensing GL1 expression and the abaxial trichome initiation. Our results thus reveal a novel molecular mechanism by which a heteroblastic trait is governed by integrating age and leaf polarity cue in plants.
Asunto(s)
Proteínas de Arabidopsis/metabolismo , Arabidopsis/crecimiento & desarrollo , Regulación del Desarrollo de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Hojas de la Planta/crecimiento & desarrollo , Regiones Promotoras Genéticas , Análisis Espacio-Temporal , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , MicroARNs/genética , Mutación , Fenotipo , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Plantas Modificadas Genéticamente/genética , Plantas Modificadas Genéticamente/crecimiento & desarrollo , Plantas Modificadas Genéticamente/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Activación TranscripcionalRESUMEN
Prophylactic application of emollients has been an effective strategy against infant atopic dermatitis (AD); however, the difference of different emollients is unknown. We performed this network meta-analysis to compare different emollients in preventing infant AD. A systematic search was performed in PubMed, EMBASE and Cochrane library to identify relevant studies from their inception through 28 February, 2022. We evaluated the quality of eligible studies using the Cochrane risk of bias assessment tool. Data analysis was performed using STATA 14.0. Eleven studies were included for data analysis. Direct meta-analysis suggested that early application of emollients effectively prevented AD development in high-risk infants (risk ratio [RR], 0.64; 95% confidence interval [CI], 0.47 to 0.88). Network meta-analysis suggested that emollient emulsion might the better option for preventing infant AD development, with a surface under the cumulative ranking curve (SUCRA) of 82.6% for all populations, 78.0% for high-risk populations and 79.2% for populations with food sensitization. Moreover, subjects receiving emollients more frequently experienced adverse events. Overall, early application of emollients is an effective strategy for preventing AD development in high-risk infants and emollient emulsion may be the optimal type. Future study with well-designed and large scale are warranted to validate our findings.
Asunto(s)
Dermatitis Atópica , Emolientes , Humanos , Lactante , Dermatitis Atópica/prevención & control , Dermatitis Atópica/tratamiento farmacológico , Emolientes/uso terapéutico , Emulsiones , Metaanálisis en Red , Factores de RiesgoRESUMEN
Objective: In the context of the rising prevalence of eosinophilic chronic sinusitis accompanied by nasal polyps, this study aims toinvestigate the role of CD23 in the pathogenesis of eosinophilic chronic sinusitis with nasal polyps. Methods: The cross-sectional study was conducted, 75 patients with chronic sinusitis and nasal polyps treated in our hospital from January 2019 to May 2021 were selected, including 40 cases of eosinophilic patients with the average age of 29.92 years and 35 cases of non-eosinophilic patients with the average age of 30.05 years and 30 patients with the average age of 30.14 years who underwent skull base benign tumor resection in our hospital were selected as the control group, the expression of CD23 in polyp tissue was detected by immunohistochemistry, and the expression of CD23, p-ERK and CCL20 in polyp tissue were detected by Western blot. Specifically, tissue samples were processed and subjected to staining using specific antibodies targeting CD23. The stained sections were then visualized under a microscope to determine the expression levels of CD23. CD23, p-ERK, and CCL20 expressions in polyp tissue were evaluated via Western blot. Total protein was extracted, separated on a gel, transferred to a membrane, and probed with specific antibodies. Chemiluminescence allowed visualization and quantification of protein expressions. Results: Immunohistochemistry showed that CD23 expression was high in the eosinophilic group but low in the non-eosinophilic and control groups. The relative expression levels of CD23 protein, p-ERK protein, and CCL20 protein in polyp tissue s of the eosinophilic group were (0.892 ± 0.092), (0.733 ± 0.101) and (0.813 ± 0.106), respectively, which were significantly higher than those in non-eosinophilic group and control group (P < .05). The relative expression levels of CD23 protein, p-ERK protein, and CCL20 protein in the non-eosinophilic group were (0.461 ± 0.087), 0.412 ± 0.096) and (0.424 ± 0.098), which were significantly higher than those in the control group (P < .05). The relative expression level of CD23 protein in the eosinophilic group was positively correlated with the relative expression levels of p-ERK protein and CCL20 protein (P < .05). The Lund-Kennedy score in the eosinophilic group was (6.10 ± 1.01), which was significantly higher than that in the non-eosinophilic group (P < .05). The relative expression level of CD23 protein in the eosinophilic group was positively correlated with Lund-Kennedy score (P < .05). Conclusion: Eosinophilic chronic sinusitis with nasal polyp mucosal tissue CD23 expression is up-regulated, which is positively correlated with the ERK signaling pathway and disease severity. This study provides valuable insights into potential therapeutic targets that could be explored to develop future treatment modalities. The potential clinical significance of the study is to reveal the important role of CD23 in the pathogenesis of chronic sinusitis with nasal polyps. The upward adjustment of CD23 is positively related to the severity of the disease, which provides valuable guidance for future treatment strategies. This discovery may provide new ways for the development of CD23 treatment methods, so as to better control the progress of the disease of eosinophilic chronic sinusitis with nasal polyps. Further research can explore the molecular mechanism of CD23 regulation, further verify the feasibility of CD23 as the treatment target, and evaluate the potential value of CD23 as a prognostic logo.
Asunto(s)
Pólipos Nasales , Rinitis , Sinusitis , Humanos , Adulto , Rinitis/complicaciones , Pólipos Nasales/complicaciones , Pólipos Nasales/patología , Estudios Transversales , Sinusitis/complicaciones , Sinusitis/patología , Transducción de Señal , Enfermedad CrónicaRESUMEN
BACKGROUND: The blue-crowned laughingthrush (Garrulax courtoisi) is a critically endangered songbird endemic to Wuyuan, China, with population of ~323 individuals. It has attracted widespread attention, but the lack of a published genome has limited research and species protection. RESULTS: We report two laughingthrush genome assemblies and reveal the taxonomic status of laughingthrush species among 25 common avian species according to the comparative genomic analysis. The blue-crowned laughingthrush, black-throated laughingthrush, masked laughingthrush, white-browed laughingthrush, and rusty laughingthrush showed a close genetic relationship, and they diverged from a common ancestor between ~2.81 and 12.31 million years ago estimated by the population structure and divergence analysis using 66 whole-genome sequencing birds from eight laughingthrush species and one out group (Cyanopica cyanus). Population inference revealed that the laughingthrush species experienced a rapid population decline during the last ice age and a serious bottleneck caused by a cold wave during the Chinese Song Dynasty (960-1279 AD). The blue-crowned laughingthrush is still in a bottleneck, which may be the result of a cold wave together with human exploitation. Interestingly, the existing blue-crowned laughingthrush exhibits extremely rich genetic diversity compared to other laughingthrushes. These genetic characteristics and demographic inference patterns suggest a genetic heritage of population abundance in the blue-crowned laughingthrush. The results also suggest that fewer deleterious mutations in the blue-crowned laughingthrush genomes have allowed them to thrive even with a small population size. We believe that cooperative breeding behavior and a long reproduction period may enable the blue-crowned laughingthrush to maintain genetic diversity and avoid inbreeding depression. We identified 43 short tandem repeats that can be used as markers to identify the sex of the blue-crowned laughingthrush and aid in its genetic conservation. CONCLUSIONS: This study supplies the missing reference genome of laughingthrush, provides insight into the genetic variability, evolutionary potential, and molecular ecology of laughingthrush and provides a genomic resource for future research and conservation.
Asunto(s)
Passeriformes , Animales , Evolución Biológica , Cruzamiento , Variación Genética , Genoma , Genómica , Humanos , Passeriformes/genéticaRESUMEN
Blue-crowned laughingthrush (Garrulax courtoisi), passeriformes, is a critically endangered bird endemic to China. Gut microbiota is well known to play a pivotal role in host health and survival. Thus, the understanding of the microbial communities associated with Garrulax courtoisi could be beneficial to save this species from the brink of extinction. In this study, we used 16 s rDNA amplicon sequencing to investigate the gut community composition and microbial diversity of the Garrulax courtoisi population reared in Nanchang Zoo. The results showed that there were 31 phyla that were dominated by Firmicutes, Proteobacteria, Bacteroidetes, and Cyanobacteria in the intestine of Garrulax courtoisi. Compared with previous studies on birds, the Cyanobacteria exhibited an excessive abundance, which may be largely related to the personal lifestyle of Garrulax courtoisi. At the genus level, a total of 552 genera were identified, among which, 21 key genera constituted the core microbiome, including some culturable bacterial genera such as Lactobacillus, Acinetobacter, and Deinococcus. In the meanwhile, we found that there were remarkable intraspecific differences both in terms of microbial community structures, representative biomarkers and predicted functions between the parental generation and their offspring of the population investigated in this study. Furthermore, we also summarized their different eating behaviors and predicted its association with gut microbiota. This study provided the needed pieces of information about these extremely rare birds, Garrulax courtoisi, whose community composition and microbial diversity are hardly known. Importantly, these findings could contribute to our knowledge of the gut health of Garrulax courtoisi and advance the comprehensive conservation of this endangered bird.
Asunto(s)
Microbioma Gastrointestinal , Microbiota , Passeriformes , Animales , Firmicutes/genética , Microbioma Gastrointestinal/genética , Microbiota/genética , Passeriformes/genética , ARN Ribosómico 16S/genéticaRESUMEN
In response to the accumulation of genetic mutations and cellular changes, ultraviolet radiation B (UVB) skin lesions undergo dysplasia and transform into a cutaneous squamous cell carcinoma (CSCC). Consistent with our previous findings that secreted frizzled-related protein 1 (SFRP1), a member of the SFRP gene family, was downregulated in human CSCC tissue samples, we found a significant downregulation of SFRP1 in HaCaT, A431, and SCL-1 cells after UVB irradiation. DNA methyltransferase 1 (DNMT1) was significantly increased in CSCC tissues as well as UVB-exposed A431 and SCL-1 cells. Bisulfite genomic sequencing analysis showed that the downregulation of SFRP1 was mainly due to methylation of the SFRP1 promoter, as indicated by increased methylation rate of SFRP1 after UVB irradiation in HaCaT cells. Moreover, demethylation treatment with 5-aza'-deoxycytidine (5-AzaC) increased SFRP1 expression and reduced the methylation rate of SFRP1 in HaCaT cells. Flow cytometry analyses demonstrated that 5-AzaC treatment or overexpression of SFRP1 ameliorated UVB-induced apoptosis, while knockdown of SFRP1 promoted UVB-induced apoptosis in HaCaT cells. In addition, a comet assay confirmed that 5-AzaC treatment reduced DNA damage following UVB irradiation, while knockdown of SFRP1 enhanced DNA damage following UVB irradiation. In conclusion, our study identified DNA methylation of SFRP1 as a key mediator in the UVB-induced apoptosis of keratinocytes. These findings indicate that reinforcing SFRP1 defences by 5-AzaC may help prevent UVB-induced skin damage.
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Carcinoma de Células Escamosas , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Proteínas de la Membrana/metabolismo , Neoplasias Cutáneas , Apoptosis , Carcinoma de Células Escamosas/genética , Daño del ADN , Metilación de ADN , Humanos , Péptidos y Proteínas de Señalización Intracelular , Queratinocitos/efectos de la radiación , Rayos Ultravioleta/efectos adversosRESUMEN
With the improvement in sequencing technology and the decrease in sequencing cost, increasing amounts of genomic data for pigs have been uploaded to public databases. However, no researchers have to date integrated all currently available data to uncover the global genetic status of pigs. Meanwhile, little is known about the introgression from European to Chinese pigs and its underlying influences. Therefore, we integrated the effective genotype data of 3907 pigs from 193 populations worldwide using population genetic analysis, gene flow analysis and a sharing-IBD study. These findings illustrate not only the population structure of 59 Chinese native breeds and others but also the amounts of gene flow and introgression that have occurred between Western and Chinese pigs. In addition, we demonstrate the presence of introgressed European haplotypes in Chinese indigenous breeds and identify relevant introgressed regions that contain genes associated with growth and feed efficiency. Moreover, we compare the introgression patterns of Western and Chinese pigs and further discuss possible explanations for why the level of introgression differs between Chinese pig breeds and Western modern breeds. Collectively, this study provides a fine global population structure analysis of pigs and presents evidence of European pigs being interbred with local breeds in China.
Asunto(s)
Polimorfismo de Nucleótido Simple , Sus scrofa , Animales , China , Variación Genética , Genética de Población , Haplotipos , Sus scrofa/genética , Porcinos/genéticaRESUMEN
Exposure to the external environment may lead to instability and dysfunction of the skin, resulting in refractory wound, skin aging, pigmented dermatosis, hair loss, some immune-mediated dermatoses, and connective tissue diseases. Nowadays, many skin treatments have not achieved a commendable balance between medical recovery and cosmetic needs. Exosomes are cell-derived nanoscale vesicles carrying various biomolecules, including proteins, nucleic acids, and lipids, with the capability to communicate with adjacent or distant cells. Recent studies have demonstrated that endogenic multiple kinds of exosomes are crucial orchestrators in shaping physiological and pathological development of the skin. Besides, exogenous exosomes, such as stem cell exosomes, can serve as novel treatment options to repair, regenerate, and rejuvenate skin tissue. Herein, we review new insights into the role of endogenic and exogenous exosomes in the skin microenvironment and recent advances in applications of exosomes related to dermatology and cutaneous medical aesthetics. The deep understanding of the mechanisms by which exosomes perform biological functions in skin is of great potential to establish attractive therapeutic methods for the skin.
Asunto(s)
Exosomas , Enfermedades de la Piel/terapia , Piel/metabolismo , Administración Cutánea , Animales , Exosomas/metabolismo , Exosomas/trasplante , Humanos , Regeneración , Medicina Regenerativa , Piel/patología , Enfermedades de la Piel/metabolismo , Enfermedades de la Piel/patología , Fenómenos Fisiológicos de la PielRESUMEN
BACKGROUND: Epithelial-mesenchymal transition (EMT) is a key process in the onset and development of idiopathic pulmonary fibrosis (IPF) with unclear mechanisms. Our previous studies found that bleomycin and tunicamycin could induce ER stress and consequently trigger EMT accompanying with IL-32 overexpression. This study was aimed to investigate the effects of IL-32 on EMT and ER stress to elucidate the pathogenesis of IPF. METHODS: Human lung adenocarcinoma A549 cells were treated with recombinant human (rh)IL-32, IL-32 siRNA and EMT inducer tunicamycin, or 4-phenylbutyric acid (4-PBA), respectively. Then the cell morphology was observed and the expression of ER-related markers and EMT-related markers were detected by RT-qPCR or western blotting. RESULTS: Stimulation of A549 cells with rhIL-32 led to a morphological change from a pebble-like shape to an elongated shape in a portion of the cells, accompanied by down regulated expression of the epithelial cell marker E-cadherin and up regulated expression of the mesenchymal cell markers N-cadherin, Vimentin, and Zeb-1. However, these rhIL-32 induced changes were inhibited by the ER stress inhibitor 4-PBA. Suppression of IL-32 expression with siRNA inhibited TM-induced EMT. Further stimulation of the A549 cells with rhIL-32 demonstrated an increase in the expression of GRP78, although this increase was also inhibited by 4-PBA. CONCLUSIONS: These results suggest that IL-32 induces EMT in A549 cells by triggering ER stress, and IL-32 may be a novel marker for IPF.
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Estrés del Retículo Endoplásmico/efectos de los fármacos , Células Epiteliales/patología , Transición Epitelial-Mesenquimal/efectos de los fármacos , Fibrosis Pulmonar Idiopática/metabolismo , Interleucinas/sangre , Células A549 , Cadherinas/metabolismo , Chaperón BiP del Retículo Endoplásmico , Humanos , Interleucinas/genética , Interleucinas/farmacología , Células Madre Mesenquimatosas/metabolismo , Isoformas de Proteínas/farmacología , Proteínas Recombinantes/farmacología , Vimentina/metabolismoRESUMEN
OBJECTIVE: To study the semen parameters of infertile men carrying hepatitis B virus (HBV) and the influence of HBV infection on semen quality. METHODS: We collected the semen samples from 782 infertility males aged 25ï¼35 years old. According to the results of serological examinations, we divided the patients into groups A (HBsAg, HBeAb and HBcAb positive, n = 286), B (HBsAg, HBeAg and HBcAb positive, n = 230) and C (non-HBV control, n = 266), and comparatively analyzed the routine semen parameters, sperm acrosin activity, sperm DNA fragmentation index (DFI) and high DNA stainability (HDS) among the three groups of patients. RESULTS: Compared with the patients of groups B and C, those of group A showed markedly decreased sperm concentration (ï¼»88.20 ± 82.62ï¼½ and ï¼»89.29 ± 53.80ï¼½ vs ï¼»71.49 ± 60.03ï¼½ ×106/ml, P<0.05), progressively motile sperm (PMS) (ï¼»34.88 ± 15.60ï¼½% and ï¼»37.82 ± 13.63ï¼½% vs ï¼»30.70 ± 14.79ï¼½%, P<0.05), sperm motility (ï¼»45.77 ± 16.58ï¼½% and ï¼»48.16 ± 14.03ï¼½% vs ï¼»42.67 ± 17.23ï¼½%, P<0.05), sperm viability (ï¼»82.55 ± 7.55ï¼½% and ï¼»85.26 ± 6.39ï¼½% vs ï¼»81.07 ± 10.19ï¼½%, P>0.05) and morphologically normal sperm (MNS) (ï¼»6.93 ± 4.45ï¼½% and ï¼»7.27 ± 4.43ï¼½% vs ï¼»5.72 ± 3.47ï¼½%, P<0.05), with sperm concentration, PMS, sperm motility, sperm viability and MNS remarkably lower in group B than in C. Sperm acrosin activity was significantly reduced in group A in comparison with groups B and C (ï¼»57.07 ± 26.38ï¼½ vs ï¼»63.03 ± 28.75ï¼½ and ï¼»78.00 ± 33.49ï¼½ µIU/106, P<0.01), remarkably lower in group B than in C (P<0.01). The sperm DFI and HDS, however, were markedly higher in group A than in B (ï¼»14.79 ± 9.46ï¼½% vs ï¼»12.95 ± 7.29ï¼½% and ï¼»11.60 ± 5.98ï¼½%, P<0.05; ï¼»9.62 ± 6.20ï¼½% vs ï¼»8.43 ± 4.72ï¼½% and ï¼»8.41 ± 4.59ï¼½%, P<0.05), and both higher in group B than in C. CONCLUSIONS: Semen quality is lower in infertile men carrying HBV and therefore HBV infection is one of the causes of male infertility.
Asunto(s)
Hepatitis B/complicaciones , Infertilidad Masculina/etiología , Análisis de Semen , Adulto , Fragmentación del ADN , Humanos , Masculino , Semen , Recuento de Espermatozoides , Motilidad Espermática , EspermatozoidesRESUMEN
Plant cells are totipotent and competent to regenerate from differentiated organs. It has been shown that two phytohormones, auxin and cytokinin, play critical roles within this process. As in animals, the regenerative capacity declines with age in plants, but the molecular basis for this phenomenon remains elusive. Here, we demonstrate that an age-regulated microRNA, miR156, regulates shoot regenerative capacity. As a plant ages, the gradual increase in miR156-targeted SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) transcription factors leads to the progressive decline in shoot regenerative capacity. In old plants, SPL reduces shoot regenerative capacity by attenuating the cytokinin response through binding with the B-type ARABIDOPSIS RESPONSE REGULATORs, which encode the transcriptional activators in the cytokinin signaling pathway. Consistently, the increased amount of exogenous cytokinin complements the reduced shoot regenerative capacity in old plants. Therefore, the recruitment of age cues in response to cytokinin contributes to shoot regenerative competence.
Asunto(s)
Arabidopsis/fisiología , MicroARNs/metabolismo , Nicotiana/fisiología , Brotes de la Planta/genética , Brotes de la Planta/fisiología , Regeneración/genética , Arabidopsis/genética , Citocininas/farmacología , Genes de Plantas , MicroARNs/genética , Proteínas de Plantas/metabolismo , Nicotiana/genéticaRESUMEN
YAP signaling has been reported to be dysregulated in numerous cancer types. However, its roles in nasopharyngeal carcinoma (NPC) are poorly understood. Although several studies have shown that FOXC2 promotes the progression of NPC, the underlying molecular mechanism remains largely unknown. Here, we have shown that FOXC2 interacted with YAP and TEAD, and activated YAP signaling. Furthermore, FOXC2-YAP signaling positively regulated the expression of Hexokinase 2 (HK2) and promoted the glycolysis. Moreover, the inhibitor of HK2, 3-BrPA effectively inhibited the tumorigenesis of NPC cells in vitro and in vivo. Collectively, our study demonstrated that FOXC2 promoted the glycolysis in progression of NPC by activating YAP signaling, and suggested that FOXC2 might be promising therapeutic target.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Carcinoma/metabolismo , Factores de Transcripción Forkhead/metabolismo , Regulación Neoplásica de la Expresión Génica/fisiología , Glucólisis/fisiología , Neoplasias Nasofaríngeas/metabolismo , Fosfoproteínas/metabolismo , Transducción de Señal , Proteínas Adaptadoras Transductoras de Señales/genética , Línea Celular Tumoral , Proliferación Celular/fisiología , Factores de Transcripción Forkhead/genética , Humanos , Carcinoma Nasofaríngeo , Fosfoproteínas/genética , Transducción de Señal/fisiología , Factores de Transcripción , Proteínas Señalizadoras YAPRESUMEN
Metabolism alteration is one of the hallmarks of cancer cells. Although several studies have demonstrated that glycolysis played important roles in the progression of nasopharyngeal carcinoma (NPC), the functions of specific metabolism-associated genes remain largely unknown. In this study, it was found that Pyruvate dehydrogenase B (PDHB), which catalyzed the conversion of pyruvate to Acetyl-CoA, was downregulated in NPC cells. Forced expression of PDHB in NPC cells inhibited cell growth and migration, while knocking down the expression of PDHB promoted the growth, migration, and tumorigenesis of NPC cells. Mechanism study showed that PDHB inhibited ERK signaling and cell growth driven by RasV12. Collectively, our study demonstrated the suppressive roles of PDHB in the progression of NPC, and restoring the function of PDHB might be a promising strategy for NPC therapy.
Asunto(s)
Carcinoma/patología , Neoplasias Nasofaríngeas/patología , Proteínas de Neoplasias/fisiología , Piruvato Deshidrogenasa (Lipoamida)/fisiología , Animales , Carcinoma/enzimología , División Celular , Línea Celular Tumoral , Movimiento Celular , Técnicas de Silenciamiento del Gen , Glucólisis , Xenoinjertos , Humanos , Sistema de Señalización de MAP Quinasas , Ratones , Ratones Desnudos , Neoplasias Nasofaríngeas/enzimología , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/genética , Proteínas Proto-Oncogénicas p21(ras)/fisiología , Piruvato Deshidrogenasa (Lipoamida)/antagonistas & inhibidores , Piruvato Deshidrogenasa (Lipoamida)/genética , Interferencia de ARN , ARN Interferente Pequeño/genética , Proteínas Recombinantes de Fusión/metabolismo , Transducción de SeñalRESUMEN
Telomeres are protein-DNA structures found at the ends of linear chromosomes and are crucial for genome integrity. Telomeric DNA length is primarily maintained by the enzyme telomerase. Cells lacking telomerase will undergo senescence when telomeres become critically short. In Saccharomyces cerevisiae, a very small percentage of cells lacking telomerase can remain viable by lengthening telomeres via two distinct homologous recombination pathways. These "survivor" cells are classified as either Type I or Type II, with each class of survivor possessing distinct telomeric DNA structures and genetic requirements. To elucidate the regulatory pathways contributing to survivor generation, we knocked out the telomerase RNA gene TLC1 in 280 telomere-length-maintenance (TLM) gene mutants and examined telomere structures in post-senescent survivors. We uncovered new functional roles for 10 genes that affect the emerging ratio of Type I versus Type II survivors and 22 genes that are required for Type II survivor generation. We further verified that Pif1 helicase was required for Type I recombination and that the INO80 chromatin remodeling complex greatly affected the emerging frequency of Type I survivors. Finally, we found the Rad6-mediated ubiquitination pathway and the KEOPS complex were required for Type II recombination. Our data provide an independent line of evidence supporting the idea that these genes play important roles in telomere dynamics.
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ADN Helicasas , Recombinación Homóloga , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Telomerasa/genética , Cromosomas/genética , ADN Helicasas/genética , ADN Helicasas/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Inestabilidad Genómica , ARN/genética , ARN/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Transducción de Señal , Telomerasa/metabolismo , Telómero/genética , Homeostasis del Telómero/genética , UbiquitinaciónRESUMEN
Two new homoisoflavans, 4'-hydroxy-7-methoxy-3-benzyl-2H-chromene (1) and 3,4-cis-di-O-3-hydroxy-7-methoxy-3-(4-hydroxybenzyl)-4-ethoxychroman (2), one new coumarin, 7-methoxy-3-(4-hydroxybenzyl)coumarin (4), together with seven known phenolic compounds, bonducellin (3), anemarcoumarin A (5), (+)-syringaresinol (6), curuilignan D (7), scopoletin (8), and p-hydroxybenzaldehyde (9), were isolated from Tara (Caesalpinia spinosa Kuntze). The structures of the new compounds were characterized from their 1D and 2D NMR spectral data. All the compounds were isolated from this plant for the first time.
Asunto(s)
Caesalpinia/química , Fenoles/aislamiento & purificación , Benzopiranos , Cumarinas , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Fenoles/química , Hojas de la Planta/químicaRESUMEN
It is recognized that the stability and journey in the body of nanoparticles are important issues for drug formulations. In this study, we prepared folate-conjugated pullulan acetate nanoparticles (FPANs) and epirubicin loaded FPANs (FPA/EPI) using dialysis method. The storage stability of FPANs and FPA/EPI at 4 degrees C could be up to 3 months. Using folate receptor overexpressed Hela cells, dose dependent cellular uptake and receptor-mediated endocytosis of FPA/EPI were confirmed. From the in vivo pharmacokinetics test, compared to free EPI, half-life time (t½) of FPA/EPI was extended 1.57 times and the area under-the-curve (AUC) increased 3.95 times as well. In addition, biodistribution data showed that, EPI concentration in tumor in FPA/EPI group was 2.01 times higher than that in free EPI group after 96 h; The concentration of drug in liver treated by FPA/EPI was 5.7-11.6 times, while in heart, kidney, especially in stomach and intestine were much lower than those in free EPI group from 24 to 96 h. Furthermore, blank FPANs showed no apparent acute toxicity at dose up to 125 mg/kg. All results suggested that FPA/EPI showed a promising potential on treating cervical carcinoma and its metastatic hepatocellular carcinoma in future because of the high stability, less toxicity and tumor targeting.
Asunto(s)
Antineoplásicos/farmacocinética , Portadores de Fármacos/toxicidad , Epirrubicina/farmacocinética , Ácido Fólico/farmacocinética , Glucanos/toxicidad , Nanopartículas/toxicidad , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Peso Corporal/efectos de los fármacos , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Estabilidad de Medicamentos , Epirrubicina/química , Epirrubicina/farmacología , Femenino , Ácido Fólico/química , Glucanos/química , Células HeLa , Humanos , Masculino , Ratones , Ratones Endogámicos ICR , Ratones Desnudos , Nanopartículas/química , Ratas Wistar , Distribución Tisular , Neoplasias del Cuello UterinoRESUMEN
Sesbania gum (SG), as an environmentally friendly and resourceful natural polymer, has attracted a lot of attention due to its favorable properties. The size distribution of SG powders was broadened owing to the growth. Therefore, it inevitably resulted in the differences in reaction activity, structure and properties of different SG particles. The results showed that small SG particles exhibited higher reaction activity in cross-linking, carboxymethylation and oxidation than its large counterparts. Compared with those of large SG particles, the sedimentation volume of small SG particles could be reduced by 1.1 mL, while their substitution degree of carboxymethyl groups and aldehyde content could be increased by 0.0824 and 18.11 %, respectively. The swelling capacity, freeze-thaw stability, acid and alkali resistance of small SG particles were greater than those of large SG particles, but their retrogradation was weaker than that of large counterparts. The crystalline degree of small SG particles consisting of more long molecular chains could be reduced by 9.8 % compared to large SG particles. The DSC curve of small SG particles was significantly different from that of large SG particles, while the difference in TGA curves between small particles and large particles was relatively small. The enthalpy change of small SG particle was reduced by 48.4 J/g compared to large SG particles. The peak viscosity, final viscosity, breakdown and setback of tapioca starch were obviously influenced by the addition of small SG particles. And their emulsification stability was also better than large SG particles.
Asunto(s)
Sesbania , Tamaño de la Partícula , Sesbania/química , Oxidación-Reducción , Viscosidad , Termodinámica , Almidón/químicaRESUMEN
The Changle goose (CLG), a Chinese indigenous breed, is celebrated for its adaptability, rapid growth, and premium meat quality. Despite its agricultural value, the exploration of its genomic attributes has been scant. Our study entailed whole-genome resequencing of 303 geese across CLG and five other Chinese breeds, revealing distinct genetic diversity metrics. We discovered significant migration events from Xingguo gray goose to CLG and minor gene flow between them. We identified genomic regions through selective sweep analysis, correlating with CLG's unique traits. An elevated inbreeding coefficient in CLG, alongside reduced heterozygosity and rare single nucleotide polymorphisms (RSNPs), suggests a narrowed genetic diversity. Genomic regions related to reproduction, meat quality, and growth were identified, with the GATA3 gene showing strong selection signals for meat quality. A non-synonymous mutation in the Sloc2a1 gene, which is associated with reproductive traits in the CLG, exhibited significant differences in allelic frequency. The roles of CD82, CDH8, and PRKAB1 in growth and development, alongside FABP4, FAF1, ESR1, and AKAP12 in reproduction, were highlighted. Additionally, Cdkal1 and Mfsd14a may influence meat quality. This comprehensive genetic analysis underpins the unique genetic makeup of CLG, providing a basis for its conservation and informed breeding strategies.
RESUMEN
Fifteen compounds were obtained from the twigs and leaves of Caesalpinia minax. Their structures were identified as apigenin (1), 5,7,3',4'- tetrahydroxy-3-methoxyflavone (2), luteolin-5, 3 '-dimethyl-ether (3), thevetiaflavon (4), apigenin-7-O-beta-D-glucuronide (5), bonducellin (6), 7-hydroxy-3-( 4-hydroxybenzylidene )-chroman-4-one (7), 3-deoxysappanchalcone (8), 5-acetonyl-7-hydroxy-2-methyl chromone (9), 4-(trans)-acetyl-3,6,8-trihydroxy-3-methyl-dihydronaphthalenone (10), 4-(cis)-acetyl-3,6,8-trihydroxy-3-methyl-dihydronaphthalenone (11), vanillic acid (12), omega-hydroxypropioquaiacone (13), syringaresinol (14) and uracil (15). All compounds were isolated from C. minax for the first time. Compounds 1-14 were phenolic compounds and compounds 1-5, 9-13 and 15 were isolated from the genus Caesalpinia for the first time.