skin-biopsy-for-diagnosing-discoid-lupus-erythematosus

Skin Biopsy for Diagnosing Discoid Lupus Erythematosus

Discoid lupus erythematosus (DLE) is the most common variant of cutaneous lupus erythematosus (CLE). It typically affects the scalp, face, auricle, and ...

a-verified-workflow-for-mirna-seq-data-processing-bioinformatics

A Verified Workflow for MiRNA-Seq Data Processing and Bioinformatics Analysis Using R

MicroRNAs (miRNAs) are critical post-transcriptional regulators that influence a wide range of physiological and pathological processes. With the ...

Tongji University School of Medicine

905th Hospital of PLA Navy, Naval Medical University

The CXCL12/CXCR4 axis is strongly implicated as key determinant of tumor invasion and metastasis in ovarian cancer. However, little is known about the potential downstream signals of the CXCL12/CXCR4 axis that contribute to ovarian cancer cell invasion and metastasis. ARHGAP10, a member of Rho GTPase activating proteins is a potential tumor suppressor gene in ovarian cancer. In this study, a negative correlation between the protein levels of CXCL12, CXCR4, vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor-2 (VEGFR2) and ARHGAP10 was uncovered in ovarian cancer tissues and paired adjacent noncancerous tissues. CXCL12 stimulation reduced the expression of ARHGAP10. Furthermore, the pretreatment of CXCR4 inhibitor (AMD3100) or the vascular endothelial growth factor receptor-2 (VEGFR2) inhibitor (SU1498) abrogated the CXCL12-deduced expression of ARHGAP10. Finally, an in vitro functional assay revealed that CXCL12 did not stimulate ovarian cancer cell invasion when ARHGAP10 was overexpressed or when ovarian cancer cells were pre-treated with AMD3100 or SU1498. Knockdown of ARHGAP10 significantly suppressed the inhibitory effects of SU1498 on ovarian cancer cell invasion and lung metastasis. In summary, these findings suggest that CXCL12/CXCR4 promotes ovarian cancer cell invasion by suppressing ARHGAP10 expression, which is mediated by VEGF/VEGFR2 signaling.

CXCL12 promotes human ovarian cancer cell invasion through suppressing ARHGAP10 expression.

Cancer antigen 125 (CA125), encoded by the mucin 16 cell surface associated (MUC16) gene, has been widely used as a biomarker for ovarian cancer (OC) screening. However, it has yet to be elucidated as to why its levels increase with tumor progression as well as with certain other non-malignant conditions. Based on our knowledge of the inflammatory microenvironment (IME) in OC, HEY cells were treated with several inflammation-associated factors as well as their antagonists, and it was observed that inflammation-associated factors upregulated MUC16 gene expression. Considering the role of nuclear factor (NF)-κB in the inflammatory signaling network and our previous research on OC, chromatin immunoprecipitation was performed, and it was observed that activated NF-κB bound to the MUC16 gene promoter and enhanced its expression, thereby elevating secreted CA125 levels. These findings demonstrated that IME and MUC16 gene expression were associated in OC, partly elucidating the role of IME in tumor progression, explaining the elevated serum CA125 levels in some non-malignant conditions, and confirming IME as a potential target for OC therapy.

Inflammatory signals induce MUC16 expression in ovarian cancer cells via NF-κB activation.

Adenomyosis usually causes dysmenorrhea and anemia. Clinically, it is difficult to be treated with medicine or by traditional surgery, however, hysterectomy is always performed for radical treatment. In this article, we introduce a new method that could control the dysmenorrhea and the anemia through laparoscopic uterine artery occlusion (LUAO) combined with uterine-sparing pelvic plexus block and partial adenomyomectomy for uterus preservation.

Laparoscopic Uterine Artery Occlusion Combined with Uterine-sparing Pelvic Plexus Block and Partial Adenomyomectomy for Adenomyosis: A Video Case Report.

Pulmonary arterial hypertension (PAH) is an immune-mediated disease with poor prognosis and associated with various inflammatory immune diseases. In fact, its pathogenesis is far from clear. Although long non-coding RNAs (lncRNAs) have been implicated in PAH, the molecular mechanisms remain largely unknown. For the first time, in lungs of monocrotaline-induced PAH rat models, we simultaneously detected the expression profiles of lncRNAs and mRNAs by high-throughput sequencing, and explored their roles with bioinformatics analysis and cell assay to discover more potential pathogenesis about PAH. Our data identified that a total of 559 lncRNAs and 691 mRNAs were differentially expressed in lungs during the pathogenesis of PAH. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses demonstrated that these dysregulated lncRNAs and mRNAs participated in important biological processes and pathways of PAH, among which inflammatory and immune responses represented the chief enriched pathway. The lncRNA-mRNA co-expression network was developed to uncover the hidden interactions between lncRNAs and mRNAs. Further, the expression levels of lncRNAs (NONRATT018084.2, NONRATT009275.2, NONRATT007865.2, and NONRATT026300.2) and mRNAs (LGALS3, PDGFC, SERPINA1, and NFIL3) were confirmed using quantitative real-time PCR. In the end, lncRNA NONRATT009275.2 could facilitate macrophage polarization to M2 type and be involved in inflammatory immune response. In conclusion, this study provided candidate drug targets and potential roles on lncRNAs in the pathogenesis of PAH, and several key regulatory genes were identified, which laid the initial foundation for further mechanism study in PAH.

Profiling and Molecular Mechanism Analysis of Long Non-Coding RNAs and mRNAs in Pulmonary Arterial Hypertension Rat Models.

Pulmonary arterial hypertension (PAH) is a malignant pulmonary vascular syndrome characterized by a progressive increase in pulmonary vascular resistance and pulmonary arterial pressure, which eventually leads to right heart failure and even death. Although the exact mechanism of PAH is not fully understood, pulmonary vasoconstriction, vascular remodeling, immune and inflammatory responses, and thrombosis are thought to be involved in the development and progression of PAH. In the era of non-targeted agents, PAH had a very dismal prognosis with a median survival time of only 2.8 years. With the deep understanding of the pathophysiological mechanism of PAH as well as advances in drug research, PAH-specific therapeutic drugs have developed rapidly in the past 30 years, but they primarily focus on the three classical signaling pathways, namely the endothelin pathway, nitric oxide pathway, and prostacyclin pathway. These drugs dramatically improved pulmonary hemodynamics, cardiac function, exercise tolerance, quality of life, and prognosis in PAH patients, but could only reduce pulmonary arterial pressure and right ventricular afterload to a limited extent. Current targeted agents delay the progression of PAH but cannot fundamentally reverse pulmonary vascular remodeling. Through unremitting efforts, new therapeutic drugs such as sotatercept have emerged, injecting new vitality into this field. This review comprehensively summarizes the general treatments for PAH, including inotropes and vasopressors, diuretics, anticoagulants, general vasodilators, and anemia management. Additionally, this review elaborates the pharmacological properties and recent research progress of twelve specific drugs targeting three classical signaling pathways, as well as dual-, sequential triple-, and initial triple-therapy strategies based on the aforementioned targeted agents. More crucially, the search for novel therapeutic targets for PAH has never stopped, with great progress in recent years, and this review outlines the potential PAH therapeutic agents currently in the exploratory stage to provide new directions for the treatment of PAH and improve the long-term prognosis of PAH patients.

Medical Management of Pulmonary Arterial Hypertension: Current Approaches and Investigational Drugs.

Neutrophils, a primary type of immune cell, play critical roles in numerous biological processes. Both umbilical cord blood (UCB) and peripheral blood are rich in neutrophils. UCB is more abundant than peripheral blood, with cells generally at a more immature stage. However, comparative data between these two cell sources is lacking. This study aims to elucidate differences between UCB-derived neutrophils (UCBN) and peripheral blood-derived neutrophils (PBN). UCBN and PBN were isolated from fresh human umbilical cord blood and peripheral blood, respectively. Transcriptomic profiling was performed and compared against neutrophil RNA from three different donors. Bioinformatics analysis was employed to compare cell phenotypes. A cytokine cocktail (IFN-β, IFN-γ, and LPS) was used to activate UCBN and PBN in vitro. A united multi-omic approach, combining transcriptomic and proteomic analysis, was followed by experimental validation through flow cytometry, cell killing assays, and proteome profiler array to verify cell functions. Transcriptomic analysis revealed that the most upregulated genes in freshly isolated umbilical cord blood neutrophils (UCBN) compared to peripheral blood neutrophils (PBN) predominantly involve neutrophil activation and cell-killing functions. Validation through flow cytometry and cell-killing experiments demonstrated that highly viable UCBN exhibited significantly stronger ovarian tumor cell-killing activity in vitro compared to PBN. Both transcriptomic and proteomic analyses indicated that the primary upregulated genes in activated UCBN are chiefly involved in biological processes related to the regulation of cytokine secretion. Integrative multi-omic analysis, including a proteome profiler array, confirmed that UCBN indeed secrete elevated levels of cytokines. In conclusion: UCBN shows higher viability and cellular activity compared with PBN, particularly in tumor cell-killing and cytokine secretion.

ArticleTotal : 2	Year
Publication title Cited by 2	2025
Publication title	2025

Article	Year
CXCL12 promotes human ovarian cancer cell invasion through suppressing ARHGAP10 expression. Biochemical and biophysical research communications\| PubMed ID: 31445707	2019
Inflammatory signals induce MUC16 expression in ovarian cancer cells via NF-κB activation. Experimental and therapeutic medicine\| PubMed ID: 33456530	2021
Laparoscopic Uterine Artery Occlusion Combined with Uterine-sparing Pelvic Plexus Block and Partial Adenomyomectomy for Adenomyosis: A Video Case Report. Journal of minimally invasive gynecology\| PubMed ID: 34051355	2021
Profiling and Molecular Mechanism Analysis of Long Non-Coding RNAs and mRNAs in Pulmonary Arterial Hypertension Rat Models. Frontiers in pharmacology\| PubMed ID: 34267668	2021
Medical Management of Pulmonary Arterial Hypertension: Current Approaches and Investigational Drugs. Pharmaceutics\| PubMed ID: 37376028	2023
Umbilical cord blood-derived neutrophils possess higher viability than peripheral blood derived neutrophils. American journal of cancer research\| PubMed ID: 38590402	2024

Dandan Chen

Biography

JoVE Journal Publications

Other Publications