RESUMEN
PURPOSE: Mitogen-activated protein kinase 12 (MAPK12), also known as p38γ, is a member of the p38 MAPK family and plays a crucial role in tumor occurrence and invasion. However, there is still uncertainty regarding MAPK12 involvement in diffuse large B-cell lymphoma (DLBCL). METHODS: Our study investigated the expression of MAPK12 mRNA in various types of cancer using bioinformatic analysis. Furthermore, we performed immunohistochemistry (IHC) to detect the expression of MAPK12 in patients with DLBCL and compared clinical indicators and survival rates. RESULTS: We found that the high expression rate of MAPK12 was 43.1% in DLBCL patients. Several clinical indicators, including IPI scores, Hans classifications, LDH levels, and Ki-67 expression were closely associated with MAPK12 expression. Survival analysis revealed that higher expression of MAPK12 was significantly correlated with shorter progression-free survival (PFS) and overall survival (OS) in DLBCL patients. In addition, both univariate and multivariate analyses revealed IPI score, MAPK12 expression, and rituximab use as the independent OS risk factors (P < 0.05). To explore the functional role of MAPK12 in DLBCL, weighted gene co-expression network analysis (WGCNA) and gene ontology (GO) were used to confirm the involvement of MAPK12 in the regulation of type II interferon production, positive regulation of lymphocyte proliferation, and other related biological processes. CONCLUSION: DLBCL patients have poor prognoses when MAPK12 levels are high, which is expected to be a therapeutic target and prognostic factor.
RESUMEN
The subcortical maternal complex, which consists of maternal-effect genes, plays a crucial role in the development of oocytes and preimplantation embryo until the activation of the zygote genome. One such gene, known as peptidyl-arginine deiminase VI (Padi6), is involved in the oocyte maturation, fertilization and embryonic development. However, the precise function of Padi6 gene in buffalo is still unclear and requires further investigation. In this study, the sequence, mRNA and protein expression patterns of Padi6 gene were analyzed in oocytes, preimplantation embryos and somatic tissues of buffalo. The coding sequence of gene was successfully cloned and characterized. Real-time quantitative PCR results indicated an absence of Padi6 transcripts in somatic tissues. Notably, the expression levels of Padi6 in oocytes showed an increased from the germinal vesicle stage to metaphase II stage, followed by a rapid decrease during the morula and blastocyst stages. Immunofluorescence analysis confirmed these findings, revealing a noticeable decline in protein expression levels. Our research provides the initial comprehensive expression profile of Padi6 in buffalo oocytes and preimplantation embryos, serving as a solid foundation for further investigations into the functionality of maternal-effect genes in buffalo.
RESUMEN
BACKGROUND: Transmembrane protein 92 (TMEM92) has been implicated in the facilitation of tumor progression. Nevertheless, comprehensive analyses concerning the prognostic significance of TMEM92, as well as its role in immunological responses across diverse cancer types, remain to be elucidated. METHODS: In this study, data was sourced from a range of publicly accessible online platforms and databases, including TCGA, GTEx, UCSC Xena, CCLE, cBioPortal, HPA, TIMER2.0, GEPIA, CancerSEA, GDSC, exoRBase, and ImmuCellAI. We systematically analyzed the expression patterns of TMEM92 at both mRNA and protein levels across diverse human organs, tissues, extracellular vesicles (EVs), and cell lines associated with multiple cancer types. Subsequently, analyses were conducted to determine the relationship between TMEM92 and various parameters such as prognosis, DNA methylation, copy number variation (CNV), the tumor microenvironment (TME), immune cell infiltration, genes with immunological relevance, tumor mutational burden (TMB), microsatellite instability (MSI), mismatch repair (MMR), and half-maximal inhibitory concentration (IC50) values. RESULTS: In the present study, we observed a pronounced overexpression of TMEM92 across a majority of cancer types, which was concomitantly associated with a less favorable prognosis. A notable association emerged between TMEM92 expression and both DNA methylation and CNV. Furthermore, a pronounced relationship was discerned between TMEM92 expression, the TME, and the degree of immune cell infiltration. Intriguingly, while TMEM92 expression displayed a positive correlation with macrophage presence, it inversely correlated with the infiltration level of CD8 + T cells. Concurrently, significant associations were identified between TMEM92 and the major histocompatibility complex, TMB, MSI, and MMR. Results derived from Gene Set Enrichment Analysis and Gene Set Variation Analysis further substantiated the nexus of TMEM92 with both immune and metabolic pathways within the oncogenic context. CONCLUSIONS: These findings expanded the understanding of the roles of TMEM92 in tumorigenesis and progression and suggest that TMEM92 may have an immunoregulatory role in several malignancies.
Asunto(s)
Proteínas de la Membrana , Neoplasias , Microambiente Tumoral , Humanos , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Variaciones en el Número de Copia de ADN , Metilación de ADN , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , Regulación Neoplásica de la Expresión Génica , Linfocitos Infiltrantes de Tumor/inmunología , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Inestabilidad de Microsatélites , Neoplasias/genética , Neoplasias/inmunología , Neoplasias/patología , Neoplasias/metabolismo , Pronóstico , Microambiente Tumoral/inmunologíaRESUMEN
Increased global attention is being paid to the food-health-climate trilemma. In this study, we evaluate the climate impacts of Mexico's food consumption patterns by creating a high-resolution (262 sectors) Environmentally Extended Input-Output (EEIO) model called MXEEIO. We focus on the differences between food away from home (FAFH) and food at home (FAH) and compare Mexico's results with those of the USA. The results show that the main components of food spending in Mexico were meat, baked products, and beverages, raising concerns about their potential negative health effects if consumed excessively. Mexico's total greenhouse gas (GHG) emissions from food consumption were estimated at 149 million metric tons (MMT) in 2013, as opposed to 797 MMT for the USA. Meat and dairy products were the main contributors to Mexico's food-related GHG emissions, accounting for 57% of total emissions. Mexico spent a much smaller proportion of food-related income on FAFH than the USA (13% vs. 52%), suggesting great potential for growth as Mexico's per capita GDP continues to rise. Detailed contribution analysis shows that reducing Mexico's food-related GHG emissions would benefit most from a transition to low-carbon cattle farming, but mitigation efforts in other sectors such as crop cultivation and electricity generation are also important. Overall, our study underscores the significance of food-related GHG emissions in Mexico, especially those from meat and dairy products, and the mitigation challenges these sectors face.
Asunto(s)
Huella de Carbono , Gases de Efecto Invernadero , México , Gases de Efecto Invernadero/análisis , Humanos , Modelos Teóricos , AlimentosRESUMEN
BACKGROUND: tRF-RNA-a representative of non-coding RNA (ncRNA)-is a precursor or fragment of mature tRNA and plays a crucial regulatory role in the occurrence and development of cancer. There is currently little research on tRF-RNA as a diagnostic marker in cancer, especially for NSCLC from serum exosomes. METHOD: Serum exosomes were successfully extracted from serum; their physical morphology was captured by transmission electron microscopy (TEM); appropriate particle size detection was performed using qNano; surface labeling was verified through western blotting. Serum exosomes i-tRF-AspGTC and tRF-1-SerCGA were selected through gene microarray, and qPCR was used to validate their significance in 242 patients and 201 healthy individuals. The area under the curve (AUC) was used to evaluate the diagnostic indicators of non-small cell lung cancer (NSCLC). RESULT: Compared with 201 healthy individuals, i-tRF-AspGTC and tRF-1-SerCGA were significantly downregulated in 242 NSCLC patients and 95 early-stage patients. For tRF-AspGTC and tRF-1-SerCGA, the predictive diagnostic efficiency rates of AUC were 0.690 and 0.680, respectively, whereas the early diagnostic efficiency rates were 0.656 and 0.688, respectively. The result of combined diagnosis with CEA and CYFRA21-1 was 0.928, and the early diagnostic efficiency was 0.843, which is a very high biological predictive factor for NSCLC. CONCLUSION: The expression of serum exosomes i-tRF-AspGTC and tRF-1-SerCGA was significantly downregulated in NSCLC patients. These exosomes could be used as predictive indicators for diagnosis or early diagnosis of NSCLC.
Asunto(s)
Biomarcadores de Tumor , Carcinoma de Pulmón de Células no Pequeñas , Exosomas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/sangre , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/patología , Exosomas/metabolismo , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Masculino , Femenino , Persona de Mediana Edad , Biomarcadores de Tumor/sangre , Estudios de Casos y Controles , Anciano , Adulto , PronósticoRESUMEN
PURPOSE: Metabolic syndrome (MetS), characterized by insulin resistance, is closely associated with the prognosis of various cancer types, but has not been reported in diffuse large B-cell lymphoma (DLBCL). The aim of this study is to examine how other clinicopathological variables and the MetS influence the prognosis of DLBCL. METHODS: Clinical and pathological data were collected from 319 patients with DLBCL who were admitted to our hospital between January 2012 and December 2020. The data accessible with SPSS 27.0 enables the utilization of various statistical methods for clinical data analysis, including independent sample t test and univariate and multivariate COX regression. RESULTS: The presence of MetS was linked to both overall survival (OS) and progression-free survival (PFS), in addition to other clinicopathological characteristics as age, IPI score, rituximab usage, and Ki-67 expression level. This link with OS and PFS indicated a poor prognosis, as shown by survival analysis. Subsequent univariate analysis identified IPI score, Ki-67 expression level, tumor staging, rituximab usage, lactate dehydrogenase expression level, and the presence or absence of MetS as factors linked with OS and PFS. Furthermore, multivariate Cox regression analysis confirmed the independent risk factor status of IPI score, Ki-67 expression level, rituximab usage, and the presence of MetS in evaluating the prognosis of patients with DLBCL. CONCLUSION: This study's findings indicate that patients with pre-treatment MetS had a poor prognosis, with relatively shorter OS and PFS compared to those without pre-treatment MetS. Furthermore, the presence of MetS, IPI score, Ki-67 expression level, and rituximab usage were identified as independent risk factors significantly affecting the prognosis of DLBCL.
Asunto(s)
Linfoma de Células B Grandes Difuso , Síndrome Metabólico , Rituximab , Humanos , Linfoma de Células B Grandes Difuso/patología , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Síndrome Metabólico/complicaciones , Pronóstico , Anciano , Rituximab/uso terapéutico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios Retrospectivos , Anciano de 80 o más Años , Doxorrubicina/uso terapéutico , Factores de Riesgo , Antígeno Ki-67/metabolismo , Antígeno Ki-67/análisis , Supervivencia sin Progresión , L-Lactato Deshidrogenasa/sangre , L-Lactato Deshidrogenasa/metabolismo , Tasa de Supervivencia , Estadificación de Neoplasias , Adulto Joven , Vincristina/uso terapéutico , Ciclofosfamida/uso terapéutico , Modelos de Riesgos ProporcionalesRESUMEN
The intestinal microbiome plays an important role in mammalian health, disease, and immune function. In light of this function, recent studies have aimed to characterize the microbiomes of various bat species, which are noteworthy for their roles as reservoir hosts for several viruses known to be highly pathogenic in other mammals. Despite ongoing bat microbiome research, its role in immune function and disease, especially the effects of changes in the microbiome on host health, remains nebulous. Here, we describe a novel methodology to investigate the intestinal microbiome of captive Jamaican fruit bats (Artibeus jamaicensis). We observed a high degree of individual variation in addition to sex- and cohort-linked differences. The intestinal microbiome was correlated with intestinal metabolite composition, possibly contributing to differences in immune status. This work provides a basis for future infection and field studies to examine in detail the role of the intestinal microbiome in antiviral immunity.
Asunto(s)
Quirópteros , Microbioma Gastrointestinal , Humanos , Animales , Femenino , Masculino , Jamaica , Caracteres Sexuales , Mamíferos , MetabolomaRESUMEN
BACKGROUND: A pathogenic filamentous fungus causing eyelid cellulitis was isolated from the secretion from a patient's left eyelid, and a phylogenetic analysis based on the rDNA internal transcribed spacer region (ITS) and single-copy gene families identified the isolated strain as Paraconiothyrium brasiliense. The genus Paraconiothyrium contains the major plant pathogenic fungi, and in our study, P. brasiliense was identified for the first time as causing human infection. To comprehensively analyze the pathogenicity, and proteomics of the isolated strain from a genetic perspective, whole-genome sequencing was performed with the Illumina NovaSeq and Oxford Nanopore Technologies platforms, and a bioinformatics analysis was performed with BLAST against genome sequences in various publicly available databases. RESULTS: The genome of P. brasiliense GGX 413 is 39.49 Mb in length, with a 51.2% GC content, and encodes 13,057 protein-coding genes and 181 noncoding RNAs. Functional annotation showed that 592 genes encode virulence factors that are involved in human disease, including 61 lethal virulence factors and 30 hypervirulence factors. Fifty-four of these 592 virulence genes are related to carbohydrate-active enzymes, including 46 genes encoding secretory CAZymes, and 119 associated with peptidases, including 70 genes encoding secretory peptidases, and 27 are involved in secondary metabolite synthesis, including four that are associated with terpenoid metabolism. CONCLUSIONS: This study establishes the genomic resources of P. brasiliense and provides a theoretical basis for future studies of the pathogenic mechanism of its infection of humans, the treatment of the diseases caused, and related research.
Asunto(s)
Celulitis (Flemón) , Factores de Virulencia , Humanos , Filogenia , Péptido Hidrolasas/genéticaRESUMEN
Abstract Objective Our study aimed to elucidate the effect of PAI-1 (Plasminogen Activator Inhibitor-1) and t-PA (Tissue-type Plasminogen Activator) in tissue remodeling in nasal polyps patients. Methods Samples were streamed as early Nasal Polyps (eNP, n = 10) and inferior tissue from the same patient, mature Nasal Polyps (mNP, n = 14), and Control group (n = 15), respectively. Immunohistochemistry and immunofluorescence were applied to detect localization. Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and Western blot were used to measure different levels among three groups. The mNP tissue was cultured in vitro and treated with TGF-β1 (Transforming Growth Factor-beta 1) activator, TGF-β1 inhibitor (SB431542), and PAI-1 inhibitor (TM5275); then Western blot, qRT-PCR, and ELISA were used to assess changes. Results The immunohistochemistry and immunofluorescence showed that PAI-1 expression decreased in eNP and mNP, mainly in epithelium and glands. The transcriptional expression and protein level of TGF-β1/t-PA/PAI-1/Collagen1 were lower in eNP than IT while mNP group demonstrated lower mRNA expression and protein level of TGF-β1/t-PA/PAI-1/Collagen1 than Control group. In mNP tissue culture in vitro, TGF-β1 activator elevated t-PA, PAI-1, and Collagen1 with higher release of PAI-1 and Collagen1 in supernatant, whereas SB431542 suppressed above reactions; TM5275 lowered transcriptional and protein level of Collagen1 in supernatant. Conclusion Early Nasal polyps' formation in middle meatus mucous is related with fibrillation system PAI-1/t-PA and tissue remodeling; moreover, nasal polyps' development is regulated by TGF-β1-mediated PAI-1 reduction. Level of evidence 3b.
RESUMEN
BACKGROUND: The tumor microenvironment plays a crucial role in the oncogenesis and treatment of diffuse large B-cell lymphoma (DLBCL). The H3K9me3-specific histone methyltransferase Suppressor of variegation 3-9 homolog 1 (SUV39H1) is a significant gene that promotes the progression of various malignancies. However, the specific expression of SUV39H1 in DLBCL remains unclear. METHODS: By retrieving data from GEPIA, UCSC XENA and TCGA public databases, we observed the high expression of SUV39H1 in DLBCL. Combined with an immunohistochemical validation assay, we analyzed our hospital's clinical characteristics and prognosis of 67 DLBCL patients. The results showed that high SUV39H1 expression was closely associated with age over 50 years (P = 0.014) and low albumin levels (P = 0.023) of patients. Furthermore, the experiments in vitro were deployed to evaluate the regulation of SUV39H1 on the DLBCL immune microenvironment. RESULTS: The results showed that high SUV39H1 expression was closely associated with age over 50 years (P = 0.014) and low albumin levels (P = 0.023) of patients. The prognostic analysis showed that the high SUV39H1 expression group had a lower disease-free survival (DFS) rate than the low SUV39H1 expression group (P < 0.05). We further discovered that SUV39H1 upregulated the expression of CD86+ and CD163+ tumor-associated macrophages by DLBCL patients' tissues and cell experiments in vitro (P < 0.05). And SUV39H1-associated T lymphocyte subsets and cytokines IL-6/CCL-2 were downregulated in DLBCL (P < 0.05). CONCLUSIONS: In summary, SUV39H1 might be not only a potential target for treating DLBCL but also a clinical indicator for doctors to evaluate the trend of disease development.
Asunto(s)
Linfoma de Células B Grandes Difuso , Humanos , Persona de Mediana Edad , Pronóstico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Subgrupos de Linfocitos T/metabolismo , Subgrupos de Linfocitos T/patología , Citocinas/metabolismo , Albúminas/uso terapéutico , Microambiente Tumoral , Metiltransferasas/metabolismo , Proteínas Represoras/metabolismoRESUMEN
OBJECTIVE: Our study aimed to elucidate the effect of PAI-1 (Plasminogen Activator Inhibitor-1) and t-PA (Tissue-type Plasminogen Activator) in tissue remodeling in nasal polyps patients. METHODS: Samples were streamed as early Nasal Polyps (eNP, n=10) and inferior tissue from the same patient, mature Nasal Polyps (mNP, n=14), and Control group (n=15), respectively. Immunohistochemistry and immunofluorescence were applied to detect localization. Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and Western blot were used to measure different levels among three groups. The mNP tissue was cultured in vitro and treated with TGF-ß1 (Transforming Growth Factor-beta 1) activator, TGF-ß1 inhibitor (SB431542), and PAI-1 inhibitor (TM5275); then Western blot, qRT-PCR, and ELISA were used to assess changes. RESULTS: The immunohistochemistry and immunofluorescence showed that PAI-1 expression decreased in eNP and mNP, mainly in epithelium and glands. The transcriptional expression and protein level of TGF-ß1/t-PA/PAI-1/Collagen1 were lower in eNP than IT while mNP group demonstrated lower mRNA expression and protein level of TGF-ß1/t-PA/PAI-1/Collagen1 than Control group. In mNP tissue culture in vitro, TGF-ß1 activator elevated t-PA, PAI-1, and Collagen1 with higher release of PAI-1 and Collagen1 in supernatant, whereas SB431542 suppressed above reactions; TM5275 lowered transcriptional and protein level of Collagen1 in supernatant. CONCLUSION: Early Nasal polyps' formation in middle meatus mucous is related with fibrillation system PAI-1/t-PA and tissue remodeling; moreover, nasal polyps' development is regulated by TGF-ß1-mediated PAI-1 reduction. LEVEL OF EVIDENCE: 3b.
Asunto(s)
Pólipos Nasales , Factor de Crecimiento Transformador beta1 , Humanos , Inhibidor 1 de Activador Plasminogénico/genética , Inhibidor 1 de Activador Plasminogénico/metabolismo , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
ABSTRACT Purpose: To investigate the incidence, risk factors, and visual outcomes of epiretinal membrane development following rhegmatogenous retinal detachment repair. Methods: This was a retrospective study of 309 eyes that underwent initial surgery for primary uncomplicated rhegmatogenous retinal detachment. Examinations were conducted preoperatively and then postoperatively at 1, 3, 6, and 12 months. The study patients were categorized into two groups depending on the presence or absence of the epiretinal membrane. Results: The incidence of postoperative epiretinal membrane was 28.5%; 42.7% of these patients had severe epiretinal membrane development and therefore underwent the epiretinal membrane removal. Logistic regression analyses revealed that giant retinal tears (OR: 2.66; 95% CI: 1.045-6.792, p=0.040) and horseshoe tears (OR: 0.534; 95% CI: 0.295-0.967, p=0.039) were the significant predictors of postoperative epiretinal membrane. Triamcinolone acetonide staining was significantly associated with the prevention of epiretinal membrane (p=0.022). A total of 34 patients showed a better or an equal final best-corrected visual acuity; of which 4 eyes were evaluated at the final follow-up visit and exhibited a reduced best-corrected visual acuity. Conclusion: Our analysis demonstrated that horseshoe tears and giant retinal tears represent the risk factors for the postoperative epiretinal membrane. Triamcinolone acetonide staining had a significant preventive effect on the postoperative epiretinal membrane. Furthermore, a second round of pars plana vitrectomy, including membrane removal, led to a significant improvement in the final best-corrected visual acuity as per the last follow-up examination, albeit the recovery was limited.
RESUMO Objetivos: Investigar a incidência, fatores de risco e desfechos visuais do desenvolvimento da membrana epirretiniana após reparo do descolamento regmatogênico da retina. Métodos: Trata-se de um estudo retrospectivo de 309 olhos submetidos à cirurgia inicial para descolamento regmatogênico da retina primário sem complicações. Os exames foram realizados no pré-operatório aos 1, 3, 6 e 12 meses pós-operatórios. Os pacientes foram divididos em dois grupos, dependendo da presença ou ausência de membrana epirretiniana. Resultados: A incidência de membrana epirretiniana pós-operatória foi de 28,5%; 42,7% desses pacientes apresentaram desenvolvimento grave da membrana epirretiniana e, portanto, foram submetidos à remoção desta membrana. A regressão logística mostrou que as lágrimas retinianas gigantes (RC: 2,66; 95% IC: 1,045 - 6,792, p=0,040) e lágrimas em ferradura (RC: 0,534; 95% IC: 0,295-0,967, p=0,039), foram preditores significativos de membrana epirretiniana pós-operatória. A coloração com acetonida de triancinolona foi significativamente associada à prevenção da membrana epirretiniana (p=0,022). Trinta e quatro pacientes apresentaram acuidade visual melhorada, ou igual, ou acuidade visual final melhor corrigida; 4 olhos foram avaliados na consulta final de acompanhamento e apresentaram redução da acuidade visual melhor corrigida. Conclusão: Nossa análise demonstra que as lágrimas de ferradura e as lágrimas retinianas gigantes representam fatores de risco para a membrana epirretiniana pós-operatória. A coloração com acetonida de triancinolona teve um efeito preventivo significativo na membrana epirretiniana no pós-operatório. Além disso, uma segunda rodada de vitrectomia pars plana, incluindo remoção da membrana, levou a uma melhora significativa da acuidade visual final melhor corrigida na última consulta de acompanhamento, embora a recuperação tenha sido limitada.
RESUMEN
OBJECTIVES: Osteoblasts are derived from Bone Marrow-derived Mesenchymal Stem Cells (BM-MSCs), which play an indispensable role in bone formation. In this study, the authors aim to investigate the role of IRF4 in the osteogenic differentiation of BM-MSCs and its potential molecular mechanism. METHODS: The authors used lentivirus infection to overexpress IRF4 in BM-MSCs. The expression of IRF4 and osteogenesis-related genes were detected by qRT-PCR and western blot analysis. The osteogenic differentiation of BM-MSCs was evaluated by Alkaline Phosphatase (ALP) activity, Alizarin red staining, and Alkaline Phosphatase (ALP) staining. Chromatin Immunoprecipitation (ChIP), Dual-Luciferase reporter assay and RNA Immunoprecipitation Assay were applied to confirm the regulatory mechanism between IRF4, miR-636 and DOCK9. RESULTS: The authors found IRF4 was down-regulated during the osteogenic differentiation of BM-MSCs, and IRF4 overexpression could decrease the osteogenic differentiation of BM-MSCs by specifically promoting the reduction of Alkaline Phosphatase (ALP) activity and down-regulating osteogenic indicators, including OCN, OPN, Runx2 and CollA1. Mechanistically, IRF4 activated microRNA-636 (miR-636) expression via binding to its promoter region, and Dedicator of Cytokinesis 9 (DOCK9) was identified as the target of miR-636 in BM-MSCs. Moreover, the damage in the capacity of osteogenic differentiation of BM-MSCs induced by IRF4 overexpression could be rescued by miR-636 inhibition. CONCLUSIONS: In summary, this paper proposed that IRF4/miR-636/DOCK9 may be considered as targets for the treatment of osteoporosis (OP).
Asunto(s)
Factores de Intercambio de Guanina Nucleótido , Factores Reguladores del Interferón , Células Madre Mesenquimatosas , MicroARNs , Fosfatasa Alcalina , Diferenciación Celular/genética , Células Cultivadas , Factores de Intercambio de Guanina Nucleótido/metabolismo , Factores Reguladores del Interferón/metabolismo , MicroARNs/genética , Osteogénesis/genéticaRESUMEN
There are many restrictions on topical medications for the oral cavity. Various factors affect the topical application of drugs in the oral cavity, an open and complex environment. The complex physical and chemical environment of the oral cavity, such as saliva and food, will influence the effect of free drugs. Therefore, drug delivery systems have served as supporting structures or as carriers loading active ingredients, such as antimicrobial agents and growth factors (GFs), to promote antibacterial properties, tissue regeneration, and engineering for drug diffusion. These drug delivery systems are considered in the prevention and treatment of dental caries, periodontal disease, periapical disease, the delivery of anesthetic drugs, etc. These carrier materials are designed in different ways for clinical application, including nanoparticles, hydrogels, nanofibers, films, and scaffolds. This review aimed to summarize the advantages and disadvantages of different carrier materials. We discuss synthesis methods and their application scope to provide new perspectives for the development and preparation of more favorable and effective local oral drug delivery systems.
Asunto(s)
Caries Dental , Enfermedades de la Boca , Nanofibras , Nanopartículas , Caries Dental/tratamiento farmacológico , Caries Dental/prevención & control , Sistemas de Liberación de Medicamentos , Humanos , Enfermedades de la Boca/tratamiento farmacológicoRESUMEN
Abstract Objectives Osteoblasts are derived from Bone Marrow-derived Mesenchymal Stem Cells (BM-MSCs), which play an indispensable role in bone formation. In this study, the authors aim to investigate the role of IRF4 in the osteogenic differentiation of BM-MSCs and its potential molecular mechanism. Methods The authors used lentivirus infection to overexpress IRF4 in BM-MSCs. The expression of IRF4 and osteogenesis-related genes were detected by qRT-PCR and western blot analysis. The osteogenic differentiation of BM-MSCs was evaluated by Alkaline Phosphatase (ALP) activity, Alizarin red staining, and Alkaline Phosphatase (ALP) staining. Chromatin Immunoprecipitation (ChIP), Dual-Luciferase reporter assay and RNA Immunoprecipitation Assay were applied to confirm the regulatory mechanism between IRF4, miR-636 and DOCK9. Results The authors found IRF4 was down-regulated during the osteogenic differentiation of BM-MSCs, and IRF4 overexpression could decrease the osteogenic differentiation of BM-MSCs by specifically promoting the reduction of Alkaline Phosphatase (ALP) activity and down-regulating osteogenic indicators, including OCN, OPN, Runx2 and CollA1. Mechanistically, IRF4 activated microRNA-636 (miR-636) expression via binding to its promoter region, and Dedicator of Cytokinesis 9 (DOCK9) was identified as the target of miR-636 in BM-MSCs. Moreover, the damage in the capacity of osteogenic differentiation of BM-MSCs induced by IRF4 overexpression could be rescued by miR-636 inhibition. Conclusions In summary, this paper proposed that IRF4/miR-636/DOCK9 may be considered as targets for the treatment of osteoporosis (OP).
RESUMEN
Abstract There are many restrictions on topical medications for the oral cavity. Various factors affect the topical application of drugs in the oral cavity, an open and complex environment. The complex physical and chemical environment of the oral cavity, such as saliva and food, will influence the effect of free drugs. Therefore, drug delivery systems have served as supporting structures or as carriers loading active ingredients, such as antimicrobial agents and growth factors (GFs), to promote antibacterial properties, tissue regeneration, and engineering for drug diffusion. These drug delivery systems are considered in the prevention and treatment of dental caries, periodontal disease, periapical disease, the delivery of anesthetic drugs, etc. These carrier materials are designed in different ways for clinical application, including nanoparticles, hydrogels, nanofibers, films, and scaffolds. This review aimed to summarize the advantages and disadvantages of different carrier materials. We discuss synthesis methods and their application scope to provide new perspectives for the development and preparation of more favorable and effective local oral drug delivery systems.
RESUMEN
PURPOSE: To investigate the incidence, risk factors, and visual outcomes of epiretinal membrane development following rhegmatogenous retinal detachment repair. METHODS: This was a retrospective study of 309 eyes that underwent initial surgery for primary uncomplicated rhegmatogenous retinal detachment. Examinations were conducted preoperatively and then postoperatively at 1, 3, 6, and 12 months. The study patients were categorized into two groups depending on the presence or absence of the epiretinal membrane. RESULTS: The incidence of postoperative epiretinal membrane was 28.5%; 42.7% of these patients had severe epiretinal membrane development and therefore underwent the epiretinal membrane removal. Logistic regression analyses revealed that giant retinal tears (OR: 2.66; 95% CI: 1.045-6.792, p=0.040) and horseshoe tears (OR: 0.534; 95% CI: 0.295-0.967, p=0.039) were the significant predictors of postoperative epiretinal membrane. Triamcinolone acetonide staining was significantly associated with the prevention of epiretinal membrane (p=0.022). A total of 34 patients showed a better or an equal final best-corrected visual acuity; of which 4 eyes were evaluated at the final follow-up visit and exhibited a reduced best-corrected visual acuity. CONCLUSION: Our analysis demonstrated that horseshoe tears and giant retinal tears represent the risk factors for the postoperative epiretinal membrane. Triamcinolone acetonide staining had a significant preventive effect on the postoperative epiretinal membrane. Furthermore, a second round of pars plana vitrectomy, including membrane removal, led to a significant improvement in the final best-corrected visual acuity as per the last follow-up examination, albeit the recovery was limited.
Asunto(s)
Membrana Epirretinal , Desprendimiento de Retina , Perforaciones de la Retina , Membrana Epirretinal/epidemiología , Membrana Epirretinal/cirugía , Humanos , Incidencia , Complicaciones Posoperatorias/cirugía , Desprendimiento de Retina/epidemiología , Desprendimiento de Retina/etiología , Desprendimiento de Retina/cirugía , Perforaciones de la Retina/complicaciones , Perforaciones de la Retina/epidemiología , Perforaciones de la Retina/cirugía , Estudios Retrospectivos , Factores de Riesgo , Triamcinolona Acetonida , Agudeza Visual , Vitrectomía/efectos adversosRESUMEN
OBJECTIVE: This study aimed to identify the most useful ultrasound (US) features associated with definite neonatal necrotizing enterocolitis (NEC) and their prognostic values, particularly the calculated markers combined with important features. METHODS: A total of 213 suspected NEC cases were collected from the neonatal department of our hospital from January 2015 to August 2017. Each infant received both X-ray and US examinations. RESULTS: No differences were found in sex composition and delivery modes between groups. NEC-positive neonates had poorer prognosis compared to negative ones. The NEC group showed a higher frequency of abnormal signals. US showed higher NEC-related frequencies in different parameters. A variable (named predictor in US [PUS]) with five features was constructed. For NEC diagnosis, this variable provided a much higher area under the curve Q2 (AUC) (0.965) than other parameters. In this model, PUS had a cutoff value of 0.376 with a 0.900 sensitivity and 0.922 specificity. In prognosis, the closest factors were selected to draw a receiver operating characteristic curve, as well as a novel calculated variable US prognostic (USPro) marker. USPro had a much higher AUC (0.86) than other single features and showed a cutoff value of 0.18145, with 0.75 sensitivity and 0.84 specificity. This variable had a weaker power in prognosis when compared with PUS in diagnosis. CONCLUSIONS: The application of abdominal color Doppler US can provide high accuracy and sensitivity in NEC diagnosis and also contribute to its prognosis, without induction of radiation. Suspected neonates should be examined using this technique as early as possible.
Asunto(s)
Enterocolitis Necrotizante , Enfermedades del Recién Nacido , Enterocolitis Necrotizante/diagnóstico por imagen , Humanos , Lactante , Recién Nacido , Pronóstico , Curva ROC , UltrasonografíaRESUMEN
BACKGROUND: 2R,3R-butanediol dehydrogenase (R-BDH) and other BDHs contribute to metabolism of 3R/3S-Acetoin (3R/3S-AC) and 2,3-butanediol (2,3-BD), which are important bulk chemicals used in different industries. R-BDH is responsible for oxidizing the hydroxyl group at their (R) configuration. Bacillus species is a promising producer of 3R/3S-AC and 2,3-BD. In this study, R-bdh gene encoding R-BDH from Bacillus sp. DL01 was isolated, expressed and identified. RESULTS: R-BDH exerted reducing activities towards Diacetyl (DA) and 3R/3S-AC using NADH, and oxidizing activities towards 2R,3R-BD and Meso-BD using NAD+ , while no activity was detected with 2S,3S-BD. The R-BDH showed its activity at a wide range of temperature (25 C to 65 C) and pH (5.08.0). The R-BDH activity was increased significantly by Cd2+ when DA, 3R/3S-AC, and Meso-BD were used as substrates, while Fe2+ enhanced the activity remarkably at 2R,3R-BD oxidation. Kinetic parameters of the R-BDH from Bacillus sp. DL01 showed the lowest Km, the highest Vmax, and the highest Kcat towards the racemic 3R/3S-AC substrate, also displayed low Km towards 2R,3R-BD and Meso-BD when compared with other reported R-BDHs. CONCLUSIONS: The R-BDH from Bacillus sp. DL01 was characterized as a novel R-BDH with high enantioselectivity for R-configuration. It considered NAD+ and Zn2+ dependant enzyme, with a significant affinity towards 3R/3S-AC, 2R,3R-BD, and Meso-BD substrates. Thus, R-BDH is providing an approach to regulate the production of 3R/3S-AC or 2,3-BD from Bacillus sp. DL01.