Integration of clinical characteristics and molecular signatures of the tumor microenvironment to predict the prognosis of neuroblastoma
This study aimed to analyze the clinical characteristics, cell types, and molecular characteristics of the tumor microenvironment to better predict the prognosis of neuroblastoma (NB). The gene expression data and corresponding clinical information of 498 NB patients were obtained from the Gene Expression Omnibus (GEO: GSE62564) and ArrayExpress (accession: E-MTAB-8248). The relative cell abundances were estimated using single-sample gene set enrichment analysis (ssGSEA) with th e R gene set variation analysis (GSVA) package. We performed Cox regression analyses to identify marker genes indicating cell subsets and combin...
Source: Journal of Molecular Medicine - September 15, 2023 Category: Molecular Biology Source Type: research
MicroRNA signature from extracellular vesicles of HCV/HIV co-infected individuals differs from HCV mono-infected
AbstractHepatitis C virus (HCV) coinfection with human immunodeficiency virus (HIV) has a detrimental impact on disease progression. Increasing evidence points to extracellular vesicles (EVs) as important players of the host-viral cross-talk. The microRNAs (miRNAs), as essential components of EVs cargo, are key regulators of normal cellular processes and also promote viral replication, viral pathogenesis, and disease progression. We aimed to characterize the plasma-derived EVs miRNA signature of chronic HCV infected and HIV coinfected patients to unravel the molecular mechanisms of coinfection. EVs were purified and charac...
Source: Journal of Molecular Medicine - September 14, 2023 Category: Molecular Biology Source Type: research
Insufficient SIRT1 in macrophages promotes oxidative stress and inflammation during scarring
AbstractMacrophage is a critical regulator in wound healing and scar formation, and SIRT1 is related to macrophage activation and polarization, while the specific mechanism is still unclear. To explore the specific effects of SIRT1 in scarring, we established a skin incision mouse model and LPS-induced inflammation cell model. The expression of SIRT1 in tissue and macrophage was detected, and the level of SIRT1 was changed to observe the downstream effects. LPS-induced macrophages with or without SIRT1 deficiency were used for TMT-based quantitative proteomic analysis. SIRT1 was suppressed in scar while increased in macrop...
Source: Journal of Molecular Medicine - September 14, 2023 Category: Molecular Biology Source Type: research
GSK-3 α aggravates inflammation, metabolic derangement, and cardiac injury post-ischemia/reperfusion
AbstractReperfusion after acute myocardial infarction further exaggerates cardiac injury and adverse remodeling. Irrespective of cardiac cell types, loss of specifically the α isoform of the protein kinase GSK-3 is protective in chronic cardiac diseases. However, the role of GSK-3α in clinically relevant ischemia/reperfusion (I/R)-induced cardiac injury is unknown. Here, we challenged cardiomyocyte-specific conditional GSK-3α knockout (cKO) and littermate control mic e with I/R injury and investigated the underlying molecular mechanism using an in vitro GSK-3α gain-of-function model in AC16 cardiomyocytes post-hypoxia/...
Source: Journal of Molecular Medicine - September 14, 2023 Category: Molecular Biology Source Type: research
SPP1/osteopontin: a driver of fibrosis and inflammation in degenerative ascending aortic aneurysm?
In conclusion, the present findings suggest that SPP1 may be involved in the development of the degenerative type of AscAA.Key messagesIn the original manuscript titled “SPP1/osteopontin, a driver of fibrosis and inflammation in degenerative ascending aortic aneurysm?” by David Freiholtz, Otto Bergman, Saliendra Pradhananga, Karin Lång, Flore-Anne Poujade, Carl Granath, Christian Olsson, Anders Franco-Cereceda, Pelin Sahlén, Per Eriksson, and Hanna M Björck, we present novel findings on regulatory factors on osteopontin (SPP1) expression in immune cells involved in degenerative ascending aortic aneurysms (AscAA).The...
Source: Journal of Molecular Medicine - September 12, 2023 Category: Molecular Biology Source Type: research
The mechanisms of exosomes in diabetic foot ulcers healing: a detailed review
AbstractAs time goes by, the morbidity of diabetes mellitus continues to rise, and the economic burden of diabetic foot ulcers as a common and serious complication of diabetes is increasing. However, currently there is no unified clinical treatment strategy for this complication, and the therapeutic efficacy is unsatisfactory. Recent studies have revealed that biological effects of exosomes involved in multiple stages of the process of wound closure are similar to source cells. Compared with source cells, exosomes possess lowly immunogenicity, highly stability and easily stored, etc. Accumulating evidence confirmed that ex...
Source: Journal of Molecular Medicine - September 11, 2023 Category: Molecular Biology Source Type: research
An atlas of genome-wide gene expression and metabolite associations and possible mediation effects towards body mass index
In conclusion, here, we present the largest available multi-omics integration of genome-wide transc riptome data and metabolite data of amino acid and fatty acid metabolism and further leverage these findings to characterize potential mediation effects towards BMI proposing candidate mechanisms of obesity and related metabolic diseases.Key messagesThousands of associations of 72 amino acid and acylcarnitine metabolites and 8579 genes expand the knowledge of metabolome-transcriptome associations.A mediation analysis of effects on body mass index revealed large mediation networks of thousands of obesity-related gene-metaboli...
Source: Journal of Molecular Medicine - September 6, 2023 Category: Molecular Biology Source Type: research
The plasma exosomes from patients with primary Sj ögren’s syndrome contain epithelial cell–derived proteins involved in ferroptosis
This study analyzed the plasma exosomes of pSS patients using proteomics and revealed the presence of 24 differentially expressed proteins (DEPs) involved in the primary biological processes and signaling pathways related to ferroptosis. The DEPs enriched in the ferroptosis-related items were represented by downregulated ceruloplasmin (CP) and transferrin (TF). CC analysis of GO enrichment showed that CP and TF were localized at the apical plasma membrane, which is currently found only in epithelial cells. PPI analysis indicated that these exosomal DEPs formed a clustering network containing CP and TF. Among them, C5, C9, ...
Source: Journal of Molecular Medicine - September 1, 2023 Category: Molecular Biology Source Type: research
Evaluation of drug sensitivity, immunological characteristics, and prognosis in melanoma patients using an endoplasmic reticulum stress-associated signature based on bioinformatics and pan-cancer analysis
AbstractWe aimed to develop endoplasmic reticulum (ER) stress-related risk signature to predict the prognosis of melanoma and elucidate the immune characteristics and benefit of immunotherapy in ER-related risk score-defined subgroups of melanoma based on a machine learning algorithm. Based on The Cancer Genome Atlas (TCGA) melanoma dataset (n = 471) and GTEx database (n = 813), 365 differentially expressed ER-associated genes were selected using the univariate Cox model and LASSO penalty Cox model. Ten genes impacting OS were identified to construct an ER-related signature by using the multivariate Cox regression ...
Source: Journal of Molecular Medicine - August 31, 2023 Category: Molecular Biology Source Type: research
Role of the pioneer transcription factor GATA2 in health and disease
AbstractThe transcription factor GATA2 is involved in human diseases ranging from hematopoietic disorders, to cancer, to infectious diseases. GATA2 is one of six GATA-family transcription factors that act as pioneering transcription factors which facilitate the opening of heterochromatin and the subsequent binding of other transcription factors to induce gene expression from previously inaccessible regions of the genome. Although GATA2 is essential for hematopoiesis and lymphangiogenesis, it is also expressed in other tissues such as the lung, prostate gland, gastrointestinal tract, central nervous system, placenta, fetal ...
Source: Journal of Molecular Medicine - August 25, 2023 Category: Molecular Biology Source Type: research
A novel RBBP8(p.E281*) germline mutation is a predisposing mutation in familial hereditary cancer syndrome
AbstractScreening tumor susceptibility genes helps in identifying powerful biomarkers for hereditary cancer monitoring, prevention, and diagnosis, providing opportunities for understanding potential molecular mechanisms and biomarkers for the precise treatment of hereditary cancer syndromes. Whole-exome sequencing of blood and bioinformatics analysis uncovered a novel RBBP8(p.E281*) germline mutation in a family with hereditary cancer syndrome, which was verified by Sanger sequencing. Cell proliferation, colony formation, cell migration, and in vivo tumorigenesis were investigated by CCK8, colony formation, Transwell, and ...
Source: Journal of Molecular Medicine - August 24, 2023 Category: Molecular Biology Source Type: research
The role of immunosuppressive myofibroblasts in the aging process and age-related diseases
AbstractTissue-resident fibroblasts are mesenchymal cells which control the structural integrity of the extracellular matrix (ECM). Fibroblasts possess a remarkable plasticity to allow them to adapt to the changes in the microenvironment and thus maintain tissue homeostasis. Several stresses, also those associated with the aging process, convert quiescent fibroblasts into myofibroblasts which not only display fibrogenic properties but also act as immune regulators cooperating both with tissue-resident immune cells and those immune cells recruited into affected tissues. TGF- β cytokine and reactive oxygen species (ROS) are...
Source: Journal of Molecular Medicine - August 22, 2023 Category: Molecular Biology Source Type: research
Distinctive metabolic remodeling in TYMP deficiency beyond mitochondrial dysfunction
This study aimed to elucidate the characteristic metabolic alterations and associated homeostatic regulation caused by TYMP deficiency. The pathogenicity of novel TYMP variants was evaluated in terms of clinical features, genetic analysis, and structural instability. We analyzed plasma samples from three patients with MNGIE; three patients with m.3243A > G mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS); and four healthy controls (HC) using both targeted and untargeted metabolomics techniques. Transcriptomics analysis and bioenergetic studies were performed on skin fibroblasts from ...
Source: Journal of Molecular Medicine - August 21, 2023 Category: Molecular Biology Source Type: research
Targeting ACC1 in T cells ameliorates psoriatic skin inflammation
AbstractPsoriasis is a chronic inflammatory skin disease driven by the IL-23/IL-17 axis. It results from excessive activation of effector T cells, including T helper (Th) and cytotoxic T (Tc) cells, and is associated with dysfunctional regulatory T cells (Tregs). Acetyl-CoA carboxylase 1 (ACC1), a rate-limiting enzyme of fatty acid synthesis (FAS), directs cell fate decisions between Th17 and Tregs and thus could be a promising therapeutic target for psoriasis treatment. Here, we demonstrate that targeting ACC1 in T cells by genetic ablation ameliorates skin inflammation in an experimental model of psoriasis by limiting Th...
Source: Journal of Molecular Medicine - August 18, 2023 Category: Molecular Biology Source Type: research
The ever wider clinical spectrum of RMND1-related disorders and limitedness of phenotype-based classifications
AbstractRMND1 has been identified as a mitochondriopathy-associated gene less than 12 years ago. The most common phenotype related to this gene is an early onset, severe form of encephalomyopathy that leads to death in a medium time of three years after birth. However, milder and later onset presentations have been reported in some individuals, including two in whom the mitochondri opathy was identified at ~ 40 years of age, and the early onset presentations have been the object of no reports in those who survived beyond age 10. It is thus unclear how lethalRMND1-related conditions really are. We herein describe the...
Source: Journal of Molecular Medicine - August 16, 2023 Category: Molecular Biology Source Type: research
