Electronic Journal of Biotechnology

Identification and validation of adenylate uridylate (AU)-rich element (ARE)-related biomarkers in the process of treating lung cancer mice with Wenyang Hualiu Tang through bulk RNA sequencing and animal model

Wen-xin Li, Teng-yu Wang, Hui-ting Wu, Ming-feng Xiong — Wed, 15 Jul 2026 00:00:00 +0000

Background: Lung cancer (LC) remains the leading cause of cancer-related mortality. While the traditional formula Wenyang Hualiu Tang (WYHLT) has shown efficacy against LC, the role of adenylate uridylate (AU)-rich element (ARE)-related genes (AREGs) in this disease and its treatment is unexplored. This study aimed to elucidate the mechanism by which AREGs are involved in WYHLT treatment of LC.

Results: Transcriptome sequencing of a mouse LC model with WYHLT intervention (low, medium, high dose) identified four key biomarkers: GREB1, MUC2, NPTX2, and PPIP5K1. Enrichment analysis linked MUC2, NPTX2, and PPIP5K1 to translation. A constructed regulatory network revealed interactions involving three biomarkers (PPIP5K1, GREB1, NPTX2), 16 long non-coding RNAs (lncRNAs), and 10 circular RNAs (circRNAs), with lncRNA Malat1 targeting four microRNAs (miRNAs). Drug prediction analysis identified seven drugs targeting MUC2 and one targeting NPTX2, with PD-98059 showing the highest binding affinity for MUC2. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) validation confirmed that WYHLT intervention increased PPIP5K1 and MUC2 expression and decreased GREB1 and NPTX2 expression compared to the LC model.

Conclusions: This study identifies GREB1, MUC2, NPTX2, and PPIP5K1 as potential biomarkers involved in WYHLT treatment of LC. The findings provide new insights into the molecular mechanisms of WYHLT and novel directions for LC therapeutic research.

Surfactant protein D regulates Notch activity for secretory cell repair and regeneration to prevent post-acute pancreatitis diabetes

Jiexin Yan, Shuxiong Liu, Jian He — Wed, 15 Jul 2026 00:00:00 +0000

Background: Pancreatic endocrine dysfunction following acute pancreatitis (AP) can lead to glucose intolerance and even diabetes. Surfactant protein D (SP-D), as an immune regulatory molecule, has not yet been clarified whether it participates in the regeneration of pancreatic acinar cells and β-cells by modulating the Notch pathway, thereby improving abnormal glucose metabolism. This study aimed to elucidate the role and mechanism of SP-D in promoting the regeneration of pancreatic secretory cells following AP and preventing post-pancreatitis diabetes by regulating the activity of the Notch pathway.

Results: Using wild-type and SP-D gene knockout (SP-D⁻/⁻) mice as models, dynamic observations were made after AP induction by Cerulein. Western blot analysis of pancreatic tissue revealed that in the SP-D⁻/⁻-AP group (DG), the key Notch pathway molecules NICD and Hes1 were persistently upregulated; the expression of acinar cell regeneration marker SOX9 and β-cell precursor differentiation marker NGN3 was reduced, and the recovery of the β-cell function marker insulin was delayed. Glucose metabolism testing revealed that the DG had significantly elevated fasting blood glucose (7.6 ± 0.5 mmol/L) at 30 d and an increased area under the curve in the oral glucose tolerance test. Sustained elevation of serum amylase and insufficient insulin secretion were observed, along with a markedly delayed repair process.

Conclusions: SP-D promotes the regeneration and functional recovery of pancreatic acinar cells and β-cells by inhibiting the overactivation of the Notch pathway, thereby improving abnormal glucose metabolism following AP.

Integrated single-cell RNA sequencing and multi-database analysis reveal THBS2 promotes high glucose-induced mesangial cell oxidative stress and fibrosis in diabetic nephropathy

Lin Lei, Jingxia Guo, Xin Wang, Min Liu, Chenxi Liu — Wed, 15 Jul 2026 00:00:00 +0000

Background: Single-cell RNA sequencing (scRNA-seq) has provided unprecedented resolution for the study of many diseases, including diabetic nephropathy (DN). However, the effective genes regulating oxidative stress and fibrosis in mesangial cells in DN remain to be revealed. In this study, scRNA-seq and multi-database analysis were used to identify thrombospondin 2 (THBS2) as a key gene in regulating DN progression.

Results: The scRNA-seq revealed a total of 6 important cell types in diabetic kidney disease (DKD) from the Gene Expression Omnibus (GEO) database (GSE209781). GO and KEGG analysis showed that the differential genes in mesangial cells of DKD had multi-function and multi-pathway regulation. A total of 4 target genes (ITGB1, THBS2, TIMP1 and COL18A1) were screened by taking the intersection of scRNA-seq (mesangial cells-related genes), GEO database (GSE1009) and GeneCards database (oxidative stress-related genes and renal fibrosis-related genes). THBS2 was overexpressed in high glucose (HG)-induced mesangial cells, and its knockdown inhibited HG-induced mesangial cell oxidative stress and fibrosis.

Conclusions: Based on scRNA-seq, multi-database analysis and experimental verification, this study showed that THBS2 might promote HG-induced mesangial cell oxidative stress and fibrosis in DN.

Identification of MORC2 via bioinformatics and machine learning reveals its transcriptional activation by PAX2 in NSCLC malignancy

Junyan Cao, Fang Cai, Jun Jia, Jiangtao Guo, Xiu Yang — Wed, 15 Jul 2026 00:00:00 +0000

Background: Non-small cell lung cancer (NSCLC) represents the top contributor to cancer-associated deaths globally, and its suboptimal clinical outcomes are linked to late-stage detection and acquired resistance to existing therapies. Microrchidia family CW-type zinc finger 2 (MORC2) has been found to exhibit oncogenic potential in NSCLC, but its transcriptional regulatory mechanisms and role in glycolytic reprogramming remain unclear.

Results: As a key gene, MORC2 was found to be overexpressed in NSCLC and linked to poor prognosis. MORC2 silencing impaired cell proliferation, stemness, and invasion, diminished glycolysis, and enhanced apoptosis. PAX2 was confirmed to directly transcriptionally activate MORC2; overexpression of MORC2 reversed the defects in malignant phenotypes induced by PAX2 knockdown. In vivo, depletion of PAX2 suppressed tumor growth, which was partially rescued by MORC2 overexpression.

Conclusions: The PAX2/MORC2 axis was demonstrated to drive NSCLC malignancy, supporting MORC2 as a potential prognostic marker and therapeutic target for NSCLC.

ABL1-STAT3-NLRP3 axis attenuates pyroptosis and alleviates diabetic retinopathy

Lili Hu, Gong Chen, Haoning Pan, Shaoxin Pan — Wed, 15 Jul 2026 00:00:00 +0000

Background: Diabetic retinopathy is a major microvascular complication of diabetes and a leading cause of vision loss. Persistent low-grade inflammation drives disease progression. Pyroptosis, characterized by its pro-inflammatory nature, is involved in several inflammatory diseases, yet the molecular mechanisms specific to diabetic retinopathy remain largely undefined. This study aimed to identify the key molecular drivers and regulatory pathways of pyroptosis in diabetic retinopathy.

Results: Five key pyroptosis-related genes were identified: ubiquitin-specific peptidase 24, signal transducer and activator of transcription 3, and ABL proto-oncogene 1 were upregulated, while tripartite motif containing 24 and tubulin beta 6 class VI were downregulated in diabetic retinopathy. High glucose exposure induced pyroptotic morphology and increased lactate dehydrogenase, interleukin-1 beta, and interleukin-18 levels. Functional assays demonstrated that ABL proto-oncogene 1 acts upstream of signal transducer and activator of transcription 3 to activate the NOD-like receptor family pyrin domain-containing 3 inflammasome, ultimately leading to pyroptosis. Signal transducer and activator of transcription 3 showed strong diagnostic value with an area under the curve exceeding 0.9.

Conclusions: This study identifies a novel ABL proto-oncogene 1–signal transducer and activator of transcription 3–NOD-like receptor family pyrin domain containing 3 signaling axis as a central regulator of pyroptosis in diabetic retinopathy. These findings provide insights into inflammation-induced retinal pathology and suggest candidate molecular targets for therapeutic intervention.