Biomedical subjects

Dandan Zhang

Publications and source records attributed to Dandan Zhang.

5 recordsLinked to original sources

PubMed2026

Mycobacterium tuberculosis Rv0158 negatively regulates the cGAS-STING pathway mediated type I IFN production and enhances intracellular survival.

BACKGROUND: Type I interferons (IFN) play an important role in the host defense against Mycobacterium tuberculosis (M. tb) infection and disease pathogenesis. Although M. tb has evolved several mechanisms to evade host immune surveillance, the mechanism used to regulate type I IFN expression remains unclear. METHODS: In this study, genome-wide high-throughput loss-of-function screening was performed to screen M. tb determinants that regulate the Type I IFN pathway, and the role for M. tb Rv0158 in inhibiting type I IFN responses was identified in vitro and in vivo. RESULTS: The M. tb coding protein Rv0158 was identified among many transposon (Tn) insertion mutants, which increased the expression of IFN-β and some pro-inflammatory cytokines. The results suggested that Rv0158 is associated with reduced STING protein levels and suppression of cGAS-STING-mediated innate immune responses, suggesting that Rv0158 may indirectly facilitate STING degradation or modulate its stability through host-interacting partners. Rv0158 also down-regulated the transcription of interferon-stimulated genes (ISGs) and increased the bacterial load in mice. CONCLUSION: Overall, our finding identified a new bacterial factor Rv0158, these results reveal an important role for M. tb Rv0158 in inhibiting Type I IFN responses, which improves our understanding of the immune evasion mechanisms of M. tb.

Immune escape↗

PubMed2026

Ethylene signaling negatively regulates rapeseed resistance to Plasmodiophora brassicae.

Clubroot, caused by Plasmodiophora brassicae, poses a serious threat to the rapeseed (Brassica napus) industry. Due to B. napus being an allopolyploid with a complex genome and the current scarcity of available resistance gene resources, the molecular basis of rapeseed resistance to P. brassicae remains poorly understood. Here, we performed a functional characterization of BnEIN2 (ethylene-insensitive protein) to explore the role of ethylene signaling in rapeseed resistance to P. brassicae. The Bnein2 mutants generated through CRISPR/Cas9 technology exhibited enhanced resistance to P. brassicae, along with reduced 1-aminocyclopropane-1-carboxylic acid (ACC)/S-adenosyl-L-methionine (SAM) accumulation and ethylene insensitivity. Pharmacological assays demonstrated that inhibitors of ethylene biosynthesis or signaling improved the resistance of Bnein2 mutant plants to P. brassicae. Transcriptome analysis revealed that loss-of-function of BnEIN2 affected the expression of ethylene-, auxin-, and cytokinin-related genes. Moreover, the increased resistance of Bnein2 mutants to P. brassicae was accompanied by a reduction in auxin (indole-3-acetic acid, IAA) biosynthesis and degradation of cytokinin (trans-zeatin, TZ). Collectively, these findings establish the negative regulatory role of ethylene signaling in rapeseed resistance to P. brassicae. This study represents the first effort to elucidate rapeseed resistance to P. brassicae by directly obtaining rapeseed genetic material and offer novel insights into the hormonal regulatory network underlying disease resistance and valuable resources for breeding clubroot-resistant varieties.

BnEIN2↗

PubMed2026

Chronic heart failure and GPX3 promoter methylation: A clinical-epigenetic analysis.

BACKGROUND: Selenoprotein GPX3 is linked to Chronic Heart Failure (CHF), but its promoter methylation patterns in CHF remain unclear. OBJECTIVE: To explore CpG methylation in the GPX3 promoter region and its association with clinical parameters in CHF. METHODS: Twenty CHF patients and twenty healthy controls were included. Methylation levels of CpG sites within the GPX3_FA28 promoter region were quantified. Group differences were assessed using appropriate statistical tests. Restricted cubic spline (RCS) models were applied to explore dose-response associations between differentially methylated CpG sites and clinical indicators across multiple physiological systems. RESULTS: Significant locus-specific methylation alterations were identified in CHF patients. CpG_5 showed hypermethylation (P = 0.017), while CpG_9 (P = 0.045) and CpG_19 (P = 0.008) were hypomethylated compared with controls. Patients with NYHA class I/II exhibited higher methylation at CpG_1 (P = 0.028) and CpG_2 (P = 0.040). CpG_5 methylation displayed nonlinear associations (P < 0.05) with total bilirubin (inverted U-shape), carbon dioxide (triphasic), total cholesterol (U-shape), and plateletcrit (wave-like). CpG_9 correlated with activated partial thromboplastin time and hematopoietic markers, while CpG_19 was linked to eosinophil percentage and erythrocyte parameters. CONCLUSIONS: GPX3 promoter methylation displays apparent locus specificity in CHF. Different CpG sites may contribute to CHF pathophysiology through distinct epigenetic mechanisms. These findings highlight the potential of GPX3 methylation as a stratified biomarker in CHF.

Humans↗

PubMed2026

Novel serum small extracellular vesicle miRNAs with multi-target RCA-CRISPR sensor for liver cancer detection.

BACKGROUND: Detecting liver cancer (LC) remains a significant challenge in clinical practice. Small extracellular vesicle (sEV) miRNAs show promise as non-invasive biomarkers for LC detection, yet their diagnostic potential remains largely unexplored. This study aimed to identify specific sEV miRNA signatures for LC detection and develop a novel synchronized multi-miRNA detection platform to enhance diagnostic efficiency and sensitivity. METHODS: High-throughput sequencing was conducted across four distinct cohorts: normal controls (NC), hepatitis B virus (HBV) patients, liver cirrhosis patients, and LC patients. This sequencing process identified miRNAs with differential expression, followed by RT-qPCR validation in serum sEV miRNAs from LC patients and NC. An innovative detection method, RCA-CRISPR, was introduced, combining rolling circle amplification (RCA) with CRISPR/Cas12a (RCA-CRISPR) for quick and sensitive miRNAs detection. RESULTS: Sequencing results showed a consistent elevation of hsa-miR-203b-5p, hsa-miR-4661-5p, and hsa-miR-219a-2-3p across all cohorts. RT-qPCR validations confirmed significant upregulation of these miRNAs in serum sEVs from LC patients, and the combined three-miRNA panel exhibited high diagnostic accuracy (p = 0.0003; AUC = 0.81). The RCA-CRISPR method demonstrated a detection limit of 3.12 pM for simultaneous multi-target miRNA detection, highlighting its exceptional sensitivity. CONCLUSIONS: Our study identifies hsa-miR-203b-5p, hsa-miR-4661-5p, and hsa-miR-219a-2-3p as promising sEV miRNA biomarkers for LC detection. The developed RCA-CRISPR sensor provides a robust tool for multi-miRNA analysis, potentially advancing non-invasive LC diagnostics. Future validation in larger, prospectively collected cohorts is essential to establish the clinical utility and performance of this biomarker panel and RCA-CRISPR sensor.

MicroRNAs↗

PubMed2024

Decoding the trajectory of antibiotic resistance genes in saline and alkaline soils: Insights from different fertilization regimes.

The soil salinity and alkalinity play an important role in the occurrence and proliferation of antibiotic resistance genes (ARGs). Yet, little is known the underlying mechanism by which soil salinity and alkalinity affect antibiotic resistance evolution. Here we investigated the ARGs variation in soil salinity and alkalinity environments created by different fertilization, and explored the biological mechanisms that salinity and alkalinity alter the evolutionary paradigm of antibiotic resistance. The results showed the soil treated by organic fertilizer exhibited a low salinity, neutral level (TSD 239.20 μS/cm, pH 7.17). The ARG abundance in the OF treatment was the highest, keeping an average of 67.83 TPM. Beside the effect of direct input of organic fertilizer at the beginning, it was important to note that, ARGs abundance during planting showed significant correlations with pH and electric conductivity. We observed that changes in microbial survival strategies under different salinity and alkalinity conditions further affected ARG hosts abundance. Indoor experiments demonstrated that there was a survival trade-off between the growth of resistant bacteria and the evolution of antibiotic resistance in salinity and alkalinity environments. Meta-genomic and Meta-transcriptomic analysis consistently demonstrated bacterial antibiotic resistance was primarily associated with pyruvate, energy and lipid metabolic pathways. The functional gene related to salinity and alkalinity, like cysH, cysK, plsB and plsC showed negative correlations with MDR. Prokaryotic transcription assays validated these relations. This study well explains the prevalence of soil ARGs after different fertilization regimes and will give a deeper understanding for the effect of soil salinity and alkalinity on antibiotic resistance evolution.

Soil↗