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The prevalence of periodontal and peri-implant diseases has been increasing worldwide and has gained a lot of attention. As multifunctional nanomaterials with enzyme-like activity, nanozymes have earned a place in the biomedical field. In periodontics and implantology, nanozymes have contributed greatly to research on maintaining periodontal health and improving implant success rates. To highlight this progress, we review nanozymes for antimicrobial therapy, anti-inflammatory therapy, tissue regeneration promotion, and synergistic effects in periodontal and peri-implant diseases. The future prospects of nanozymes in periodontology and implantology are also discussed along with challenges.
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Implantes Dentales , Nanoestructuras , Periimplantitis , Humanos , PeriodonciaRESUMEN
BACKGROUND: Telocytes (TCs) are experimentally evidenced as an alternative of cell therapies for organ tissue injury and repair. The aims of the present studies are to explore direct roles of TCs and the roles of TC-derived exosomes in support of experimental acute lung injury (ALI) in vivo or in vitro. MATERIALS AND METHODS: The roles of TCs in experimental ALI were firstly estimated. Phosphoinositide 3-kinase (PI3K) p110δ and α/δ/ß isoform inhibitors were used in study dynamic alterations of bio-behaviors, and in expression of functional factors of TCs per se and TC-co-cultured airway epithelial cells during the activation with lipopolysaccharide (LPS). TC-driven exosomes were furthermore characterized for intercellular communication by which activated or non-activated TCs interacted with epithelia. RESULTS: Our results showed that TCs mainly prevented from lung tissue edema and hemorrhage and decreased the levels of VEGF-A and MMP9 induced by LPS. Treatment with CAL101 (PI3K p110δ inhibitor) and LY294002 (PI3Kα/δ/ß inhibitor) could inhibit TC movement and differentiation and increase the number of dead TCs. The expression of Mtor, Hif1α, Vegf-a, or Mmp9 mRNA increased in TCs challenged with LPS, while Mtor, Hif1α, and Vegf-a even more increased after adding CAL101 or Mtor after adding LY. The rate of epithelial cell proliferation was higher in co-culture of human bronchial epithelial (HBE) and TCs than that in HBE alone under conditions with or without LPS challenge or when cells were treated with LPS and CAL101 or LY294002. The levels of mTOR, HIF1α, or VEGF-A significantly increased in mono-cultured or co-cultured cells, challenged with LPS as compared with those with vehicle. LPS-pretreated TC-derived exosomes upregulated the expression of AKT, p-AKT, HIF1α, and VEGF-A protein of HBE. CONCLUSION: The present study demonstrated that intraperitoneal administration of TCs ameliorated the severity of lung tissue edema accompanied by elevated expression of VEGF-A. TCs could nourish airway epithelial cells through nutrients produced from TCs, increasing epithelial cell proliferation, and differentiation as well as cell sensitivity to LPS challenge and PI3K p110δ and α/δ/ß inhibitors, partially through exosomes released from TCs.
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Lesión Pulmonar Aguda , Exosomas , Telocitos , Humanos , Metaloproteinasa 9 de la Matriz/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Lipopolisacáridos/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Exosomas/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Pulmón/metabolismo , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Fosfatidilinositol 3-Quinasa/metabolismo , Telocitos/metabolismoRESUMEN
Gasdermin (GSDM) family, the key executioners of pyroptosis, play crucial roles in anti-pathogen and anti-tumor immunities, although little is known about the expression of GSDM in lung diseases at single-cell resolution, especially in lung epithelial cells. We comprehensively investigated the transcriptomic profiles of GSDM members in various lung tissues from healthy subjects or patients with different lung diseases at single cell level, e.g., chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), lung adenocarcinoma (LUAD), or systemic sclerosis (SSC). The expression of GSDM members varied among pulmonary cell types (immune cells, structural cells, and especially epithelial cells) and even across lung diseases. Regarding disease-associated specificities, we found that GSDMC or GSDMD altered significantly in ciliated epithelia of COPD or LUAD, GSDMD in mucous, club, and basal cells of LUAD and GSDMC in mucous epithelia of para-tumor tissue, as compared with the corresponding epithelia of other diseases. The phenomic specificity of GSDM in lung cancer subtypes was noticed by comparing with 15 non-pulmonary cancers and para-cancer samples. GSDM family gene expression changes were also observed in different lung epithelial cell lines (e.g., HBE, A549, H1299, SPC-1, or H460) in responses to external challenges, including lipopolysaccharide (LPS), lysophosphatidylcholine (lysoPC), cigarette smoking extract (CSE), cholesterol, and AR2 inhibitor at various doses or durations. GSDMA is rarely expressed in those cell lines, while GSDMB and GSDMC are significantly upregulated in human lung epithelia. Our data indicated that the heterogeneity of GSDM member expression exists at different cells, pathologic conditions, challenges, probably dependent upon cell biological phenomes, functions, and behaviors, upon cellular responses to external changes, and the nature and severity of lung disease. Thus, the deep exploration of GSDM phenomes may provide new insights into understanding the single-cell roles in the tissue, regulatory roles of the GSDM family in the pathogenesis, and potential values of biomarker identification and development.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Proteínas de Neoplasias/metabolismo , Transcriptoma/genética , Células Epiteliales/metabolismo , Neoplasias Pulmonares/genética , Enfermedad Pulmonar Obstructiva Crónica/genética , Biomarcadores de Tumor/genética , Proteínas Citotóxicas Formadoras de Poros/genéticaRESUMEN
Developing a universal strategy to measure catalase (CAT)/CAT-like activity, on one hand, overcomes limitations on current assays, such as moderate sensitivity and limited sample scope; on the other hand, facilitates insightful studies on applications of CAT and CAT-like nanozymes. Herein, the oxygen-sensitive and H2O2-inhibitory self-polymerization of dopamine (DA) was demonstrated as an activity indicator of CAT or CAT-like nanozymes, which monitors the catalytically generated O2 in a hypoxic environment. A typical assay for natural CAT was achieved under the optimized conditions. Moreover, this assay was suitable for diverse types of samples, ranging from nanozymes, animal tissues, to human saliva. By comparing the merits and limitations of common methods, this assay shows all-round advantages in sensitivity, specificity, and versatility, facilitating the formulation of measurement criteria and the development of potential standardized assays for CAT (or CAT-like nanozyme) activity.
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Dopamina , Peróxido de Hidrógeno , Animales , Catalasa , Humanos , Oxígeno , Especies Reactivas de OxígenoRESUMEN
The complexity of higher eukaryote genomes is far from being explained by linear information. There is a need to understand roles of genome regulation at the organism level through defining a comprehensive profile of chromosomal organization. Chromosome conformation capture (3C)-based studies reveal that higher-order of chromatin include not only long-range chromatin loops, but also compartments and topologically associating domains as the basis of genome structure and functions. However, the molecular machinery how the genome is spatially organized is still inadequate. Exciting progress has been made with the development of today's technology, we find that heterogeneous nuclear ribonucleoprotein U, initially identified as a structural nuclear protein, plays important role in three-dimensional (3D) genome organization by high-throughput assays. The disruption of this protein not only results in compartment switching on of the genome, it also reduces of TAD boundary strengths at borders between two types of compartments, and regulates chromatin loop by decrease its intensities. In addition, HNRNPU mainly binds to active chromatin. Most of HNRNPU peaks is consistent with CTCF or RAD21.It also plays an irreplaceable role in the processes of mitosis. This review aims to discuss the role of HNRNPU in maintaining the 3D chromatin architecture, as well as the recent development and human diseases involved in this nuclear matrix (NM)-associated protein.
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Cromatina/genética , Genoma Humano/genética , Ribonucleoproteína Heterogénea-Nuclear Grupo U/metabolismo , Cromatina/metabolismo , HumanosRESUMEN
A cohesin-loading factor (NIPBL) is one of important regulatory factors in the maintenance of 3D genome organization and function, by interacting with a large number of factors, e.g. cohesion, CCCTC-binding factor (CTCF) or cohesin complex component. The present article overviews the critical and regulatory roles of NIBPL in cohesion loading on chromotin and in gene expression and transcriptional signaling. We explore molecular mechanisms by which NIPBL recruits endogenous histone deacetylase (HDAC) to induce histone deacetylation and influence multi-dimensions of genome, through which NIPBL "hop" movement in chromatin regulates gene expression and alters genome folding. NIPBL regulates the process of CTCF and cohesion into chromatin loops and topologically associated domains, binding of cohesion and H3K4mes3 through interaction among promoters and enhancers. HP1 recruits NIPBL to DNA damage site through RNF8/RNF168 ubiquitylation pathway. NIPBL contributes to regulation of genome-controlled gene expression through the influence of cohesin in chromosome structure. NIPBL interacts with cohesin and then increases transcriptional activities of REC8 promoter, leading to up-regulation of gene expression. NIPBL movement among chromosomal loops regulates gene expression through dynamic alterations of genome organization. Thus, we expect a new and deep insight to understand dynamics of chromosome and explore potential strategies of therapiesc on basis of NIPBL.
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Proteínas de Ciclo Celular/metabolismo , Cromosomas Humanos/genética , Inestabilidad Genómica , Cromosomas Humanos/metabolismo , Expresión Génica , HumanosRESUMEN
Multi-dimensions dynamics of the genome play important roles in the maintenance of cell function, regulation of transcriptional signals and occurrence of diseases. With rapid development of methodologies, the genome organization and structure are found as three-dimensional (3D) or with dynamic changes (4D), and regulated by a large number of factors. The present article aims to overview the 3C derivation method Hi-C and ChIA-PET assay technologies coupled with newdata analysis methods, capture the spatial interactions between different loci across the entire genome, reveal the regularity of the genome spatial structure. Its relationship with gene regulation is for better understanding of the spatial structure of the genome. From two mainstream methods of ChIA-PET and Hi-C, we obtain some special proteins mediated chromatin interaction and whole genome chromatin interaction, transform frequency relation to distance relation for further coordinates, and predict 3D architecture. ChIA-PET method more focuses on one protein binding effect of chromatin activities, while Hi-C method more comprehensive with challenges in data process. Data of chromatin interaction, thermogram, and chromatin spatial structure from integrated analyses of two methods indicates the further need of deep mining and exploration.
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Cromatina/genética , Mapeo Cromosómico , Genoma/genética , Análisis de Secuencia de ADN , HumanosRESUMEN
Lung cancer heterogeneity plays an important role in the development of drug resistance. Comprehensive molecular characterizations of lung cancer can describe hereditary and somatic gene changes, mutation, and heterogeneity. We discuss heterogeneity specificity, characterization, and roles of PIK3CD, TP53, and KRAS, as well as target-driven therapies and strategies applied in clinical trials based on a proposed precise self-validation system. The system is a specifically selected strategy of treatment for patients with cancer gene mutations and heterogeneity based on gene sequencing, following validation of the strategies in the patient's own cancer cells or in patient-derived xenografts using their own cancer cells isolated during surgery or biopsies. These results will be more precise if the drugs used in the strategies are selected through protein structure-guided compound screening or a DNA-encoded chemical library before validation in the patient's own cancer cells. Thus, a deeper understanding of heterogeneity mechanisms and improved validation of the therapeutic strategy will result in more precise treatments for patients.
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Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Heterogeneidad Genética/efectos de los fármacos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Animales , Ensayos Clínicos como Asunto , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Quimioterapia/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Mutación/genéticaRESUMEN
PURPOSE: To evaluate the safety of pupillary dilation in primary angle-closure suspects (PACS) with concurrent visually significant cataract (VSC), to identify risk factors associated with elevated intraocular pressure (IOP), and to describe changes in anterior segment anatomy after pupillary dilation. DESIGN: Prospective study. PARTICIPANTS: Patients with PACS and VSC and no prior laser or intraocular surgery were recruited. Visually significant cataract was defined as best-corrected visual acuity ≤ 20/40 due to cataract. METHODS: Subjects' eyes were dilated with 0.5% tropicamide and 0.5% phenylephrine hydrochloride. A standardized eye examination, biometry, and swept-source OCT (SS-OCT) were performed before dilation. Intraocular pressure and SS-OCT were repeated 1, 4, and 6 hours postdilation (PDH1, PDH4, and PDH6, respectively). All parameters were compared between time points before and after dilation using paired t test. Linear regression models were used to determine the risk factors associated with postdilation IOP changes. MAIN OUTCOME MEASURES: Change in IOP and SS-OCT parameters from baseline. RESULTS: Seventy-eight eyes from 78 patients were included, with 78, 66, and 12 patients completing the study at PDH1, PDH4, and PDH6, respectively. Mean IOP increased from 14.8 ± 2.6 mmHg at baseline to 15.5 ± 3.5 mmHg at PDH1 (P = 0.03) and decreased to 14.9 ± 3.1 mmHg at PDH4 (P = 0.09). Four patients (5.13%) and 3 patients (3.85%) had an increase in IOP ≥ 5 mmHg at PDH1 and PDH4, respectively. Two patients (2.56%) and 1 patient (1.28%) had an increase in IOP ≥ 8 mmHg at PDH1 and PDH4, respectively. None developed acute primary angle-closure during the observation period. Almost all anterior chamber parameters showed a significant increase after dilation at PDH1 and PDH4, except lens vault and iris volume, which decreased at PDH1 and PDH4 from baseline. Increase in anterior chamber depth was negatively associated with the level of IOP elevation after dilation (P < 0.01). CONCLUSIONS: Dilation of patients' eyes with PACS and VSC in this cohort appears to have a low risk for IOP spike. This may be associated with relaxation of the ciliary muscle leading to posterior displacement of the lens-iris diaphragm and deepening of the anterior chamber.
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Cámara Anterior/diagnóstico por imagen , Dilatación/métodos , Glaucoma de Ángulo Cerrado/fisiopatología , Presión Intraocular/fisiología , Anciano , Anciano de 80 o más Años , Biometría , Femenino , Glaucoma de Ángulo Cerrado/diagnóstico , Glaucoma de Ángulo Cerrado/terapia , Gonioscopía , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Tomografía de Coherencia ÓpticaRESUMEN
BACKGROUND: Nasopharyngeal carcinoma (NPC) is a malignant head and neck tumor, and more than 70% of new cases are in East and Southeast Asia. However, association between NPC and pseudogenes playing important roles in genesis of multiple tumor types is still not clear and needs to be investigated. METHODS: Using RNA-Sequencing (RNA-seq) technology, we analyzed pseudogene expression in 13 primary NPC and 6 recurrent NPC samples as well as their paracancerous counterparts. Quantitative PCR was used to validate the differentially expressed pseudogenes. RESULTS: We found 251 differentially expressed pseudogenes including 73 up-regulated and 178 down-regulated ones between primary NPC and paracancerous tissues. Enrichment analysis of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were conducted to filter out the key pseudogenes. We reported that pseudogenes from cytochrome P450 (CYP) family, such as CYP2F2P, CYP2G1P, CYP4F24P, CYP2B7P and CYP2G2P were significantly down-regulated in NPC compared to paracancerous tissues, while IGHV1OR15-2, IGHV3-11, FCGR1CP and IGHV3-69-1 belonging to Fc gamma receptors were significantly up-regulated. CYP2B7P, CYP2F2P and CYP4F26P were enriched in arachidonic acid metabolism pathway. The qRT-PCR analysis validated the lower expression of pseudogenes CYP2F2P and CYP2B7P in NPC tissues and cell lines compared to paracancerous tissues and normal human nasopharyngeal epithelial cell line. CYP2B7P overexpression weakened migratory and invasive capacity of NPC cell line. Moreover, the expression pattern of those pseudogenes in recurrent NPC tissues was different from the primary NPC. CONCLUSION: This study suggested the role of pseudogenes in tumorigenesis and progression, potentially functioning as therapeutic targets to NPC.
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Sistema Enzimático del Citocromo P-450/genética , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Recurrencia Local de Neoplasia/genética , Seudogenes , Receptores de IgG/genética , Análisis de Secuencia de ARN , Adulto , Anciano , Ácido Araquidónico/metabolismo , Línea Celular Tumoral , Movimiento Celular , Familia 2 del Citocromo P450/genética , Regulación hacia Abajo , Femenino , Ontología de Genes , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/patología , Invasividad Neoplásica , Seudogenes/fisiología , Reacción en Cadena en Tiempo Real de la Polimerasa , Transfección/métodos , Regulación hacia ArribaRESUMEN
BACKGROUND: Microsurgery training has become an important part of ophthalmology teaching and one of the main topics of examination. Accurate and effective evaluation of microsurgery skills is vital for the training and teaching of residents. In this study, we aimed to establish a pterygium surgery assessment scale for use by ophthalmic residents and evaluate its reliability and validity. METHODS: Based on a literature search, experienced pterygium surgeons developed the preliminary scale according to the standard surgical procedure. The preliminary scale and a questionnaire were sent to teaching and research experts in the field for feedback. Face and content validity and reliability of the scale were determined by rounds of modifications based on expert feedback. For construct validity, existing assessment scales were obtained and a range of factors were tested. RESULTS: Nineteen expert surgeons completed the questionnaire and modifications were made until all surgeons agreed on the final scale. Good construct validity was found by evaluation against 257 existing scales. For reliability, 280 evaluation scales were completed. Inter- and intra-rater reliability analysis both found Intraclass Correlation Coefficient (ICC) > 0.8 for all items and total scores. CONCLUSION: The pterygium surgery assessment scale developed in this study has good reliability and validity, and is an effective measurement tool for the evaluation of ophthalmology residents' pterygium surgical skills.
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Internado y Residencia , Oftalmología , Pterigion , Competencia Clínica , Evaluación Educacional , Humanos , Oftalmología/educación , Pterigion/diagnóstico , Pterigion/cirugía , Reproducibilidad de los ResultadosRESUMEN
Patients are diagnosed as anaplastic lymphoma kinase (ALK) positive, i.e. exhibiting the ALK rearrangement, and comprise 3-7% of non-small-cell lung cancer (NSCLC) cases. Three generations of ALK inhibitors have been developed and used in targeted therapy, although there are still improving spaces of drug resistance at the initiation of each treatment. The current review discusses the pathophysiology of ALK-positive NSCLC and the role of three generations of ALK target inhibitors including crizotinib, ceritinib, alectinib and lorlatinib, as well as the mechanisms of the secondary resistance. We mainly focused on the point mutations that are the most important resistance-producing mechanism and most common form caused by each inhibitor. In addition, we examine the three-dimensional structure of ALK to understand the functional impact of these mutations and analyse the underlying molecular mechanisms of the resistance to each generation of ALK inhibitor to benefit the selection decision of the most rational therapy and improve therapeutic effects to the disease.
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Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/enzimología , Resistencia a Antineoplásicos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/enzimología , Proteínas Tirosina Quinasas Receptoras/metabolismo , Quinasa de Linfoma Anaplásico , Carcinoma de Pulmón de Células no Pequeñas/fisiopatología , Humanos , Neoplasias Pulmonares/fisiopatología , Mutación Puntual/genética , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Tirosina Quinasas Receptoras/genéticaRESUMEN
Lung cancer development is a complex and dynamic progression with cancer cell mutations itself and its' orchestrate with the tumor microenvironment. Targeted therapies have been stated to heterogeneous lung cancer mutations while have a modest consequence. The tumor immune microenvironment influences lung cancer outcome by balancing the suppressive versus cytotoxic responses. The immune microenvironment heterogeneity may play an important role in lung cancer heterogeneity. In this review, we summarized the immune cells, its related cytokines and partial immune genes diversity in tumor microenvironment and its targeted potential mono and combined therapies. It will help us to make better understand the lung cancer heterogeneity and mechanisms of the drug resistance to find a way out.
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Biomarcadores de Tumor/metabolismo , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/terapia , Microambiente Tumoral/inmunología , Animales , Humanos , Modelos Biológicos , Transducción de SeñalRESUMEN
PURPOSE: To observe the long-term changes in dry eye symptoms and vision-related quality of life in age-related cataract patients after phacoemulsification. METHODS: A total of 101 cataract patients after phacoemulsification combined with IOL implantation (Ph-IOL) in one eye were enrolled. Visual acuity, tear film breakup time (BUT), and Schirmer test 1 (ST1) were measured before and 1, 3, and 6 months after surgery. Ocular Surface Disease Index (OSDI) scores were used to evaluate the severity of dry eye symptoms. Utility values were assessed by the time trade-off (TTO), standard gamble for death (SGD), standard gamble for blindness (SGB) and rating scale (RS). RESULTS: The average LogMAR visual acuity in the operated eye was 1.35 ± 0.50 and increased rapidly after Ph-IOL, approaching a peak at 3 months (0.26 ± 0.15). The BUT and ST1 results decreased abruptly 1 month after surgery and gradually recovered until 6 months. OSDI scores increased significantly after surgery and gradually decreased until 6 months. Utility values evaluated by TTO, SGD, SGB and RS before surgery were 0.67 ± 0.19, 0.75 ± 0.15, 0.67 ± 0.20 and 0.2 ± 0.18, respectively, and increased to 0.91 ± 0.06, 0.98 ± 0.04, 0.92 ± 0.52 and 0.91 ± 0.06, 6 months after. Utility values measured with TTO, SGB or RS correlated significantly (P < 0.05) with visual acuity and OSDI scores pre- and postoperatively. CONCLUSIONS: Dry eye symptoms persist more than 3 months after Ph-IOL. Utility values were negatively influenced by dry eye symptoms.
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Síndromes de Ojo Seco/etiología , Facoemulsificación/efectos adversos , Complicaciones Posoperatorias/etiología , Calidad de Vida , Agudeza Visual , Adulto , Anciano , Anciano de 80 o más Años , China/epidemiología , Síndromes de Ojo Seco/epidemiología , Síndromes de Ojo Seco/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/fisiopatología , Estudios Prospectivos , Encuestas y Cuestionarios , Factores de TiempoRESUMEN
Lung cancer as the leading cause of cancer-related deaths can be initiated and progressed by the interaction between dynamically genetic and epigenetic elements, although mechanisms mediating lung cancer development and progression remain unclear. Tumor progenitor genes may contribute to lung carcinogenesis and cancer progression, are epigenetically disrupted at the early stages of malignancies even before mutations, and alter cell differentiation throughout tumor evolution. The present review explores potential roles and mechanisms of epigenetic modulators, modifiers and mediators in the development of lung cancer. We also overviewed potential mechanisms by which epigenetic modulators, modifiers and mediators control and regulate 3D nuclear architectures, and discussed translational efforts to epigenetic modifications for treatment of lung cancer. Deep understanding of epigenetic modulators, modifiers and mediators will benefit the discovery and development of new diagnostics and therapies for lung cancer.
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Carcinogénesis/genética , Metilación de ADN/genética , Epigénesis Genética , Neoplasias Pulmonares/genética , Regulación Neoplásica de la Expresión Génica , Terapia Genética , Histonas/genética , Humanos , Neoplasias Pulmonares/patología , MutaciónRESUMEN
Lung cancer is a highly intricate and heterogeneous disease with genomic diversity in each subtype. Global analyses of gene expression and sequencing provided us new understanding of the genetic variation between small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC), including adenocarcinoma (ADC), and squamous cell carcinoma (SCC). The genetic variations of lung cancer subtypes in genomic studies were integrated and further analyzed using bioinformatics methods. The lung cancer subtypes share some genetic variations such as the dysfunction of tumor suppressor gene TP53, and also harbor specific variations of their own such as MET in ADC, FGFR1 and FGFR3 in SCC and MYC in SCLC. The activated pathway in lung ADC and SCC mainly focuses on MAPK and PI3K with different key genes of each, respectively, and the activated pathway of SCLC mainly focuses on JAK-STAT pathway. The diagnosis of lung cancer subtypes based on these genetic variations such as SNP was also evaluated. These results provide further insights into the different pathogenesis of lung cancer subtypes.
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Adenocarcinoma/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Células Escamosas/genética , Neoplasias Pulmonares/genética , Adenocarcinoma/clasificación , Adenocarcinoma del Pulmón , Carcinoma de Pulmón de Células no Pequeñas/clasificación , Carcinoma de Células Escamosas/clasificación , Biología Computacional , Regulación Neoplásica de la Expresión Génica , Genes Supresores de Tumor , Genoma Humano , Humanos , Neoplasias Pulmonares/clasificación , Proteínas de Neoplasias/genética , Transducción de SeñalRESUMEN
Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) as a serious event has high mortality and medical costs. Systemic inflammation and immune response are the major factors influencing the outcome and quality of patient with AECOPD. On basis of identification and validation of AECOPD-specific inflammatory biomarkers, the present study aimed to identify AECOPD-specific immunomodulatory mediators by evaluating dynamic genomic and proteomic profiles of peripheral blood mononuclear cells (PBMCs) and plasma in patients with AECOPD on day 1, 3, and 10 after the hospital admission, to compare with healthy controls or patients with stable COPD. We found that genes and proteins of C1QC and C1RL were co-differentially up-expressed in patients with COPD or AECOPD, while haptoglobin (HP), ORM1, SERPING1, and C3 were identified as a panel of AECOPD-specific immunomodulatory mediators. We also found that inflammatory stimuli could up-regulate osteopontin (OPN)-associated HP expression through the PI3K signal pathway in A549 cells. Block of autocrine production of OPN by gene inhibition could reduce HP production from inflammation-induced lung epithelial cells. The complex network of AECOPD- or COPD-specific immunomodulatory mediators will benefit the development of precision or personalized medicine strategies for prevention and treatment of AECOPD.
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Proteínas Sanguíneas/genética , Factores Inmunológicos , Inflamación/sangre , Enfermedad Pulmonar Obstructiva Crónica/sangre , Células A549 , Anciano , Biomarcadores/sangre , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Haptoglobinas/análisis , Haptoglobinas/genética , Humanos , Factores Inmunológicos/sangre , Factores Inmunológicos/genética , Leucocitos Mononucleares/inmunología , Masculino , Persona de Mediana Edad , Osteopontina/sangre , Osteopontina/genética , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Pruebas de Función Respiratoria , TranscriptomaRESUMEN
BACKGROUND: More and more concerns have been arisen about the ability of new medical graduates to meet the demands of today's practice environment. In this study, we wanted to develop a valid, reliable and standardized assessment tool for evaluating the basic microsurgical skills of residents in a microsurgery laboratory, to get them well prepared before entering the surgical realm of ophthalmology. METHODS: Twenty-three experts who have teaching experience reviewed the assessment scale. Constructive comments were incorporated to ensure face and content validity. Twenty-one attendings from different specialties then graded eight corneal rupture suturing videos with the scale to investigate interrater reliability. Fourteen of them graded the same videos 3 months later to investigate intrarater reliability (repeatability). RESULTS: A total of 280 assessment scales were completed. All the ICC values of interrater reliability were greater than 0.8 with 75% data greater than 0.9 (range 0.860-0.976). All the ICC values of intrarater reliability (repeatability) were also greater than 0.8 with 63% data greater than 0.9 (range 0.833-0.954). CONCLUSIONS: The assessment scale we developed is valid and reliable. This tool could be useful to ensure that junior residents achieve a certain level of microsurgical technique in a laboratory environment before training in the operation room. Hopefully, this tool will provide a structured template for other residency programs to assess their residents for basic microsurgical skills.
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Competencia Clínica/normas , Evaluación Educacional/métodos , Internado y Residencia , Microcirugia/educación , Procedimientos Quirúrgicos Oftalmológicos/educación , Oftalmología/educación , Técnicas de Sutura/educación , Lesiones de la Cornea/cirugía , Humanos , Reproducibilidad de los Resultados , Encuestas y CuestionariosRESUMEN
PURPOSE: To investigate common origins and features of anterior epistaxis. METHODS: Patients (168) with anterior nose bleed were studied from May to October 2013. Endoscopic examination with angled endoscope and then subsequent management (radiofrequency, selective packing,) was performed. RESULTS: Under thorough nasal endoscopy, anterior nasal bleeding origin was ranked in turn as follows: the anterior nasal septum (NS 83.3%), the small area of anterior lateral wall of nasal cavity corresponding to the nasal back (NB 7.1%), the anterior end of the inferior turbinate (IT 5.4%), and the nasal part of the nasal cavity roof (NR 4.2%). Arterial lesion and hypertension led to large instant quantity of bleeding; hypertension and negligible bleeding origin prolonged bleeding duration. Bleeding was successfully controlled with nasal endoscopy and radiofrequency or selective packing. CONCLUSIONS: The arterial bleeding small area of anterior lateral wall of nasal cavity corresponding to the nasal back and the nasal part of the nasal cavity roof accounted for more than 10% of anterior epistaxis and a thorough endoscopic examination should include these area with angled endoscope. Then radiofrequency and selective packing will sharply reduce the bleeding duration.
Asunto(s)
Ablación por Catéter , Epistaxis/etiología , Técnicas Hemostáticas , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Endoscopía , Epistaxis/cirugía , Epistaxis/terapia , Femenino , Humanos , Hipertensión/complicaciones , Masculino , Persona de Mediana Edad , Cavidad Nasal/patología , Tabique Nasal/patología , Tapones Quirúrgicos de Gaza , Cornetes Nasales/patología , Adulto JovenRESUMEN
PURPOSE: To calculate crystalline lens power and to determine the relationship between ocular biometry and diabetic retinopathy (DR) in an adult population with type 2 diabetes mellitus (T2DM). DESIGN: Cross-sectional, population-based study. PARTICIPANTS: Patients with T2DM from the Beixinjing community, Changning district, Shanghai. METHODS: Random clustering sampling was used to identify adults with T2DM in the Beixinjing community. Spherical equivalent (SE) was determined by subjective refraction that achieved the best corrected vision. Axial length (AL), corneal power (CP), and anterior chamber depth (ACD) were measured using the IOLMaster. Diabetic retinopathy and diabetic macular edema (DME) were assessed according to the international DR classification. MAIN OUTCOME MEASURES: The crystalline lens power was calculated using the Bennett-Rabbetts formula. The AL-to-corneal radius ratio (AL/CR ratio) was defined as the axial length divided by the mean corneal radius of curvature. RESULTS: A total of 4011 eyes of 2057 subjects with T2DM were included in the analysis. In multivariate logistic models adjusting for age, sex, duration of diabetes, glycosylated hemoglobin A1c, serum creatinine, body mass index, systolic blood pressure, and cataract, after categorizing values into quartiles, there were trend associations between lens power and any DR (P = 0.01), between AL/CR ratio and any DR (P = 0.02), and between AL and any DR (P = 0.03), between lens power and moderate DR (P = 0.02), and between AL and moderate DR (P = 0.02); eyes with higher AL/CR ratio were less likely to have any DR (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.24-0.78; P = 0.01 per 1 increase) and moderate DR (OR, 0.44; 95% CI, 0.21-0.93; P = 0.03 per 1 increase), eyes with longer AL were less likely to have any DR (OR, 0.88; 95% CI, 0.81-0.95; P = 0.002 per millimeter increase) or moderate DR (OR, 0.89; 95% CI, 0.80-0.98; P = 0.02 per millimeter increase), and eyes with higher SE were more likely to have any DR (OR, 1.08; 95% CI, 1.03-1.13; P = 0.003 per diopter increase). CONCLUSIONS: In persons with T2DM, lens power, AL/CR ratio, and AL were associated with the presence of any DR and moderate DR. These findings suggested that globe elongation plays a major role in protective effects against DR, with contributions from lens power and other refractive components.