1.Rapid discovery of drug-introduced multiple organ dysfunction via NIR-II fluorescent imaging.
Pu JIANG ; Ruihu SONG ; Yue HU ; Xin HE ; Zewei ZHANG ; Xuemei WEI ; Zhiming WANG ; De-An GUO ; Hao CHEN
Acta Pharmaceutica Sinica B 2025;15(8):4285-4299
The precise and rapid monitoring of multiple organ dysfunction is crucial in drug discovery. Traditional methods, such as pathological analysis, are often time-consuming and inefficient. Here, we developed a multiplexed near-infrared window two (NIR-II) fluorescent bioimaging method that allows for real-time, rapid, and quantitative assessment of multiple organ dysfunctions. Given that existing probes did not fully meet requirements, we synthesized a range of NIR-II hemicyanine dyes (HDs) with varying absorption and emission wavelengths. By modifying these dyes, we achieved high spatial and temporal resolution imaging of the liver, kidneys, stomach, and intestines. This method was further applied to investigate disorders induced by cisplatin, a drug known to cause gastric emptying issues along with liver and kidney injuries. By monitoring the metabolic rate of the dyes in these organs, we accurately quantified multi-organ dysfunction, which was also confirmed by gold-standard pathological analysis. Additionally, we evaluated the effects of five aristolochic acids (AAs) on multiple organ dysfunction. For the first time, we identified that AA-I and AA-II could cause gastric emptying disorders, which was further validated through transcriptomics analysis. Our study introduces a novel approach for the simultaneous monitoring of multi-organ dysfunction, which may significantly enhance the evaluation of drug side effects.
2.Non-target metabolomic analysis of buccal pouch squamous cell carcinoma in Chinese hamsters
Ruihu ZHANG ; Yuan WANG ; Guoqiang XU ; Jiping GAO ; Guohua SONG ; Zhaoyang CHEN ; Rui-Jing XUAN
Journal of Practical Stomatology 2024;40(5):608-613
Objective:To explore the metabolic basis and related molecular mechanism of oral squamous cell carcinoma(OSCC)path-ogenesis.Methods:20 Chinese hamsters were divided into 2 groups(n=10).OSCC models were induced by dimethylbenzanthracene(DMBA)in 10 of the animals and the other 10 were used as the controls.LC-MS chromatography-mass spectrometry was used to iden-tify the metabolites in the buccal pouch,and multidimensional statistical analysis of the metabolites was performed with the orthogonal partial least squares discriminant analysis model.Variable Importance for the Projection(VIP)>1 and P<0.05 were used as the criteria to screen the differential metabolites between the 2 groups.KEGG pathway annotation and enrichment analysis for the metabolites were performed to screen the significantly differential pathways.Results:The hamster cheek pouches painted with 0.5%DMBA for 18 weeks were diffused with leukoplakia and loaded obvious papillary protrusions,which were diagnosed as OSCC by pathological examination.Lipids and lipid-like molecules were the main differential metabolites.Reprogramming of unsaturated fatty acid biosynthesis,cholesterol accumulation,enhanced catabolism of tryptophan,up-regulation of aspartate,increased synthesis of pyrimidine and purine,etc.were important metabolic features in the occurrence and development of OSCC.Conclusion:Molecular intervention targeting the related met-abolic pathways is expected to inhibit OSCC pathogenesis and progression.
3.Protective effect of Liensinine on lipopolysaccharide ( LPS)-induced acute lung injury in mice
Zhaoyang CHEN ; Ru YAO ; Lu WANG ; Chenyang WANG ; Min GUO ; Guohua SONG ; Ruihu ZHANG
Acta Laboratorium Animalis Scientia Sinica 2018;26(3):343-348
Objective To investigate the effect of Liensinine on lipopolysaccharide ( LPS)-induced acute lung injury (ALI) in mice. Methods BALB/c mice were randomly divided into six group: control group, LPS group, LPS+Liensinine (2 mg/kg, 4 mg/kg, 8 mg/kg) groups, and dexamethasone group. Acute lung injury in mice was induced by nasal instillation of LPS. After 12 h, the pathological changes of lung tissue were observed. The levels of TNF-α, IL-6 and IL-1β in bronchoalveolar lavage fluid (BALF) were detected by ELISA. The number of neutrophils in BALF was detected using Wright-Giemsa staining. Total protein content was detected by BCA protein quantification assay. The pulmonary capillary permeability was examined with Evans blue. The MPO activity, MDA content, SOD activity, and GSH content in lung homogenate supernatant were detected by spectrophotometry. The content of ROS in lung tissue was detected by flow cytometry. Results The LPS group showed inflammatory cell infiltration, thickening of bronchial alveolar wall and pulmonary congestion in the lung tissue, while Liensinine improved the lung injury. In the LPS group, the contents of TNF- α, IL-6 and IL-1β in BALF were significantly increased, the number of neutrophils and the content of total protein were significantly increased, pulmonary capillary permeability, MPO activity and MDA content were increased, SOD activity and GSH content were decreased, the content of ROS was increased; while the Liensinine group reduced the contents of TNF-α, IL-6, IL-1β in BALF, reduced the number of neutrophils and total protein content, decreased the pulmonary capillary permeability, attenuated MPO activity and MDA contents and increased SOD activity and GSH content, and reduced ROS content in the LPS-challenged lung tissue. Conclusions Liensinine protects mice from LPS-induced acute lung injury by its anti-inflammatory and anti-oxidative activities.
4.Expression of apoptosis-related genes caspase-3, caspase-9, Bax and Bcl-2 during oral buccal mucosa carcinogenesis in Chinese hamster
Wenbiao PANG ; Lihong LI ; Fubing HUANG ; Maolin LIU ; Ruihu ZHANG ; Guohua SONG
Acta Laboratorium Animalis Scientia Sinica 2017;25(3):263-269
Objective To study the expression and significance of apoptosis-related genes caspase-3,caspase-9,Bax and Bcl-2 in oral normal mucosa,oral simple hyperplasia,oral epithelial dysplasia and oral squamous cell carcinomas (OSCC) in Chinese hamsters.Methods The expressions of mRNA and protein of caspase-3,caspase-9,Bax and Bcl-2 in the oral normal mucosa,oral simple hyperplasia,oral epithelial dysplasia and OSCC tissues in Chinese hamsters were examined by immunohistochemistry and RT-PCR.Results During the process of oral carcinogenesis,the expression of Bcl-2 protein was significantly higher in OSCC than in oral normal mucosa,oral simple hyperplasia,and oral epithelial dysplasia (P<0.05).In dysplastic epithelia,the protein expressions of caspase-3,caspase-9 and Bax were more than that of normal epithelia,and along with the increased dysplasis,the expression level was decreased.Further analysis showed that expression of Bcl-2 was negatively related with the expressions of Bax,caspase-3 and caspase-9 (P<0.05).The result of RT-PCR showed that Bcl-2 was significantly increased in OSCC compared with normal mucosa,while the expressions of caspase-3,caspase-9 and Bax were decreased (P<0.05).Conclusions In the Chinese hamster squamous carcinoma,the expressions of caspase-3,caspase-9 and Bax are reduced and the Bcl-2 expression are increased,indicating that the expressions of caspase-3,caspase-9,Bax and Bcl-2 are closely related with the occurrence and development of oral squamous cell cancinoma.This study can offer some clues for gene therapy of OSCC,or can provide a reference for evaluating the biological characteristics and prognosis of OSCC.
5.Study of mitochondrial genomes and molecular genetic marker of microsatellite in chinese hamster
Guohua SONG ; Zhaoyang CHEN ; Tianfu LIU ; Wenbiao PANG ; Jiping GAO ; Ruihu ZHANG ; Maolin LIU ; Linhua FAN
Chinese Journal of Comparative Medicine 2017;27(5):4-5,15
Chinese hamster is an important laboratory animal in medical and biological researches,but the molecular genetic markers research was rarely reported.In our study the base composition,gene structure,genetic evolution and other characteristics of mitochondrial genome of Chinese hamster were analyzed using the methods of bioinformatics and comparative genomics,genetic quality detection system of Chinese hamster were also established.These results would supply genome data for animal models of human diseases,and lay the foundation for scientific evaluation and reasonable utilization.

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