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1.
Plants (Basel) ; 13(12)2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38931046

ABSTRACT

As global ecological degradation intensifies, the long-term impacts of afforestation on productivity and soil fertility in barren lands have become critical in improving global ecological security and productivity. Through meta-analysis, this study integrates data from 109 barren land afforestation sites across China, aiming to comprehensively analyze the effects on plant productivity and soil fertility while identifying the key environmental drivers of these changes. We found that afforestation consistently enhances plant productivity across 60 years. However, soil fertility and moisture initially surged significantly after afforestation but gradually declined after the first decade, indicating the limited long-term benefits. Climatic factors, namely precipitation and humidity index, are crucial in enhancing plant productivity, while geographic factors, specifically lower elevations and gentler slopes, are associated with greater increases in soil fertility. Elevation and slope are two key factors that influence soil moisture after afforestation. These findings highlight the need for ongoing soil management and ecological maintenance in afforestation projects to sustain the soil fertility benefits. Our study provides a robust scientific foundation for afforestation strategies aimed at barren land restoration and offers valuable insights for policy formulation in barren land afforestation.

2.
Eur J Med Chem ; 261: 115833, 2023 Dec 05.
Article in English | MEDLINE | ID: mdl-37797564

ABSTRACT

Pan-HDAC inhibitors exhibit significant inhibitory activity against multiple myeloma, however, their clinical applications have been hampered by substantial toxic side effects. In contrast, selective HDAC6 inhibitors have demonstrated effectiveness in treating multiple myeloma. Compounds belonging to the class of 1H-benzo[d]imidazole hydroxamic acids have been identified as novel HDAC6 inhibitors, with the benzimidazole group serving as a specific linker for these inhibitors. Notably, compound 30 has exhibited outstanding HDAC6 inhibitory activity (IC50 = 4.63 nM) and superior antiproliferative effects against human multiple myeloma cells, specifically RPMI-8226. Moreover, it has been shown to induce cell cycle arrest in the G2 phase and promote apoptosis through the mitochondrial pathway. In a myeloma RPMI-8226 xenograft model, compound 30 has demonstrated significant in vivo antitumor efficacy (T/C = 34.8%) when administered as a standalone drug, with no observable cytotoxicity. These findings underscore the immense potential of compound 30 as a promising therapeutic agent for the treatment of multiple myeloma.


Subject(s)
Antineoplastic Agents , Multiple Myeloma , Humans , Multiple Myeloma/pathology , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Histone Deacetylase 6 , Cell Proliferation , Imidazoles/pharmacology , Imidazoles/therapeutic use , Histone Deacetylase Inhibitors/pharmacology , Histone Deacetylase Inhibitors/therapeutic use , Hydroxamic Acids/pharmacology , Cell Line, Tumor
3.
PLoS One ; 15(12): e0243911, 2020.
Article in English | MEDLINE | ID: mdl-33326461

ABSTRACT

Peroxisome proliferator-activated receptor α/δ (PPAR α/δ), regulating glucolipid metabolism and immune inflammation, has been identified as an effective therapeutic target in non-alcoholic steatohepatitis (NASH). Dual PPAR α/δ agonist, such as GFT505 (also known as elafibranor), demonstrated potential therapeutic effect for NASH in clinical trials. To profile the regulatory network of PPAR α/δ agonist in NASH, the choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) induced NASH model was used to test the pharmacodynamics and transcriptome regulation of GFT505 in this study. The results showed that GFT505 ameliorated hepatic steatosis, inflammation and fibrosis in CDAHFD mice model. RNA-sequencing yielded 3995 up-regulated and 3576 down-regulated genes with GFT505 treatment. And the most significant differentialy expressed genes involved in glucolipid metabolism (Pparα, Acox1, Cpt1b, Fabp4, Ehhadh, Fabp3), inflammation (Ccl6, Ccl9, Cxcl14) and fibrosis (Timp1, Lamc3, Timp2, Col3a1, Col1a2, Col1a1, Hapln4, Timp3, Pik3r5, Pdgfα, Pdgfß, Tgfß1, Tgfß2) were confirmed by RT-qPCR. The down-regulated genes were enriched in cytokine-cytokine receptor interaction pathway and ECM-receptor interaction pathway, while the up-regulated genes were enriched in PPAR signaling pathway and fatty acid degradation pathway. This study provides clues and basis for further understanding on the mechanism of PPAR α/δ agonist on NASH.


Subject(s)
Choline Deficiency/genetics , Non-alcoholic Fatty Liver Disease/genetics , PPAR alpha/genetics , Receptors, Cytoplasmic and Nuclear/genetics , Amino Acids/metabolism , Animals , Chalcones/pharmacology , Choline/genetics , Choline Deficiency/pathology , Diet, High-Fat/adverse effects , Disease Models, Animal , Gene Expression Regulation/genetics , Humans , Mice , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/pathology , PPAR alpha/agonists , Propionates/pharmacology , Receptors, Cytoplasmic and Nuclear/agonists , Signal Transduction/genetics
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