Endothelial cells are integral components of the tumor microenvironment and play a multifaceted role in tumor immunotherapy. Targeting endothelial cells and related signaling pathways can improve the effectiveness of immunotherapy by normalizing tumor blood vessels and promoting immune cell infiltration. However, to date, there have been no comprehensive studies analyzing the role of endothelial cells in the diagnosis and treatment of prostate adenocarcinoma (PRAD).

Liquid-liquid phase separation (LLPS) is essential for the formation of membraneless organelles and significantly influences cellular compartmentalization, chromatin remodeling, and gene regulation. Previous research has highlighted the critical function of liquid-liquid biopolymers in the development of hepatocellular carcinoma (HCC).

Pancreatic cancer is characterized by a complex tumor microenvironment that hinders effective immunotherapy. Identifying key factors that regulate the immunosuppressive landscape is crucial for improving treatment strategies.

Thioredoxin1 (TRX1) and telomerase are both attractive oncology targets that are tightly implicated in tumor initiation and development. Here, we reported that the 6-dithio-2-deoxyguanosine analog thiotert exhibits an effective cytotoxic effect on myelodysplastic syndromes (MDS) cell SKM-1 and lymphoma cell U-937. Further studies confirmed that thiotert effectively disrupts cellular redox homeostasis, as evidenced by elevated intracellular reactive oxygen species (ROS) levels, increased MnSOD, accelerated DNA impairment, and activated apoptosis signal. Mechanistically, our present study revealed that thiotert treatment effectively inhibited the function of the TRX1/TRXR1 system and telomerase reverse transcriptase (TERT), rendering oxidative damage and impairment of telomeres. Meanwhile, pharmacological administration of glutathione (GSH), N-acetylcysteine (NAC), and mitoquinone (MitoQ), or genetic overexpression of TRX1 or TERT in MDS and cells could dampen the toxicity caused by thiotert. Remarkably, the in vivo mouse model of MDS demonstrated that thiotert administration exhibited greater efficacy in tumor reduction compared to the conventional chemotherapy drug cytarabine. Collectively, these results provide experimental insights into the mechanism of thiotert-induced MDS and lymphoma cell death and unveil that thiotert may be an effective and promising new drug for future MDS and lymphoma treatment.

Pancreatic cancer is a lethal disease with an insidious onset, and little is known about its early molecular events. Here, we found that the sterol regulatory element-binding protein 1 (SREBP1) expression is gradually upregulated during the initiation of pancreatic cancer. Through in vitro 3D culture of pancreatic acinar cells and experiments in LSL-Kras;Pdx1-Cre (KC) mice, we found that pharmacological inhibition of SREBP1 suppressed pancreatic tumorigenesis. In vitro, either knockdown or pharmacological inhibition of SREBP1 suppressed tumor proliferation but SREBP1 overexpression promoted tumor proliferation. In LSL-Kras;Trp53;Pdx1-Cre (KPC) mice, we confirmed the tumor-promoting role of SREBP1 in pancreatic cancer progression. Mechanistically, we revealed SOX9 as a downstream target of SREPB1. SREBP1 inhibition decreased SOX9 expression in both acinar cells and pancreatic cancer cells. Indeed, we identified SREBP1 binding sites in the SOX9 promoter region and reported that SOX9 is transcriptionally regulated by SREBP1. Taken together, our findings demonstrate that SREBP1/SOX9 inhibition suppresses pancreatic cancer initiation and growth, suggesting that SREBP1 could serve as a potential target for cancer screening and treatment.

Bladder cancer (BC) is a malignant tumor. Methyltransferase-like 7B (MEETL7B) is a methyltransferase and its role in BC has not yet been revealed.

Tumor microenvironment (TME) takes an essential part in the bladder cancer progression, which is associated with intercellular cross-talk between stroma cells and cancer. We aimed use bioinformatics tools to analyze tumor microenvironment remodeling in bladder cancer. CIBERSORT and ESTIMATE are bioinformatics tools based on deconvolution for calculating proportions of tumor-infiltrating immune cells and stromal components in TME. We utilized these two algorithms to analyze the immune components of 433 bladder cancer cases from The Cancer Genome Atlas database, aiming to compensate for the current lack of large-sample single-cell information. Then we used Cox regression to analyze the prognostic value of differentially expressed genes, and the protein-protein interaction network was constructed. Matrix Metalloproteinase-9 (MMP9) was identified as a predictive biomarker related to immune microenvironment. Using Gene Set Enrichment Analysis, the genes from the group with high MMP9 expression gathered in items related to immune diseases, and genes in the group with low MMP9 expression were negatively associated with valine, leucine and isoleucine degradation and glycosylphosphatidylinositol anchor biosynthesis. MMP9 expression and presence of macrophages M0 were positively correlated, while naïve B cells, activated dendritic cells, monocytes and plasma cells were negatively correlated. The results were confirmed by brightfield and multiplex fluorescence immunohistochemistry using stained bladder cancer and normal tissue.

Advances in sequencing technologies are reshaping clinical diagnostics, prompting the development of new software tools to decipher big data. To this end, we developed functional genomic imaging (FGI), a visualization tool designed to assist clinicians in interpreting RNA-Seq results from patient samples. FGI uses weighted gene co-expression network analysis (WGCNA), followed by a modified Phenograph clustering algorithm to identify co-expression gene clusters. These gene modules were annotated and projected onto a t-SNE map for visualization. Annotation of FGI gene clusters revealed three categories: tissue-specific, functional, and positional. These clusters may be used to build tumor subtypes with pre-annotated functions. At the multi-cancer cohort level, tissue-specific clusters are enriched, whereas at the single cancer level, such as in lung cancer or ovarian cancer, positional clusters can be more prominent. Moreover, FGI analysis could also reveal molecular tumor subtypes not documented in clinical records and generated a more detailed co-expression gene cluster map. Based on different levels of FGI modeling, each individual tumor sample can be customized to display various types of information such as tissue origin, molecular subtypes, immune activation status, stromal signaling pathways, cell cycle activity, and potential amplicon regions which can aid in diagnosis and guide treatment decisions. Our results highlight the potential of FGI as a robust visualization tool for personalized medicine in molecular diagnosis.

Diabetic nephropathy (DN) is a common diabetes-related complication with unclear underlying pathological mechanisms. Although recent studies have linked glycolysis to various pathological states, its role in DN remains largely underexplored.

Regeneration is the preferred approach to restore the structure and function after tissue damage. Rapid proliferation of cells over the site of damage is integral to the process of regeneration. However, even subtle mutations in proliferating cells may cause detrimental effects by eliciting abnormal differentiation. Interestingly deer antlers, arguably the fastest regenerating mammalian tissue, have not been reported, thus far, to grow malignant tumors. They provide a mammalian model to understand the possible mechanism by which rapid regeneration is achieved while avoiding the development of malignancies. Antler regeneration is based on the proliferation and differentiation of antler stem cells (AnSCs).

Multiple myeloma (MM) is a hematological malignancy characterized by uncontrolled proliferation of plasma cells and is currently incurable. Despite advancements in therapeutic strategies, resistance to proteasome inhibitors, particularly bortezomib (BTZ), poses a substantial challenge to disease management. This study aimed to explore the efficacy of boanmycin, a novel antitumor antibiotic, in overcoming resistance to BTZ in MM.

Despite the increasing body of evidence that mitochondrial activities implicate in chronic obstructive pulmonary disease (COPD), we are still far from a causal-logical and mechanistic understanding of the mitochondrial malfunctions in COPD pathogenesis.

Carotid atherosclerotic plaque is the primary cause of cardiovascular and cerebrovascular diseases. It is closely related to oxidative stress and immune inflammation. This bioinformatic study was conducted to identify key oxidative stress-related genes and key immune cell infiltration involved in the formation, progression, and stabilization of plaques and investigate the relationship between them.

Oral squamous cell carcinoma (OSCC) is the most frequent type of oral malignancy with high metastasis and poor prognosis. The deubiquitinating enzyme Ubiquitin Specific Peptidase 44 (USP44) regulates the mitotic checkpoint, and its deficiency leads to aneuploidy and increases tumor incidence. However, the role of USP44 in OSCC is not well understood. Herein, we analyzed mRNA sequencing data of OSCC samples downloaded from the TCGA and GEO databases and found that USP44 was decreased in human OSCC tissues and was positively correlated to the survival of OSCC patients. To investigate the biological impact of USP44, we used recombinant lentiviruses to overexpress or knockdown USP44 expression in OSCC cell lines, which were also injected subcutaneously or into the lateral tail vein of Male BALB/c nude mice to model tumorigenesis or lung metastasis in vivo, respectively. The results showed that overexpression of USP44 inhibited malignant cell phenotypes in vitro and suppressed tumor growth and lung metastasis in vivo, while its downregulation had the opposite effects. Comprehensive proteomic analyses through Co-IP mass spectrometry and label-free quantitative LC-MS/MS methods identified 112 differentially expressed proteins positively regulated by USP44, among which 13 were involved in cancer-related pathways including apoptotic signaling and cell cycle regulation. PPI analysis identified Hexamethylene Bis-Acetamide-Inducible Protein 1 (HEXIM1) as the hub protein. Upregulation of USP44 enhanced HEXIM1 protein stability, leading to its higher expression in OSCC cells. Silencing of HEXIM1 further enhanced the malignant phenotype of OSCC cells. At the same time, HEXIM1 knockdown reversed the antitumor effects of USP44. These findings demonstrated that USP44 acted as a critical tumor suppressor in OSCC by inhibiting cell proliferation and metastasis through the stabilization of HEXIM1 protein, suggesting that USP44-HEXIM1 axis is a promising target for OSCC therapy.

Alveolar macrophages (AMs) is critical to exacerbate acute lung injury (ALI) induced by lipopolysaccharide (LPS) via inhibiting inflammation, which could by shifted by mesenchymal stem cell-derived exosomes (MSC-exos). But the underlying rationale is not fully clarified. Our study aimed to analyze the significance of itaconic acid (ITA) in mediating the protective effects of MSC-exos on LPS-induced ALI.

Intrauterine adhesion (IUA) is a common cause of clinically refractory infertility, and there exists significant heterogeneity in the treatment outcomes among IUA patients with the similar severity after transcervical resection of adhesion(TCRA). The underlying mechanism of different treatment outcomes occur remains elusive, and the precise contribution of various cell subtypes in this process remains uncertain.

Spermatogonial stem cells (SSCs) form haploid gametes through the precisely regulated process of spermatogenesis. Within the testis, SSCs undergo self-renewal through mitosis, differentiation, and then enter meiosis to generate mature spermatids. This study utilized single-cell RNA sequencing on 26,888 testicular cells obtained from five Holstein bull testes, revealing the presence of five distinct germ cell types and eight somatic cell types in cattle testes. Gene expression profiling and enrichment analysis were utilized to uncover the varied functional roles of different cell types involved in cattle spermatogenesis. Additionally, unique gene markers specific to each testicular cell type were identified. Moreover, differentially expressed genes in spermatogonia exhibited notable enrichment in GO terms and KEGG pathway linked to alternative splicing. Notably, our study has shown that the activity of the YY1 regulation displays distinct expression patterns in spermatogonia, specifically targeting spliceosome proteins including RBM39, HNRNPA2B1, HNRNPH3, CPSF1, PCBP1, SRRM1, and SRRM2, which play essential roles in mRNA splicing. These results emphasize the importance of mRNA processing in spermatogonia within cattle testes, providing a basis for further investigation into their involvement in spermatogonial development.

Hepatocellular carcinoma (HCC) is the leading cause of cancer-related deaths worldwide, and the lack of effective biomarkers for early detection leads to poor therapeutic outcomes. Prostaglandin E Synthase 3 (PTGES3) is a putative prognostic marker in many solid tumors; however, its expression and biological functions in HCC have not been determined. The proteolysis-targeting chimera (PROTAC) is an established technology for targeted protein degradation. Compared to the small-molecule PROTAC, the peptide PROTAC (p-PROTAC) utilizes peptides bound to target proteins to mediate the ubiquitination and degradation of undruggable proteins. This study aimed to use the PROTAC technology to develop a PTGES3 degrader liposome complex containing a PTGES3-binding peptide and the E3 ubiquitin ligase ligand pomalidomide for regulating cell function and provide a novel pathway for treating HCC.

Integrating multi-layered information can enhance the accuracy of genomic prediction for complex traits. However, the improvement and application of effective strategies for genomic prediction (GP) using multi-omics data remains challenging.

Prostate cancer is the most common diagnosed tumor and the fifth cancer related death among men in Europe. Although several genetic alterations such as ERG-TMPRSS2 fusion, MYC amplification, PTEN deletion and mutations in p53 and BRCA2 genes play a key role in the pathogenesis of prostate cancer, specific gene alteration signature that could distinguish indolent from aggressive prostate cancer or may aid in patient stratification for prognosis and/or clinical management of patients with prostate cancer is still missing. Therefore, here, by a multi-omics approach we describe a prostate cancer carrying the fusion of TMPRSS2 with ERG gene and deletion of 16q chromosome arm.