Biomedical subjects

Jing Gong

Publications and source records attributed to Jing Gong.

13 recordsLinked to original sources

PubMed2026

Large-scale pleiotropic analysis across cancers reveals shared genetic mechanisms and identifies novel functional genes.

Pleiotropic genetic loci have been increasingly reported in cancer, and identifying genetic variants with pleiotropic associations can reveal shared biological pathways influencing multiple cancers. Using summary statistics from genome-wide association studies for 37 cancer types (N = 433 836), we identified extensive genome-wide and local genetic correlations among cancers. Through pairwise pleiotropic analysis, we identified 75 243 significant pleiotropic single nucleotide polymorphisms (SNPs) across 372 cancer pairs, among which 3472 were lead SNPs with potential regulatory functions. Using FUMA and MAGMA, we identified 2527 pleiotropic risk loci and 4272 candidate pleiotropic genes. Notably, genes such as TERT (5p15.33), POU5F1B (8q24.21), and FANCA (16q24.3) exhibited widespread pleiotropy across multiple cancer types. Pathway enrichment analysis highlighted the critical roles of pigment synthesis, metabolism, and apoptosis in skin-related cancers, while cross-cancer enrichment analysis emphasized pathways related to apoptosis, chromatin structure, and intermediate filaments. We also identified 33 novel functional genes harboring previously unreported cancer risk variants. Drug-gene interaction analysis revealed several repositionable FDA-approved drugs. Importantly, drug sensitivity assays demonstrated that bosutinib and cobimetinib exhibited promising therapeutic potential in breast cancer cell lines. Finally, we developed the PleioCancer database (https://gonglab.hzau.edu.cn/PleioCancer/), providing a comprehensive resource for cancer pleiotropy research. These findings have important implications for carcinogenesis cancer, prevention and treatment.

Humans↗

PubMed2026

Genetic regulation of CPEB3-mediated alternative polyadenylation associated with survival of patients with hepatocellular carcinoma.

BACKGROUND: Alternative polyadenylation (APA) is a key post-transcriptional mechanism that regulates gene expression by modulating 3'UTR length, its dysregulation has been implicated in carcinogenesis. How genetic variants influence APA to affect hepatocellular carcinoma (HCC) prognosis remains unclear. METHODS: Prognosis-APA quantitative trait loci (apaQTL) were performed using genotype and APA profiling from TCGA data. A two-stage survival analysis in 848 Chinese and 369 TCGA LIHC patients and functional validation were used to identify prognostic apaQTL in HCC progression. RESULTS: A total of 2,025 and 817 significant APA events were identified in Chinese and TCGA cohort, respectively. Besides, 859 events were associated with poor prognosis in HCC and enriched in RNA splicing / metabolism pathways. We detected 32,034 significant apaQTLs, predominantly enriched in 3'UTRs and RBP-binding regions. CPEB3 was prioritized as a key APA regulator RBP; its low expression correlated with poor patient survival and promoted proliferation, migration, and invasion in HCC cells. Notably, a functional apaQTL variant rs2037547, located in GSK3B and mediated by CPEB3, demonstrated a poor survival of HCC patients in both cohort (pooled HR=1.29, p=0.016). Mechanistically, rs2037547 promoted aberrant APA at proximal poly(A) sites of GSK3B through CPEB3, leading to increased expression of short 3'UTR isoform. This regulatory alteration enhanced HCC cell proliferation, invasion, and migration, and contributed to HCC progression. CONCLUSION: These findings elucidated the distinct role of apaQTL-mediated APA dysregulation in HCC prognosis, providing insights for prognostic stratification and potential targets for personalized therapy in HCC.

RNA-binding proteins↗

PubMed2026

Genome-wide annotation of human multi-nucleotide variants reveals widespread functional differences from single nucleotide variants.

Multi-nucleotide variants (MNVs) represent a crucial yet underexplored category of genetic variation. Despite previous studies highlighting the prevalence and potential biological impact of MNVs in populations, comprehensive identification and detailed functional annotation of MNVs remain challenging. Here, we develop MNVAnno, a toolbox for rapid identification and annotation of complex MNVs, and utilize it to identify 3,984,258 MNVs from 700,134 human samples, expanding the human MNV list to 8,199,654. Our analysis reveals that MNVs can not only lead to distinct amino acid changes from their constituent single-nucleotide variants, but also significantly impact the function of non-coding regions. Furthermore, through genome-wide association studies, we identify some MNVs associated with multiple cancers, and establish the Human MNV Database to facilitate MNV research. Our study emphasizes the importance of MNV annotation, broadens the human MNV landscape, and opens avenues for exploring genetic variation in phenotypes and diseases.

Humans↗

PubMed2026

A Foundation Model Based CT Biomarker for Non-Invasive Prediction of Response to Neoadjuvant Immunochemotherapy in Non-Small Cell Lung Cancer.

Predicting pathological complete response (pCR) to neoadjuvant immunochemotherapy in non-small cell lung cancer (NSCLC) is clinically important yet remains challenging. Here, we introduce a foundation model-derived computed tomography (CT) imaging biomarker established from a multi-center cohort of 702 patients. Specifically, we developed and validated a non-invasive baseline CT-based model for risk stratification of pathological response. To address scanner and protocol heterogeneity, we first built a 3D Vision Mamba-based CT super-resolution model trained on 2494 cases for image standardization. We then fine-tuned a lung cancer-specific CT foundation model from a pretrained 3D model (VoCo) using 6643 chest CT scans. Finally, we constructed a multi-task Swin Transformer that jointly performs risk stratification and segments tumors to generate the imaging biomarker. Across five centers, the model achieved consistently strong generalization (AUC: 0.75-0.87) for pCR prediction. Genomic analysis revealed that the biomarker was independent of tumor mutational burden but significantly associated with TP53 mutations, suggesting an association with a radiogenomic phenotype related to this alteration. Together, these results demonstrate a generalizable and biologically meaningful foundation model-based biomarker for non-invasive risk stratification of pathological response in NSCLC.

Female↗

PubMed2006

Novel in vivo imaging shows up-regulation of death receptors by paclitaxel and correlates with enhanced antitumor effects of receptor agonist antibodies.

Susceptibility to apoptosis by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is mediated through cognate death receptor signaling. We hypothesized that auto-amplification of this apparatus would enhance antitumor effects in vivo and could be optimized using the results obtained from novel imaging techniques. We therefore imaged mice bearing human colorectal cancer (Colo205) tumor xenografts with HGS-ETR1 and HGS-ETR2 agonist antibodies to TRAIL receptor-1 (TRAIL-R1) and TRAIL-R2, respectively, after radiolabeling the antibodies. Paclitaxel significantly increased in vivo expression of TRAIL-R1 and TRAIL-R2 in a time-dependent manner. The imaging results were confirmed by immunoblots for steady-state protein levels (>20-fold increase in TRAIL-R1 and TRAIL-R2 levels in tumor xenografts by 48 h after paclitaxel administration). TRAIL-R1 and TRAIL-R2 mRNA expression did not change, suggesting that these effects were posttranscriptional. Sequential treatment with paclitaxel followed by HGS-ETR1 or HGS-ETR2 after 48 h resulted in markedly enhanced antitumor activity against Colo205 mouse xenografts. Our experiments suggest that sequential taxane treatment followed by TRAIL-R agonist antibodies could be applied in the clinic, and that novel imaging techniques using radiolabeled receptor antibodies may be exploitable to optimize sequence timing and patient selection.

Animals↗

PubMed2006

Associations of apolipoprotein B with pulse pressure and glucose in Chinese families with familial combined hyperlipidemia.

Familial combined hyperlipidemia (FCHL), with a marked elevation of apolipoprotein B (apoB), is estimated to cause 10-20% of premature coronary artery disease. However, little data are available to demonstrate the associations of apoB with pulse pressure and glucose levels in FCHL families in China. This study was to investigate the potential influence factors for blood pressure and glucose phenotypes in FCHL families by multiple linear regression analysis. We recruited 147 FCHL relatives and 90 spouses, aged 30 to 60 years, from 42 Chinese families with FCHL. Our results showed that triglyceride and low density lipoprotein cholesterol were associated with fasting glucose levels (all P<0.05). Body mass index and glucose significantly correlated to systolic blood pressure, diastolic blood pressure, and mean arterial pressure, respectively (all P<0.05). Furthermore, apoB was significantly related to pulse pressure and glucose in FCHL families (all P<0.05). Thus, this study demonstrates that apoB is significantly associated with pulse pressure and glucose levels in FCHL families. Accordingly, our data suggest that apoB may be a candidate risk marker for pulse pressure and glucose in FCHL populations.

Adult↗

PubMed2006

[Glycolytic and fatty acid metabolic enzyme changes early after acute myocardial ischemia].

OBJECTIVE: To explore the changes of mRNA and protein expressions of glycolytic and fatty acid metabolic enzymes early after acute myocardial ischemia. METHODS: Twelve dogs were randomly divided into 3 groups (sham, 20 min ischemia and 40 min ischemia, n = 4 each). Myocardial samples from ischemic and nonischemic zone were obtained for histology examination, and the mRNA expressions for Phosphofructokinase (PFK), Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), GLUT1, GLUT4, Medium-chain acyl-CoA dehydrogenase (MCAD) and Heart-fatty acid binding protein (H-FABP) were determined by Real Time PCR-SYBR Green RT-PCR. GLUT1 protein expression was determined by immunohistochemistry. The apoptotic cardiomyocytes was evaluated by TUNEL. RESULTS: Compared to sham hearts, H-FABP mRNA was decreased in nonischemic and ischemic zone (P < 0.05) while GLUT1 mRNA expression was significantly increased in nonischemic and ischemic zone (P < 0.05) in dogs underwent 20 and 40 min ischemia. PFK mRNA tended to be higher in ischemic myocardium (P = 0.065) and GAPDH, MCAD as well as GLUT4 remained unchanged post ischemia (all P > 0.05). Positive GLUT1 protein staining was visualized in ischemic myocardium of hearts underwent 20 and 40 min ischemia. The myocardial apoptosis cells was 6.4% +/- 0.9% in sham hearts, 28.0% +/- 3.7% in hearts underwent 20 min ischemia (P < 0.05 vs. sham) and 38.4% +/- 1.9% in hearts underwent 40 min ischemia (P < 0.05 vs. sham). CONCLUSIONS: Significant down and up-regulated glycolytic and fatty acid metabolic enzymes early after myocardial ischemia suggested that these enzymes might play an important role in acute myocardial ischemia.

Animals↗

PubMed2006

[Effects of high temperature on laboratory Trichogramma ostriniae population].

In this paper, the life tables of laboratory Trichogramma ostriniae population reared on Corcyra cephalonica eggs at 26 degrees C, 29 degrees C, 32 degrees C and 35 degrees C were constructed, and the effects of high temperature on the development and reproduction of this population were analyzed. The results showed that high temperature (32 degrees C to approximately 35 degreees C) greatly affected the development of T. ostriniae. The egg-larva survival rate was 94.2% at 26 degrees C and 88.6% at 29 degrees C, and decreased to 80.1% at 32 degrees C and 53.2% at 35 degrees C. The pupa survival rate also descended with the raise of temperature. The egg load and the body- and egg sizes of newly emerged female wasps were negatively responded to temperature. 12 h-old adult female had an egg load of 37.9, which was decreased with the raise of temperature, and about 29.6, 21.6 and 13.7 mature eggs were found at 29 degrees C, 32 degrees C and 35 degrees C, respectively. All females could complete their normal copulation and oviposition at 26 degrees C and 29 degrees C, but about 6.7% and 60% females could not reproduce at 32 degrees C and 35 degrees C, respectively.

Animals↗

PubMed2005

Primary adenosquamous carcinoma of the jejunum.

Adenosquamous carcinomas of the small intestine are extremely rare, with only three documented jejunal and three ileal cases being reported in the English-language medical literature. Presented herein is a case of primary jejunal adenosquamous carcinoma in an 80-year-old woman. The jejunal carcinoma consisted predominantly of a squamous component throughout the tumor but peritoneal nodules carrying metastases from the adenocarcinoma element were noted, making it the first case of jejunal adenosquamous carcinoma with metastases from the adenocarcinoma component. The finding that metastases could arise from the minor component of a jejunal adenosquamous carcinoma indicates that an accurate diagnosis must be based upon thorough examination of both the primary and the metastases, not just mesenteric nodule biopsy alone. Histological foci of closely intermingled squamous and glandular components with apparent morphological transition were noted, indicating the pathogenetic possibility that the squamous component might arise by transformation from the glandular element. The squamous component was strongly positive with immunostaining for p63 (nuclear staining) and for cytokeratin 10/13 (cytoplasmic staining), while the adenocarcinoma element was negative. The immunohistochemical results suggest that p63 and cytokeratin 10/13 might be useful in identifying squamous differentiation in jejunal carcinoma.

Aged↗

PubMed2005

[The frequency of API2-MALT1 fusion gene variants in MALT lymphoma and its correlation with apoptosis of MALT lymphoma].

OBJECTIVE: To investigate the frequency of different variant of API2-MALT1 fusion gene in extranodal marginal zone B-cell lymphoma of mucosa-associated tissue(MALT1) lymphoma and the correlation between API2-MALT1 transcript and apoptosis of MALT lymphoma. METHODS: The API2-MALT1 fusion transcripts were detected in 62 cases of MALT lymphoma by reverse transcription-polymeras chain reaction(RT-PCR) and Nested PCR. Five cases with reactive proliferation of lymph node were in use for negative control, and beta-actin was regarded as internal control; the apoptosis index, mRNA and protein of API2 were assayed in all samples by means of TUNEL, RT-PCR and immunohistochemistry respectively. RESULTS: API2-MALT1 transcript was detected in 28 of 62 cases with MALT lymphoma (45.16%). Two kinds of API2-MALT1 variants (A1446-M1123 and A1446-M814) were detected. Variant A1446-M1123 was detected more frequently as compared with A1446-M814. The frequency of API2-MALT1 transcript was lower in thyroid MALT lymphoma(1/12) but similar in pulmonary and gastrointestinal MALT lymphoma. In the group of API2-MALT1(+), the apoptosis index was higher and the API2 mRNA and protein were lower when compared against those in the group of API2MALT1(-). But no significant differences in the levels of apoptosis and API2 were observed between the group of A1446-M1123(+) and A1446-M814(+). CONCLUSION: API2-MALT1 transcript displayed variable frequency in MALT lymphomas of different sites. A1446-M1123 was noted to be probably the main type of API2-MALT1 variant in MALT lymphoma of Chinese. API2-MALT1 transcript was confirmed to be associated with the levels of apoptosis and API2 of MALT lymphoma.

Apoptosis↗

PubMed2005

[Effect of triptolide on urinary monocyte chemottractant protein-1 in patients with diabetic nephropathy].

OBJECTIVE: To observe the change of urinary monocyte chemottractant protein-1 (MCP-1) in patients with diabetic nephropathy (DN), and to explore the therapeutic effect and mechanism of triptolide (TL) in treating DN. METHODS: Thirty-five patients in the treated group were treated with TL plus benazepril and thirty two patients in the control group were treated with benazepril alone for six months. The change of urinary MCP-1 was measured before and after treatment. RESULTS: Level of urinary MCP-1 in DN patients was significantly higher than that in healthy subjects (P < 0.01), but it could be significantly decreased after TL treatment, showing significant difference as compared with that in the control group (P < 0.05). CONCLUSION: Determination of urinary MCP-1 level is beneficial to know the degree of kidney inflammation in DN patients. TL can inhibit inflammatory reaction to decrease the level of urinary MCP-1, and thus improve the renal function.

Adult↗

PubMed2004

Optical coding of mammalian cells using semiconductor quantum dots.

Cell-based assays are widely used to screen compounds and study complex phenotypes. Few methods exist, however, for multiplexing cellular assays or labeling individual cells in a mixed cell population. We developed a generic encoding method for cells that is based on peptide-mediated delivery of quantum dots (QDs) into live cells. The QDs are nontoxic and photostable and can be imaged using conventional fluorescence microscopy or flow cytometry systems. We created unique fluorescent codes for a variety of mammalian cell types and show that our encoding method has the potential to create > 100 codes. We demonstrate that QD cell codes are compatible with most types of compound screening assays including immunostaining, competition binding, reporter gene, receptor internalization, and intracellular calcium release. A multiplexed calcium assay for G-protein-coupled receptors using QDs is demonstrated. The ability to spectrally encode individual cells with unique fluorescent barcodes should open new opportunities in multiplexed assay development and greatly facilitate the study of cell/cell interactions and other complex phenotypes in mixed cell populations.

Animals↗

PubMed2004

[An association of apolipoprotein B with pulse pressure in Chinese pedigrees with familial combined hyperlipidemia].

OBJECTIVE: To investigate the influencing factors of blood pressure phenotypes and the distribution of FDH in FCHL families. METHODS: Forty-two FCHL families with 435 members, 147 consanguine members and 90 members without consanguinity from Beijing area were studied. Eleven of the 42 FCHL families (26.2%) were identified as families with FDH syndrome. Stepwise regression analysis was used to analyze the association between the target variables and blood pressure phenotypes, such as systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and pulse pressure (PP), of the 237 FCHL members aged 30 to 60 years. RESULTS: The prevalence of dyslipidemic hypertension in the FCHL relatives was significantly higher than that in the spouses (29.9% versus 8.9%, P < 0.01), with an odds ratio of 3.37 (95% CI 1.44 to 8.14). In the FCHL families body mass index (BMI), age and blood sugar were independent contributors to SBP, DBP, and MAP, respectively (all P < 0.05). Age and apolipoprotein B (apoB) were important contributors to pulse pressure (both P < 0.05). CONCLUSIONS: BMI and glucose are significant contributors to different phenotypes of blood pressure. Moreover, apoB is a significant contributor to pulse pressure in FCHL families.

Adult↗