Resident vascular Sca1+ progenitors differentiate into endothelial cells in vascular remodeling via miR-145-5p/ERG signaling pathway.

Endothelial cell (EC) damage or dysfunction serves as the initial event in the pathogenesis of various cardiovascular diseases. Progenitor cells have been postulated to be able to differentiate into ECs, facilitate endothelial regeneration, and alleviate vascular pathological remodeling. However, the precise cellular origins and underlying mechanisms remain elusive. Through single-cell RNA sequencing (scRNA-seq), we identified an increasing population of progenitors expressing stem cell antigen 1 (Sca1) during vascular remodeling in mice. Using both mouse femoral artery injury and vein graft models, we determined that Sca1+ cells differentiate into ECs, restored endothelium in arterial and venous remodeling processes. Notably, we have observed that the differentiation of Sca1+ cells into ECs is negatively regulated by the microRNA-145-5p (miR-145-5p)-Erythroblast transformation-specific-related gene (ERG) pathway. Inhibiting miR-145-5p promoted Sca1+ cell differentiation and reduced neointimal formation after vascular injury. Finally, a similar downregulation of miR-145-5p in human arteriovenous fistula was observed comparing to healthy veins.

The conversion of monolignans to sesquilignans and dilignans is closely correlated to the regulation of Arctium lappa seed germination.

MAIN CONCLUSION: The secondary metabolic conversion of monolignans to sesquilignans/dilignans was closely related to seed germination and seedling establishment in Arctium lappa. Arctium lappa plants are used as a kind of traditional Chinese medicines for nearly 1500 years, and so far, only a few studies have put focus on the key secondary metabolic changes during seed germination and seedling establishment. In the current study, a combined approach was used to investigate the correlation among secondary metabolites, plant hormone signaling, and transcriptional profiles at the early critical stages of A. lappa seed germination and seedling establishment. Of 50 metabolites in methonolic extracts of A. lappa samples, 35 metabolites were identified with LC-MS/MS and 15 metabolites were identified with GC-MS. Their qualitative properties were examined according to the predicted chemical structures. The quantitative analysis was performed for deciphering their metabolic profiles, discovering that the secondary metabolic conversion from monolignans to sesquilignans/dilignans was closely correlated to the initiation of A. lappa seed germination and seedling establishment. Furthermore, the critical transcriptional changes in primary metabolisms, translational regulation at different cellular compartments, and multiple plant hormone signaling pathways were revealed. In addition, the combined approach provides unprecedented insights into key regulatory mechanisms in both gene transcription and secondary metabolites besides many known primary metabolites during seed germination of an important traditional Chinese medicinal plant species. The results not only provide new insights to understand the regulation of key medicinal components of 'ARCTII FRUCTUS', arctiin and arctigenin at the stages of seed germination and seedling establishment, but also potentially spur the development of seed-based cultivation in A. lappa plants.

Host CD34+ cells are replacing donor endothelium of transplanted heart.

BACKGROUND: Endothelium dysfunction is a central problem for early rejection due to the host alloimmune response and the late status of arteriosclerosis in heart transplantation. However, reliable pieces of evidence are still limited concerning the source of the regenerated endothelium within the transplanted heart. METHODS: We analyzed single-cell RNA sequencing data and constructed an inducible lineage tracing mouse, combined heart transplantation with bone marrow transplantation and a parabiosis model, cellular components, and endothelial cell populations in cardiac graft lesions. RESULTS: Our single-cell RNA sequencing analysis of a transplanted heart allowed for the establishment of an endothelial cell atlas with a heterogeneous population, including arterial, venous, capillary, and lymphatic endothelial cells. Along with genetic cell lineage tracing, we demonstrated that the donor cells were mostly replaced by recipient cells in the cardiac allograft, up to 83.29% 2 weeks after transplantation. Furthermore, recipient nonbone marrow CD34+ endothelial progenitors contributed significantly to extracellular matrix organization and immune regulation, with higher apoptotic ability in the transplanted hearts. Mechanistically, peripheral blood-derived human endothelial progenitor cells differentiate into endocardial cells via Vascular endothelial growth factor receptor-mediated pathways. Host circulating CD34+ endothelial progenitors could repair the damaged donor endothelium presumably through CCL3-CCR5 chemotaxis. Partial depletion of host CD34+ cells resulted in delayed endothelial regeneration. CONCLUSIONS: We created an annotated fate map of endothelial cells in cardiac allografts, indicating how recipient CD34+ cells could replace the donor endothelium via chemokine CCL3-CCR5 interactions. The mechanisms we discovered could have a potential therapeutic effect on the long-term outcomes of heart transplantation.

Cardiovascular Complications of Pan-Cancer Therapies: The Need for Cardio-Oncology.

It is more likely that a long-term survivor will have both cardiovascular disease and cancer on account of the progress in cancer therapy. Cardiotoxicity is a well-recognized and highly concerning adverse effect of cancer therapies. This side effect can manifest in a proportion of cancer patients and may lead to the discontinuation of potentially life-saving anticancer treatment regimens. Consequently, this discontinuation may adversely affect the patient's survival prognosis. There are various underlying mechanisms by which each anticancer treatment affects the cardiovascular system. Similarly, the incidence of cardiovascular events varies with different protocols for malignant tumors. In the future, comprehensive cardiovascular risk assessment and clinical monitoring should be considered for cancer treatments. Baseline cardiovascular evaluation risk should be emphasized prior to initiating clinical therapy in patients. Additionally, we highlight that there is a need for cardio-oncology to avoid or prevent cardiovascular side effects. Cardio-oncology service is based on identifying cardiotoxicity, developing strategies to reduce these toxicities, and minimizing long-term cardiotoxic effects.

The impact of hypertension for metabolites in patients with acute coronary syndrome.

Background: Acute coronary syndrome (ACS) is one of the leading causes of death and is often accompanied by hypertension. Methods: We investigated whether hypertension affects the metabolism of patients with ACS. Serum samples were provided from healthy controls (HCs; n=26), patients with ACS (n=20), or those patients with ACS complicated with hypertension (HTN, n=21), and all were subjected to non-targeted metabolomics analyses based on gas chromatography-mass spectrometry (GC/MS). Differential metabolites were screened using principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal partial least squares discriminant analysis (OPLS-DA). Kyoto Encyclopedia of Genes and Genomes (KEGG) provided metabolic pathways related to these metabolites. Results: Compared to those in the HC group, 12 metabolites were significantly upregulated and 6 significantly downregulated in the ACS group; among these, L-cystine and isocitric acid showed the most obvious differences, respectively. Compared to those in the ACS group, 3 metabolites were significantly upregulated and 2 metabolites were significantly downregulated in the ACS-HTN group, among which oleic acid and chenodeoxycholic acid showed the most marked difference, respectively. The five most prominent metabolic pathways involved in differential metabolites between the ACS and HC groups were arginine biosynthesis; oxidative phosphorylation; alanine, aspartate and glutamate metabolism; citrate cycle; and glucagon signaling pathway. The metabolic pathways between the ACS and ACS-HTN groups were steroid biosynthesis, fatty acid biosynthesis, arginine biosynthesis, primary bile acid biosynthesis, and tyrosine metabolism. Conclusions: A comprehensive study of the changes in circulatory metabolomics and the influence of HTN was conducted in patients with ACS. A serum metabolomics test can be used to identify differentially metabolized molecules and allow the classification of patients with ACS or those complicated with HTN.

Sequencing and comparative analysis of chloroplast genomes of three medicinal plants: Gentiana manshurica, G. scabra and G. triflora.

Three species of Gentiana (Gentiana manshurica kitag., Gentiana scabra bunge., and Gentiana triflora pall.) were the main source for an important traditional Chinese medicine, "Longdan", which was first mentioned in " Shennong materia medica Sutra " 2000 years ago. Until recently, there were very few reports on taxonomic classification of these three traditional medicinal Gentiana species. In the current study, chloroplast genomes of the three Gentiana species were sequenced and the phylogenetic analyses were performed in combination with 31 NCBI downloaded Gentiana species sequences and two species of Swertia as outgroup. Based on the phylogenetic results, a new taxonomic classification for Gentiana was proposed, including 4 independent clades with 6 subdivisions (Group 1-Group 6). All the general features, SSR characteristics and gene composition of Gentiana chloroplast genomes strongly supported such a new classification system for Gentiana, which could lay a theoretical foundation for Gentiana in the molecular evolutionary research. Finally, phylogenetic analyisis also demonstrated that the three examined species from Gentiana could cluster together into one group (Group 6), which was far away from the evolutionary position of the medicinal species, Gentiana rigescens Franch, which was consistent with the traditional classification in traditional medicinal uses and taxonomy. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-022-01217-0.

[Comparison of chloroplast genomes of medicinal plants in Aristolochiaceae].

In this study, the chloroplast genome of Asarum sieboldii f. seoulense was sequenced, analyzed, and compared with chloroplast genomes of other medicinal plants in Aristolochiaceae downloaded from GenBank, aiming to clarify the characteristics of the chloroplast genome of A. sieboldii f. seoulense and the differences in chloroplast genome among medicinal plants of Aristolochiaceae. To be specific, the chloroplast genome of A. sieboldii f. seoulense was sequenced and assembled by high-throughput sequencing, and the general characteristics, repeats, inverted repeat(IR) boundary, and phylogenetic relationship of the chloroplast genomes of 11 medicinal species in Aristolochiaceae were analyzed with REPuter. The result showed that the genome of A. sieboldii f. seoulense was 167 293 bp, with large single-copy(LSC) region of 89 840 bp, small single-copy(SSC) region of 21 415 bp, IR region of 28 019 bp, and GC content of 37.9%. A total of 133 genes were annotated, including 89 protein-coding genes, 36 tRNA genes and 8 rRNA genes. The chloroplast genomes of the 11 medicinal species were 159 308-167 293 bp, with 130-134 genes annotated. Forward(F), reverse(R), complement(C), and palindromic(P) long repeats and simple sequence repeat(SSR) were found in the chloroplast genomes of five species. Among them, A. sieboldii f. seoulense had six types of SSR. In the phylogenetic tree, A. sieboldii f. seoulense and A. heterotropoides were in the same clade. The result is expected to lay a basis for the classification, identification, and phylogeny of medicinal plants in Aristolochiaceae.