INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2023
·Vol. 24
·期 18
·13682
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IF 5.6
Shiyao Wang,Dongfa Lin,Jiaofei Cao,Liping Wang
Animal studies have proven that 1-acetyl-5-phenyl-1H-pyrrol-3-yl acetate (APPA) is a powerful antioxidant as a novel aldose reductase inhibitor independently synthesized by our laboratory; however, there is no current information on APPA’s anti-aging mechanism. Therefore, this study examined the impact and mechanism of APPA’s anti-aging and anti-oxidation capacity using theCaenorhabditis elegansmodel. The results demonstrated that APPA increasesC. elegans’ longevity without affecting the typical metabolism ofEscherichia coliOP50 (OP50). APPA also had a non-toxic effect onC. elegans, increased locomotor ability, decreased the levels of reactive oxygen species, lipofuscin, and fat, and increased anti-stress capacity. QRT-PCR analysis further revealed that APPA upregulated the expression of antioxidant genes, includingsod-3,gst-4, andhsp-16.2, and the critical downstream transcription factors,daf-16,skn-1, andhsf-1of the insulin/insulin-like growth factor (IGF) receptor,daf-2. In addition,fat-6andnhr-80were upregulated. However, the APPA’s life-prolonging effects were absent on thedaf-2,daf-16,skn-1, andhsf-1mutants implying that the APPA’s life-prolonging mechanism depends on the insulin/IGF-1 signaling system. The transcriptome sequencing also revealed that the mitochondrial route was also strongly associated with the APPA life extension, consistent withmev-1andisp-1mutant life assays. These findings aid in the investigation of APPA’s longevity extension mechanism.Keywords:APPA;lifespan;stress resistant;insulin/IGF-1;Caenorhabditis elegans
研究领域:
衰老研究
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分子生物学
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遗传学
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高影响因子
EBioMedicine
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2026
·
IF 11.2
Zixuan Li,Pingping Wang,Haiting Gao,Mengfan Zhi,Xiufeng Gu,Tianyong Sun,Yushang Wang,Song Shen,Xiaomei Ma,Xiaoli Ji,Xiumei Zhang,Dongxu Liu,Qiang Feng
Background Periodontitis poses a significant threat to human oral health, and microorganisms serving as the initiating factor in its pathogenesis. Parvimonas micra ( P. micra ), a Gram-positive anaerobic bacterium prevalent within the oral cavities of patients with periodontitis, remains underexplored in terms of its full contribution to periodontitis pathogenesis. Methods 16S rRNA sequencing was performed on human gingival crevicular fluid samples, whilst micro-CT was used in experimental rat models to assess the impact of P. micra on periodontitis progression. Single-cell RNA sequencing was employed to examine dynamic alterations in rat periodontal cell composition and the enrichment of gene pathways during P. micra infection. Finally, His pull-down assay combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used to identify key virulence factors of P. micra and host cell receptors. Findings In this study, we examined the abundance of P. micra in gingival crevicular fluid and validated its pathogenic potential in vivo . Single-cell RNA sequencing revealed that P. micra disrupted the periodontal immune and mineralisation microenvironment. Further investigation showed that P. micra manipulated its surface adhesins to bind receptors on periodontal ligament stem cells, activating the intracellular NF-κB and ERK1/2 signalling pathways and impairing osteogenic activity. Finally, we identified a mechanism by which P. micra employed a surface protein to evade autophagic clearance, thereby facilitating immune escape. Interpretation This study identifies P. micra as a pivotal periodontal pathogen, and the elucidation of its molecular mechanisms provides potential therapeutic targets for periodontitis and related systemic conditions. Funding This work was supported by the National Natural Science Foundation of China (No. 82270980, 82071122), Noncommunicable Chronic Diseases-National Science and Technology Major Project (2023ZD0501400), Taishan TePin Scientist Project of Shandong Province (tstp20250546), the Natural Science Foundation of Jiangsu Province (No. BK20240268), High-Level Hospital Construction Project of Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University (No. 0024C035), Shandong Provincial Key Research and Development Program (Competitive Innovation Platform, 2025CXPT042), the Major Innovation Projects in Shandong Province (No. 2021SFGC0502), and the Shandong Province Key Research and Development Program (No. 2021ZDSYS18).
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高影响因子
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