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Molecular editing promises to facilitate the rapid diversification of complex molecular architectures by rapidly and conveniently altering core frameworks. This approach has the potential to accelerate both drug discovery and total synthesis. In this study, we present a novel protocol for the molecular editing of pyrroles. Initially, N-Boc pyrroles and alkynes are converted into N-bridged compounds through a Diels-Alder reaction. These compounds then undergo deprotection of the Boc group, nitrosylation, and cheletropic N2O extrusion to yield benzene or naphthalene products. By using benzyne as a substrate, this method can be conceptually viewed as a fusion of skeletal editing of the pyrrole ring and site-selective peripheral editing of the benzene ring. Furthermore, this proof-of-concept protocol has demonstrated its potential to transform the (hetero)arene motif from commercially available drugs, offering the possibility of generating new biologically active compounds.
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BACKGROUND: The relationship between thyroid hormone (TH) levels in vivo and osteoarthritis (OA) remains inconclusive. This study aims to investigate the association between TH levels and OA, analyze the effect of triiodothyronine on hypertrophic chondrocyte differentiation and OA progression, and identify potential target genes of triiodothyronine in OA to evaluate its diagnostic value. METHODS: Two-sample mendelian randomization method was used to probe the causal links between hyperthyroidism and OA. Differentially expressed genes (DEGs) from two RNA-sequencing data in Gene Expression Omnibus (GSE199847 and GSE114007) and enrichment analysis of DEGs (166 commonly upregulated genes and 71 commonly downregulated genes of GSE199847 and GSE114007) was performed to analyze the effect of triiodothyronine (T3) on hypertrophic chondrocyte differentiation and OA. C28/I2 cells treated with T3 and reverse transcription and quantitative real-time polymerase chain reaction were used to validate T3 targeted genes. The diagnostic performance of target genes was assessed by the receiver operating characteristic (ROC) curve and area under the curve (AUC). RESULTS: There was a positive causal association between hyperthyroidism and OA (IVW result, OR = 1.330, 95% CI 1.136-1.557, P = 0.0004). Weighted median and Weighted mode analysis also demonstrated that hyperthyroidism had a positive causal association with OA (p < 0.05, OR > 1). Bioinformatics analysis indicated T3 can partially induce the emergence of late hypertrophic chondrocyte and promote OA through extracellular matrix organization, blood vessel development, skeletal system development and ossification. Post-T3 treatment, MAFB, C1QTNF1, COL3A1 and ANGPTL2 were significantly elevated in C28/I2 cells. ROC curves in GSE114007 showed that AUC of all above genes were ≥ 0.7. CONCLUSIONS: This study identified that hyperthyroidism has a positive causal association with OA by MR analysis. T3 induced hypertrophic chondrocytes promote OA progression by upregulating genes such as MAFB, C1QTNF1, COL3A1 and ANGPTL2, which can also serve as OA diagnosis.
Subject(s)
Hyperthyroidism , Mendelian Randomization Analysis , Osteoarthritis , Sequence Analysis, RNA , Triiodothyronine , Mendelian Randomization Analysis/methods , Osteoarthritis/genetics , Humans , Hyperthyroidism/genetics , Hyperthyroidism/complications , Triiodothyronine/blood , Sequence Analysis, RNA/methods , Chondrocytes/metabolism , Cell Differentiation/genetics , Disease ProgressionABSTRACT
The mechanism linking psoriasis to metabolic syndrome (MetS) remains poorly understood. Recent reports indicate upregulation of glycolysis-related proteins in psoriatic keratinocytes (KCs). However, the role of glucose metabolism reprogramming in psoriatic KCs, psoriasis, and psoriasis with MetS remains unclear. In this study, we confirmed glucose metabolism reprogramming in psoriatic KCs by examining glycolysis-related genes, proteins, and metabolites. We found that inhibiting glucose metabolism reprogramming in psoriasiform KCs led to improvements in psoriasiform features. Notably, we observed enhanced glucose metabolism reprogramming in KCs within psoriatic skin lesions of patients with MetS. In vitro, high-glucose and high-fat culture intensified glucose metabolism reprogramming in psoriasiform KCs partially via the AKT/mTOR pathway. These findings highlight a strong link between the glycolytic switch and KC function and suggest that glucose metabolism reprogramming in KCs contributes to heightened psoriatic inflammation in MetS.
Subject(s)
Glucose , Glycolysis , Keratinocytes , Metabolic Syndrome , Psoriasis , TOR Serine-Threonine Kinases , Psoriasis/metabolism , Humans , Keratinocytes/metabolism , Metabolic Syndrome/metabolism , Glucose/metabolism , TOR Serine-Threonine Kinases/metabolism , Cells, Cultured , Male , Proto-Oncogene Proteins c-akt/metabolism , Female , Signal Transduction , Middle Aged , Cellular Reprogramming , Adult , Skin/pathology , Skin/metabolism , Metabolic ReprogrammingABSTRACT
INTRODUCTION: Despite numerous treatment options for nail lichen planus (NLP), a validated method for measuring the severity of NLP and therapeutic response in clinical trials is absent. The aim of the study was to develop and validate a measurement instrument, Typical Nail Lichen Planus Severity Index (tNLPSI), for typical NLP that could be used in clinical trials. METHODS: A total of 48 patients pathologically confirmed with typical NLP were enrolled in this study. Five dermatologists were trained to use the tNLPSI activity scale and the Physician's Global Assessment (PGA) scale to score samples independently to estimate inter-rater and intra-rater reliability across two sessions. In addition, tNLPSI activity scores were compared with PGA scores to assess the construct validity. RESULTS: The tNLPSI activity scale had excellent internal consistency and inter-rater reliability (Cronbach's alpha 0.990; ICC = 0.954; 95% CI = 0.930-0.971), and the correlations between the different graders' scores indicate good consistency (rp = 0.934-0.968). In addition, the tNLPSI activity scale demonstrated high intra-rater reliability (ICC = 0.996; 95% CI = 0.993-0.998), showing good reproducibility. And tNLPSI activity scores and PGA scores showed good construct validity (Spearman's rho = 0.941 and Spearman's rho = 0.903-0.935, respectively; p < 0.01). CONCLUSION: The tNLPSI activity scale was demonstrated to be consistent, reliable, reproducible, and feasible, making it a potential valuable tool for evaluating the treatment response in typical NLP clinical trials.
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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/methodsABSTRACT
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/immunologyABSTRACT
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 IIIABSTRACT
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/metabolismABSTRACT
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.
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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/geneticsABSTRACT
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.
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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.
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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/metabolismABSTRACT
BACKGROUND: Xeligekimab (GR1501) is a fully human monoclonal antibody that selectively neutralizes interleukin (IL)-17A and has shown potential efficacy in treating moderate-to-severe psoriasis in preliminary trials. OBJECTIVES: 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 200â mg xeligekimab every 2 weeks (n = 281) or placebo (n = 139) for the first 12 weeks, followed by an extension of the treatment schedule to xeligekimab every 4 weeks for a further 40 weeks. Efficacy was assessed by evaluating achievement of Physician Global Assessment (PGA) 0/1 and 75%, 90% and 100% improvement in Psoriasis Area and Severity Index (PASI 75, PASI 90 and PASI 100, respectively). The safety profile was also evaluated. RESULTS: At week 12, PASI 75, PASI 90 and PASI 100 were achieved in 90.7%, 74.4% and 30.2% of patients in the xeligekimab group vs. 8.6%, 1.4% and 0% of patients in the placebo group, respectively. PGA 0/1 was achieved in 74.4% patients in the xeligekimab group and 3.6% of patients in the placebo group. PASI 75 and PGA 0/1 were maintained until week 52. No unexpected adverse events were recorded. CONCLUSIONS: Xeligekimab showed high efficacy and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.
Psoriasis is a skin disease characterized by scaly and raised patches of skin on any part of the body. The condition can be caused by a combination of how a person's immune system works, their genes and their environment. A cytokine is a substance secreted by certain cells of the immune system that have an effect on other cells. One such cytokine, called IL-17A, has been associated with different inflammatory diseases, including psoriasis. We conducted a large trial in Chinese people with moderate-to-severe psoriasis to look at the efficacy (ability to produce the intended result) and safety of a medicine called xeligekimab (known as a 'monoclonal antibody') which works by targeting IL-17A. We randomly assigned 420 Chinese patients to receive 200â mg of xeligekimab every 2 weeks or a 'placebo' (no active medicine) for the first 12 weeks. We extended the treatment schedule of xeligekimab to every 4 weeks for a further 40 weeks. To assess how the medicine worked, we measured people's psoriasis symptoms and severity. To assess how safe the medicine was, we looked at the side-effects (or 'adverse events'). The results of this trial showed that xeligekimab improved people's psoriasis and itching starting at week 4 of receiving treatment, and more than 60% of people achieved improvement or remission by week 6, which was sustained up to week 52. The safety of xeligekimab was similar to another medicine classed as a monoclonal antibody (called secukinumab) and there were no new or unexpected adverse events reported. Overall, our findings suggest that xeligekimab is a safe and effective medicine for the treatment of psoriasis in Chinese people.
Subject(s)
Antibodies, Monoclonal, Humanized , Psoriasis , Humans , Psoriasis/drug therapy , Male , Double-Blind Method , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/administration & dosage , Female , Middle Aged , Adult , Treatment Outcome , Dermatologic Agents/adverse effects , Dermatologic Agents/therapeutic use , Dermatologic Agents/administration & dosage , Drug Administration Schedule , Interleukin-17/antagonists & inhibitors , Severity of Illness Index , Aged , Young AdultABSTRACT
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/methodsABSTRACT
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 , SkinABSTRACT
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 ImagingSubject(s)
Azetidines , Lichen Planus , Nail Diseases , Humans , Azetidines/therapeutic use , Janus Kinase 1 , Lichen Planus/drug therapy , Purines/therapeutic use , Male , AdultABSTRACT
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.
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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.