-
American Journal of Translational... 2023Lung adenocarcinoma (LUAD) is recognized as one of the most prevalent and deadliest malignancies around the globe. The molecular mechanisms behind LUAD have not been...
OBJECTIVES
Lung adenocarcinoma (LUAD) is recognized as one of the most prevalent and deadliest malignancies around the globe. The molecular mechanisms behind LUAD have not been fully elucidated. This study was launched to explore LUAD-associated hub genes and their enriched pathways using bioinformatics methods.
METHODS
Information on GSE10072 was retrieved from the Gene Expression Omnibus (GEO) database and analyzed via the Limma package-based GEO2R tool to obtain the top 100 differentially expressed genes (DEGs) in LUAD. The protein-protein interaction (PPI) network of the DEGs was drawn using the STRING website and was shifted into Cytoscape to screen the top 6 hub genes via the CytoHubba application. Furthermore, the expression analysis and validation of hub genes in LUAD samples and cell lines were done using UALCAN, OncoDB, and GENT2 databases. Moreover, OncoDB was also used for analyzing hub gene DNA methylation levels. In addition, cBioPortal, GSEA tool, Kaplan-Meier (KM) plotter, Enrichr, CancerSEA, and DGIdb were performed to explore some other important aspects of hub genes in LUAD.
RESULTS
We identified Interleukin 6 (IL6), Collagen, type I, alpha 1 (COL1A1), TIMP metallopeptidase inhibitor 1 (TIMP1), CD34 molecule (CD34), Decorin (DCN), and Secreted Phosphoprotein 1 (SPP1) genes as the hub genes in LUAD, out of which IL6, CD34, and DCN were significantly down-regulated while COL1A1, TIMP1, and SPP1 were significantly up-regulated in LUAD cell lines and samples of diverse clinical variables. In this study, we also documented some important correlations between hub genes and other parameters such as DNA methylation, genetic alterations, Overall Survival (OS), and 14 important states at the single cell level. Lastly, we also identified hub genes associated with the ceRNA network and 11 important chemotherapeutic drugs.
CONCLUSION
We identified 6 hub genes involved in the development and progression of LUAD. These hub genes can also be helpful in the accurate detection of LUAD and provide novel ideas for treatment.
PubMed: 37056815
DOI: No ID Found -
Frontiers in Bioengineering and... 2023We carried out a histological characterization analysis of the stromal layer of human heterotypic cornea substitutes generated with extra-corneal cells to determine...
We carried out a histological characterization analysis of the stromal layer of human heterotypic cornea substitutes generated with extra-corneal cells to determine their putative usefulness in tissue engineering. Human bioartificial corneas were generated using nanostructured fibrin-agarose biomaterials with corneal stromal cells immersed within. To generate heterotypical corneas, umbilical cord Wharton's jelly stem cells (HWJSC) were cultured on the surface of the stromal substitutes to obtain an epithelial-like layer. These bioartificial corneas were compared with control native human corneas and with orthotypical corneas generated with human corneal epithelial cells on top of the stromal substitute. Both the corneal stroma and the basement membrane were analyzed using histological, histochemical and immunohistochemical methods in samples kept in culture and grafted for 12 months in the rabbit cornea. Our results showed that the stroma of the bioartificial corneas kept showed very low levels of fibrillar and non-fibrillar components of the tissue extracellular matrix. However, implantation resulted in a significant increase of the contents of collagen, proteoglycans, decorin, keratocan and lumican in the corneal stroma, showing higher levels of maturation and spatial organization of these components. Heterotypical corneas grafted for 12 months showed significantly higher contents of collagen fibers, proteoglycans and keratocan. When the basement membrane was analyzed, we found that all corneas grafted showed intense PAS signal and higher contents of nidogen-1, although the levels found in human native corneas was not reached, and a rudimentary basement membrane was observed using transmission electron microscopy. At the epithelial level, HWJSC used to generate an epithelial-like layer in corneas were mostly negative for p63, whereas orthotypical corneas and heterotypical corneas grafted were positive. These results support the possibility of generating bioengineered artificial corneas using non-corneal HWJSC. Although heterotypical corneas were not completely biomimetic to the native human corneas, especially , grafted corneas demonstrated to be highly biocompatible, and the animal cornea became properly differentiated at the stroma and basement membrane compartments. These findings open the door to the future clinical use of these bioartificial corneas.
PubMed: 37034263
DOI: 10.3389/fbioe.2023.1124995 -
Genes Mar 2023Musculocontractural Ehlers-Danlos syndrome caused by mutations in the carbohydrate sulfotransferase 14 gene (mcEDS-) is a heritable connective tissue disorder...
Musculocontractural Ehlers-Danlos syndrome caused by mutations in the carbohydrate sulfotransferase 14 gene (mcEDS-) is a heritable connective tissue disorder characterized by multiple congenital malformations and progressive connective tissue fragility-related manifestations in the cutaneous, skeletal, cardiovascular, visceral, and ocular systems. Progressive skeletal deformities are among the most frequent and serious complications affecting the quality of life and activities of daily living in patients. After establishing induced pluripotent stem cells (iPSCs) from cultured skin fibroblasts of three patients with mcEDS-, we generated a patient iPSC-based human osteogenesis model and performed an in vitro assessment of the phenotype and pathophysiology of skeletal deformities. Patient-derived iPSCs presented with remarkable downregulation of osteogenic-specific gene expression, less alizarin red staining, and reduced calcium deposition compared with wild-type iPSCs at each stage of osteogenic differentiation, including osteoprogenitor cells, osteoblasts, and osteocytes. These findings indicated that osteogenesis was impaired in mcEDS- iPSCs. Moreover, the decrease in decorin () expression and increase in collagen () expression in patient-derived iPSCs elucidated the contribution of dysfunction to skeletal deformities in mcEDS-. In conclusion, this disease-in-a-dish model provides new insight into the pathophysiology of EDS and may have the potential for personalized gene or drug therapy.
Topics: Humans; Induced Pluripotent Stem Cells; Activities of Daily Living; Osteogenesis; Quality of Life; Sulfotransferases; Ehlers-Danlos Syndrome
PubMed: 36981001
DOI: 10.3390/genes14030730 -
Frontiers in Cell and Developmental... 2023Collagen XII, a fibril-associated collagen with interrupted triple helices (FACIT), influences fibrillogenesis in numerous tissues. In addition to this extracellular... (Review)
Review
Collagen XII, a fibril-associated collagen with interrupted triple helices (FACIT), influences fibrillogenesis in numerous tissues. In addition to this extracellular function, collagen XII also directly regulates cellular function. Collagen XII is widely expressed in connective tissues, particularly tendons, ligaments, and the periodontium and periosteum, where it is enriched in the pericellular regions. Mutations in the collagen XII gene cause myopathic Ehlers-Danlos syndrome (mEDS), an early-onset disease characterized by overlapping connective tissue abnormalities and muscle weakness. Patients with mEDS exhibit delayed motor development, muscle weakness, joint laxity, hypermobility, joint contractures, and abnormal wound healing. A mEDS mouse model was generated by deletion of the gene, resulting in skeletal and muscle abnormalities with disorganized tissue structures and altered mechanical properties. Extracellularly, collagen XII interacts with collagen I fibrils and regulates collagen fibril spacing and assembly during fibrillogenesis. Evidence for the binding of collagen XII to other EDS-related molecules (e.g., decorin and tenascin X) suggests that disruption of ECM molecular interactions is one of the causes of connective tissue pathology in mEDS. Collagen XII also has been shown to influence cell behavior, such as cell shape and cell-cell communication, by providing physical connection between adjacent cells during tissue development and regeneration. The focus of this review is on the functions of collagen XII in development, regeneration, and disease.
PubMed: 36936682
DOI: 10.3389/fcell.2023.1129000 -
International Journal of Hyperthermia :... 2023Benign breast lesions are often associated with hard nodule formation after microwave ablation (MWA), which persists for a long time and causes problems in patients. The...
Decorin inhibits the formation of hard nodules after microwave ablation by inhibiting the TGF-β1/SMAD and MAPK signaling pathways: in a Bama miniature pig model of mammary gland hyperplasia.
BACKGROUND
Benign breast lesions are often associated with hard nodule formation after microwave ablation (MWA), which persists for a long time and causes problems in patients. The aim of this study was to evaluate the efficacy of decorin in the treatment of hard nodule formation and its potential mechanism of action.
METHODS
Using a Bama miniature pig model of mammary gland hyperplasia, immunohistochemistry, Masson's trichrome and western blotting were firstly applied to compare the extent of fibrosis and activation of key members of the TGF-β1/SMAD and MAPK signaling pathways of hard nodule in the control and MWA groups, and then the extent of fibrosis and expression of signaling pathways in hard nodule were examined after application of decorin.
RESULTS
The results showed that the MWA group had increased levels of TGF-β1, p-SMAD2/3, p-ERK1/2, and collagen I proteins and increased fibrosis at 2 weeks, 4 weeks, and 3 months after MWA. After decorin treatment, the expression levels of each protein were significantly downregulated, and the degree of fibrosis was reduced at 2 weeks, 4 weeks, and 3 months after MWA compared with the MWA group.
CONCLUSION
In conclusion, these results suggest that activation of TGF-β1 may play an important role in hard nodule formation and that decorin may reduce hard nodule formation after MWA in a model of mammary gland hyperplasia by inhibiting the TGF-β1/SMAD and MAPK signaling pathways.
Topics: Animals; Swine; MAP Kinase Signaling System; Decorin; Swine, Miniature; Transforming Growth Factor beta1; Microwaves; Hyperplasia; Signal Transduction; Fibrosis
PubMed: 36919520
DOI: 10.1080/02656736.2023.2188151 -
International Journal of Molecular... Mar 2023Titanium implants are regarded as a promising treatment modality for replacing missing teeth. Osteointegration and antibacterial properties are both desirable...
Vapor-Induced Pore-Forming Atmospheric-Plasma-Sprayed Zinc-, Strontium-, and Magnesium-Doped Hydroxyapatite Coatings on Titanium Implants Enhance New Bone Formation-An In Vivo and In Vitro Investigation.
OBJECTIVES
Titanium implants are regarded as a promising treatment modality for replacing missing teeth. Osteointegration and antibacterial properties are both desirable characteristics for titanium dental implants. The aim of this study was to create zinc (Zn)-, strontium (Sr)-, and magnesium (Mg)-multidoped hydroxyapatite (HAp) porous coatings, including HAp, Zn-doped HAp, and Zn-Sr-Mg-doped HAp, on titanium discs and implants using the vapor-induced pore-forming atmospheric plasma spraying (VIPF-APS) technique.
METHODS
The mRNA and protein levels of osteogenesis-associated genes such as collagen type I alpha 1 chain (COL1A1), decorin (DCN), osteoprotegerin (TNFRSF11B), and osteopontin (SPP1) were examined in human embryonic palatal mesenchymal cells. The antibacterial effects against periodontal bacteria, including and , were investigated. In addition, a rat animal model was used to evaluate new bone formation via histologic examination and micro-computed tomography (CT).
RESULTS
The ZnSrMg-HAp group was the most effective at inducing mRNA and protein expression of TNFRSF11B and SPP1 after 7 days of incubation, and TNFRSF11B and DCN after 11 days of incubation. In addition, both the ZnSrMg-HAp and Zn-HAp groups were effective against and . Furthermore, according to both in vitro studies and histologic findings, the ZnSrMg-HAp group exhibited the most prominent osteogenesis and concentrated bone growth along implant threads.
SIGNIFICANCE
A porous ZnSrMg-HAp coating using VIPF-APS could serve as a novel technique for coating titanium implant surfaces and preventing further bacterial infection.
Topics: Rats; Humans; Animals; Durapatite; Osteogenesis; Titanium; Magnesium; Zinc; X-Ray Microtomography; Hydroxyapatites; Gases; Strontium; Coated Materials, Biocompatible; Surface Properties
PubMed: 36902368
DOI: 10.3390/ijms24054933 -
Medicine Mar 2023Dietary counseling and nutritional support (DCNS) are generally accepted as being necessary for patients with oral cancer and oropharyngeal cancer (OC). However, there...
BACKGROUND
Dietary counseling and nutritional support (DCNS) are generally accepted as being necessary for patients with oral cancer and oropharyngeal cancer (OC). However, there is no evidence that dietary counseling plays a significant role in weight loss. In this study, we examined the DCNS based on persistent weight loss during and after treatment in oral cancer and OC patients, as well as the effect of body mass index (BMI) on survival in both groups.
METHODS
A retrospective chart review was conducted on 2622 patients diagnosed with cancer between 2007 and 2020, including 1836 oral and 786 oropharyngeal patients. In comparison with the sample of patients treated by DCNS, differences in proportional counts for key factors associated with survival were compared between oral cancer and OC patients using the forest plot. An analysis of cowords was conducted to determine CNS associated with weight loss and overall survival. The Sankey diagram was used to display DCNS effectiveness. The log-rank test was used to evaluate the chi-squared goodness of fit test on the null assumption model of equal survival distributions between the groups.
RESULTS
Almost 41% of the patients (=1064/2262) received DCNS, with a frequency ranging from 1 to 44. Counts for 4 DCNS categories were 566, 392, 92, and 14, respectively, against BMI increases or decreases from much to less with counts of 3, 44, 795, 219, and 3, respectively. In the first year following treatment, DCNS decreased sharply to 50%. One year after hospital discharge, the overall weight loss increased from 3 to 9% (mean = -4%, standard deviation = 14%). Patients with a BMI above average had a significantly longer survival time (P < .001). Statistically, OC patients have a significantly higher survival rate than oral cancer patients.
CONCLUSION
Despite receiving frequent DCNS, patients continued to lose body weight during and 1 year after treatment. The survival time of an individual with a BMI above average appears to be increased. Future studies should preferably use randomized trials to compare standard DCNS with more intensive DCNS, which includes earlier and/or prolonged treatment.
Topics: Humans; Retrospective Studies; Nutritional Support; Counseling; Oropharyngeal Neoplasms; Weight Loss; Mouth Neoplasms; Decorin
PubMed: 36897724
DOI: 10.1097/MD.0000000000033164 -
The Journal of Maternal-fetal &... Dec 2023This study analyzed the levels of peripheral blood tumor necrosis factor-α (TNF-α), Decorin (DCN) and Mitogen-activated protein kinase 1 (MAPK1) mRNA in neutrophils...
This study analyzed the levels of peripheral blood tumor necrosis factor-α (TNF-α), Decorin (DCN) and Mitogen-activated protein kinase 1 (MAPK1) mRNA in neutrophils of patients with preeclampsia and their correlations, in order to provide more thoughts on the diagnosis and treatment of clinical patients. 81 patients with preeclampsia who had regular prenatal checkups and delivered in our hospital from June 2020 to April 2022 were analyzed, including 26 patients with early-onset and 55 patients with late-onset, and 50 pregnant women with normal pregnancy who had prenatal checkups and delivered in our hospital during the same period were selected as the control group. Record the clinical data of patients, record the expression of peripheral blood TNF-α, DCN and neutrophils MAPK1 mRNA of patients with early-onset, late-onset and the control group, and record the correlation between DCN level, MAPK1 mRNA expression and TNF-α level of patients with preeclampsia. The diastolic and systolic blood pressures were significantly higher in early-onset and late-onset patients, and the gestational week of delivery was significantly lower in early-onset and late-onset patients, respectively ( < .05); there was no statistically significant difference in the average age, BMI, average pregnancy time, and average births between the three groups ( > .05). The expressions of peripheral blood TNF-α, DCN, and neutrophils MAPK1 mRNA of the early-onset and late-onset groups were all higher than those in the control group ( < .05); and the expressions of TNF-α, DCN, and MAPK1 mRNA in the peripheral blood of the early-onset group were all higher than those in the late-onset group ( < .05); correlation analysis showed that DCN level and TNF-α level in patients with preeclampsia were positively correlated ( = 0.98639, < .05); Neutrophils MAPK1 mRNA expression and TNF-α level were positively correlated ( = 0.9611, < .05). TNF-α, DCN and neutrophils MAPK1 mRNA were all highly expressed in the peripheral blood of patients with pre-eclampsia and were more significantly elevated in patients with early-onset preeclampsia, and the expression levels of DCN and MAPK1 mRNA were positively correlated with TNF-α levels. It is possible that all three factors are involved in the pathogenesis of preeclampsia, and are expected to be used as indicators for early prediction and diagnosis.
Topics: Female; Humans; Pregnancy; Clinical Relevance; Decorin; Mitogen-Activated Protein Kinase 1; Neutrophils; Pre-Eclampsia; Tumor Necrosis Factor-alpha; RNA, Messenger
PubMed: 36852440
DOI: 10.1080/14767058.2023.2183745 -
Genes Jan 2023Loss-of-function mutations in () cause musculocontractural Ehlers-Danlos syndrome- (mcEDS-), characterized by multiple congenital malformations and progressive...
Loss-of-function mutations in () cause musculocontractural Ehlers-Danlos syndrome- (mcEDS-), characterized by multiple congenital malformations and progressive connective tissue fragility-related manifestations in the cutaneous, skeletal, cardiovascular, visceral and ocular system. The replacement of dermatan sulfate chains on decorin proteoglycan with chondroitin sulfate chains is proposed to lead to the disorganization of collagen networks in the skin. However, the pathogenic mechanisms of mcEDS- are not fully understood, partly due to the lack of in vitro models of this disease. In the present study, we established in vitro models of fibroblast-mediated collagen network formation that recapacitate mcEDS- pathology. Electron microscopy analysis of mcEDS--mimicking collagen gels revealed an impaired fibrillar organization that resulted in weaker mechanical strength of the gels. The addition of decorin isolated from patients with mcEDS- and mice disturbed the assembly of collagen fibrils in vitro compared to control decorin. Our study may provide useful in vitro models of mcEDS- to elucidate the pathomechanism of this disease.
Topics: Animals; Mice; Decorin; Sulfotransferases; Ehlers-Danlos Syndrome; Extracellular Matrix; Collagen
PubMed: 36833235
DOI: 10.3390/genes14020308 -
Biomedicines Feb 2023The human xylosyltransferase isoform XT-I catalyzes the initial step in proteoglycan biosynthesis and represents a biomarker of myofibroblast differentiation....
The human xylosyltransferase isoform XT-I catalyzes the initial step in proteoglycan biosynthesis and represents a biomarker of myofibroblast differentiation. Furthermore, XT-I overexpression is associated with fibrosis, whereby a fibrotic process initially develops from a dysregulated wound healing. In a physiologically wound healing process, extracellular matrix-producing myofibroblasts enter acute senescence to protect against fibrosis. The aim of this study was to determine the role of XT-I in acute senescent proto-myofibroblasts. Normal human dermal fibroblasts were seeded in a low cell density to promote myofibroblast differentiation and treated with HO to induce acute senescence. Initiation of the acute senescence program in human proto-myofibroblasts resulted in a suppression of mRNA expression compared to the control, whereby the isoform was more affected than . Moreover, the XT-I protein expression and enzyme activity were also reduced in HO-treated cells compared to the control. The examination of extracellular matrix remodeling revealed reduced expression of collagen I, fibronectin and decorin. In summary, acute senescent proto-myofibroblasts formed an anti-fibrotic phenotype, and suppression of XT-I during the induction process of acute senescence significantly contributed to subsequent ECM remodeling. XT-I therefore plays an important role in the switch between physiological and pathological wound healing.
PubMed: 36830996
DOI: 10.3390/biomedicines11020460