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1.
Brief Bioinform ; 25(3)2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38704671

ABSTRACT

Computational analysis of fluorescent timelapse microscopy images at the single-cell level is a powerful approach to study cellular changes that dictate important cell fate decisions. Core to this approach is the need to generate reliable cell segmentations and classifications necessary for accurate quantitative analysis. Deep learning-based convolutional neural networks (CNNs) have emerged as a promising solution to these challenges. However, current CNNs are prone to produce noisy cell segmentations and classifications, which is a significant barrier to constructing accurate single-cell lineages. To address this, we developed a novel algorithm called Single Cell Track (SC-Track), which employs a hierarchical probabilistic cache cascade model based on biological observations of cell division and movement dynamics. Our results show that SC-Track performs better than a panel of publicly available cell trackers on a diverse set of cell segmentation types. This cell-tracking performance was achieved without any parameter adjustments, making SC-Track an excellent generalized algorithm that can maintain robust cell-tracking performance in varying cell segmentation qualities, cell morphological appearances and imaging conditions. Furthermore, SC-Track is equipped with a cell class correction function to improve the accuracy of cell classifications in multiclass cell segmentation time series. These features together make SC-Track a robust cell-tracking algorithm that works well with noisy cell instance segmentation and classification predictions from CNNs to generate accurate single-cell lineages and classifications.


Subject(s)
Algorithms , Cell Lineage , Cell Tracking , Single-Cell Analysis , Cell Tracking/methods , Single-Cell Analysis/methods , Humans , Image Processing, Computer-Assisted/methods , Neural Networks, Computer , Deep Learning , Microscopy, Fluorescence/methods
2.
Balkan Med J ; 41(3): 174-185, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38700313

ABSTRACT

Background: Psoriasis is a chronic inflammatory skin disease that has no cure. While the specific cause of psoriasis is unknown, interactions between immune cells and inflammatory cytokines are believed to be important in its pathogenesis. Thymic stromal lymphopoietin (TSLP) is a cytokine produced by epithelial cells that profoundly affects dendritic cells (DCs) and is involved in allergy and inflammatory diseases. In some studies, its expression is higher in the skin of psoriasis patients, whereas it is increased in treated psoriasis patients when compared with untreated patients in others. Aims: To investigate the role of TSLP in the pathogenesis of psoriasis. Study Design: In vitro and in vivo study. Methods: To investigate the effect of TSLP on psoriasis in vivo, a mouse psoriasis model and shRNA targeting TSLP to reduce its expression were used. Mouse primary bone marrow dendritic cells (BMDCs) were cultured in vitro and used to investigate the signaling pathways activated by TSLP. Results: We found that reducing TSLP expression in psoriasis skin alleviated disease severity. TSLP activated the Janus kinase (JAK)/SYK pathway in psoriatic skin. In vitro studies with BMDCs demonstrated that TSLP increased DC maturation through the JAK/SYK pathway and activated DCs-secreted cytokines that stimulated CD4+ T cells to develop into T helper 17 (Th17) cells by activating STAT3 signaling. The JAK/SYK pathway inhibitor reduced the effect of TSLP on activating BMDCs and promoting Th17 differentiation by CD4+ T cells. Conclusion: These findings indicated that TSLP exerted its immune-modulating effect in psoriasis through the JAK/SYK pathway.


Subject(s)
Cytokines , Dendritic Cells , Psoriasis , Th17 Cells , Thymic Stromal Lymphopoietin , Animals , Humans , Mice , Cytokines/metabolism , Cytokines/drug effects , Dendritic Cells/drug effects , Dendritic Cells/immunology , Disease Models, Animal , Janus Kinases , Signal Transduction/drug effects , Syk Kinase , Th17 Cells/drug effects , Th17 Cells/immunology
3.
Front Immunol ; 15: 1307748, 2024.
Article in English | MEDLINE | ID: mdl-38601143

ABSTRACT

Background: Monocyte/macrophage (Mo/Mp) is a critical cell population involved in immune modulation of rheumatoid synovitis (RA) across different pathotypes. This study aims to investigate the contribution of Mo/Mp clusters to RA activity, and the biological function of particular subtypes in RA remission. Methods: We integrated single-cell RNA sequencing datasets from 4 published and 1 in-house studies using Liger selected by comparison. We estimated the abundance of Mo/Mp subtypes in bulk RNA-seq data from the 81 patients of the Pathobiology of Early Arthritis Cohort (PEAC) using deconvolution analysis. Correlations between Mo/Mp subtypes and RA clinical metrics were assessed. A particular cell type was identified using multicolor immunofluorescence and flow cytometry in vivo and successfully induced from a cell line in vitro. Potential immune modulation function of it was performed using immunohistochemical staining, adhesion assay, and RT-qPCR. Results: We identified 8 Mo/Mp clusters. As a particular subtype among them, COL3A1+ Mp (CD68+, COL3A1+, ACTA2-) enriched in myeloid pathotype and negatively correlated with RA severity metrics in all pathotypes. Flow cytometry and multicolor immunofluorescence evidenced the enrichment and M2-like phenotype of COL3A1+ Mp in the myeloid pathotype. Further assays suggested that COL3A1+ Mp potentially attenuates RA severity via expressing anti-inflammatory cytokines, enhancing Mp adhesion, and forming a physical barrier at the synovial lining. Conclusion: This study reported unexplored associations between different pathologies and myeloid cell subtypes. We also identified a fibroblast-and-M2-like cluster named COL3A1+ Mp, which potentially contributes to synovial immune homeostasis. Targeting the development of COL3A1+ Mp may hold promise for inducing RA remission.


Subject(s)
Arthritis, Rheumatoid , Synoviocytes , Synovitis , Humans , Synovitis/metabolism , Macrophages , Synoviocytes/metabolism , Phenotype , Collagen Type III
4.
J Cosmet Dermatol ; 23(6): 2270-2278, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38634239

ABSTRACT

BACKGROUND: Ultraviolet radiation causes skin photoaging by producing a variety of enzymes, which impact both skin health and hinder beauty. Currently, the early diagnosis and treatment of photoaging remain a challenge. Bioinformatics analysis has strong advantages in exploring core genes and the biological pathways of photoaging. AIMS: To screen and validate key risk genes associated with plasminogen in photoaging and to identify potential target genes for photoaging. METHODS: Two human transcriptome datasets were obtained by searching the Gene Expression Omnibus (GEO) database, and the mRNAs in the GSE131789 dataset were differentially analyzed, and then the weighted gene co-expression network analysis (WGCNA) was performed to find out the strongest correlations. Template genes, interaction analysis of differentially expressed genes (DEGs), modular genes with the most WGCNA correlations, and genecard database genes related to plasminogen were performed, and further Kyoto genes and Genome Encyclopedia (KEGG) pathway analysis. Two different algorithms, least absolute shrinkage and selection operator (LASSO) and support vector machines-recursive feature elimination (SVM-RFE), were used to find key genes. Then the data set (GSE206495) was validated and analyzed. Real-time PCR was performed to validate the expression of key genes through in vitro cellular experiments. RESULTS: IFI6, IFI44L, HRSP12, and BMP4 were screened from datasets as key genes for photoaging and further analysis showed that these genes have significant diagnostic value for photoaging. CONCLUSION: IFI6, IFI44L, HRSP12, and BMP4 play a key role in the pathogenesis of photoaging, and serve as promising potential predictive biomarkers for photoaging.


Subject(s)
Computational Biology , Plasminogen , Skin Aging , Humans , Skin Aging/genetics , Skin Aging/radiation effects , Plasminogen/genetics , Ultraviolet Rays/adverse effects , Transcriptome , Gene Expression Profiling , Genes, Regulator/genetics , Databases, Genetic , Support Vector Machine , Gene Regulatory Networks , Skin/radiation effects , Skin/metabolism
5.
Org Lett ; 26(13): 2523-2528, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38536882

ABSTRACT

A migratory insertion of carbenes into distal γ-C(sp3)-H bonds of aliphatic amines has been successfully developed. The synergistic interplay among a palladium catalyst, picolinamide directing group, a carefully selected base additive, and an essential ligand proved crucial in achieving high yields. These findings hold significant value for advancing the exploration of regioselective carbene insertions into nonactivated C(sp3)-H bonds.

6.
Genes (Basel) ; 15(3)2024 Mar 02.
Article in English | MEDLINE | ID: mdl-38540386

ABSTRACT

Nitrogen (N) is one of the essential nutrients for the growth and development of crops. The adequate application of N not only increases the yield of crops but also improves the quality of agricultural products, but the excessive application of N can cause many adverse effects on ecology and the environment. In this study, genome-wide association analysis (GWAS) was performed under low- and high-N conditions based on 788,396 SNPs and phenotypic traits relevant to N uptake and utilization (N content and N accumulation). A total of 75 QTLs were obtained using GWAS, which contained 811 genes. Of 811 genes, 281 genes showed different haplotypes, and 40 genes had significant phenotypic differences among different haplotypes. Of these 40 genes, 5 differentially expressed genes (Os01g0159250, Os02g0618200, Os02g0618400, Os02g0630300, and Os06g0619000) were finally identified as the more valuable candidate genes based on the transcriptome data sequenced from Longjing31 (low-N-tolerant variety) and Songjing 10 (low-N-sensitive variety) under low- and high-N treatments. These new findings enrich the genetic resources for N uptake and utilization in rice, as well as lay a theoretical foundation for improving the efficiency of N uptake and utilization in rice.


Subject(s)
Oryza , Seedlings , Seedlings/genetics , Chromosome Mapping , Oryza/genetics , Genome-Wide Association Study , Nitrogen , Crops, Agricultural/genetics
7.
Front Microbiol ; 15: 1308871, 2024.
Article in English | MEDLINE | ID: mdl-38328429

ABSTRACT

Background: The microbiome plays a pivotal role in mediating immune deviation during the development of early-life viral infections. Recurrent infections in children are considered a risk factor for disease development. This study delves into the metagenomics of the microbiome in children suffering from severe infections, seeking to identify potential sources of these infections. Aims: The aim of this study was to identify the specific microorganisms and factors that significantly influence the treatment duration in patients suffering from severe infections. We sought to understand how these microbial communities and other variables may affect the treatment duration and the use of antibiotics of these patients with severe infections. Method: Whole-genome shotgun sequencing was conducted on samples collected from children aged 0-14 years with severe infections, admitted to the Pediatrics Department of Xiamen First Hospital. The Kraken2 algorithm was used for taxonomic identification from sequence reads, and linear mixed models were employed to identify significant microorganisms influencing treatment duration. Colwellia, Cryptococcus, and Citrobacter were found to significantly correlate with the duration of clinical treatment. Further analysis using propensity score matching (PSM) and rank-sum test identified clinical indicators significantly associated with the presence of these microorganisms. Results: Using a linear mixed model after removed the outliers, we identified that the abundance of Colwellia, Cryptococcus, and Citrobacter significantly influences the treatment duration. The presence of these microorganisms is associated with a longer treatment duration for patients. Furthermore, these microorganisms were found to impact various clinical measures. Notably, an increase in hospitalization durations and medication costs was observed in patients with these microorganisms. In patients with Colwellia, Cryptococcus, and Citrobacter, we discover significant differences in platelets levels. We also find that in patients with Cryptococcus, white blood cells, hemoglobin, and neutrophils levels are lower. Conclusion: These findings suggest that Colwellia, Cryptococcus, and Citrobacter, particularly Cryptococcus, could potentially contribute to the severity of infections observed in this cohort, possibly as co-infections. These microorganisms warrant further investigation into their pathogenic roles and mechanisms of action, as their presence in combination with disease-causing organisms may have a synergistic effect on disease severity. Understanding the interplay between these microorganisms and pathogenic agents could provide valuable insights into the complex nature of severe pediatric infections and guide the development of targeted therapeutic strategies.

8.
J Dermatolog Treat ; 35(1): 2309305, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38297481

ABSTRACT

Background: Psoriatic patients tend to develop metabolic syndrome (MS). MS accelerates psoriasis, but the exact molecular mechanisms are poorly understood.Objectives: We aim to investigate the impact of leptin on keratinocyte insulin sensitivity and explore its underlying molecular mechanism, which might play a role in the pathogenesis of this disease.Methods: ELISA and immunohistochemistry were applied respectively to detect the level of leptin in serum and in lesion of psoriatic patients with and without MS. The HaCaT cell line was cultured and western-blot assay was performed to assess the change of insulin sensibility. q-PCR and western-blot assay were applied to detect the SOCS3 expressions. Knockdown of SOCS3 were generated in HaCaT cell line by siRNA. Leptin and insulin were treated for 6 days and K10 expression was evaluated by western-blot assay.Results: Patients with MS had higher level of leptin in serum and lesions than their counterparts without MS. Serum levels of leptin was negatively correlated to PASI decline index in psoriatic patients. Long-term treatment of leptin induced insulin resistance in HaCaT cell line, as indicated by elevated expression of p-IRS-1 (ser636) and lower p-PKB (ser473). Leptin treatment up-regulated the mRNA and protein expression of SOCS3. Knockdown of SOCS3 blocked the effect of leptin-induced insulin resistance. Leptin treatment attenuated insulin-elicited K10 expression.Conclusions: Leptin induces insulin resistance by upregulating SOCS3 and give rise to differentiation disorder of keratinocyte. Insulin resistance may serve as a target for anti-psoriatic therapies.


Subject(s)
Insulin Resistance , Insulins , Metabolic Syndrome , Psoriasis , Humans , Leptin , Psoriasis/chemically induced , Keratinocytes , Insulins/adverse effects , Insulins/metabolism
9.
Br J Dermatol ; 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38366639

ABSTRACT

BACKGROUND: Xeligekimab is a fully human monoclonal antibody that selectively neutralizes IL-17A and had shown potential efficacy in preliminary trials. OBJECTIVE: To evaluate the efficacy and safety of Xeligekimab in Chinese patients with moderate-to-severe psoriasis. METHODS: A total of 420 Chinese patients were randomized to 200 mg Xeligekimab every 2 weeks (n = 281) or placebo (n = 139) for the first 12 weeks, followed by extending the treatment schedule to GR1501 every 4 weeks for further 40 weeks. Efficacy was assessed by evaluating the Physician's Global Assessment (PGA) 0/1 and Psoriasis Area and Severity Index (PASI) 75/90/100 improvement. The safety profile was also evaluated. RESULTS: At week 12, The PASI 75/90/100 were achieved in 90.7%/74.4%/30.2%% patients in GR1501 group compared with 8.6%/1.4%/0% patients in placebo group, respectively. The PGA 0/1 were achieved in 74.4% patients of GR1501 group and 3.6% patients in placebo group, respectively. The PASI 75 and PGA 0/1 maintained until week 52. No unexpected adverse events were observed. CONCLUSION: Xeligekimab showed high efficacy and is well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.

10.
Clin Cosmet Investig Dermatol ; 17: 365-382, 2024.
Article in English | MEDLINE | ID: mdl-38352064

ABSTRACT

Background: Psoriasis is a frequent form of chronic inflammation in dermatology that is unmistakably linked to the metabolic syndrome (MetS) and its elements. This study was to explore the current status and new developments in the global research, and the holistic landscape of this field more intuitively through bibliometric analysis of scientific output and activity. Methods: Publications regarding psoriasis and MetS were searched and chosen from the database of the Web of Science Core Collection. Excel 2019, VOSviewer, and CiteSpace software were utilized to conduct bibliometric analysis. Results: There were 1096 publications included. The scientific outputs in this field had increased from 2004 to 2022, and the expansion could continue in the following years. The United States contributed the most publications (241, 21.99%) and had the most citation frequency (13,489 times). The University of California System was the most productive affiliation. Girolomoni G., Armstrong A.W., Gisondi P. and Gelfand J.M. were key and influential researchers. Journal of the European Academy of Dermatology and Venereology published the greatest number of articles (65 articles). By analyzing keyword frequency and clustering, we have identified the following areas of research interest and frontiers: prevalence, risk, association, gene expression, waist circumference, adipose tissue inflammation, vascular inflammation, cardiovascular disease, psoriatic arthritis, and fibrosis. Conclusion: This bibliometric analysis elucidates research domain of psoriasis and MetS, portraying present hotspots and future emerging trends. This field has generated significant interest and displays potential for further growth. The United States has made distinguished contributions, and currently dominates this field.

11.
Photodiagnosis Photodyn Ther ; 45: 103962, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38211778

ABSTRACT

Inflammatory pseudotumour (IP) is a rare proliferative disease characterized by a dense infiltrate of plasma cells, lymphocytes, eosinophils and neutrophils in the fibrous stroma. It primarily affects the lungs of pediatric patients or young adults. Cutaneous IP is an extremely rare condition, with limited documentation in the English literature. In this case report, we presented an unusual instance of a 62-year-old male endured recalcitrant cutaneous IP for 8 years and exhibited poor response to topical glucocorticoid therapy, as well as intralesional injections of pingyangmycin and/or corticosteroid. Notably, after undergoing four sessions of 5-aminolevulinic acid photodynamic therapy (ALA-PDT), the patient experienced a significant reduction in erythema and nodules. This observation suggests that ALA-PDT may represent a promising and safe treatment option for cutaneous IP.


Subject(s)
Granuloma, Plasma Cell , Photochemotherapy , Male , Young Adult , Humans , Child , Middle Aged , Photochemotherapy/methods , Photosensitizing Agents/therapeutic use , Granuloma, Plasma Cell/drug therapy , Aminolevulinic Acid/therapeutic use , Skin
12.
Sci Rep ; 14(1): 2167, 2024 01 25.
Article in English | MEDLINE | ID: mdl-38272954

ABSTRACT

Parkinson's disease (PD) is a progressive neurodegenerative disease whose etiology is attributed to development of Lewy bodies and degeneration of dopaminergic neurons in the substantia nigra (SN). Currently, there are no definitive diagnostic indicators for PD. In this study, we aimed to identify potential diagnostic biomarkers for PD and analyzed the impact of immune cell infiltrations on disease pathogenesis. The PD expression profile data for human SN tissue, GSE7621, GSE20141, GSE20159, GSE20163 and GSE20164 were downloaded from the Gene Expression Omnibus (GEO) database for use in the training model. After normalization and merging, we identified differentially expressed genes (DEGs) using the Robust rank aggregation (RRA) analysis. Simultaneously, DEGs after batch correction were identified. Gene interactions were determined through venn Diagram analysis. Functional analyses and protein-protein interaction (PPI) networks were used to the identify hub genes, which were visualized through Cytoscape. A Lasso Cox regression model was employed to identify the potential diagnostic genes. The GSE20292 dataset was used for validation. The proportion of infiltrating immune cells in the samples were determined via the CIBERSORT method. Sixty-two DEGs were screened in this study. They were found to be enriched in nerve conduction, dopamine (DA) metabolism, and DA biosynthesis Gene Ontology (GO) terms. The PPI network and Lasso Cox regression analysis revealed seven potential diagnostic genes, namely SLC18A2, TAC1, PCDH8, KIAA0319, PDE6H, AXIN1, and AGTR1, were subsequently validated in peripheral blood samples obtained from healthy control (HC) and PD patients, as well as in the GSE20292 dataset. The results revealed the exceptional sensitivity and specificity of these genes in PD diagnosis and monitoring. Moreover, PD patients exhibited a higher number of plasma cells, compared to HC individuals. The SLC18A2, TAC1, PCDH8, KIAA0319, PDE6H, AXIN1, and AGTR1 are potential diagnostic biomarkers for PD. Our findings also reveal the essential roles of immune cell infiltration in both disease onset and trajectory.


Subject(s)
Neurodegenerative Diseases , Parkinson Disease , Humans , Transcriptome , Gene Regulatory Networks , Parkinson Disease/diagnosis , Parkinson Disease/genetics , Parkinson Disease/metabolism , Neurodegenerative Diseases/metabolism , Proteins/metabolism , Biomarkers/metabolism , Substantia Nigra/metabolism , Gene Expression Profiling/methods
14.
J Orthop Surg Res ; 18(1): 826, 2023 Nov 02.
Article in English | MEDLINE | ID: mdl-37919746

ABSTRACT

BACKGROUND: Knee injuries are prevalent, and early diagnosis is crucial for guiding clinical therapy. MRI is the diagnostic gold standard for bone marrow edema (BME) in patients with acute knee injuries, yet there are still limitations. Dual-energy CT, a possible viable replacement, is being explored (DECT). METHODS: We systematically retrieved studies from EMBASE, Scopus, PUBMED, and the Cochrane Library and collected gray literatures. In accordance with the PRISMA-DTA standards, a systematic review was conducted between the study's initiation and July 31, 2021, utilizing an MRI reference standard and at least 10 adult patients with acute knee injuries to evaluate the diagnostic effectiveness of DECT for diagnosing BME. Two reviewers collected the study's details independently. For the meta-analysis, a bivariate mixed-effects regression model was utilized, and subgroup analysis was employed to determine the sources of variability. RESULTS: The research included nine studies that examined 290 individuals between the ages of 23 and 53 with acute knee injuries who had DECT and MRI. Overall, the sensitivity, specificity, and AUC of the BME were 85% (95% confidence interval [CI]: 77-90%), 96% (95% CI: 93-97%), and 0.97 (95% CI: 0.95-0.98), respectively. To account for the assumed diversity of research, there were no statistically significant differences between the comparison groups in terms of specificity and sensitivity. CONCLUSION: DECT is a viable alternative to MRI for individuals with acute knee injuries when MRI is inappropriate or unavailable.


Subject(s)
Bone Marrow Diseases , Knee Injuries , Adult , Humans , Young Adult , Middle Aged , Bone Marrow , Sensitivity and Specificity , Tomography, X-Ray Computed , Bone Marrow Diseases/diagnostic imaging , Bone Marrow Diseases/etiology , Knee Injuries/complications , Knee Injuries/diagnostic imaging , Edema/diagnostic imaging , Edema/etiology , Magnetic Resonance Imaging
15.
Cancer Cell Int ; 23(1): 196, 2023 Sep 05.
Article in English | MEDLINE | ID: mdl-37670275

ABSTRACT

BACKGROUND: The prognosis of tumor patients can be assessed by measuring the levels of lncRNAs (long non-coding RNAs), which play a role in controlling the methylation of the RNA. Prognosis in individuals with colorectal adenocarcinoma (CRC) is strongly linked to lncRNA expression, making it imperative to find lncRNAs that are associated with RNA methylation with strong prognostic value. METHODS: In this study, by analyzing TCGA dataset, we were able to develop a risk model for lncRNAs that are associated with m5C with prognostic significance by employing LASSO regression and univariate Cox proportional analysis. There were a number of methods employed to ensure the model was accurate, including multivariate and univariate Cox regression analysis, Kaplan analysis, and receiver operating characteristic curve analysis. The principal component analysis, GSEA and GSVA analysis were used for risk model analysis. The CIBERSORT instrument and the TIMER database were used to evaluate the link between the immune cells that infiltrate tumors and the risk model. In vitro experiments were also performed to validate the predicted m5C-related significant lncRNAs. RESULTS: The m5c regulators were differentially expressed in colorectal cancer and normal tissue. Based on the screening criteria and LASSO regression, 11 m5c-related lncRNAs were identified for developing the prognostic risk model. Multivariate and univariate Cox regression analysis showed the risk score is a crucial prognostic factor in CRC patients. The 1-year, 3-year, and 5-year AUC curves showed the risk score was higher than those identified for other clinicopathological characteristics. A nomogram using the risk score as a quantitative tool was developed for predicting patients' outcomes in clinical settings. In addition, the risk profile of m5C-associated lncRNAs can discriminate between tumor immune cells' characteristics in CRC. Mutation patterns and chemotherapy were analyzed between high- and low- risk groups of CRC patients. Moreover, TNFRSF10A-AS1 was chosen for the in vitro verification of the m5C-connected lncRNA to demonstrate impressive effects on the proliferation, migration and invasion of CRC cells. CONCLUSION: A risk model including the prognostic value of 11 m5C-associated lncRNAs proves to be a useful prognostic tool for CRC and improves the care of patients suffering from CRC based on these findings.

16.
Front Endocrinol (Lausanne) ; 14: 1154741, 2023.
Article in English | MEDLINE | ID: mdl-37538794

ABSTRACT

Background: Breast cancer (BRCA) has become the most diagnosed cancer worldwide for female and seriously endanger female health. The epithelial-mesenchymal transition (EMT) process is associated with metastasis and drug resistance in BRCA patients. However, the prognostic value of EMT-related lncRNA in BRCA still needs to be revealed. The aim of this study is to construct an EMT-related lncRNA (ERL) signature with accuracy predictive ability for the prognosis of BRCA patients. Methods: RNA-seq expression data and Clinical characteristics obtained from the TCGA (The Cancer Genome Atlas) were used in the study. First, we identified the EMT-related lncRNA by the Pearson correlation analysis. An EMT-related lncRNAs prognostic risk signature was constructed using univariate Cox regression and Lasso-penalized Cox regression analyses. The model's performance was validated using Kaplan-Meier (KM) survival analysis, ROC curve and C-index. Finally, a nomogram was constructed for clinical practice in evaluating the patients with BRCA and validated by calibration curve and decision curve analysis (DCA). We also evaluated the drug sensitivity of signature lncRNA and the tumor immune cell infiltration in breast cancer. Results: We constructed a 10-lncRNA risk score signature based on the lncRNAs associated with the EMT process. We could assign BRCA patients to the high- and low-risk group according to the median risk score. The prognostic risk signature showed excellent accuracy and demonstrated sufficient independence from other clinical characteristics. The immune cell infiltration analysis showed that the prognostic risk signature was related to the infiltration of the immune cell subtype. Drug sensitivity analysis proved ERLs signature could effectively predict the sensitivity of patients to common chemotherapy drugs in BRCA and provide guidance for chemotherapy drugs for high-risk and low-risk patients. Conclusion: Our ERL signature and nomogram have excellent prognostic value and could become reliable tools for clinical guidance.


Subject(s)
Breast Neoplasms , RNA, Long Noncoding , Humans , Female , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , RNA, Long Noncoding/genetics , Epithelial-Mesenchymal Transition/genetics , Women's Health , Drug Resistance
17.
Clin Cosmet Investig Dermatol ; 16: 2297-2307, 2023.
Article in English | MEDLINE | ID: mdl-37641663

ABSTRACT

Purpose: The underlying pathophysiology linking psoriasis vulgaris (PV) and metabolic syndrome (MetS) is not fully understood. The present study aimed to investigate the serum level of interleukin (IL)-9 and tissue levels of IL-9 and its receptor in PV patients with MetS and analyze the correlation of IL-9 levels with psoriasis disease severity and MetS. Methods: This study enrolled 75 PV patients with MetS, 57 PV patients without MetS, 20 healthy blood donors, and 7 healthy skin donors. Clinical, socio-demographic, and anthropometric data were obtained from all individuals. Fasting blood glucose, insulin, lipid profile levels, and serum levels of IL-9 and IL-17A were measured. The expression of IL-9 and its receptor in skin specimens in PV patients and healthy controls was determined using immunohistochemistry. Normal human epidermal keratinocytes were stimulated with five pro-inflammatory cytokines (tumor necrosis factor-α, oncostatin M, IL-22, IL-17A, and IL-1α) to establish a psoriatic keratinocyte model and subsequently treated with IL-9. Their mRNA levels of antimicrobial peptides and chemokines were measured using quantitative real-time polymerase chain reaction. Results: Serum level of IL-9 and tissue levels of IL-9 and its receptor were upregulated in PV patients with MetS. IL-9 level was positively correlated to IL-17A level; however, no significant correlation of IL-9 level with psoriasis area severity index was observed. IL-9 level had a positive correlation with the presence of MetS and its components. Correspondingly, IL-9 level positively correlated with waist circumference, body mass index, homeostasis model assessment-insulin resistance, blood pressure, and triglyceride level and negatively correlated with high-density lipoprotein cholesterol level. Additionally, IL-9 stimulated the expression of antimicrobial peptides and chemokines in a psoriatic keratinocyte model. Conclusion: Our findings confirmed that higher IL-9 level is associated with PV complicated by MetS, suggesting that IL-9 may be a link between PV and MetS.

18.
Nanomaterials (Basel) ; 13(13)2023 Jun 30.
Article in English | MEDLINE | ID: mdl-37446500

ABSTRACT

Plasmonic effect-enhanced Z-type heterojunction photocatalysts comprise a promising solution to the two fundamental problems of current TiO2-based photocatalysis concerning low-charge carrier separation efficiency and low utilization of solar illumination. A plasmonic effect-enhanced TiN@anatase-TiO2/rutile-TiO2 Z-type heterojunction photocatalyst with the strong interface of the N-O chemical bond was synthesized by hydrothermal oxidation of TiN. The prepared photocatalyst shows desirable visible light absorption and good visible-light-photocatalytic activity. The enhancement in photocatalytic activities contribute to the plasma resonance effect of TiN, the N-O bond-connected charge transfer channel at the TiO2/TiN heterointerface, and the synergistically Z-type charge transfer pathway between the anatase TiO2 (A-TiO2) and rutile TiO2 (R-TiO2). The optimization study shows that the catalyst with a weight ratio of A-TiO2/R-TiO2/TiN of approximately 15:1:1 achieved the best visible light photodegradation activity. This work demonstrates the effectiveness of fabricating plasmonic effect-enhanced Z-type heterostructure semiconductor photocatalysts with enhanced visible-light-photocatalytic activities.

19.
Breast Cancer ; 30(6): 965-975, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37470943

ABSTRACT

BACKGROUND: HER2-low breast cancer (BC) is proposed to be a special population of patients with an immunohistochemistry (IHC) score of 1 + or 2 + and non-amplified in situ hybridization (ISH) results. The role and prognostic impact of HER2-low BC is still controversial. This meta-analysis aims to explore the prognostic difference between of HER2-low and HER2-zero characteristic in BC patients. METHODS: A meta-analysis was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and eligible studies were search in PubMed, Web of Science and EMBASE databases. Quality assessment of included studies were performed by Quality in Prognostic Studies (QUIPS) tool. Hazard ratios (HRs) and corresponding 95% confidence interval (CI) for overall survival (OS) and disease-free survival (DFS) were pooled in a meta-analysis. Furthermore, subgroup analysis, sensitivity analysis, and analysis for publication bias were conducted. RESULTS: Eighteen studies comprising a total of 93,317 patients were included for meta-analysis. BC patients with HER2-low characteristic have longer OS (HRs 0.87, 95% CI 0.81-0.93, p < 0.0001) and DFS (HRs 0.82, 95% CI 0.73-0.93, p = 0.001) compared to those with HER2-zero characteristic. Subgroup analysis indicate that the source of heterogeneity may come from the hormone receptor (HR) status group. Although, the publication bias was detected, sensitivity analysis and the trim-and-fill method analysis demonstrated the stability and reliability of the results. CONCLUSION: HER2-low BC patients have longer OS and DFS compared to HER2-zero BC patients, and its prognostic value is consistent among different HR status patients. Whether HER2-low breast cancer is an independent subtype of breast cancer is still a subject of ongoing research, and more studies are needed to fully understand the molecular and clinical features of this subtype.


Subject(s)
Breast Neoplasms , Humans , Female , Reproducibility of Results , Prognosis , Proportional Hazards Models , Disease-Free Survival
20.
J Surg Res ; 290: 126-132, 2023 10.
Article in English | MEDLINE | ID: mdl-37263083

ABSTRACT

INTRODUCTION: To compare the overall morbidity and recurrence of papillary thyroid cancer (PTC) after total thyroidectomy (TT) with or without prophylactic central compartment neck dissection (CCND) in cases of both preoperative and intraoperative nonsuspicious central lymph nodes (CLNs). METHODS: A total of 570 PTC patients who harbored no preoperative and intraoperative suspicious CLNs at two institutions were enrolled. They were randomly assigned to TT alone or TT with prophylactic CCND (pCCND) after intraoperative assessment of CLNs during the surgery. Lymph nodes that were hard or large enough to be palpated were regarded as suspicious metastatic lymph nodes during the surgery. The characteristics, postoperative complications, and locoregional recurrence of the two groups were recorded and compared. RESULTS: With a median follow-up of 5 y, the rates of lymph node recurrence in the TT alone and TT with pCCND groups were similar (7.3% versus 4.6%, P = 0.247), but there were significantly higher rates of overall morbidity (6.6% versus 19.1%, P < 0.001) when pCCND was performed. CONCLUSIONS: pCCND is not recommended for patients with clinically node-negative PTC preoperatively and intraoperatively because of the high complication rate and lack of benefit of reducing recurrence.


Subject(s)
Carcinoma, Papillary , Surgeons , Thyroid Neoplasms , Humans , Carcinoma, Papillary/surgery , Carcinoma, Papillary/pathology , Lymph Nodes/pathology , Neck Dissection/adverse effects , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/prevention & control , Neoplasm Recurrence, Local/pathology , Retrospective Studies , Thyroid Cancer, Papillary/surgery , Thyroid Cancer, Papillary/pathology , Thyroid Neoplasms/surgery , Thyroid Neoplasms/pathology , Thyroidectomy/adverse effects , Thyroidectomy/methods
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