1.Multi-organ inflammatory phenotypes and transcriptomic characterization in an inflammation-driven mouse model of preeclampsia induced by LPS.
Ning WANG ; Jing-Qiu FENG ; Ying XIE ; Meng-Can SUN ; Qi WANG ; Zhe WANG ; Lu GAO
Acta Physiologica Sinica 2025;77(5):775-791
Preeclampsia (PE) is a severe gestational disorder characterized by hypertension and proteinuria, with a subset of cases exhibiting an immune-driven phenotype marked by placental overexpression of proinflammatory cytokines and chronic inflammatory damage, profoundly impacting fetal development. To elucidate the pathophysiology of this PE subtype, we established an inflammation-driven PE mouse model via lipopolysaccharide (LPS) intraperitoneal injection, systematically evaluating histopathological changes in maternal heart, liver, lung, kidney, and placenta, and integrating transcriptomic profiling to uncover molecular mechanisms. LPS administration robustly induced maternal hypertension and proteinuria, hallmarks of PE, without significantly altering organ or fetal weights. Histological analyses revealed pronounced inflammatory damage in the maternal lung, kidney, and placenta, with the lung exhibiting the most severe pathology, characterized by inflammatory cell infiltration, alveolar wall thickening, and interstitial edema-challenging the conventional focus on placental and renal primacy in PE. Placental labyrinth and junctional zones displayed extensive structural disruption and necrosis, indicating functional impairment. Transcriptomic analysis identified 27 inflammation-related genes consistently upregulated across tissues, with protein-protein interaction networks pinpointing Il1β, Il6, Ccl5, Ccl2, Cxcl10, Tlr2, and Icam1 as hub genes. Quantitative PCR validation confirmed Tlr2 as a central regulator, evidenced by significant upregulation of Tlr2 in lung, kidney, and placenta of LPS-induced PE mice, while Cxcl10 exhibited placenta-specific upregulation, suggesting a synergistic inflammatory axis in placental pathology. These findings highlight the lung as a critical, yet underappreciated, target in inflammation-driven PE, reframe the multi-organ inflammatory landscape of the disease, and nominate Tlr2 and Cxcl10 as potential diagnostic biomarkers and therapeutic targets, offering new avenues for precision intervention in PE.
Animals
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Female
;
Pregnancy
;
Mice
;
Pre-Eclampsia/genetics*
;
Inflammation
;
Lipopolysaccharides/adverse effects*
;
Disease Models, Animal
;
Transcriptome
;
Placenta/pathology*
;
Phenotype
2.UBE2S promotes glycolysis in hepatocellular carcinoma by enhancing E3 enzyme-independent polyubiquitination of VHL
Renyu ZHANG ; Can LI ; Shuai ZHANG ; Lingmin KONG ; Zekun LIU ; Yixiao GUO ; Ying SUN ; Cong ZHANG ; Yule YONG ; Jianjun LV ; Meng LU ; Man LIU ; Dong WU ; Tianjiao ZHANG ; Haijiao YANG ; Ding WEI ; Zhinan CHEN ; Huijie BIAN
Clinical and Molecular Hepatology 2024;30(4):771-792
Background/Aims:
Ubiquitination is widely involved in the progression of hepatocellular carcinoma (HCC) by regulating various cellular processes. However, systematic strategies for screening core ubiquitin-related genes, clarifying their functions and mechanisms, and ultimately developing potential therapeutics for patients with HCC are still lacking.
Methods:
Cox and LASSO regression analyses were performed to construct a ubiquitin-related gene prediction model for HCC. Loss- and gain-of-function studies, transcriptomic and metabolomics analysis were used to explore the function and mechanism of UBE2S on HCC cell glycolysis and growth.
Results:
Based on 1,423 ubiquitin-related genes, a four-gene signature was successfully constructed to evaluate the prognosis of patients with HCC. UBE2S was identified in this signature with the potential to predict the survival of patients with HCC. E2F2 transcriptionally upregulated UBE2S expression by directly binding to its promoter. UBE2S positively regulated glycolysis in a HIF-1α-dependent manner, thus promoting the proliferation of HCC cells. Mechanistically, UBE2S enhanced K11-linkage polyubiquitination at lysine residues 171 and 196 of VHL independent of E3 ligase, thereby indirectly stabilizing HIF-1α protein levels by mediating the degradation of VHL by the proteasome. In particular, the combination of cephalomannine, a small molecule compound that inhibits the expression of UBE2S, and PX-478, an inhibitor of HIF-1α, significantly improved the anti-tumor efficacy.
Conclusions
UBE2S is identified as a key biomarker in HCC among the thousands of ubiquitin-related genes and promotes glycolysis by E3 enzyme-independent ubiquitination, thus serving as a therapeutic target for the treatment of HCC.
3.Association of AluYb8 insertion in the MUTYH gene with the risk of decreased left ventricular diastolic function in elderly diabetic patients
Huixian SUN ; Jie MENG ; Yushuang LIN ; Can ZHAO ; Jiali LIU ; Huiwei HE ; Xiang LU ; Wei GAO
Chinese Journal of Geriatrics 2023;42(3):297-302
Objective:To explore the relationship between AluYb8 insertion in the MUTYH gene and the risk of decreased left ventricular diastolic function in the elderly.Methods:In the retrospective analysis, 498 elderly patients with decreased left ventricular diastolic function(the disease group)and 155 people without left ventricular diastolic function(the control group)were recruited.Polymerase chain reaction was employed to analyze the genotype distribution of AluYb8 insertion in MUTYH gene.Cardiac function was measured by high-resolution color Doppler ultrasound.Results:The frequencies of the A/A, A/P and P/P genotypes were 30.1%(150/498), 48.4%(241/498)and 21.5%(107/498)in patients with decreased left ventricular diastolic function, and 27.7%(43/155), 54.8%(85/155)and 17.5%(27/155)in the control group, respectively.There were no significant differences in genotype( χ2=2.162, P=0.339)and allele frequency( χ2=1.342, P=0.794)between the two groups.Further analysis after stratification revealed that there were statistically significant differences in genotype( χ2=7.173, P=0.028)and allele frequency( χ2=8.352, P=0.015). Multivariate Logistic regression analysis showed that, in elderly patients with diabetes, P-allele carriers had a higher risk of decreased left ventricular diastolic function than non-carriers( OR=3.450, 95% CI: 1.148-10.372, P=0.027). Conclusions:AluYb8 insertion in the MUTYH gene may be associated with the risk of decreased left ventricular diastolic function in the elderly with diabetes.
4.Review of genome-wide association research of aging phenotypes.
Yue Qing WANG ; Meng XIAO ; Hai Ming YANG ; Ming Yu SONG ; Yu Xuan ZHAO ; Yuan Jie PANG ; Wen Jing GAO ; Wei Hua CAO ; Tao HUANG ; Can Qing YU ; Jun LYU ; Li Ming LI ; Dian Jian Yi SUN
Chinese Journal of Epidemiology 2022;43(8):1338-1342
"Active health" has been emphasized in "Healthy China 2030" in dealing with the challenges of population aging, so the anti-aging strategies are requires to be more precise and effective at both individual and population levels. Aging is influenced by both genetic and environmental factors. In the recent 20 years, the research of genetics of human ageing has been greatly facilitated owning to the development of high-throughput sequencing techniques, statistical methodology for multi-omics data, as well as the growing qualified evidence of large-scale population-based genomic research. This paper provides a review of genome-wide association research of aging.
Aging/genetics*
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Genome-Wide Association Study/methods*
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Genomics/methods*
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High-Throughput Nucleotide Sequencing
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Humans
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Phenotype
5.Classification and analysis of three types of blood donors based on local resident population
Chengcheng GUO ; Yuxiang CHEN ; Lin WANG ; Yifei WANG ; Mengdi MA ; Huiling MENG ; Ling HOU ; Wen LIU ; Shuanglin XUE ; Yufeng SUN ; Yang CHEN ; Linghua HOU ; Can HUANG ; Xiaoli CAO ; Xia HUANG
Chinese Journal of Blood Transfusion 2022;35(4):372-376
【Objective】 To provide reference for fine management of blood donors by classifying and analyzing different types of blood donors from domestic blood stations. 【Methods】 The resident population of 15 regions in China from 2016 to 2019 were taken as the research object, among which the blood donors were divided into three categories: age-eligible citizens, registered donors and donated donors. The average value and proportion of the three categories were calculated and statistically analyzed. 【Results】 The resident population of the 15 regions varied greatly. The mean 95% CI of the proportion of age-eligible citizens to resident population from 2016 to 2019 was (60.16%, 67.84%); registered donors to age-eligible citizens and resident population was (2.21%, 2.86%) and (1.41%, 1.79%), respectively; donated donors to registered donors, age-eligible citizens and resident population was (84.63%, 91.68%), (1.93%, 2.55%) and(1.23%, 1.59%), respectively. 【Conclusion】 There were differences in the number and proportion of different types of blood donors in different regions. The fine management of blood donors can help blood stations carry out more effective recruitment and retention strategies.
6.Research progress on self-evaluation tools for clinical nurses' cultural competence
Chinese Journal of Modern Nursing 2020;26(31):4419-4423
This article explains the related concepts of cultural competence, summarizes the development and application research status of clinical nurses' cultural competence self-evaluation tools at home and abroad, and analyzes the development characteristics and existing problems of current evaluation tools, in order to provide a reference for the development of nurses' cultural competency evaluation tools suitable for China's national conditions.
7.Cloning and expression analysis of transcription factor gene DoWRKY1 in Dendrobium officinale.
Jun ZHAO ; Shi-wei SUN ; Can-can MENG ; Qing JIN ; Hong-hong FAN ; Yi LIN ; Yong-ping CAI
China Journal of Chinese Materia Medica 2015;40(14):2807-2813
WRKY transcription factors are novel transcriptional regulatory factors, which play an important role in regulating plant development, metabolism and other physiological processes. In this study, a new Dendrobium officinale WRKY transcription factor, designated as DoWRKY1 was cloned by using RT-PCR and RACE (GenBank Accession No. KF953910). Bioinformatic analysis demonstrated that, the full-length cDNA of DoWRKY1 was 1,704 bp. And DoWRKY1 contained a 1,629 bp open reading frame (ORF) that encoding a peptide of 542 amino acid residues. The putative DoWRKY1 protein contained two conserved WRKY domains and it belonged to the group I WRKY family protein. Yeast one-hybrid experiment showed that DoWRKY1 had transcriptional activation ability in yeast, and it could activate the expression of downstream report genes (His3 and Ade2). Semi-quantitative RT-PCR experiment showed that DoWRKY1 expressed in roots, stems, leaves and protocorm-like bodies. Real-time qRT-PCR proved that DoWRKY1 could be induced by methyl jasmonate (MeJA) and chitosan (Chitosan), and the expression level of this gene can reach the expression peak at 2 h and 1 h, respectively. These results are useful for further determination of the regulation function of this gene in secondary metabolism of D. officinale.
Cloning, Molecular
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Dendrobium
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genetics
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Gene Expression Regulation, Plant
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Plant Proteins
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genetics
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Transcription Factors
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genetics
8.Preparation and characterization of nanostructured lipid carriers with difference in particle size
Huipeng LI ; Zhigui SU ; Minglei CHEN ; MENG MENG ; Minjie SUN ; Yan WANG ; Can ZHANG ; Qineng PING
Journal of China Pharmaceutical University 2015;46(4):436-443
To construct nanostructured lipid carriers(NLCs)with different particle sizes but the same other physicochemical properties, central composite design was adopted. Coumarin-6(C-6)was selected as the model drug due to its high lipophilicity and high fluorescence intensity. Physicochemical properties of NLCs with 100 nm, 200 nm and 300 nm in particle size could remain stable during certain time in K-R solution and PBS. Release experiments in vitro showed that cumulative release of C-6 in NLCs was less than 7% after 24 h. The MTT assay indicated that both blank NLCs and C-6 loaded NLCs showed low toxicity. To confirm the integrity of NLCs in gastrointestinal tract, DiR-loaded NLCs were prepared and the distribution in vivo was monitored by fluorescence imaging. After 6 h oral administration, intact DiR-loaded NLCs could stiu be found, suggesting that NLCs could be used to characterize the uptake in gastrointestinal tract.
9.Assessment of 64-slice spiral computed tomography angiography with image fusion for perigastric arteries anatomy.
Xue-hua LI ; Can-hui SUN ; Shi-ting FENG ; Chao-gui YAN ; Yu-long HE ; Fang-hai HAN ; Zi-ping LI ; Quan-fei MENG
Chinese Journal of Gastrointestinal Surgery 2012;15(6):594-598
OBJECTIVETo evaluate the efficacy and clinical significance of 64-multislice spiral computed tomography angiography(MSCTA) with image fusion for the anatomy of perigastric arteries.
METHODSA total of 53 patients underwent abdominal 64-MSCTA, among whom 26 patients with gastric cancer underwent gastrectomy. Using volume rendering techniques, computed tomography angiography(CTA) of perigastric arteries and the stomach were reconstructed respectively, and then the images were fused together. The branching pattern of the celiac trunk and the origins and courses along the stomach of the 10 perigastric arteries were assessed. The accuracy, sensitivity, and specificity of 64-MSCTA were determined based on intraoperative findings.
RESULTSCTA clearly showed the celiac trunk. The most common branching pattern of the celiac trunk was Michels type I( in 46 patients(86.8%). The anatomy of perigastric arteries and stomach could be clearly demonstrated from any angle according to image fusion. The left gastric artery and the right gastroepiploic artery were shown in 100%, the left gastroepiploic artery 94.3%(50/53), the right gastric artery 83.0%(44/53), short gastric artery 58.5%(31/53), posterior gastric artery 49.1%(26/53), the replaced left hepatic artery 15.1%(8/53). The accessory left hepatic artery, accessory left gastric artery and replaced right hepatic artery were all identified in 7.5%(4/53) patients. The accuracy of preoperative CTA in term of correctly identifying perigastric arteries ranged from 84.6% to 100%, the sensitivity 82.6% to 100%, and the specificity was 100% for all the perigastric arteries.
CONCLUSIONS64-MSCTA can clearly reveal individual perigastric arteries. The anatomy of the stomach and perigastric arteries can be shown in vivo by fused image, and can provide guidance for gastrectomy.
Adult ; Aged ; Angiography ; methods ; Arteries ; Female ; Humans ; Image Processing, Computer-Assisted ; Male ; Middle Aged ; Preoperative Care ; Sensitivity and Specificity ; Stomach ; blood supply ; Stomach Neoplasms ; diagnostic imaging ; surgery ; Tomography, Spiral Computed ; Young Adult
10.Reconstructed seminiferous tubules from ectopic grafting of testicular cells.
Ru-hui TIAN ; Hong-liang HU ; Ping LIU ; Peng LI ; Shi YANG ; Yong ZHU ; Meng MA ; Can SUN ; Sha-sha ZOU ; Xi-zhi GUO ; Yi-ran HUANG ; Zheng LI
National Journal of Andrology 2011;17(10):867-872
OBJECTIVETo investigate the ectopic grafts of mouse testicular cells by observing the reconstruction of seminiferous tubules, colonization of spermatogenic cells and spermatogenesis using immunodeficient mice as recipients.
METHODSThe testes of newborn male ICR mice were digested to obtain single cell suspension. The cells were then mixed with matrigel and subcutaneously grafted into the dorsal region of the male nude mice. The mice were castrated after the operation and the grafts were dissected from 5 of the nude mice at 4, 6, 8 and 10 weeks, respectively. The success rates of transplantation and the graft diameters were calculated, and the structure of the reconstituted seminiferous tubules, colonization of the germ cells and spermatogenesis were observed by HE staining and immunohistochemistry.
RESULTSAll the mice recipients survived after the testicular cell transplantation. Within 10 weeks after the operation, tissue masses could be observed, with the diameter increased from (3.91 +/- 0.71) mm at 4 weeks to (6.69 +/- 0.50) mm. Neovascularization was detected at the surface of the masses and seminiferous tubule structures found in the grafts. The germ cells that developed from spermatogonia to round spermatids were observed, but with no sperm in the tubules. Germ cells, Sertoli cells and Leydig cells were identified by immunochemical detection of Mvh, Gata4 and P450Scc in the grafts at 8 weeks.
CONCLUSIONSeminiferous tubules could be ectopically reconstructed from suspension of neonatal mouse testicular cells. Ectopic grafting provided a preferable model for the studies on testis tissue engineering and interactions between testicular cells during testicular development and spermatogenesis.
Animals ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred ICR ; Mice, Nude ; Seminiferous Tubules ; cytology ; Sertoli Cells ; cytology ; transplantation ; Spermatids ; cytology ; Spermatogenesis ; Testis ; cytology ; transplantation ; Transplantation, Heterologous

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