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1.
Front Immunol ; 14: 1281051, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37854598

RESUMO

[This corrects the article DOI: 10.3389/fimmu.2023.1164667.].

2.
Front Immunol ; 14: 1164667, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37215133

RESUMO

Introduction: Periodontitis is an inflammatory disease and its molecular mechanisms is not clear. A recently discovered cell death pathway called cuproptosis, may related to the disease. Methods: The datasets GSE10334 of human periodontitis and control were retrieved from the Gene Expression Omnibus database (GEO) for analysis.Following the use of two machine learning algorithms, least absolute shrinkage and selection operator (LASSO) and support vector machine-recursive feature removal (SVM-RFE) were used to find CRG-based signature. Then the Receiver operating characteristic (ROC) curves was used to evaluate the gene signature's discriminatory ability. The CIBERSORT deconvolution algorithm was used to study the link between hub genes and distinct types of immune cells. Next, the association of the CRGs with immune cells in periodontitis and relevant clusters of cuproptosis were found. The link between various clusters was ascertained by the GSVA and CIBERSORT deconvolution algorithm. Finally, An external dataset (GSE16134) was used to confirm the diagnosis capacity of the identified biomarkers. In addition, clinical samples were examined using qRT-PCR and immunohistochemistry to verifiy the expression of genes related to cuprotosis in periodontitis and the signature may better predict the periodontitis. Results: 15 periodontitis-related DE-CRGs were found,then 11-CRG-based signature was found by using of LASSO and SVM-RFE. ROC curves also supported the value of signature. CIBERSORT results of immune cell signature in periodontitis showed that signature genes is a crucial component of the immune response.The relevant clusters of cuproptosis found that the NFE2L2, SLC31A1, FDX1,LIAS, DLD, DLAT, and DBT showed a highest expression levels in Cluster2 ,while the NLRP3, MTF1, and DLST displayed the lowest level in Cluster 2 but the highest level in Cluster1. The GSVA results also showed that the 11 cuproptosis diagnostic gene may regulate the periodontitis by affecting immune cells. The external dataset (GSE16134) confirm the diagnosis capacity of the identified biomarkers, and clinical samples examined by qRT-PCR and immunohistochemistry also verified that these cuprotosis related signiture genes in periodontitis may better predict the periodontitis. Conclusion: These findings have important implications for the cuproptosis and periodontitis, and highlight further research is needed to better understand the mechanisms underlying this relationship between the cuproptosis and periodontitis.


Assuntos
Algoritmos , Apoptose , Periodontite , Humanos , Morte Celular , Bases de Dados Factuais , Aprendizado de Máquina , Periodontite/genética , Cobre
3.
Front Mol Biosci ; 10: 1112653, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37006615

RESUMO

Osteoarthritis (OA) is a chronic joint disease with increasing prevalence. Chondrocytes (CHs) are highly differentiated end-stage cells with a secretory phenotype that keeps the extracellular matrix (ECM) balanced and the cartilage environment stable. Osteoarthritis dedifferentiation causes cartilage matrix breakdown, accounting for one of the key pathogenesis of osteoarthritis. Recently, the activation of transient receptor potential ankyrin 1 (TRPA1) was claimed to be a risk factor in osteoarthritis by causing inflammation and extracellular matrix degradation. However, the underlying mechanism is still unknown. Due to its mechanosensitive property, we speculated that the role of TRPA1 activation during osteoarthritis is matrix stiffness-dependent. In this study, we cultured the chondrocytes from patients with osteoarthritis on stiff vs. soft substrates, treated them with allyl isothiocyanate (AITC), a transient receptor potential ankyrin 1 agonist, and compared the chondrogenic phenotype, containing cell shape, F-actin cytoskeleton, vinculin, synthesized collagen profiles and their transcriptional regulatory factor, and inflammation-related interleukins. The data suggest that allyl isothiocyanate treatment activates transient receptor potential ankyrin 1 and results in both positive and harmful effects on chondrocytes. In addition, a softer matrix could help enhance the positive effects and alleviate the harmful ones. Thus, the effect of allyl isothiocyanate on chondrocytes is conditionally controllable, which could be associated with transient receptor potential ankyrin 1 activation, and is a promising strategy for osteoarthritis treatment.

4.
J Orthop Translat ; 38: 213-219, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36439626

RESUMO

Background & aims: Sarcopenia is an age-related disease that increases the risk of falls and fractures in older adults. However, there is no blood biochemical marker to help to predict or diagnose sarcopenia in clinical practice. Soluble interleukin 2 receptor (sIL-2R) was reported to be associated with muscle satellite cell dysfunction which played an important role in the pathogenesis of sarcopenia. Thereby, we aimed to explore the association between serum sIL-2R and sarcopenia in older adults at high risk of fractures. Methods: A total of 429 hospitalized older adults (age ≥55 years) were enrolled in this cross-sectional study (mean age â€‹= â€‹66.62 â€‹± â€‹6.59 years; 62.7% female). Logistic regression analysis was performed to assess the association of sIL-2R with sarcopenia, muscle mass, muscle strength, and physical performance, respectively. The optimal models for the diagnosis of sarcopenia and low hand grip strength (HGS) were established by multivariable binary logistic regression analysis with backward selection, and further were evaluated for the diagnostic values by receiver operating characteristic (ROC) curve. Results: Higher sIL-2R levels were found in sarcopenia than no-sarcopenia group in male (median 421 U/mL (interquartile range [IQR] 217 U/mL) vs median 362 U/mL (IQR 157 U/mL); n â€‹= â€‹77 vs 83; p â€‹< â€‹0.01). Compared to the lowest sIL-2R tertile, the highest tertile of sIL-2R was independently associated with the risk of low HGS (odds ratio [OR] 4.608, 95% confidence interval [CI] 1.673-12.695) and the risk of sarcopenia (OR 3.306, 95% CI 1.496-7.302) in men. ROC curves revealed that the Area Under the Curve (AUC) of the optimal models for diagnosing sarcopenia and low HGS was 0.752 and 0.846. Conclusion: Our results suggest that serum sIL-2R is the independent risk factor for sarcopenia and low muscle strength only in men. sIL-2R may be developed to be a biochemical marker for sarcopenia and low muscle strength diagnoses in older men at high risk of fractures, but more prospective studies are needed to prove it. The translational potential of this article: Our results showed that the highest tertile of sIL-2R was independent of low risk of HGS and sarcopenia in men, compared to the lowest tertile. As the population ages, sIL-2R may become a potential diagnostic tool for predicting low HGS and sarcopenia among men at high risk of fractures.

5.
Nutrients ; 14(23)2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36501049

RESUMO

As new screening tools for sarcopenia, the serum sarcopenia index (SI) and creatinine/cystatin C ratio (CCR) had not been confirmd in a population with a high fragility fracture risk. This study aimed to evaluate whether SI and CCR indicators are useful for diagnosing sarcopenia and to determine their prediction values for future falls and fractures. A total of 404 hospitalized older adults were enrolled in this longitudinal follow-up study (mean age = 66.43 ± 6.80 years). The receiver operating curve (ROC) was used to assess the diagnostic accuracy of SI and CCR. Backward-selection binary logistic regression was applied to develop the optimal models for the diagnosis of new falls and fractures. SI had a significantly higher area under the curve (AUC) than CCR for predicting sarcopenia. The optimal models had acceptable discriminative powers for predicting new falls and fractures. Lower SI and CCR are the independent risks for sarcopenia, new falls, and fractures in the low-BMD population. SI and CCR, as easily accessible biochemical markers, may be useful in the detection of sarcopenia and in predicting the occurrence of new falls and fractures in patients with low BMD who have not previously experienced falls or fractures. However, further external validations are required.


Assuntos
Doenças Ósseas Metabólicas , Fraturas Ósseas , Sarcopenia , Humanos , Idoso , Pessoa de Meia-Idade , Cistatina C , Creatinina , Seguimentos , Sarcopenia/complicações , Sarcopenia/diagnóstico , Fraturas Ósseas/etiologia , Fraturas Ósseas/epidemiologia , Densidade Óssea
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