Biomedical subjects

Wen Zhang

Publications and source records attributed to Wen Zhang.

8 recordsLinked to original sources

PubMed2026

Discovery and evolution of endogenous retroviruses in the genome of crab-eating macaque (Macaca fascicularis).

Endogenous retroviruses (ERVs) are a dynamic and biologically significant component of vertebrate genomes, with integration events spanning deep evolutionary time. The crab-eating macaque (Macaca fascicularis) is an important non-human primate model for biomedical research because of its close phylogenetic relationship to humans and its conservation status as an endangered species. However, the ERV complement of its genome has not been systematically characterized. Using the current highest-quality chromosome-level genome assembly for this species, we performed a genome-wide, homology-based survey of relatively intact ERV proviruses in M. fascicularis. We identified 106 proviral loci distributed across all chromosomes. Phylogenetic reconstruction based on conserved reverse transcriptase domains classified these elements into β-, γ-, and unclassified lineages, with β- and γ-retroviral lineages predominating. LTR divergence-based dating indicated that these proviruses represent multiple waves of historical retroviral activity and span a broad range of integration ages. This curated dataset provides a high-confidence reference set for investigating the evolutionary history and genomic impact of preserved ERV proviruses in an endangered primate model; however, it does not include degraded ERV fragments or solo LTRs.

Animals↗

PubMed2026

Blood and gut virome remodeling in gastric cancer: Anellovirus expansion and novel virus discovery.

Gastric cancer (GC) is a prevalent malignancy worldwide, yet effective early diagnostic tools remain lacking, and the role of the virome, a key component of the tumor microenvironment, in GC progression is largely unknown. This study aimed to characterize the virome landscapes in peripheral blood and feces of GC patients versus healthy controls, and to identify viral signatures associated with GC onset and metastasis. We performed viral metagenomic sequencing on pooled libraries from 100 GC patients (45 non-metastatic, 55 metastatic) and 50 healthy controls, followed by taxonomic annotation, diversity assessment, LEfSe differential abundance testing, and co-occurrence network analysis. In blood, the GC virome shifted from a bacteriophage-dominated profile in controls to one overwhelmingly dominated by Anelloviridae (> 80%), with significantly decreased alpha diversity. In contrast, the gut virome of GC patients showed increased alpha diversity and coexistence of diverse bacteriophages. LEfSe identified betatorquevirus in blood as a key discriminatory taxon for GC. Network analysis revealed negative correlations between Anelloviridae and multiple bacteriophage families, suggesting niche competition. We also discovered 67 provisional novel anellovirus species and one novel gemykibivirus in GC patient blood. Collectively, our findings indicate that GC is associated with compartment-specific virome remodeling in blood and gut, and that expansion of blood anelloviruses holds promise as a non-invasive biomarker. This study provides a foundational resource for understanding the virome's role in GC.

Humans↗

PubMed2026

Targeting cancer stem cells predicts response and reverses chemoresistance in ascites-derived ovarian cancer organoids.

BACKGROUND: Ovarian cancer (OC) is frequently diagnosed at an advanced stage, where tumor heterogeneity and rapid development of chemoresistance contribute to a poor prognosis. The lack of reliable predictive biomarkers further hinders the development of effective treatment strategies. Patient-derived organoids (PDOs) have recently emerged as promising preclinical models with the potential to predict therapeutic responses. METHODS: OC PDOs were generated from ascites samples representing diverse histological subtypes. Histological and genomic fidelity to parental tumors was confirmed through histopathological analysis and whole-exome sequencing. Drug sensitivity to cisplatin and poly (ADP-ribose) polymerase (PARP) inhibitors was evaluated and correlated with 1-year clinical outcomes. We also investigated the therapeutic efficacy of oncolytic herpes simplex virus 2 (OH2) both as a single agent and in combination with cisplatin. The expression of cancer stem cell (CSC) markers CD44 and ALDH1A1 under treatment conditions was analyzed using immunohistochemistry and flow cytometry. RESULTS: PDOs were successfully established with an 86.2% success rate. These PDOs faithfully recapitulated the histopathological and genomic features of their corresponding tumors, maintaining intratumoral heterogeneity, and were amenable to xenotransplantation. Drug sensitivity assays demonstrated that PDOs accurately predicted patient-specific responses to cisplatin and PARP inhibitors. OH2 exhibited direct cytotoxicity in both cisplatin-sensitive and cisplatin-resistant PDOs, reducing cell viability by 20-60%. Notably, the combination treatment with OH2 and cisplatin enhanced antitumor efficacy, resulting in a significant reduction of the CD44+CSC subpopulation. CONCLUSIONS: Ascites-derived OC PDOs represent a robust platform for individualized drug testing. The combination of OH2 and cisplatin offers a novel and effective strategy for circumventing chemoresistance in OC.

Female↗

PubMed2026

AGRN activates GPX4 via the Wnt/beta-catenin signaling pathway to suppress ferroptosis in cervical cancer cells.

Cervical cancer remains a leading cause of cancer-related deaths among women worldwide. Targeting ferroptosis, a regulated form of cell death driven by lipid peroxidation, has emerged as a promising therapeutic strategy. This study aimed to elucidate the mechanisms by which cervical cancer cells acquire resistance to ferroptosis. AGRN expression and its prognostic significance were analyzed in cervical cancer using TCGA and GTEx data. In vitro, AGRN levels were measured in HeLa, CaSki, and Ect1/E6E7 cells via qRT-PCR. mRNA and protein expression levels of AGRN, beta-catenin, and ferroptosis-related markers were evaluated by qRT-PCR and western blot (WB). Cell viability, RSL3 sensitivity (IC50), and lipid ROS were assessed via CCK-8 assay and flow cytometry. In a xenograft model, RSL3's effect on tumor growth was examined. Immunohistochemistry (IHC) and molecular analyses (qRT-PCR, WB, and flow cytometry) were performed on tumor tissues to evaluate AGRN, beta-catenin, Ki-67, ferroptosis-related genes, and lipid ROS. It is found through research that, AGRN was significantly upregulated in cervical cancer tissues and cell lines. Its overexpression activated Wnt/beta-catenin signaling, resulting in elevated GPX4 and SLC7A11 levels and reduced CHAC1 and PTGS2 expression levels. These alterations decreased lipid ROS accumulation and enhanced resistance to RSL3-induced ferroptosis, an effect further confirmed in xenograft models. In short, In short, AGRN promotes ferroptosis resistance in cervical cancer by activating the Wnt/beta-catenin signaling pathway and upregulating GPX4 expression. Targeting the AGRN-Wnt/beta-catenin-GPX4 axis may represent a novel therapeutic approach for cervical cancer.

Humans↗

PubMed2025

Diversity and evolutionary history of endogenous retroviruses in the genome of Manis pentadactyla.

Endogenous retroviruses (ERVs), remnants of ancient viral infections integrated into host genomes, serve as invaluable molecular fossils for studying viral evolution. In this study, we performed a genomic analysis of the Chinese pangolin (Manis pentadactyla), identifying novel full-length endogenous retroviruses, designated as Manis pentadactyla ERVs (MPERVs). MPERVs span three retroviral genera: Alpha-, Beta-, and Gamma-retroviruses. Using genomic screening and phylogenetic analysis, we classified MPERVs and reconstructed their evolutionary history, uncovering evidence of complex recombination events and cross-species transmission. Estimated insertion times for MPERVs range from very recent to 18.38 million years ago. MPERVs exhibit diverse structural features, notably including conserved retroviral domains and functional motifs and highlighting their preservation across extensive evolutionary periods. These findings shed light on the evolutionary dynamics of ERVs in Chinese pangolin and suggest the potential for expanded host ranges among certain retrovirus genera.IMPORTANCEEndogenous retroviruses are unique viruses distinguished by the fact that they are retained as part of the host genome after an exogenous retrovirus infects the host. The Chinese pangolin, as a host with a long independent evolutionary history, likely holds valuable insights in its genome regarding retrovirus endogenization and transmission. In this study, we identified the footprints of exogenous retroviruses from three different genera in the pangolin genome: Alpharetrovirus, Betaretrovirus, and Gammaretrovirus. Additionally, by calculating the integration times of the pangolin's endogenous retroviruses and analyzing the domains of the three main functional proteins (GAG, POL, and ENV), we found that the insertions are relatively young. This suggests that these endogenous retroviruses infected the Chinese pangolin long before their endogenization. This study represents the exploration of endogenous retroviruses in the Chinese pangolin genome, expanding our understanding of endogenous retroviruses in mammals. Furthermore, our findings provide new evidence for the phenomenon of the cross-species transmission of retroviruses prior to endogenization.

Endogenous Retroviruses↗

PubMed2025

Development and application of a novel beta-tubulin genotyping tool reveals host-specific transmission cluster in Balantioides coli.

Balantioides coli is a zoonotic ciliated protozoan that infects humans and other mammals. Conventional and ITS-based genotyping approaches have limitations that hinder precise molecular epidemiological investigations. The objective of this study was to develop a new β-tubulin gene-based approach to enhance the detection and genotyping of B. coli. We performed single-cell isolation and whole-genome sequencing on two B. coli isolates from pigs and two from guinea pigs. We then used the β-tubulin gene sequences to design PCR primers for the new genotyping assay. We validated the assay using 56 ITS-confirmed B. coli-positive fecal DNA samples from pigs, cattle, sheep, and guinea pigs. Phylogenetic analyses were conducted using both β-tubulin and ITS sequences. The β-tubulin-based nested PCR assay exhibited 100% detection efficiency and greater specificity than ITS-based methods. Phylogenetic analysis of the β-tubulin gene sequences classified B. coli into three genotypes (I-III). Genotype III appears to be specific to guinea pigs. Genotypes I and II were found across multiple hosts, indicating potential cross-species transmission. Of the five full-length B. coli β-tubulin sequences obtained in this study, 264 polymorphic sites (19.8%) were identified, including both synonymous and non-synonymous mutations. Frequent recombination events within the β-tubulin locus were detected, indicating substantial genetic diversity. Therefore, the β-tubulin gene is a robust marker for genotyping and epidemiological studies of B. coli. The novel nested PCR assay overcomes the limitations of ITS-based methods and has produced data revealing previously unrecognized genetic diversity and host specificity patterns of B. coli.

Tubulin↗

PubMed2025

Effects of Different Feeding Patterns on the Gut Virome of 6-Month-Old Infants.

The gut microbiome is essential for infant health, and in recent years, the impact of enteroviruses on infant health and disease has received increasing attention. The transmission of breast milk phages to the infant gastrointestinal tract contributes to the shaping of the infant gut virome, while breastfeeding regulates the colonization of the infant gut virome. In this study, we collected fecal samples from healthy infants and analyzed the distribution characteristics of infant viral communities by viral metagenomic analysis, and analyzed the differences in infant viral communities under different feeding practices. Our results indicate that the infant intestinal virome consists of phages and eukaryotic viruses. Caudovirales and Microviridae dominated the phage composition, and except for Siphoviridae, which was more predominant in the intestines of formula-fed infants, there were no significant differences in the overall abundance of other Caudovirales and Microviridae in the intestines of infants with different feeding patterns. Breastfeeding can lead to a higher diversity of infant gut viruses through vertical transmission, and a highly diverse gut virome helps maintain the maturation of the gut microbiome. This study informs the shaping of gut virome in healthy infants by breastfeeding and contributes to further research on infant gut virome characteristics and formation processes.

Humans↗

PubMed2018

E3 Ligase VHL Promotes Group 2 Innate Lymphoid Cell Maturation and Function via Glycolysis Inhibition and Induction of Interleukin-33 Receptor.

Group 2 innate lymphoid cells (ILC2s) are a specialized subset of lymphoid effector cells that are critically involved in allergic responses; however, the mechanisms of their regulation remain unclear. We report that conditional deletion of the E3 ubiquitin ligase VHL in innate lymphoid progenitors minimally affected early-stage bone marrow ILC2s but caused a selective and intrinsic decrease in mature ILC2 numbers in peripheral non-lymphoid tissues, resulting in reduced type 2 immune responses. VHL deficiency caused the accumulation of hypoxia-inducible factor 1α (HIF1α) and attenuated interleukin-33 (IL-33) receptor ST2 expression, which was rectified by HIF1α ablation or inhibition. HIF1α-driven expression of the glycolytic enzyme pyruvate kinase M2 downmodulated ST2 expression via epigenetic modification and inhibited IL-33-induced ILC2 development. Our study indicates that the VHL-HIF-glycolysis axis is essential for the late-stage maturation and function of ILC2s via targeting IL-33-ST2 pathway.

Animals↗