Immune infiltration plays an important role in the course of abdominal aortic aneurysm (AAA) development, and copper death (cuproptosis) is a new type of programmed cell death recently discovered. Currently, there are no studies on the role of cuproptosis regulating immune infiltration in AAA. We extracted a published GEO dataset (GSE57691), with 49 AAA and 10 control transcriptome sequencing samples. Then, we analyzed the difference of cuproptosis related genes (CRGs) expression between AAA and normal groups. LIPT1, FDX1 and CDKN2A were upregulated in AAA samples (P < 0.05). Subsequently, we analyzed the difference of immune infiltrate cells between the AAA and normal samples. Compared to the normal group, Dendritic cells, Mast activated cells, Monocytes, M0 macrophages, neutrophils, Plasma cells, CD4-naive T cells, follicular-helper T cells and Treg cells were upregulated in the AAA group, while M1 and M2 macrophages, CD4-memory T cells and gamma delta T cells were downregulated. AAA samples were then classified into two subtypes according to the expression profiles of CRGs, the immunological characteristics and function had significant differences between subtypes. Furthermore, we mined 20 hub genes by using Weighted Gene Co-expression Network Analysis (WGCNA) to construct a co-expression network. Three drugs were identified that interacting with eight hub genes based on the gene-drug interaction database. We finally verified the mRNA differences of the CRGs in the aorta of AAA and healthy mice in vitro. LIPT1, CDKN2A and FDX1 may play a role in regulating the development of AAA through immune infiltration. Eight NDUF subunits, including NDUFA1, NDUFA4, and NDUFB1, may also play an important role in this process. In addition, Metformin, ME-344 and NV-128 may be therapeutic agents for AAA by regulating the cuproptosis.

01 Oct 2024·Archives of Oral Biology

Correlation of disulfidptosis and periodontitis: New insights and clinical significance

Article

Author: Liu, Zhihui ; Liu, Wantong ; Wang, Bowei ; Li, Sining ; Kong, Chen ; Zhao, Qi ; Qi, Le ; Fan, Yixin ; Ren, Jiwei ; Li, Zhiwei ; Zou, He

OBJECTIVESThis study aims to investigate and predict the therapeutic agents associated with disulfidptosis in periodontitis.DESIGNThe dataset GSE10334 was downloaded from the Gene Expression Omnibus (GEO) database and used to train a least absolute shrinkage and selection operator (LASSO) regression and support vector machine recursive feature elimination (SVM-RFE) algorithm to identify genes associated with disulfidptosis in periodontitis. GSE16134 validation sets, polymerase chain reaction (PCR), and gingival immunofluorescence were used to verify the results.Single-gene Gene Set Enrichment Analysis (GSEA) was performed to explore the potential mechanisms and functions of the characterized genes. Immune infiltration and correlation analyses were performed, and competing endogenous RNA (ceRNA) networks were constructed. Effective therapeutic drugs were then predicted using the DGIdb database, and molecular docking was used to validate binding affinity.RESULTSSix genes (SLC7A11, SLC3A2, RPN1, NCKAP1, LRPPRC, and NDUFS1) associated with disulfidptosis in periodontitis were obtained. Validation results from external datasets and experiments were consistent with the screening results. Single-gene GSEA analysis was mainly enriched for antigen presentation and immune-related pathways and functions.Immune infiltration and correlation analyses revealed significant regulatory relationships between these genes and plasma cells, resting dendritic cell, and activated NK cells. The ceRNA network was visualized. And ME-344, NV-128, and RILUZOLE, which have good affinity to target genes, were identified as promising agents for the treatment of periodontitis.CONCLUSIONSSLC7A11, SLC3A2, RPN1, NCKAP1, LRPPRC, and NDUFS1 are targets associated with disulfidptosis in periodontitis, and ME-344, NV-128, and RILUZOLE are promising agents for the treatment of periodontitis.

03 Apr 2022·AutoimmunityQ4 · MEDICINE

Drug repurposing for rheumatoid arthritis: Identification of new drug candidates via bioinformatics and text mining analysis

Q4 · MEDICINE

Article

Author: Unal, Ulku ; Demirtas, Talip Yasir ; Gov, Esra ; Comertpay, Betul

Rheumatoid arthritis (RA) is an autoimmune disease that results in the destruction of tissue by attacks on the patient by his or her own immune system. Current treatment strategies are not sufficient to overcome RA. In the present study, various transcriptomic data from synovial fluids, synovial fluid-derived macrophages, and blood samples from patients with RA were analysed using bioinformatics approaches to identify tissue-specific repurposing drug candidates for RA. Differentially expressed genes (DEGs) were identified by integrating datasets for each tissue and comparing diseased to healthy samples. Tissue-specific protein-protein interaction (PPI) networks were generated and topologically prominent proteins were selected. Transcription-regulating biomolecules for each tissue type were determined from protein-DNA interaction data. Common DEGs and reporter biomolecules were used to identify drug candidates for repurposing using the hypergeometric test. As a result of bioinformatic analyses, 19 drugs were identified as repurposing candidates for RA, and text mining analyses supported our findings. We hypothesize that the FDA-approved drugs momelotinib, ibrutinib, and sodium butyrate may be promising candidates for RA. In addition, CHEMBL306380, Compound 19a (CHEMBL3116050), ME-344, XL-019, TG100801, JNJ-26483327, and NV-128 were identified as novel repurposing candidates for the treatment of RA. Preclinical and further validation of these drugs may provide new treatment options for RA.

News (Medical) associated with NV-128

22 Sep 2009

·www.biospace.com

Marshall Edwards, Inc. Receives Nasdaq Notice of Minimum Bid Price Non-Compliance

NEW CANAAN, CT--(Marketwire - September 22, 2009) - Marshall Edwards, Inc. (NASDAQ: MSHL), a specialist oncology company focusing on the clinical development of novel anti-cancer therapeutics, today announced that on September 16, 2009, as management expected, the Company received a letter from The Nasdaq Stock Market notifying the Company that for the last 30 consecutive business days the bid price of the Company's common stock closed below the minimum $1.00 per share requirement for continued inclusion on the Nasdaq Global Market under Nasdaq Rule 5450(a)(1). According to Nasdaq's letter, the Company will be afforded a grace period of 180 calendar days, or until March 15, 2010, to regain compliance in accordance with Nasdaq Rule 5810(c)(3)(A). In order to regain compliance, shares of the Company's common stock must maintain a minimum bid closing price of at least $1.00 per share for a minimum of ten consecutive business days during the grace period. The Company intends to actively monitor the bid price of its common stock between now and March 15, 2010. About Marshall Edwards, Inc. Marshall Edwards, Inc. is a specialist oncology company focused on the clinical development of novel anti-cancer therapeutics. These derive from a flavonoid technology platform, which has generated a number of novel compounds characterized by broad ranging activity against a range of cancer cell types with few side effects. The combination of anti-tumor cell activity and low toxicity is believed to be a result of the ability of these compounds to target an enzyme present in the cell membrane of cancer cells, thereby inhibiting the production of pro-survival proteins within the cell. Marshall Edwards has licensed rights from Novogen Limited (ASX: NRT) (NASDAQ: NVGN) to bring four oncology drugs -- phenoxodiol, triphendiol NV-143 and NV-128 -- to market globally. Marshall Edwards is majority owned by Novogen, an Australian biotechnology company that is specializing in the development of therapeutics based on a flavonoid technology platform. Novogen is developing a range of therapeutics across the fields of oncology, cardiovascular disease and inflammatory diseases. More information on phenoxodiol and on the Novogen group of companies can be found at and . Under U.S. law, a new drug cannot be marketed until it has been investigated in clinical trials and approved by the FDA as being safe and effective for the intended use. Statements included in this press release that are not historical in nature are "forward-looking statements" within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. You should be aware that our actual results could differ materially from those contained in the forward-looking statements, which are based on management's current expectations and are subject to a number of risks and uncertainties, including, but not limited to, our failure to successfully commercialize our product candidates; costs and delays in the development and/or FDA approval, or the failure to obtain such approval, of our product candidates; uncertainties in clinical trial results; our inability to maintain or enter into, and the risks resulting from our dependence upon, collaboration or contractual arrangements necessary for the development, manufacture, commercialization, marketing, sales and distribution of any products; competitive factors; our inability to protect our patents or proprietary rights and obtain necessary rights to third party patents and intellectual property to operate our business; our inability to operate our business without infringing the patents and proprietary rights of others; general economic conditions; the failure of any products to gain market acceptance; our inability to obtain any additional required financing; technological changes; government regulation; changes in industry practice; and one-time events. We do not intend to update any of these factors or to publicly announce the results of any revisions to these forward-looking statements. CONTACTS: Warren Lancaster +1-203-966-2556 (USA) Email Contact David Sheon +1 202 547-2880 (USA) Email Contact

100 Deals associated with NV-128

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Indication	Highest Phase	Country/Location	Organization	Date
Ovarian Epithelial Carcinoma	Preclinical	United States	Yale School of Medicine	01 May 2009
Ovarian Epithelial Carcinoma	Preclinical	Australia	University of Sydney Union	01 May 2009
Ovarian Epithelial Carcinoma	Preclinical	Australia	Marshall Edwards, Inc.	01 May 2009
Neoplasms	Preclinical	-	Kazia Therapeutics Ltd.	-
Neoplasms	Preclinical	-	MEI Pharma, Inc.	-

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