RESUMEN
Obesity-induced chronic liver inflammation is a hallmark of nonalcoholic steatohepatitis (NASH)-an aggressive form of nonalcoholic fatty liver disease. However, it remains unclear how such a low-grade, yet persistent, inflammation is sustained in the liver. Here, we show that the macrophage phagocytic receptor TREM2, induced by hepatocyte-derived sphingosine-1-phosphate, was required for efferocytosis of lipid-laden apoptotic hepatocytes and thereby maintained liver immune homeostasis. However, prolonged hypernutrition led to the production of proinflammatory cytokines TNF and IL-1ß in the liver to induce TREM2 shedding through ADAM17-dependent proteolytic cleavage. Loss of TREM2 resulted in aberrant accumulation of dying hepatocytes, thereby further augmenting proinflammatory cytokine production. This ultimately precipitated a vicious cycle that licensed chronic inflammation to drive simple steatosis transition to NASH. Therefore, impaired macrophage efferocytosis is a previously unrecognized key pathogenic event that enables chronic liver inflammation in obesity. Blocking TREM2 cleavage to restore efferocytosis may represent an effective strategy to treat NASH.
Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Hipernutrición , Humanos , Enfermedad del Hígado Graso no Alcohólico/patología , Hipernutrición/patología , Hígado/patología , Inflamación/patología , Obesidad/patología , Glicoproteínas de Membrana , Receptores InmunológicosRESUMEN
Although large-scale and accurate identification of cis-regulatory elements on pig protein-coding and long non-coding genes has been reported, similar study on pig miRNAs is still lacking. Here, we systematically characterized the cis-regulatory elements of pig miRNAs in muscle and fat by adopting miRNAomes, ChIP-seq, ATAC-seq, RNA-seq and Hi-C data. In total, the cis-regulatory elements of 257 (85.95%) expressed miRNAs including 226 known and 31 novel miRNAs were identified. Especially, the miRNAs associated with super-enhancers, active promoters, and "A" compartment were significantly higher than those associated by typical enhancers, prompters without H3K27ac, and "B" compartment, respectively. The tissue specific transcription factors were the primary determination of core miRNA expression pattern in muscle and fat. Moreover, the miRNA promoters are more evolutionarily conserved than miRNA enhancers, like other type genes. Our study adds additional important information to existing pig epigenetic data and provides essential resource for future in-depth investigation of pig epigenetics.
Asunto(s)
Epigenómica , MicroARNs , Animales , Secuenciación de Inmunoprecipitación de Cromatina , MicroARNs/genética , Músculos , Secuencias Reguladoras de Ácidos Nucleicos , Porcinos/genéticaRESUMEN
Alumina particles experience phase transition as an undercooling process along the plume, during which the liquid alumina clusters transform into multiphase, and then into α phase. The phase transformation model was built by an improved diffusion limited aggregation (DLA) algorithm with monomers of stratified structure. The effects of phase transformation on the ultraviolet optical characteristics of alumina clusters were studied using the superposition T-matrix method (STMM). We found that the alumina clusters in phase transition had completely different optical properties compared with the fixed phase ones. Forward scattering, absorption efficiency and asymmetry parameter gradually decreased, whereas backward scattering, scattering efficiency, and single-scattering albedo gradually increased during the phase transformation process. Besides, multiphase alumina clusters were compared with the other two equivalent models, including the sphere model approximated by equivalent volume sphere (EVS) and the equivalent surface sphere (ESS) approaches and single-phase cluster model approximated by Maxwell-Garnett (MG) and Bruggeman (BR) approaches. Generally speaking, the optical properties of the single-phase cluster approximated by MG and BR approaches were relatively close to those of the real multiphase alumina cluster. Whereas the spheres approximated by EVS and ESS had great deviations, especially when the number of monomers in the cluster was 20, the relative error of scattering efficiency calculated by ESS was up to 52%. Therefore, approximate approaches for multiphase clusters should be chosen cautiously. Our results give further the understanding of the optical properties of alumina clusters. As the phase states are usually closely related to the plume radiation and burning process, these kinds of researches will be helpful to aircraft detection, identiï¬cation, and other related fields.
RESUMEN
Embryonic and neonatal skeletal muscles grow via the proliferation and fusion of myogenic cells, whereas adult skeletal muscle adapts largely by remodelling pre-existing myofibers and optimizing metabolic balance. It has been reported that miRNAs played key roles during skeletal muscle development through targeting different genes at post-transcriptional level. In this study, we show that a single miRNA (miR-208b) can modulate both the myogenesis and homoeostasis of skeletal muscle by distinct targets. As results, miR-208b accelerates the proliferation and inhibits the differentiation of myogenic cells by targeting the E-protein family member transcription factor 12 (TCF12). Also, miR-208b can stimulate fast-to-slow fibre conversion and oxidative metabolism programme through targeting folliculin interacting protein 1 (FNIP1) but not TCF12 gene. Further, miR-208b could active the AMPK/PGC-1a signalling and mitochondrial biogenesis through targeting FNIP1. Thus, miR-208b could mediate skeletal muscle development and homoeostasis through specifically targeting of TCF12 and FNIP1.
Asunto(s)
Metabolismo Energético , Regulación del Desarrollo de la Expresión Génica , Homeostasis , MicroARNs/genética , Desarrollo de Músculos/genética , Músculo Esquelético/metabolismo , Interferencia de ARN , Animales , Diferenciación Celular/genética , Células Cultivadas , Ratones , Ratones Transgénicos , Mitocondrias/genética , Mitocondrias/metabolismo , Modelos Biológicos , Mioblastos/citología , Mioblastos/metabolismo , ARN Mensajero/genéticaRESUMEN
Screening α-glucosidase inhibitors with novel structures is an important field in the development of anti-diabetic drugs due to their application in postprandial hyperglycemia control. Boldine is one of the potent natural antioxidants with a wide range of pharmacological activities. Virtual screening and biochemical inhibition kinetics combined with molecular dynamics simulations were conducted to verify the inactivation function of boldine on α-glucosidase. A series of inhibition kinetics and spectrometry detections were conducted to analyze the α-glucosidase inhibition. Computational simulations of molecular dynamics/docking analyses were conducted to detect boldine docking sites' details and evaluate the key binding residues. Boldine displayed a typical reversible and mixed-type inhibition manner. Measurements of circular dichroism and fluorescence spectrum showed boldine changed the secondary structure and loosened the tertiary conformation of target α-glucosidase. The computational molecular dynamics showed that boldine could block the active pocket site through close interaction with binding key residues, and two phenolic hydroxyl groups of boldine play a core function in α-glucosidase inhibition via ligand binding. This investigation reveals the boldine function on interaction with the α-glucosidase active site, which provides a new inhibitor candidate.Communicated by Ramaswamy H. Sarma.
RESUMEN
ABSTRACT: With the rise of generative artificial intelligence (AI) and AI-powered chatbots, the landscape of medicine and healthcare is on the brink of significant transformation. This perspective delves into the prospective influence of AI on medical education, residency training and the continuing education of attending physicians or consultants. We begin by highlighting the constraints of the current education model, challenges in limited faculty, uniformity amidst burgeoning medical knowledge and the limitations in 'traditional' linear knowledge acquisition. We introduce 'AI-assisted' and 'AI-integrated' paradigms for medical education and physician training, targeting a more universal, accessible, high-quality and interconnected educational journey. We differentiate between essential knowledge for all physicians, specialised insights for clinician-scientists and mastery-level proficiency for clinician-computer scientists. With the transformative potential of AI in healthcare and service delivery, it is poised to reshape the pedagogy of medical education and residency training.
Asunto(s)
Educación Médica , Médicos , Humanos , Inteligencia Artificial , Estudios Prospectivos , Educación ContinuaRESUMEN
Skeletal muscle health and function is a critical determinant of clinical outcomes in patients with peripheral arterial disease (PAD). Herein, we identify fatty infiltration, the ectopic deposition of adipocytes in skeletal muscle, as a histological hallmark of end-stage PAD, also known as chronic limb threatening ischemia (CLTI). Leveraging single cell transcriptome mapping in mouse models of PAD, we identify a pro-adipogenic mesenchymal stromal cell population marked by expression of Vcam1 (termed Vcam1+ FAPs) that expands in the ischemic limb. Mechanistically, we identify Sfrp1 and Nr3c1 as regulators of Vcam1+ FAP adipogenic differentiation. Loss of Sfrp1 and Nr3c1 impair Vcam1+ FAP differentiation into adipocytes in vitro. Finally, we show that Vcam1+ FAPs are enriched in human CLTI patients. Collectively, our results identify a pro-adipogenic FAP subpopulation in CLTI patients and provide a potential therapeutic target for muscle regeneration in PAD.
RESUMEN
OBJECTIVES: To provide balanced consideration of the opportunities and challenges associated with integrating Large Language Models (LLMs) throughout the medical school continuum. PROCESS: Narrative review of published literature contextualized by current reports of LLM application in medical education. CONCLUSIONS: LLMs like OpenAI's ChatGPT can potentially revolutionize traditional teaching methodologies. LLMs offer several potential advantages to students, including direct access to vast information, facilitation of personalized learning experiences, and enhancement of clinical skills development. For faculty and instructors, LLMs can facilitate innovative approaches to teaching complex medical concepts and fostering student engagement. Notable challenges of LLMs integration include the risk of fostering academic misconduct, inadvertent overreliance on AI, potential dilution of critical thinking skills, concerns regarding the accuracy and reliability of LLM-generated content, and the possible implications on teaching staff.
Asunto(s)
Competencia Clínica , Educación Médica , Humanos , Reproducibilidad de los Resultados , Lenguaje , AprendizajeRESUMEN
OBJECTIVE: To explore the application value of the self-management manual combined with the case management model in postoperative management of nasopharyngeal carcinoma after radiotherapy. METHODS: Eighty-four patients with nasopharyngeal carcinoma admitted to Yingtan People's Hospital from May 2020 to April 2022 were retrospectively included in this study. They were divided into the experimental group (receiving self-management manual combined with case management mode scheme, n=42) and the control group (receiving continuous management after conventional nasopharyngeal carcinoma radiotherapy, n=42) according to mode differences. The cancer-related fatigue [Cancer Fatigue Scale (CFS)], comfort status [General Comfort Questionnaire (GCQ)], self-management efficacy [Chinese Strategies Used by People to Promote Health (C-SUPPH)], self-care ability (self-care ability measurement), pain score [Visual analogue scale (VAS)], and quality of life [European Organization for Research and Treatment of Cancer QLQ-C30 (EORTC QLQ-C30)] were compared between the two groups after 4 weeks of radiotherapy. The adverse reactions of the two groups were recorded. Combined with periodic review and follow-up records, the prognostic factors of the two groups of patients were analyzed. RESULTS: After treatment, the scores of physical fatigue (12.83±1.10), emotional fatigue (9.78±1.32), cognitive fatigue (5.62±1.31), and total score of CFS (28.24±2.26) in the experimental group were 12.83±1.10. The control group physical fatigue (13.90±1.25) points, emotional fatigue (10.55±1.40) points, cognitive fatigue (6.80±1.75) points, and total CFS (31.33±2.59) points in both groups were lower than before treatment. The experimental group was lower than the control group (ALL P<0.05). The physiological, psychological, spiritual, socio-cultural, and environmental scores of the experimental group were higher than those of the control group (all P<0.05). The scores of health knowledge, self-care skills, self-care responsibility, and self-concept score of patients in the experimental group were higher than the control group (all P<0.05). After intervention, the VAS score of the experimental group was lower than that of the control group (P<0.05). After intervention, the EORTC QLQ-C30 score of both groups increased significantly as compared with pre-intervention. The score in the experimental group was significantly higher than that in the control group [(80.05±10.72) vs (68.11±12.10), P<0.05]. Postoperative (various) adverse reactions in the experimental group were lower than the control group (all P<0.05). The factors influencing the prognosis of nasopharyngeal carcinoma patients were age, tumor stage, and intervention mode by Cox model analysis (all P<0.05). CONCLUSION: The self-management manual combined with the case management mode can alleviate cancer fatigue, improve postoperative self-management ability, self-care ability, and quality of life of patients with nasopharyngeal cancer radiotherapy, reduce the occurrence of adverse reactions and improve the prognosis of patients. It is worth promoting in clinical settings.
RESUMEN
Transposable elements (TEs) are parasitic DNA sequences accounting for over half of the human genome. Tight control of the repression and activation states of TEs is critical for genome integrity, development, immunity and diseases, including cancer. However, precisely how this regulation is achieved remains unclear. Here we develop a targeted proteomic proximity labeling approach to capture TE-associated proteins in human embryonic stem cells (hESCs). We find that the RNA N6-methyladenosine (m6A) reader, YTHDC2, occupies genomic loci of the primate-specific TE, LTR7/HERV-H, specifically through its interaction with m6A-modified HERV-H RNAs. Unexpectedly, YTHDC2 recruits the DNA 5-methylcytosine (5mC)-demethylase, TET1, to remove 5mC from LTR7/HERV-H and prevent epigenetic silencing. Functionally, the YTHDC2/LTR7 axis inhibits neural differentiation of hESCs. Our results reveal both an underappreciated crosstalk between RNA m6A and DNA 5mC, the most abundant regulatory modifications of RNA and DNA in eukaryotes, and the fact that in hESCs this interplay controls TE activity and cell fate.
Asunto(s)
Elementos Transponibles de ADN , Células Madre Pluripotentes , Animales , Humanos , Diferenciación Celular/genética , Cromatina , Metilación de ADN/genética , Elementos Transponibles de ADN/genética , Oxigenasas de Función Mixta/genética , Células Madre Pluripotentes/metabolismo , Primates/genética , Proteómica , Proteínas Proto-Oncogénicas/genética , ARN Interferente Pequeño/genéticaRESUMEN
Chronic limb-threatening ischemia (CLTI), representing the end-stage of peripheral arterial disease (PAD), is associated with a one-year limb amputation rate of âË»15-20% and significant mortality. A key characteristic of CLTI is the failure of the innate regenerative capacity of skeletal muscle, though the underlying mechanisms remain unclear. Here, single-cell transcriptome analysis of ischemic and non-ischemic muscle from the same CLTI patients demonstrated that ischemic-damaged tissue is enriched with pro-inflammatory macrophages. Comparable results were also observed in a murine CLTI model. Importantly, integrated analyses of both human and murine data revealed premature differentiation of muscle satellite cells (MuSCs) in damaged tissue and indications of defects in intercellular signaling communication between MuSCs and their inflammatory niche. Collectively, our research provides the first single-cell transcriptome atlases of skeletal muscle from CLTI patients and murine models, emphasizing the crucial role of macrophages and inflammation in regulating muscle regeneration in CLTI through interactions with MuSCs.
RESUMEN
BACKGROUND: Chronic limb-threatening ischemia (CLTI), a severe manifestation of peripheral arterial disease (PAD), is associated with a 1-year limb amputation rate of approximately 15-20% and substantial mortality. A key feature of CLTI is the compromised regenerative ability of skeletal muscle; however, the mechanisms responsible for this impairment are not yet fully understood. In this study, we aim to delineate pathological changes at both the cellular and transcriptomic levels, as well as in cell-cell signaling pathways, associated with compromised muscle regeneration in limb ischemia in both human tissue samples and murine models of CLTI. METHODS: We performed single-cell transcriptome analysis of ischemic and non-ischemic muscle from the same CLTI patients and from a murine model of CLTI. In both datasets, we analyzed gene expression changes in macrophage and muscle satellite cell (MuSC) populations as well as differential cell-cell signaling interactions and differentiation trajectories. RESULTS: Single-cell transcriptomic profiling and immunofluorescence analysis of CLTI patient skeletal muscle demonstrated that ischemic-damaged tissue displays a pro-inflammatory macrophage signature. Comparable results were observed in a murine CLTI model. Moreover, integrated analyses of both human and murine datasets revealed premature differentiation of MuSCs to be a key feature of failed muscle regeneration in the ischemic limb. Furthermore, in silico inferences of intercellular communication and in vitro assays highlight the importance of macrophage-MuSC signaling in ischemia induced muscle injuries. CONCLUSIONS: Collectively, our research provides the first single-cell transcriptome atlases of skeletal muscle from CLTI patients and a murine CLTI model, emphasizing the crucial role of macrophages and inflammation in regulating muscle regeneration in CLTI through interactions with MuSCs.
Asunto(s)
Células Satélite del Músculo Esquelético , Humanos , Animales , Ratones , Células Satélite del Músculo Esquelético/metabolismo , Células Satélite del Músculo Esquelético/patología , Músculo Esquelético/metabolismo , Isquemia/metabolismo , Isquemia/patología , Diferenciación Celular , Regeneración , Macrófagos/metabolismo , Factores de Riesgo , Resultado del Tratamiento , Estudios RetrospectivosRESUMEN
Objective: We aimed to determine the efficacy of different idiopathic macular hole treatment methods to improve recovery time and patient outcomes using Frequency Domain Optical Coherence Tomography (SD-OCT) and Optical Coherence Tomography Angiography (OCTA). Methods: This retrospective study included patients with idiopathic macular hole who were admitted to our hospital between 1st January 2019 and 31st October 2021. The control group was treated with internal limiting membrane tamponade, and the study group was treated with clamshell therapy. Treatment conditions (internal limiting membrane treatment duration and hole closure rate), best corrected visual acuity (BCVA) before and after surgery, OCTA measurements, and SD-OCT were assessed. The retinal nerve fiber layer (RNFL), retinal ganglion cell layer (GCL), and retinal pigment epithelium (RPE) thicknesses were also analyzed. Results: The treatment time and hole closure rate of the internal limiting membrane in the study group were higher than those in the control group. The curative effect of the study group was better than that of the control group. The postoperative DCP blood vessel density in both groups was higher than that before operation, and the study group was higher than the control group. The FAZ area and circumference were lower than those before surgery, and the study group was lower than the control group. At 3 months after operation, the thickness of DIOA, nasal temporal RNFL, and GCL were decreased in both groups, and the observed values in the study group were lower than those in the control group. At 3-month follow-up, there was no significant difference in RPE thickness between the two groups. Conclusion: Flip and cover therapy is the most effective treatment. SD-OCT and OCTA provide an objective basis for clinical intervention by comparing the effects of different procedures on the retinal condition of patients.
Asunto(s)
Perforaciones de la Retina , Angiografía , Humanos , Perforaciones de la Retina/diagnóstico por imagen , Perforaciones de la Retina/cirugía , Estudios Retrospectivos , Tomografía de Coherencia Óptica/métodos , Vitrectomía/métodosRESUMEN
In adult skeletal muscle, satellite cells are in a quiescent state, which is essential for the future activation of muscle homeostasis and regeneration. Multiple studies have investigated satellite cell proliferation and differentiation, but the molecular mechanisms that safeguard the quiescence of satellite cells remain largely unknown. In this study, we purposely activated dormant satellite cells by using various stimuli and captured the in vivo-preserved features from quiescence to activation transitions. We found that retinoic acid signaling was required for quiescence maintenance. Mechanistically, retinoic acid receptor gamma (RARγ) binds to and stimulates genes responsible for Akt dephosphorylation and subsequently inhibits overall protein translation initiation in satellite cells. Furthermore, the alleviation of retinoic acid signaling released the satellite cells from quiescence, but this restraint was lost in aged cells. Retinoic acid also preserves the quiescent state during satellite cell isolation, overcoming the cellular stress caused by the isolation process. We conclude that active retinoic acid signaling contributes to the maintenance of the quiescent state of satellite cells through regulation of the protein translation initiation process.
Asunto(s)
Proteínas Proto-Oncogénicas c-akt , Tretinoina , Adulto , Anciano , División Celular , Rayos gamma , Humanos , Mioblastos , Tretinoina/farmacologíaRESUMEN
Although major advances in genomics have initiated an exciting new era of research, a lack of information regarding cis-regulatory elements has limited the genetic improvement or manipulation of pigs as a meat source and biomedical model. Here, we systematically characterize cis-regulatory elements and their functions in 12 diverse tissues from four pig breeds by adopting similar strategies as the ENCODE and Roadmap Epigenomics projects, which include RNA-seq, ATAC-seq, and ChIP-seq. In total, we generate 199 datasets and identify more than 220,000 cis-regulatory elements in the pig genome. Surprisingly, we find higher conservation of cis-regulatory elements between human and pig genomes than those between human and mouse genomes. Furthermore, the differences of topologically associating domains between the pig and human genomes are associated with morphological evolution of the head and face. Beyond generating a major new benchmark resource for pig epigenetics, our study provides basic comparative epigenetic data relevant to using pigs as models in human biomedical research.
Asunto(s)
Epigenómica , Secuencias Reguladoras de Ácidos Nucleicos , Porcinos/genética , Animales , Secuenciación de Inmunoprecipitación de Cromatina , Epigénesis Genética , Expresión Génica , Genoma , Genoma Humano , Células HEK293 , Humanos , Ratones , RNA-Seq , Receptores Acoplados a Proteínas G/metabolismo , TranscriptomaRESUMEN
miRNAs reportedly participate in various biological processes, such as skeletal muscle proliferation and differentiation. However, the regulation of differentially expressed (DE) miRNAs and their function in myogenesis remain unclear. Herein, miRNA expression profiles and regulation during C2C12 differentiation were analyzed in relation to chromatin states by RNA-seq, ATAC-seq, and ChIP-seq. We identified 19 known and nine novel differentially expressed miRNAs at days 0, 1, 2, and 4. The expression of the differentially expressed miRNAs was related to the chromatin states of the 113 surrounding open chromatin regions defined by ATAC-seq peaks. Of these open chromatin regions, 44.25% were colocalized with MyoD/MyoG binding sites. The remainder of the above open chromatin regions were enriched with motifs of the myoblast-expressed AP-1 family, Ctcf, and Bach2 transcription factors (TFs). Additionally, the target genes of the above differentially expressed miRNAs were enriched primarily in muscle growth and development pathways, especially the Hippo signaling pathway. Moreover, via combining a loss-of-function assay with Q-PCR, western blotting, and immunofluorescence, we confirmed that the Hippo signaling pathway was responsible for C2C12 myoblast differentiation. Thus, our results showed that these differentially expressed miRNAs were regulated by chromatin states and affected muscle differentiation through the Hippo signaling pathway. Our findings provide new insights into the function of these differentially expressed miRNAs and the regulation of their expression during myoblast differentiation.
Asunto(s)
Diferenciación Celular/genética , Cromatina/metabolismo , MicroARNs/genética , Desarrollo de Músculos/fisiología , Animales , Proliferación Celular/fisiología , Ratones , Desarrollo de Músculos/genética , Músculo Esquelético/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Células Satélite del Músculo Esquelético/metabolismo , Factores de Transcripción/metabolismoRESUMEN
OBJECTIVE: This study aims to clarify the mechanisms underlying transcriptional regulation and regulatory roles of lncRNAs in skeletal muscle cell differentiation. METHODS: We analysed the expression patterns of lncRNAs via time-course RNA-seq. Then, we further combined the ATAC-seq and ChIP-seq to investigate the governing mechanisms of transcriptional regulation of differentially expressed (DE) lncRNAs. Weighted correlation network analysis and GO analysis were conducted to identify the transcription factor (TF)-lncRNA pairs related to skeletal muscle cell differentiation. RESULTS: We identified 385 DE lncRNAs during C2C12 differentiation, the transcription of which is determined by chromatin states around their transcriptional start sites. The TF-lncRNA correlation network showed substantially concordant changes in DE lncRNAs between C2C12 differentiation and satellite cell rapid growth stages. Moreover, the up-regulated lncRNAs showed a significant decrease following the differentiation capacity of satellite cells, which gradually declines during skeletal muscle development. Notably, inhibition of the lncRNA Atcayos and Trp53cor1 led to the delayed differentiation of satellite cells. Those lncRNAs were significantly up-regulated during the rapid growth stage of satellite cells (4-6 weeks) and down-regulated with reduced differentiation capacity (8-12 weeks). It confirms that these lncRNAs are positively associated with myogenic differentiation of satellite cells during skeletal muscle development. CONCLUSIONS: This study extends the understanding of mechanisms governing transcriptional regulation of lncRNAs and provides a foundation for exploring their functions in skeletal muscle cell differentiation.
Asunto(s)
Diferenciación Celular , Cromatina/genética , Desarrollo de Músculos , Músculo Esquelético/citología , ARN Largo no Codificante/genética , Animales , Línea Celular , Proliferación Celular , Perfilación de la Expresión Génica , Regulación del Desarrollo de la Expresión Génica , Ratones , Músculo Esquelético/metabolismo , Células Satélite del Músculo Esquelético/citología , Células Satélite del Músculo Esquelético/metabolismo , Activación TranscripcionalRESUMEN
DNA methylation is an important form of epigenetic regulation that can regulate the expression of genes and the development of tissues. Muscle satellite cells play an important role in skeletal muscle development and regeneration. Therefore, the DNA methylation status of genes in satellite cells is important in the regulation of the development of skeletal muscle. This study systematically investigated the changes of genome-wide DNA methylation in satellite cells during skeletal muscle development. According to the MeDIP-Seq data, 52,809-123,317 peaks were obtained for each sample, covering 0.70-1.79% of the genome. The number of reads and peaks was highest in the intron regions followed by the CDS regions. A total of 96,609 DMRs were identified between any two time points. Among them 6198 DMRs were annotated into the gene promoter regions, corresponding to 4726 DMGs. By combining the MeDIP-Seq and RNA-Seq data, a total of 202 overlap genes were obtained between DMGs and DEGs. GO and Pathway analysis revealed that the overlap genes were mainly involved in 128 biological processes and 23 pathways. Among the biological processes, terms related to regulation of cell proliferation and Wnt signaling pathway were significantly different. Gene-gene interaction analysis showed that Wnt5a, Wnt9a, and Tgfß1 were the key nodes in the network. Furthermore, the expression level of Wnt5a, Wnt9a, and Tgfß1 genes could be influenced by the methylation status of promoter region during skeletal muscle development. These results indicated that the Wnt and Tgfß signaling pathways may play an important role in functional regulation of satellite cells, and the DNA methylation status of Wnt and Tgfß signals is a key regulatory factor during skeletal muscle development. This study provided new insights into the effects of genome-wide methylation on the function of satellite cells.
RESUMEN
AIM: To evaluate the relationship between contrast sensitivity (CS) and corneal shape following overnight orthokeratology (OK). METHODS: We conducted a retrospective clinical study of 80 lens-wearing myopia patients, all of whom had undergone OK and had been evaluated by Orbscan II topography. We measured the surface irregularity index (SIRI) of corneal topography at 3 and 5 mm, the size of the flattened central corneal curvature of OK lens (zone A), the size of the cornea altered by OK lens (zone B), the size of the pupillary area at the corneal level (zone C), the area of crossover between zones A and C (zone AC), the area of crossover between zones B and C (BC), the ratio of BC to B (BC/B), and the ratio of AC to C (AC/C). CS was evaluated using the CSV-1000 with spatial frequencies of 3, 6, 12, and 18 cycles/degree (CPD). RESULTS: Multiple correlation analyses indicated significant negative correlations between CS, zone C, BC/B, and 3-mm SIRI (all P<0.01). There were no significant differences between CS, zone B, AC/A, or 5-mm SIRI (P=0.60, 0.94 and 0.11, respectively). Zone C was negatively correlated with 3, 6, 12, and 18 CPD. 5-mm SIRI were negatively correlated with 6, 12, and 18 CPD. BC/C was negatively correlated with 6 and 18 CPD. AC/C was positively correlated with 3 CPD. CONCLUSION: Zone C, 3-mm SIRI and BC/B affect the CS following overnight OK.
RESUMEN
The liver plays a key role in metabolism and affects pig production. However, the functional annotation of noncoding regions of the pig liver remains poorly understood. We revealed the landscape of cis-regulatory elements and their functional characterization in pig liver. We identified 102,373 cis-regulatory elements in the pig liver, including enhancers, promoters, super-enhancers, and broad H3K4me3 domains, and highlighted 26 core transcription regulatory factors in the pig liver as well. We found similarity of cis-regulatory elements among those of pigs, humans, and cattle. Despite the low proportion of functionally conserved enhancers (~30%) between pig and human liver tissue, ~78% of the pig liver enhancer orthologues sequence could play an enhancer role in other human tissues. Additionally, we observed that the ratio of consistent super-enhancer-associated genes was significantly higher than the ratio of functionally conserved super-enhancers. Approximately 54% of the core regulation factors driven by super-enhancers were consistent across the liver from these three species. Our pig liver annotation and functional characterization studies provide a system and resource for noncoding annotation for future gene regulatory studies in pigs. Furthermore, our study also showed the high level functional conservation of cis-regulatory elements in mammals; it also improved our understanding of regulation function of mammal cis-regulatory elements.