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Angelica dahurica is a common species of medicine and food homology, which is not only a common clinical traditional Chinese medicine, but also a spice, with a wide range of uses. In order to obtain the whole genome sequence information of A. dahurica, we used A. dahurica var. formosana leaf DNA as material, and the Nanopore sequencing technology was used to establish its nucleotide sequences database, then genome assembly, function annotation and evolution analysis were carried out by bioinformatic methods. The results were as follows:(1) A total of 662 Gb of the third-generation data were obtained after fittering the original sequencing data, with the Read N50 about 32 932 bp. The assembled A. dahurica genome size was 5.6 Gb, Contig N50 was about 806 638 bp. (2) The genes were with gene annotations accounted for 66.47% after being compared with functional databases such as NR, KOG and KEGG. The result of KOG gene annotation was that the protein function of A. dahurica concentrated in the general functional prediction, posttranslational modification, protein turnover, chaperones and signal transduction mechanisms. GO functional classification indicated that the genes of A. dahurica concentrated on cell biological processes and components. KEGG analysis found that the A. dahurica genes mostly involved in metabolic pathways. (3) And 45 genes of BGLU family were identified in A. dahurica. In this study, the whole genome of A. dahurica is resolved by the third-generation sequencing technology for the first time, which provides important theoretical references for the systematic biological study and the further study of the function of BGLU in the growth and development of A. dahurica.

Obesity-induced cardiac dysfunction is a severe global disease associated with high dietary fat intake, and its pathogenesis includes inflammation, oxidative stress, and ferroptosis. Celastrol (Cel) is a bioactive compound isolated from the herb Tripterygium wilfordii , which has a protective influence on cardiovascular diseases. In this study, the role of Cel in obesity-induced ferroptosis and cardiac injury was investigated. We found that Cel alleviated ferroptosis induced by Palmitic acid (PA), exhibiting a decrease in the LDH, CK-MB, Ptgs2, and Lipid Peroxidation levels. After cardiomyocytes were treated with additional LY294002 and LiCl, Cel exerted its protective effect through increased AKT/GSK3β phosphorylation and decreased level of lipid peroxidation and Mitochondrial ROS. The systolic left ventricle (LV) dysfunction of obese mice was alleviated via ferroptosis inhibition by elevated p-GSK3β and decreased Mitochondrial ROS under Cel treatment. Moreover, mitochondrial anomalies included swelling and distortion in the myocardium which was relieved with Cel. In conclusion, our results demonstrate that ferroptosis resistance with Cel under HFD conditions targets AKT/GSK3β signaling, which provides novel therapeutic strategies in obesity-induced cardiac injury. [Display omitted] • Celastrol suppresses PA-induced ferroptosis in cardiomyocytes. • Celastrol resists PA-induced cardiotoxicity by targeting AKT/GSK3β signaling. • Celastrol upregulates GSK3β phosphorylation and NRF2 expression in HFD mice. [ABSTRACT FROM AUTHOR]

Ferroptosis is an iron-dependent programmed cell death characterized by the accumulation of reactive oxygen species (ROS). Long-term high fat diet (HFD) was found to be associated with ferroptosis and cardiac injury. HFD-induced obesity is characterized by sustained, low-grade inflammation in adipose tissue, while macrophage infiltration plays a crucial role in inflammation. Exosomes (Exos) derived from adipose tissue macrophages (ATMs) participate in the physiological processes of recipient cells. In this study, we investigated the role of ATM-Exos in obesity-induced ferroptosis and cardiac injury. We found that HFD-induced obesity resulted in higher mRNA expression levels of specific markers, e.g., prostaglandin endoperoxide synthase 2 (PTGS2), and increased the levels of lipid peroxides, including malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE). Macrophages infiltrated the adipose tissues, as examined by flow cytometry. Exosomes derived from ATM-Exos were analyzed using transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Obese ATM-Exos administration induced higher levels of PTGS2, MDA, 4-HNE, lipid ROS, and mitochondrial injury. Obese ATM-Exos further provoked obvious cardiac injury, demonstrated by abnormal levels of cardiac enzymes and inflammatory factors. Systolic left ventricle (LV) function anomalies were induced by ATM-Exos in obese mice. miR-140-5p is abundant in obese ATM-Exos and promotes ferroptosis in cardiomyocytes. Solute carrier family 7 member 11 (SLC7A11) is a downstream target of miR-140-5p, which induces ferroptosis via inhibition of GSH synthesis by targeting SLC7A11. Attenuating exosomal-miR-140-5p expression alleviates ferroptosis and cardiac injury induced by obese ATM exosomes by alleviating GSH inhibition. In summary, the current study provides evidence that obese ATM-exosomal miR-140-5p promotes ferroptosis by regulating GSH synthesis and provides a novel therapeutic strategy for targeting obese ATM-Exos in obesity-induced cardiac injury. [Display omitted] • Diet-induced obesity evokes ferroptosis and cardiac injury in mice. • Obese ATM-exosome promotes ferroptosis and cardiac injury in mice. • miR-140-5p was overexpressed in obese adipose tissue macrophages and obese ATM-Exos. • Obese ATM-exosomal miR-140-5p promotes ferroptosis by inhibiting GSH synthesis. [ABSTRACT FROM AUTHOR]

Calcification of the bicuspid aortic valve (BAV) involves differential expression of various RNA genes, which is achieved through complex regulatory networks that are controlled in part by transcription factors and microRNAs. We previously found that miR-195–5p regulates the osteogenic differentiation of valvular interstitial cells (VICs) by targeting the TGF-β pathway. However, the transcriptional regulation of miR-195–5p in calcified BAV patients is not yet clear. In this study, stenotic aortic valve tissues from patients with BAVs and tricuspid aortic valves (TAVs) were collected. Candidate transcription factors of miR-195–5p were predicted by bioinformatics analysis and tested in diseased valves and in male porcine VICs. SP2 gene expression and the corresponding protein levels in BAV were significantly lower than those in TAV, and a low SP2 expression level environment in VICs resulted in remarkable increases in RNA expression levels of RUNX2 , BMP2 , collagen 1, MMP2 , and MMP9 and the corresponding proteins. ChIP assays revealed that SP2 directly bound to the transcription promoter region of miR-195–5p. Cotransfection of SP2 shRNA and a miR-195–5p mimic in porcine VICs demonstrated that SP2 repressed SMAD7 expression via miR-195–5p, while knockdown of SP2 increased the mRNA expression of SMAD7 and the corresponding protein and attenuated Smad 2/3 expression. Immunofluorescence staining of diseased valves confirmed that the functional proteins of osteogenesis differentiation, including RUNX2, BMP2, collagen 1, and osteocalcin, were overexpressed in BAVs. In Conclusion, the transcription factor Sp2 is expressed at low levels in VICs from BAV patients, which has a negative impact on miR-195–5p expression by binding its promoter region and partially promotes calcification through a SMAD -dependent pathway. [ABSTRACT FROM AUTHOR]

Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder caused by mutation in fibrillin-1 (FBN1). However, the molecular mechanism underlying MFS remains poorly understood. The study aimed to explore how the L-type calcium channel (Ca V 1.2) modulates disease progression of MFS and to identify a potential effective target for attenuating MFS. KEGG enrichment analysis showed that the calcium signaling pathway gene set was significantly enriched. We demonstrated that FBN1 deficiency exhibited inhibition on both the expression of Cav1.2 and proliferation of vascular smooth muscle cells (VSMCs). Then, we examined whether FBN1 mediates Cav1.2 via regulating TGF-β1. Higher levels of TGF-β1 were observed in the serum and aortic tissues from patients with MFS. TGF-β1 modulated Cav1.2 expression in a concentration-dependent manner. We evaluated the role of Cav1.2 in MFS by small interfering RNA and Cav1.2 agonist Bay K8644. The effect of Cav1.2 on cell proliferation was dependent on c-Fos activity. These results demonstrated FBN1 deficiency decreased the expression levels of Cav1.2 via regulation of TGF-β1, and downregulation of Cav1.2 inhibited cell proliferation of human aortic smooth muscle cells (HASMCs) in MFS patients. These findings suggest that Cav1.2 may be an appealing therapeutic target for MFS.

Background: For degenerative mitral disease, more and more evidences support that mitral valve plasty (MVP) has much better clincial outcomes than mitral valve replacement (MVR). However, the advantages of MVP in patients suffering from infectious endocarditis (IE) are unclear. To evaluate the appropriateness of MVP in IE patients, we conducted this meta-analysis. Based on the difference between active and healed phase, we not only compared the result of patients with IE, but also identified the subgroup with active IE., Methods: We systematically searched the clinical trials comparing clinical outcomes of MVP and MVR in patients suffering from IE. Relevant articles were searched from January 1, 2000 to March 18, 2021 in Pubmed and Cochrane Library. Studies were excluded if they were with Newcastle-Ottawa Scale (NOS) score less than 6 or lacking of direct comparisons between MVP and MVR., Results: 23 studies were involved and 25,615 patients were included. Pooled analysis showed fewer adverse events and early or long-term death in the MVP group. However, more reoperations existed in this patient group. And the reinfection rate was close between two groups. Similar results were observed after identifying active IE subgroup, but there is no difference in the freedom from reoperation due to all-events., Conclusions: Although limitimations exited in this study, patients suffering from IE can benefit from both MVP and MVR. For surgeons with consummate skills, MVP can be the preferred choice for suitable IE patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Wang, Zhou, Bian, Li, Zhang and Jiang.)