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Endothelial cell senescence is the main risk factor contributing to vascular dysfunction and the progression of aging-related cardiovascular diseases. However, the relationship between endothelial cell metabolism and endothelial senescence remains unclear. The present study provides novel insight into fatty acid metabolism in the regulation of endothelial senescence. In the replicative senescence model and H 2 O 2 -induced premature senescence model of primary cultured human umbilical vein endothelial cells (HUVECs), fatty acid oxidation (FAO) was suppressed and fatty acid profile was disturbed, accompanied by downregulation of proteins associated with fatty acid uptake and mitochondrial entry, in particular the FAO rate-limiting enzyme carnitine palmitoyl transferase 1A (CPT1A). Impairment of fatty acid metabolism by silencing CPT1A or CPT1A inhibitor etomoxir facilitated the development of endothelial senescence, as implied by the increase of p53, p21, and senescence-associated β -galactosidase, as well as the decrease of EdU-positive proliferating cells. In the contrary, rescue of FAO by overexpression of CPT1A or supplement of short chain fatty acids (SCFAs) acetate and propionate ameliorated endothelial senescence. In vivo , treatment of acetate for 4 weeks lowered the blood pressure and alleviated the senescence-related phenotypes in aortas of Ang II-infused mice. Mechanistically, fatty acid metabolism regulates endothelial senescence via acetyl-coenzyme A (acetyl-CoA), as implied by the observations that suppression of acetyl-CoA production using the inhibitor of ATP citrate lyase NDI-091143 accelerated senescence of HUVECs and that supplementation of acetyl-CoA prevented H 2 O 2 -induced endothelial senescence. Deficiency of acetyl-CoA resulted in alteration of acetylated protein profiles which are associated with cell metabolism and cell cycle. These findings thus suggest that improvement of fatty acid metabolism might ameliorate endothelial senescence-associated cardiovascular diseases., Competing Interests: The authors declare no competing interests., (Copyright © 2022 Tong Lin et al.)

Objective: To investigate the effects of Plasmodium vivax merozoite surface protein 1 (PvMSP1) on differentiation, maturation and function of dendritic cells (DC) and the mechanisms of PvMSP1 on the activation of DC via toll like receptors (TLR)., Methods: DCs were incubated with different doses of PvMSP1 (1.0, 10.0, 100.0 microg/ml) in vitro. The changes of CD83, CD86, and HLA-DR on DC were detected by flow cytometry (FCM); the expressions of cytokine IL-10 and IL-12 of DC were measured by ELISA; the expressions of TLR4 and TLR9 mRNA of DC were measured by RT-PCR; the proliferation induction to autologous lymphocytes of DC was measured by MTT. Meanwhile, the untreated DC and LPS inducing DC were as the negative control and positive control, respectively. All the data were analyzed statistically., Results: Compared with the untreated DC, the proportions of CD83, CD86 and HLA-DR on DC induced by LPS and PvMSP1 increased significantly (all P < 0.05); the expressions of IL-10 and IL-12 of DC induced by LPS increased significantly (P < 0.01), and those induced by PvMSP1 also increased significantly (all P < 0.05). In the LPS inducing group, the TLR4 mRNA production increased (P < 0.05) and the TLR9 mRNA production had no significantly changes (P > 0.05). In the PvMSP1-treated group, the DC TLR4 mRNA production increased (P < 0.01) and the TLR9 mRNA production had no significantly changes (P > 0.05); DC stimulated the proliferation of autologous lymphocytes., Conclusion: PvMSP1 enhances DC differentiation and maturation, and the mature DC induced by PvMSPI has the ability of antigen presenting. The route for PvMSP1 inducing DC maturation might be TLR4 pathway rather than TLR9 pathway.

Objective: To clone a Plasmodium vivax Duffy binding protein critical functional region II (PvDBPII) gene of central China isolate, and to express and identify the recombinant PvDBPII protein in vitro., Methods: PCR was performed to amplify PvDBPII from P. vivax DNA of a central China isolate and the PCR product was inserted into pET28a(+) vector. pET28a-PvDBPII recombinant plasmid was constructed and transformed into E. coli host BL21 (DE3+). IPTG was used to induce the recombinant PvDBPII protein fused with His tag, and the protein was purified by His-NTA affinity chromatography. The recombinant protein was identified by SDS-PAGE and Western blot., Results: The PCR product of PvDBPII gene was about 1,1 kb, meeting the expectation of predicted fragment size. The recombinant pET28a-PvDBPII plasmid was verified by sequencing that the insertion was correct both in direction and in frame, but with 4 non-synonymous mutations compared to reference P. vivax strain Sal-I. SDS-PAGE, and Western blot analysis showed that the recombinant PvDBPII protein was about 44 kDa, and could be recognized by pooled sera from vivax malaria patients., Conclusion: The PvDBPII gene of central China isolate is successfully cloned, and recombinant PvDBPII is expressed, thereby providing opportunity for further study on PvDBPII.

1. The levels of atrial natriuretic peptide(ANP) gene expression in rat atria at 2-3 and 14-18 months of age and the effects of ginsenosides on r-ANP gene expression by determining the concentration of ANP-mRNA were investigated. The male and female rats were abdominally (i.p.) injected with aqueous solution of ginsenosides prepared from ginseng stems and leaves (G-PSL) and ginseng roots (G-PR), 50 mg/kg body wt, once a day for 7 days. Atria total RNA was extracted by the cold phenol method. The ANP-mRNA contents were determined using the Northern blot and dot blot hybridization technique with alpha-32*P-labelled r-prepro-ANP-cDNA probe. 2. The ANP-mRNA contents of 14-18 month rats were remarkably less than that of 2-3 month rats. The levels of male and female rats' atria at 14-18 months were about 15 and 60%, the content of male and female rats at 2-3 months respectively. 3. G-PSL and G-PR increased the ANP-mRNA content of male rats at 14-18 months 1- and 2-fold, respectively, whereas G-PSL and G-PR decreased the ANP-mRNA content in male rats of age 2-3 months. 4. These results revealed that the ANP gene expression declined during ontogenic ageing development and ginsenosides possessed anti-ageing effects in the heart endocrineous function aspect.

1. Effects of sodium loading and dehydration on ANP gene expression were investigated in rats. 2. ANP-mRNA was determined using Northern blot and dot blot hybridization technique with alpha-32P-labeled r-preproANP-cDNA probe. Salt loading increased the ANP-mRNA content in atria. Correlation with ANP-mRNA content and the plasma sodium concentration was established. 3. Deprivation of water for 2 and 4 days increased ANP-mRNA 2.1- and 1.6-fold, respectively. 4. These results demonstrated that water-salt balance affects the ANP-gene expression.