Curcumin supplementation increases longevity and antioxidant capacity in Caenorhabditis elegans.

Curcumin is well known as a potent antioxidant and free radical scavenger and has great potential for anti-aging applications. In this study, we investigate the molecular mechanism of curcumin in prolonging the lifespan of C. elegans. Four concentrations of curcumin (10, 25, 50, and 100 µM) were administered, and the optimal treatment concentration was determined by analyzing the nematode lifespan, physiology, and biochemistry. Additionally, RNA-seq and qRT-PCR were performed to explore the antioxidant effect of curcumin and its underlying mechanism. Results revealed that curcumin could significantly improve the survival capacity of C. elegans without influencing its growth. Curcumin was observed to significantly decrease the levels of reactive oxygen species (ROS) under extreme conditions such as heat stress and paraquat stress. In addition, curcumin increased the amount of nematode mitochondrial DNA (mtDNA) replication. RNA-seq results revealed that the underlying mechanism of curcumin in C. elegans is related to the mitogen-activated protein kinase (MAPK) pathway. qRT-PCR results confirmed that the expression of oxidative stress-related genes (sod-1, sod-2, sod-3, gst-4) was increased, and the expression of MAPK signaling pathway-related genes (sek-1, pmk-1, nsy-1) was significantly downregulated. Furthermore, the administration of curcumin extended the lifespan of nematodes, potentially through the enhancement of oxidative stress resistance and the downregulation of the MAPK signaling pathway. These findings improve our understanding of both lifespan extension and the potential mechanism of curcumin in C. elegans.

The heparan sulfate mimetic Muparfostat aggravates steatohepatitis in obese mice due to its binding affinity to lipoprotein lipase.

BACKGROUND AND PURPOSE: Heparanase is the only confirmed endoglycosidase that cleaves heparan sulfate (HS), a ubiquitous glycosaminoglycan with various essential roles in multiple pathological processes. Thus, the development of heparanase inhibitors has become an attractive strategy for drug discovery, especially in tumour therapy, in which HS mimetics are the most promising compounds. The various biological effects of heparanase also suggest a role for HS mimetics in many non-cancer indications, such as type 1 diabetes. However, the potential benefits of HS mimetics in obesity-related type 2 diabetes have not been elucidated. EXPERIMENTAL APPROACH: In this study, we investigated muparfostat (PI-88), a developed HS mimetic currently enrolled in Phase III clinical trials, in obese mouse models and in vitro cultured murine hepatocytes. KEY RESULTS: Daily administration of muparfostat for 4 weeks caused hyperlipidaemia and aggravated hepatic steatosis in obese mice models, but not in lean animals. In cultured hepatocytes, muparfostat did not alter lipid accumulation. Acute tests suggested that muparfostat binds to lipoprotein lipase in competition with HS on vascular endothelial cell surfaces, thereby reducing the degradation of circulating triglycerides by lipoprotein lipase and subsequent uptake of fatty acids into vascular endothelial cells and causing hyperlipidaemia. This hyperlipidaemia aggravates hepatic steatosis and causes liver injury in muparfostat-treated obese mice. CONCLUSIONS AND IMPLICATIONS: The binding activity of HS mimetics to lipoprotein lipase should be investigated as an additional pharmacological effect during heparanase inhibitor drug discovery. This study also provides novel evidence for an increased risk of drug-induced liver injury in obese individuals.

Identification and Characterization of the Growth-Regulating Factors-Interacting Factors in Cotton.

Growth-regulating factors-interacting factors (GIFs) are a type of transcription co-activators in plants, playing crucial roles in plants' growth, development, and stress adaptation. Here, a total of 35 GIF genes were identified and clustered into two groups by phylogenetic analysis in four cotton genus. The gene structure and conserved domain analysis proved the conservative characteristics of GIF genes in cotton. The function of GIF genes was evaluated in two cotton accessions, Ji A-1-7 (33xi) and King, which have larger and smaller lateral root numbers, respectively. The results showed that the expression of GhGIF4 in Ji A-1-7 (33xi) was higher than that in King. The enzyme activity and microstructure assay showed a higher POD activity, lower MDA content, and more giant cells of the lateral root emergence part phenotype in Ji A-1-7 (33xi) than in King. A mild waterlogging assay showed the GIF genes were down-regulated in the waterlogged seedling. Further confirmation of the suppression of GhGIF4 in cotton plants further confirmed that GhGIF4 could reduce the lateral root numbers in cotton. This study could provide a basis for future studies of the role of GIF genes in upland cotton.

Genome-wide association study for seedling biomass-related traits in Gossypium arboreum L.

BACKGROUND: Seedling stage plant biomass is usually used as an auxiliary trait to study plant growth and development or stress adversities. However, few molecular markers and candidate genes of seedling biomass-related traits were found in cotton. RESULT: Here, we collected 215 Gossypium arboreum accessions, and investigated 11 seedling biomass-related traits including the fresh weight, dry weight, water content, and root shoot ratio. A genome-wide association study (GWAS) utilizing 142,5003 high-quality SNPs identified 83 significant associations and 69 putative candidate genes. Furthermore, the transcriptome profile of the candidate genes emphasized higher expression of Ga03G1298, Ga09G2054, Ga10G1342, Ga11G0096, and Ga11G2490 in four representative cotton accessions. The relative expression levels of those five genes were further verified by qRT-PCR. CONCLUSIONS: The significant SNPs, candidate genes identified in this study are expected to lay a foundation for studying the molecular mechanism for early biomass development and related traits in Asian cotton.

Resveratrol protects BV2 mouse microglial cells against LPS-induced inflammatory injury by altering the miR-146a-5p/TRAF6/NF-κB axis.

Objective: To investigate the role of miR-146a-5p in the effects of resveratrol (RSV) on inflammatory response in BV2 mouse microglial cells. Materials and methods: BV2 cells were pretreated by RSV and stimulated with lipopolysaccharide (LPS). Cell Viability was checked using a MTT assay. Real-Time PCR was performed to detect the levels of pro-inflammatory cytokines (tumor necrosisfactor-α－TNF-α, interleukin-1ß－IL-1ß and interleukin-6 － IL-6) and miR-146a-5p expression. Western blot was used to analyze the protein expression of TNF receptor associated factor 6 (TRAF6) and phospho-nuclear factor kappa B (pNF-κB). Gain-of-function and loss-of-function analysis of miR-146a-5p was performed using transfection of miR-146a-5p mimic and miR-146a-5p inhibitor, respectively. Results: Pretreatment with RSV significantly and dose dependently inhibited LPS-induced production of TNF-α, IL-1ß and IL-6 in BV2 cells. MiR-146a-5p was significantly upregulated after LPS treatment, and further increased in RSV and LPS-co-treated cells. MiR-146a-5p overexpression via miR-146a-5p mimic transfection downregulated the mRNA level of TNF-α, IL-1ß and IL-6, as well as abrogated the protein expression of TRAF6 and pNF-κB in BV2 cells exposed to LPS. More importantly, the reducion of TNF-α, IL-1ß and IL-6 level by RSV were reversed by miR-146a-5p silence via miR-146a-5p inhibitor transfection. Furthermore, silencing miR-146a-5p attenuated the inhibitory effect of RSV on the TRAF6/NF-κB pathway which was activated after induction with LPS. Conclusions: RSV can suppress LPS-induced inflammatory injury via modulating the miR-146a-5p/TRAF6/NF-κB axis in BV2 mouse microglial cells.