Single-cell RNA sequencing reveals key molecular drivers and immune landscape in uveal melanoma: implications for targeted therapy and prognostic modeling.

Background: Uveal melanoma (UM), arising from melanocytes in the choroid, accounts for 3% to 5% of all melanocytic tumors and over 70% of intraocular malignancies. Despite effective local treatments, metastasis remains a significant challenge, with more than half of patients developing metastatic disease within ten years. Conventional therapies often yield poor outcomes, highlighting the urgent need for novel therapeutic strategies to enhance survival and prognosis for UM patients.

Corrigendum: Unraveling the ecological landscape of mast cells in esophageal cancer through single-cell RNA sequencing.

[This corrects the article DOI: 10.3389/fimmu.2024.

Newly Synthesized Citral Derivatives Serve as Novel Inhibitor in HepG2 Cells.

2H-pyran compound 1 synthesized from 6-methylpyridine-2,4-diol and citral, has been used for Cu-catalyzed N-arylation with a range of arylboric acids to obtain arylated pyranopyridine core structure derivatives (yield up to 77 %). Among them, compound 3 h exhibited a much better inhibitory effect on HepG2 liver cancer cells compared to citral, and the IC value was 5.3 μM following exposure with the newly synthesized derivatives (herein named 3 h for short in this paper), which was lower than that of the cisplatin (6.

Unraveling the ecological landscape of mast cells in esophageal cancer through single-cell RNA sequencing.

Background: Esophageal cancer (EC) is a major health issue, ranking seventh in incidence and sixth in mortality worldwide. Despite advancements in multidisciplinary treatment approaches, the 5-year survival rate for EC remains low at 21%. Challenges in EC treatment arise from late-stage diagnosis, high malignancy, and poor prognosis.

IGFBP7+ subpopulation and IGFBP7 risk score in astrocytoma: insights from scRNA-Seq and bulk RNA-Seq.

Background: Glioma is the predominant malignant brain tumor that lacks effective treatment options due to its shielding by the blood-brain barrier (BBB). Astrocytes play a role in the development of glioma, yet the diverse cellular composition of astrocytoma has not been thoroughly researched.

Methods: We examined the internal diversity of seven distinct astrocytoma subgroups through single-cell RNA sequencing (scRNA-seq), pinpointed crucial subgroups using CytoTRACE, monocle2 pseudotime analysis, and slingshot pseudotime analysis, employed various techniques to identify critical subgroups, and delved into cellular communication analysis.

Identification of hub genes and therapeutic siRNAs to develop novel adjunctive therapy for Duchenne muscular dystrophy.

Objective: Duchenne muscular dystrophy (DMD) is a devastating X-linked neuromuscular disorder caused by various defects in the dystrophin gene and still no universal therapy. This study aims to identify the hub genes unrelated to excessive immune response but responsible for DMD progression and explore therapeutic siRNAs, thereby providing a novel treatment.

Methods: Top ten hub genes for DMD were identified from GSE38417 dataset by using GEO2R and PPI networks based on Cytoscape analysis.

Unraveling the intricacies of glioblastoma progression and recurrence: insights into the role of NFYB and oxidative phosphorylation at the single-cell level.

Background: Glioblastoma (GBM), with its high recurrence and mortality rates, makes it the deadliest neurological malignancy. Oxidative phosphorylation is a highly active cellular pathway in GBM, and NFYB is a tumor-associated transcription factor. Both are related to mitochondrial function, but studies on their relationship with GBM at the single-cell level are still scarce.

Prediction of potential targets and toxicological insights of Astragalus in liver cancer based on network pharmacology: Integrating systems biology, drug interaction networks, and toxicological perspectives.

This study investigates Astragalus's efficacy as a novel therapeutic option for primary liver cancer (PLC), capitalizing on its anti-inflammatory and antiviral effects. We utilized network pharmacology to unveil Astragalus's potential targets against PLC, revealing significant gene expression alterations in treated samples-20 genes were up-regulated, and 20 were down-regulated compared to controls. Our analysis extended to single-cell resolution, where we processed scRNA-seq data to discern 15 unique cell clusters within the immune, malignant, and stromal compartments through advanced algorithms like UMAP and tSNE.

Antioxidant and anti-melanogenesis activities of extracts from Houtt.

Houtt is an important anti-skin pigmentation herb used in traditional Chinese medicine. However, the molecular basis for this activity is complex and not fully understood. In this study, water and ethanol extracts and polysaccharide extract from (LJPs) were analyzed by LC-MS/MS and HPLC-DAD separately.

Polo-like kinase 1 (PLK1) O-GlcNAcylation is essential for dividing mammalian cells and inhibits uterine carcinoma.

The O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) mediates intracellular O-GlcNAcylation modification. O-GlcNAcylation occurs on Ser/Thr residues and is important for numerous physiological processes. OGT is essential for dividing mammalian cells and is involved in many human diseases; however, many of its fundamental substrates during cell division remain unknown.

Effects of dehydroabietic acid on nontarget lipidomics and proteomics of HepG2.

Studies of the effects of dehydroabietic acid on the multiomics of HepG2 hepatoma carcinoma cells are currently lacking. In this study, the molecular mechanism of the influence of dehydroabietic acid on HepG2 cells was disclosed by studying lipidomics and proteomics. Correlations among multiomics conjoint analysis results were verified.

Nitrogen Metabolism Disorder Accelerates Occurrence and Development of Lung Adenocarcinoma: A Bioinformatic Analysis and Experiments.

Background: Nitrogen metabolism (NM) plays a pivotal role in immune regulation and the occurrence and development of cancers. The aim of this study was to construct a prognostic model and nomogram using NM-related genes for the evaluation of patients with lung adenocarcinoma (LUAD).

Methods: The differentially expressed genes (DEGs) related to NM were acquired from The Cancer Genome Atlas (TCGA) database.

-GlcNAcylation of myosin phosphatase targeting subunit 1 (MYPT1) dictates timely disjunction of centrosomes.

The role of -linked -acetylglucosamine (-GlcNAc) modification in the cell cycle has been enigmatic. Previously, both -GlcNAc transferase (OGT) and -GlcNAcase (OGA) disruptions have been shown to derail the mitotic centrosome numbers, suggesting that mitotic GlcNAc oscillation needs to be in concert with mitotic progression to account for centrosome integrity. Here, using both chemical approaches and biological assays with HeLa cells, we attempted to address the underlying molecular mechanism and observed that incubation of the cells with the OGA inhibitor Thiamet-G strikingly elevates centrosomal distances, suggestive of premature centrosome disjunction.

Chk1 modulates the interaction between myosin phosphatase targeting protein 1 (MYPT1) and protein phosphatase 1cβ (PP1cβ).

Polo-like kinase 1 (Plk1) is an instrumental kinase that modulates many aspects of the cell cycle. Previous investigations have indicated that Plk1 is a target of the DNA damage response, and Plk1 inhibition is dependent on ATM/ATR and Chk1. But the exact mechanism remains elusive.

NMI and IFP35 serve as proinflammatory DAMPs during cellular infection and injury.

Damage-associated molecular patterns (DAMP) trigger innate immune response and exacerbate inflammation to combat infection and cellular damage. Identifying DAMPs and revealing their functions are thus of crucial importance. Here we report that two molecules, N-myc and STAT interactor (NMI) and interferon-induced protein 35 (IFP35) act as DAMPs and are released by activated macrophages during lipopolysaccharide-induced septic shock or acetaminophen-induced liver injury.

Aurora B-dependent phosphorylation of Ataxin-10 promotes the interaction between Ataxin-10 and Plk1 in cytokinesis.

Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant neurologic disorder caused by ATTCT expansion in the ATXN10 gene. Previous investigations have identified that depletion of Ataxin-10, the gene product, leads to cellular apoptosis and cytokinesis failure. Herein we identify the mitotic kinase Aurora B as an Ataxin-10 interacting partner.

MTHFR promotes heterochromatin maintenance.

Methylenetetrahydrofolate reductase (MTHFR), a key enzyme in the folate cycle, catalyzes the reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co-substrate for homocysteine remethylation to methionine. Methionine serves as the precursor of the active methyl donor S-adenosylmethionine, which provides methyl groups for many biological methylations. It has been reported that MTHFR is highly phosphorylated under unperturbed conditions and T34 is the priming phosphorylation site.

Synthesis and antiproliferative activity of 4-substituted-piperazine-1-carbodithioate derivatives of 2,4-diaminoquinazoline.

A novel series of 4-substituted-piperazine-1-carbodithioate derivatives of 2,4-diaminoquinazoline were synthesized and tested for their antiproliferative activities against five human cancer cell lines including A549 (lung cancer), MCF-7 (breast adenocarcinoma), HeLa (cervical carcinoma), HT29 and HCT-116 (colorectal cancer). Most of the synthesized compounds showed broad spectrum antiproliferative activity (IC50 1.47-11.

Nampt is involved in DNA double-strand break repair.

DNA double-strand break (DSB) is the most severe form of DNA damage, which is repaired mainly through high-fidelity homologous recombination (HR) or error-prone non-homologous end joining (NHEJ). Defects in the DNA damage response lead to genomic instability and ultimately predispose organs to cancer. Nicotinamide phosphoribosyltransferase (Nampt), which is involved in nicotinamide adenine dinucleotide metabolism, is overexpressed in a variety of tumors.