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1.
J Gene Med ; 26(1): e3626, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37974510

RESUMEN

Coronary heart disease is one of the most significant risk factors affecting human health worldwide. Its pathogenesis is intricate, with atherosclerosis being widely regarded as the leading cause. Aberrant lipid metabolism in macrophages is recognized as one of the triggering factors in atherosclerosis development. To investigate the role of macrophages in the formation of coronary artery atherosclerosis, we utilized single-cell data from wild-type mice obtained from the aortic roots and ascending aortas after long-term high-fat diet feeding, as deposited in GSE131776. Seurat software was employed to refine the single-cell data in terms of scale and cell types, facilitating the identification of differentially expressed genes. Through the application of differential expression genes, we conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analyses at 0, 8 and 16 weeks, aiming to uncover pathways with the most pronounced functional alterations as the high-fat diet progressed. The AddModuleScore function was employed to score the expression of these pathways across different cell types. Subsequently, macrophages were isolated and further subdivided into subtypes, followed by an investigation into intercellular communication within these subtypes. Subsequent to this, we induced THP-1 cells to generate foam cells, validating critical genes identified in prior studies. The results revealed that macrophages underwent the most substantial functional changes as the high-fat diet progressed. Furthermore, two clusters were identified as potentially playing pivotal roles in macrophage functional regulation during high-fat diet progression. Additionally, macrophage subtypes displayed intricate functionalities, with mutual functional counterbalances observed among these subtypes. The proportions of macrophage subtypes and the modulation of anti-inflammatory and pro-inflammatory functions played significant roles in the development of coronary artery atherosclerosis.


Asunto(s)
Aterosclerosis , Enfermedad de la Arteria Coronaria , Humanos , Ratones , Animales , Enfermedad de la Arteria Coronaria/genética , Macrófagos/metabolismo , Macrófagos/patología , Aterosclerosis/genética , Células Espumosas/metabolismo , Células Espumosas/patología
2.
Aesthetic Plast Surg ; 47(2): 872-879, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36414722

RESUMEN

BACKGROUND: Patients with chest keloids undergoing surgery and adjuvant radiotherapy still have a high recurrence rate, which is a critical problem. The level of keloid activity has not been studied, and a nomogram model for predicting keloid recurrence has not been established in previous studies. METHODS: A total of 145 patients with chest keloids who underwent surgery and radiotherapy between January 2015 and January 2019 at Peking Union Medical College Hospital were included in our study. Demographic and clinical features and the score of KAAS were analyzed. We compared the area under the curve (AUC) and decision curve analysis (DCA) between KAAS and the Vancouver scar scale (VSS) and established a nomogram model for predicting the risk of recurrence. We used bootstrap and calibration plots to evaluate the performance of the nomogram. RESULTS: The KAAS can predict recurrence in patients with chest keloids after surgery and radiotherapy. Areas under the curve (AUCs) of KAAS and VSS were 0.858 and 0.711, respectively (p < 0.001). Decision curve analysis (DCA) demonstrated that the KAAS was better than the VSS. Complications after treatment may be risk factors for keloid recurrence. We created a nomogram by using complications and KAAS. The AUC was 0.871 (95% CI 0.812-0.930). The ROC of the model's bootstrap was 0.865 and was well calibrated. CONCLUSIONS: The KAAS can be used to predict the recurrence and we developed a nomogram for predicting the recurrence of chest keloids after surgery and adjuvant radiotherapy. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Asunto(s)
Queloide , Humanos , Queloide/diagnóstico , Queloide/radioterapia , Queloide/cirugía , Nomogramas , Tórax , Radioterapia Adyuvante , Recurrencia , Resultado del Tratamiento
3.
Int Wound J ; 20(6): 2215-2223, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36746767

RESUMEN

Keloid infections reduce patient-reported quality of life greatly. Characteristics and risk factors of keloid infections have not been thoroughly studied. So, a retrospective cohort study was conducted focusing on the potential risk factors, microbiologic cultures and histological findings. Keloid patients consulting for surgical interventions were included in this study. Data were collected from their electronic medical records. 564 patients were recruited with the keloid infection rate being 22.4%. For adult patients, age above 40 years (OR, 2.84; P = .000), disease duration of 12 years or more (OR, 3.03; P = .000), the number of keloids over 3 (OR, 1.59; P = .050) and the presence of family history (OR, 1.91; P = .027) were significantly associated with keloid infections. Suppurative keloids were located mostly in thorax (61.79%). For the under-age subgroup(n = 25), family history was frequently seen in patients with infections. Microbiologic cultures revealed a mixed spectrum of bacteria including Staphylococcus (25%), Actinomyces (30%) and Prevotella (10%). The rate of epidermoid cysts was 19.7% in histological examination. Age > 40 years, disease duration ≥12 years, the number of keloids >3 and the presence of family history are risk factors for keloid infections.


Asunto(s)
Queloide , Adulto , Humanos , Queloide/epidemiología , Queloide/etiología , Estudios Retrospectivos , Calidad de Vida , Factores de Riesgo , Recurrencia
4.
Aesthetic Plast Surg ; 46(3): 1180-1188, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35226117

RESUMEN

BACKGROUND: Seroma formation is a common complication following mastectomy. The objective of this systematic review and meta-analysis is to evaluate the impact of flap fixation techniques that omit drainage versus conventional closed drainage on seroma formation and related complications after mastectomy. METHODS: Clinical studies of flap fixation techniques versus the conventional closure technique in patients undergoing mastectomy with or without axillary clearance were retrieved from the PubMed, Embase and Cochrane databases. Papers were eligible for inclusion if the outcome was described in terms of seroma formation. Studies older than 20 years, animal studies and studies involving patients undergoing direct breast reconstruction were excluded. RESULTS: Four randomized controlled trials (RCTs) and four cohort studies were included in our examination. Compared with the conventional drainage group, the flap fixation group had a similar incidence of seroma formation (OR 0.76, 95% CI 0.30-1.93, p = 0.57). CONCLUSION: Based on current evidence, mechanical flap fixation can replace conventional drainage without increasing seroma formation after mastectomy. Further well-designed RCTs are warranted to evaluate the effects of flap fixation. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Asunto(s)
Neoplasias de la Mama , Seroma , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/cirugía , Drenaje , Femenino , Humanos , Mastectomía/efectos adversos , Mastectomía/métodos , Complicaciones Posoperatorias/epidemiología , Seroma/etiología , Seroma/prevención & control , Seroma/cirugía
5.
Aesthetic Plast Surg ; 46(4): 2015-2022, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35149890

RESUMEN

BACKGROUND: There are many different keloid treatment modalities. One surgical technique is to keep the "shell" of the keloid to cover the defect. We named this "shell" keloid subepidermal vascular network flap (KSVNF), and we outlined the characteristics of this flap by observing 35 flaps in keloid patients. METHODS: A total of 35 KSVNFs were designed in 15 patients during 2020-2021. All patients underwent the operation and adjuvant radiotherapy as well as hyperbaric oxygen therapy. All flap lengths and widths were recorded, and the blood perfusion of the flaps was measured on the first day postoperation and the day of stitch removal. Flap survival and the quality of flaps were evaluated on the day of stitch removal. All harvested data were analyzed using the R (version 4.0.1) package. RESULTS: The mean blood perfusion on the first day postoperation (pod1) and the day of stitch removal was 120.4013 and 168.6900, respectively (p = 0.02249); 2 flaps had partial necrosis (5.714%). Receiver operating characteristic (ROC) curve analysis showed that when the length/width ratio was less than 1.05, the quality of the flap was good (AUC = 0.724), which suggests that the effective safe length/width ratio was 1.05. CONCLUSION: KSVNF is an applicable method for covering the remaining wound after keloid mass removal with sufficient blood perfusion and adequate skin quality. We recommend that the length/width ratio of the flap design not exceed 1. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Asunto(s)
Queloide , Animales , Queloide/cirugía , Piel , Colgajos Quirúrgicos/irrigación sanguínea
6.
Future Oncol ; 16(16): 1101-1113, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32314598

RESUMEN

Aim: To describe the factors affecting distant metastasis of Merkel cell carcinoma (MCC) and the prognosis of metastatic MCC. Materials & methods: The MCC patient information was downloaded from the SEER database. Logistic regression and Cox proportional hazard models were conducted to screen for significant factors. Results: A total of 3449 patients were enrolled. Surgery and chemotherapy were significantly correlated with the occurrence of distant metastasis. In the cause-specific survival rate of MCC, regional lymph node removal, sentinel lymph node biopsy, radiation and chemotherapy can significantly reduce the prognostic risk of patients with distant metastases. Conclusion: Our study screened out the factors affecting the distant metastasis and prognosis of MCC and more prospective studies are needed to verify our findings.


Asunto(s)
Neoplasias Óseas/secundario , Neoplasias Encefálicas/secundario , Carcinoma de Células de Merkel/patología , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/secundario , Neoplasias Cutáneas/patología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Óseas/terapia , Neoplasias Encefálicas/terapia , Carcinoma de Células de Merkel/terapia , Terapia Combinada , Bases de Datos Factuales , Femenino , Humanos , Neoplasias Hepáticas/terapia , Neoplasias Pulmonares/terapia , Metástasis Linfática , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Neoplasias Cutáneas/terapia , Tasa de Supervivencia
7.
Med Sci Monit ; 26: e924570, 2020 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-32653892

RESUMEN

BACKGROUND Merkel cell carcinoma (MCC) occurs primarily among elderly patients over 70 years old, but the ability to predict the prognosis of these elderly patients is poor. This population-based study aimed to identify prognostic risk factors for elderly patients with MCC. MATERIAL AND METHODS The survival and disease information of MCC patients age 65 years or older was downloaded from the SEER database, and all data were split into 2 groups based on age 80 years, with overall survival and MCC-specific survival as the main outcome indicators. RESULTS Application of the inclusion criteria yielded 1973 patients with MCC, of whom 55.6% were age 65-80 years. Among them, 1258 were males, accounting for 63.8%. In survival analysis, factors that were significantly correlated with overall survival and MCC-specific survival were N stage, M stage, liver metastasis, and lymph node surgery. CONCLUSIONS We provide epidemiological insights into Merkel cell carcinoma in elderly patients and confirmed that patients receiving lymph node surgery have better outcomes. To the best of our knowledge, this is the first study to show that the occurrence of liver metastasis is associated with poor prognosis. Our results will help strengthen monitoring of the liver condition of elderly patients and to perform necessary lymph node surgery within the patient's tolerance.


Asunto(s)
Carcinoma de Células de Merkel/epidemiología , Carcinoma de Células de Merkel/metabolismo , Carcinoma de Células de Merkel/patología , Anciano , Anciano de 80 o más Años , Carcinoma de Células de Merkel/mortalidad , Femenino , Humanos , Metástasis Linfática/fisiopatología , Masculino , Recurrencia Local de Neoplasia/patología , Pronóstico , Programa de VERF , Biopsia del Ganglio Linfático Centinela/métodos , Neoplasias Cutáneas/patología , Análisis de Supervivencia
8.
Aesthetic Plast Surg ; 43(1): 167-174, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30511162

RESUMEN

BACKGROUND: Lipoabdominoplasty is a powerful operation to maintain a youthful physique for aging people, improve body contouring, and remove excess skin caused by massive weight loss. Nonetheless, it is controversial to combine abdominoplasty and liposuction because of the potential for vascular damage of the abdominal flap and increased complications. The purpose of this article was to determine the complication rates of lipoabdominoplasty compared with traditional abdominoplasty. METHODS: PubMed, EMBASE, and Cochrane databases were searched through July of 2018. Study results were analyzed utilizing a fixed random effects model. The outcomes were expressed as relative risk (RR) and 95% confidence interval. Subgroup analyses were conducted based on complications. RESULTS: Overall, 17 trials enrolling 14,061 adult patients were searched. Of these patients, 577 (4.1%) developed seroma; 113 (0.8%) experienced hematoma; 783 (5.6%) experienced wound infection, dehiscence, or fat necrosis; 35 (0.2%) developed deep venous thrombosis; and 110 (0.7%) experienced scar deformity. A forest plot revealed fewer complications in the lipoabdominoplasty group than in the traditional abdominoplasty group (RR = 0.85; 95% CI 0.74-0.97; p = 0.017). Subgroup analysis showed that the lipoabdominoplasty group had a lower incidence of hematoma (RR = 0.56; 95% CI 0.36-0.86; p = 0.009) and seroma (RR = 0.69; 95% CI 0.57-0.85; p = 0.000). CONCLUSIONS: Lipoabdominoplasty is a valuable tool to perfect body shape. This meta-analysis showed no evidence that it was associated with higher rates of complications. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Asunto(s)
Abdominoplastia/efectos adversos , Abdominoplastia/métodos , Lipoabdominoplastía/efectos adversos , Lipoabdominoplastía/métodos , Seguridad del Paciente , Índice de Masa Corporal , Estudios de Casos y Controles , Cicatriz/epidemiología , Cicatriz/etiología , Ensayos Clínicos como Asunto , Estética , Femenino , Hematoma/etiología , Hematoma/fisiopatología , Humanos , Masculino , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/fisiopatología , Medición de Riesgo , Seroma/epidemiología , Seroma/etiología , Resultado del Tratamiento , Trombosis de la Vena/epidemiología , Trombosis de la Vena/etiología
9.
BMC Infect Dis ; 18(1): 510, 2018 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-30305033

RESUMEN

BACKGROUND: Respiratory tract infections (RTIs) are the most common illness in children, and rapid diagnosis is required for the optimal management of RTIs, especially severe infections. METHODS: Nasopharyngeal swab or sputum specimens were collected from children aged 19 days to 15 years who were admitted to a hospital in Shanghai and diagnosed with RTIs. The specimens were tested with the FilmArray Respiratory Panel, a multiplex PCR assay that detects 16 viruses, Mycoplasma pneumoniae (M. pneumoniae), Bordetella pertussis (B. pertussis) and Chlamydophila pneumoniae (C. pneumoniae). RESULTS: Among the 775 children studied, 626 (80.8%, 626/775) tested positive for at least one organism, and multiple organisms were detected in 198 (25.5%). Rhinoviruses/enteroviruses (25.5%, 198/775) were detected most often, followed by respiratory syncytial virus (19.5%, 151/775), parainfluenza virus 3 (14.8%, 115/775), influenza A or B (10.9%), adenovirus (10.8%), M. pneumoniae (10.6%) and B. pertussis (6.3%). The prevalence of organisms differed by age, and most of the viruses were more common in winter. Of the 140 children suspected of having pertussis, 35.0% (49/140) tested positive for B. pertussis. CONCLUSIONS: FilmArray RP allows the rapid simultaneous detection of a wide number of respiratory organisms, with limited hands-on time, in Chinese pediatric patients with RTIs.


Asunto(s)
Infecciones Bacterianas , Infecciones del Sistema Respiratorio , Virosis , Adolescente , Bacterias/genética , Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/epidemiología , Infecciones Bacterianas/microbiología , Infecciones Bacterianas/virología , Niño , Preescolar , China/epidemiología , Hospitales Pediátricos , Humanos , Lactante , Recién Nacido , Técnicas de Diagnóstico Molecular , Reacción en Cadena de la Polimerasa , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/microbiología , Infecciones del Sistema Respiratorio/virología , Virosis/diagnóstico , Virosis/epidemiología , Virosis/microbiología , Virosis/virología , Virus/genética
10.
Langmuir ; 33(23): 5947-5956, 2017 06 13.
Artículo en Inglés | MEDLINE | ID: mdl-28525956

RESUMEN

Understanding the enrichment and intracellular trafficking of substances is centrally important to the biological systems. Here, employing an amphiphilic molecule (denoted by TPE-11) bearing tetraphenylethene moiety, known for aggregation induced emission property, we demonstrated its localization shifting in Hela cells after prolonged incubation. Through a set of delicately designed experiments, we found that one type of cytoskeleton, i.e., microtubule, is responsible for the intracellular transportation regardless of the sources of fluorogens, via endocytosis pathways or not. As the polymerization of microtubules was blocked, the TPE-11 fluorogens were hindered to move to the inner cytoplasm, but scattered in the cells. On the contrary, blocking the polymerization of microfilament has no such effect. We assume that the dynamic polymerization of microtubules should be responsible to the transportation of TPE-11. More importantly, we found that the interaction between TPE-11 and microtubule proteins also happens during process of polymerization in vitro. The intracellular trafficking of TPE-11 by microtubules may be generalized to other amphiphilic molecules as well as endocytosis pathway, and serves as references in designing functional molecules involved in the intracellular transportation.


Asunto(s)
Microtúbulos , Transporte Biológico , Citoplasma , Células HeLa , Humanos , Espacio Intracelular
12.
Soft Matter ; 11(22): 4424-9, 2015 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-25925332

RESUMEN

In this paper, a pyrene moiety is incorporated into a bolaamphiphile to form a novel molecule denoted PRB. Above the critical micelle concentration, PRB forms nanodisks in the aqueous solution. The addition of acetate ions induces a morphological change in self-assembled aggregates, which convert into nanofibers with a diameter of several nanometers. More interestingly, along with the morphological change, the fluorescence of the assemblies was enhanced concomitantly, which can be attributed to the binding effect of acetate ions on pyridinium head groups of PRB.

13.
Soft Matter ; 11(4): 798-805, 2015 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-25503396

RESUMEN

In this paper, a new bolaamphiphile bearing 1-cyano-1,2-bis(phenyl)ethene (CNBE) has been synthesized. The self-assembly of this molecule in aqueous solution is concentration-dependent. Two distinct morphologies, monomolecular layered lamellas and helical nanofibres have been obtained with the as-prepared molecular configuration. Note worthily, the helical nanofibres provide an experimental evidence for the pure twisted structure in the liquid crystals, which is theoretically proposed by De Gennes. Due to the photoisomerization of CNBE, the self-assembled nanostructures undergo morphological changes upon irradiation. Although various nanostructures were observed in the solution-state, only nanofibres were obtained after the solution was cast on a substrate, which was attributed to a strong dewetting effect. This work illustrates concentration-dependent and light-responsive self-assembly and provides a novel avenue for fabricating smart soft materials.

14.
Soft Matter ; 10(27): 4833-9, 2014 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-24860850

RESUMEN

In this article, we have synthesized a polymer containing regulated azobenzene groups by one-pot multi-component polymerization (MCP) based on Passerini reaction, and investigated its self-assembly behavior and photo-induced deformation properties. We found that this molecule can form spherical structures with sizes ranging from hundreds of nanometers to several micrometers when dissolved in THF. NMR and FTIR studies indicate that there are associated hydrogen bonds among the molecules in the aggregates, which are responsible for the formation of the nanospheres. By controlling the stirring rate as the THF suspension is dropped into water, the nanospheres can be sorted according to their size. In this way, we have obtained nanospheres with relatively uniform diameter. When irradiated by UV light in the aqueous medium, the nanospheres tend to aggregate into large clusters, while in dry state they are ready to merge into island-like structures, showing a good photo-induced deformation property.

15.
World J Pediatr ; 2024 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-38367140

RESUMEN

BACKGROUND: Diarrhea is a common complication of hematopoietic stem cell transplantation (HSCT) and is associated with substantial morbidity, but its etiology is often unknown. Etiologies of diarrhea in this population include infectious causes, chemotherapy- or medication-induced mucosal injury and graft-versus-host disease (GVHD). Distinguishing these potential causes of diarrhea is challenging since diarrheal symptoms are often multifactorial, and the etiologies often overlap in transplant patients. The objectives of this study were to evaluate whether the FilmArray gastrointestinal (GI) panel would increase diagnostic yield and the degree to which pre-transplantation colonization predicts post-transplantation infection. METHODS: From November 2019 to February 2021, a total of 158 patients undergoing HSCT were prospectively included in the study. Stool specimens were obtained from all HSCT recipients prior to conditioning therapy, 28 ± 7 days after transplantation and at any new episode of diarrhea. All stool samples were tested by the FilmArray GI panel and other clinical microbiological assays. RESULTS: The primary cause of post-transplantation diarrhea was infection (57/84, 67.86%), followed by medication (38/84, 45.24%) and GVHD (21/84, 25.00%). Ninety-five of 158 patients were colonized with at least one gastrointestinal pathogen before conditioning therapy, and the incidence of infectious diarrhea was significantly higher in colonized patients (47/95, 49.47%) than in non-colonized patients (10/63, 15.87%) (P < 0.001). Fourteen of 19 (73.68%) patients who were initially colonized with norovirus pre-transplantation developed a post-transplantation norovirus infection. Twenty-four of 62 (38.71%) patients colonized with Clostridium difficile developed a diarrheal infection. In addition, FilmArray GI panel testing improved the diagnostic yield by almost twofold in our study (55/92, 59.78% vs. 30/92, 32.61%). CONCLUSIONS: Our data show that more than half of pediatric patients who were admitted for HSCT were colonized with various gastrointestinal pathogens, and more than one-third of these pathogens were associated with post-transplantation diarrhea. In addition, the FilmArray GI panel can increase the detection rate of diarrheal pathogens in pediatric HSCT patients, but the panel needs to be optimized for pathogen species, and further studies assessing its clinical impact and cost-effectiveness in this specific patient population are also needed.

16.
EBioMedicine ; 99: 104904, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38061241

RESUMEN

BACKGROUND: The pathology of keloid and especially the roles of bacteria on it were not well understood. METHODS: In this study, multi-omics analyses including microbiome, metaproteomics, metabolomic, single-cell transcriptome and cell-derived xenograft (CDX) mice model were used to explore the roles of bacteria on keloid disease. FINDINGS: We found that the types of bacteria are significantly different between keloid and healthy skin. The 16S rRNA sequencing and metaproteomics showed that more catalase (CAT) negative bacteria, Clostridium and Roseburia existed in keloid compared with the adjacent healthy skin. In addition, protein mass spectrometry shows that CAT is one of the differentially expressed proteins (DEPs). Overexpression of CAT inhibited the proliferation, migration and invasion of keloid fibroblasts, and these characteristics were opposite when CAT was knocked down. Furthermore, the CDX model showed that Clostridium butyricum promote the growth of patient's keloid fibroblasts in BALB/c female nude mice, while CAT positive bacteria Bacillus subtilis inhibited it. Single-cell RNA sequencing verified that oxidative stress was up-regulated and CAT was down-regulated in mesenchymal-like fibroblasts of keloid. INTERPRETATION: In conclusion, our findings suggest that bacteria and CAT contribute to keloid disease. FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.


Asunto(s)
Queloide , Humanos , Femenino , Animales , Ratones , Queloide/genética , Queloide/metabolismo , Queloide/patología , Catalasa/genética , Ratones Desnudos , Multiómica , ARN Ribosómico 16S/genética , Proliferación Celular , Células Cultivadas
17.
Am J Transl Res ; 15(3): 1607-1625, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37056826

RESUMEN

OBJECTIVES: To identify aberrantly expressed immune molecules in keloids and to explore their possible biologic significance. METHODS: Immune molecules with abnormal expression were identified based on immune gene sequencing of keloids, microarray datasets and high-throughput sequencing datasets and methylation microarray datasets from the Gene Expression Omnibus (GEO) database, and real-time quantitative PCR analysis. RESULTS: Upregulation of tumor necrosis factor superfamily member 4 (TNFSF4) in keloids was identified. Enrichment analysis found that high TNFSF4 expression was associated with immune processes, such as regulation of neutrophil chemotaxis, dendritic cell chemotaxis, and antigen processing and presentation. Single-cell RNA sequencing (scRNA) results suggested that TNFSF4 was upregulated in mesenchymal fibroblasts, which are the critical cells in skin fibrosis. This high expression of TNFSF4 enhanced cell-to-cell interactions in fibrosis-related pathways, including the fibronectin 1 (FN1) and collagen pathways. Mesenchymal fibroblasts expressing TNFSF4 significantly upregulated gene expression in extracellular matrix organization and wound healing processes. CONCLUSIONS: Our study revealed upregulation of the immune molecule TNFSF4 in keloids at the multi-omics level and its effects on intercellular crosstalk and transcriptional profiles of mesenchymal fibroblasts. Investigation of TNFSF4 as an immune checkpoint molecule may represent a new direction for keloid treatment research.

18.
Burns Trauma ; 11: tkad017, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37293384

RESUMEN

Keloids are a fibrotic disease caused by an excessive accumulation of extracellular matrix in the dermis; they have neoplasia-like properties of aggressive growth and high posttreatment recurrence rates. Therefore, it is imperative to gain additional insight into the pathobiology of keloid formation. Single-cell RNA sequencing (scRNA-seq) technology has brought data-driven innovation to understanding the pathogenesis of keloids by breaking the limitations of traditional sequencing technologies to resolve cell composition and to distinguish functional cell subtypes at an unprecedented resolution. The present review aims to cover the application of scRNA-seq technology in keloids and its exploratory findings, including the depiction of the cellular landscape of keloids, fibroblast heterogeneity, the lineage development of Schwann cells and the mesenchymal-activation phenomenon of endothelial cells. Furthermore, scRNA-seq records the transcriptional profiles of fibroblasts and immune cells in a more refined manner, and this gene expression information provides excellent material for inferring intercellular communication networks and lays an important theoretical foundation for future studies.

19.
Front Immunol ; 14: 1106289, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37275903

RESUMEN

Objectives: Keloid is a highly aggressive fibrotic disease resulting from excessive extracellular matrix deposition after dermal injury. Intra-lesional injection of triamcinolone acetonide (TAC) in combination with 5-fluorouracil (5-FU) is a commonly used pharmacological regimen and long-term repeated injections can achieve sustained inhibition of keloid proliferation. However, the molecular mechanisms underlying the inhibitory effect on keloids remain insufficiently investigated. Methods and materials: This study performed single-cell RNA sequencing analysis of keloids treated with TAC+5-FU injections, keloids, and skins to explore patterns of gene expression regulation and cellular reprogramming. Results: The results revealed that TAC+5-FU interrupted the differentiation trajectory of fibroblasts toward pro-fibrotic subtypes and induced keloid atrophy possibly by inhibiting the FGF signaling pathway in intercellular communication. It also stimulated partial fibroblasts to develop the potential for self-replication and multidirectional differentiation, which may be a possible cellular source of keloid recurrence. T cell dynamics demonstrated elevated expression of secretory globulin family members, which may be possible immunotherapeutic targets. Schwann cell populations achieved functional changes by increasing the proportion of apoptotic or senescence-associated cell populations and reducing cell clusters that promote epidermal development and fibroblast proliferation. Conclusions: Our findings elucidated the molecular and cellular reprogramming of keloids by intra-lesional injection of TAC+5-FU, which will provide new insights to understand the mechanism of action and therapeutic targets.


Asunto(s)
Queloide , Triamcinolona Acetonida , Humanos , Triamcinolona Acetonida/farmacología , Triamcinolona Acetonida/uso terapéutico , Queloide/tratamiento farmacológico , Queloide/genética , Queloide/patología , Fluorouracilo , Transcriptoma , Quimioterapia Combinada , Resultado del Tratamiento , Inyecciones Intralesiones
20.
Am J Transl Res ; 15(3): 1889-1896, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37056810

RESUMEN

BACKGROUND: Keloid subepidermal vascular network flaps (KSVNFs) have achieved satisfactory results in clinical practice. Through this retrospective study, we further examined keloid vascular structure to better understand vascular origin pattern in KSVNFs. METHODS: Paraffin-embedded keloid tissues were stained for CD31. Distances from keloid subepidermal capillaries to the skin surface were measured. The included angle between the pedicle vessels and skin surface (angle PV), as well as the included angle between the keloid margin and skin surface (angle KM), were also measured. The major and minor axes of the capillary in the central areas of keloid (KDC), adjacent skin (AS) and marginal areas of keloid (KDM) were analyzed, and the major:minor axis ratios (M/m) were calculated. Vessels in KSVNF pedicle sites (KDP) were compared with vessels in adjacent skin as a subgroup analysis. RESULTS: Twenty-nine keloid specimens in total were collected. Based on 1630 measured data points, the capillary distance to the skin surface was 387.2±96.7 µm. The angle PV was 70.1±36.6°, and the angle KM was 67.0±18.1°. The major axis of the KDM capillaries was significantly longer than that of KDC and AS (both P < 0.001). The major and minor axes were longer in KDP than in AS (both P < 0.001). CONCLUSION: Suprakeloidal blood vessels are mainly distributed at a depth of 387.2±96.7 µm from the skin. The subepidermal plexus in KSVNF pedicle sites enters the skin at an acute angle and runs parallel to the keloid margin layer. Vessels in keloid marginal areas had crushed vascular lumen, but vessels in KSVNF pedicles did not.

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