Ang-1 and VEGF: central regulators of angiogenesis.

Angiopoietin-1 (Ang-1) and Vascular Endothelial Growth Factor (VEGF) are central regulators of angiogenesis and are often inactivated in various cardiovascular diseases. VEGF forms complexes with ETS transcription factor family and exerts its action by downregulating multiple genes. Among the target genes of the VEGF-ETS complex, there are a significant number encoding key angiogenic regulators. Phosphorylation of the VEGF-ETS complex releases transcriptional repression on these angiogenic regulators, thereby promoting their expression. Ang-1 interacts with TEK, and this phosphorylation release can be modulated by the Ang-1-TEK signaling pathway. The Ang-1-TEK pathway participates in the transcriptional activation of VEGF genes. In summary, these elements constitute the Ang-1-TEK-VEGF signaling pathway. Additionally, Ang-1 is activated under hypoxic and inflammatory conditions, leading to an upregulation in the expression of TEK. Elevated TEK levels result in the formation of the VEGF-ETS complex, which, in turn, downregulates the expression of numerous angiogenic genes. Hence, the Ang-1-dependent transcriptional repression is indirect. Reduced expression of many target genes can lead to aberrant angiogenesis. A significant overlap exists between the target genes regulated by Ang-1-TEK-VEGF and those under the control of the Ang-1-TEK-TSP-1 signaling pathway. Mechanistically, this can be explained by the replacement of the VEGF-ETS complex with the TSP-1 transcriptional repression complex at the ETS sites on target gene promoters. Furthermore, VEGF possesses non-classical functions unrelated to ETS and DNA binding. Its supportive role in TSP-1 formation may be exerted through the VEGF-CRL5-VHL-HIF-1α-VH032-TGF-ß-TSP-1 axis. This review assesses the regulatory mechanisms of the Ang-1-TEK-VEGF signaling pathway and explores its significant overlap with the Ang-1-TEK-TSP-1 signaling pathway.

Hydrogen sulfide donors across time: From origins to cutting-edge applications.

This review aims to analyze the developmental trajectory of hydrogen sulfide (H2S) donors over the past three decades and explore the historical background, research hotspots, and emerging trends in related fields from a temporal perspective. A total of 5092 literature articles on H2S donors were retrieved from the Web of Science Core Collection (WoSCC), encompassing 1303 journals, 20638 authors, 10992 institutions, and 459 countries and regions. Utilizing CiteSpace as a bibliometric tool, historical features, evolving active topics, and emerging trends in the field of H2S donors were identified. Over the past 30 years, the field of H2S donors has remained in a prominent stage. This article discusses both inorganic and organic types of H2S donors, including NaHS and Na2S, GYY4137, AP39, and AP123, as well as briefly outlines research and applications of H2S donors in nanotechnology, advanced materials, composite materials, nanostructures, and optical properties. Mechanistically, the review outlines how H2S donors regulate cellular signal transduction, anti-inflammatory responses, neuroprotection, and other pathways within the organism by modulating protein S-sulfhydration, antioxidant effects, and interactions with metal proteins. In terms of applications, the review summarizes the extensive use of H2S donors in biomedical research, encompassing cardiovascular, neurological, anti-inflammatory, and anti-cancer characteristics, as well as their potential applications in the treatment of metabolic diseases. Finally, challenges and limitations faced by H2S donor research are discussed, and potential future research directions are proposed.

P53 Regulation upon Lipid Peroxidation and Ferroptosis for Intervention against Atherogenesis.

Tumor protein 53 (P53), as an intracellular regulator of antioxidant responses, participates in the expression of antioxidant defense and lipid metabolism as well as the synthesis of genes in cells. The balance of oxidation and reduction can be disrupted by many pathological conditions, and the role of the antioxidant system in protecting the equilibrium state from pathological effects, such as reactive lipids, is crucial. In particular, the excessive accumulation of lipid peroxidation products is a key factor driving the occurrence and development of various diseases. Ferroptosis is an iron-dependent, lipid peroxidation-driven cell death cascade reaction, which has become a key research area in cardiovascular diseases. Atherosclerosis (AS) is a pathological change caused by lipid metabolic disorder, inflammatory response, and endothelial cell injury, and is the most common cause of cardiovascular disease. This review briefly outlines lipid peroxidation and key components involving ferroptosis cascade reactions, summarizes and emphasizes the role of P53-related signaling pathways in mediating lipid peroxidation and ferroptosis, and focuses on the known P53 target genes that regulate these pathways, as well as explores the possibility of P53 intervention in the treatment of AS by regulating lipid peroxidation and ferroptosis processes.

Genetics of congenital heart disease.

During embryonic development, the cardiovascular system and the central nervous system exhibit a coordinated developmental process through intricate interactions. Congenital heart disease (CHD) refers to structural or functional abnormalities that occur during embryonic or prenatal heart development and is the most common congenital disorder. One of the most common complications in CHD patients is neurodevelopmental disorders (NDD). However, the specific mechanisms, connections, and precise ways in which CHD co-occurs with NDD remain unclear. According to relevant research, both genetic and non-genetic factors are significant contributors to the co-occurrence of sporadic CHD and NDD. Genetic variations, such as chromosomal abnormalities and gene mutations, play a role in the susceptibility to both CHD and NDD. Further research should aim to identify common molecular mechanisms that underlie the co-occurrence of CHD and NDD, possibly originating from shared genetic mutations or shared gene regulation. Therefore, this review article summarizes the current advances in the genetics of CHD co-occurring with NDD, elucidating the application of relevant gene detection techniques. This is done with the aim of exploring the genetic regulatory mechanisms of CHD co-occurring with NDD at the gene level and promoting research and treatment of developmental disorders related to the cardiovascular and central nervous systems.

Genomic bases underlying the adaptive radiation of core landbirds.

BACKGROUND: Core landbirds undergo adaptive radiation with different ecological niches, but the genomic bases that underlie their ecological diversification remain unclear. RESULTS: Here we used the genome-wide target enrichment sequencing of the genes related to vision, hearing, language, temperature sensation, beak shape, taste transduction, and carbohydrate, protein and fat digestion and absorption to examine the genomic bases underlying their ecological diversification. Our comparative molecular phyloecological analyses show that different core landbirds present adaptive enhancement in different aspects, and two general patterns emerge. First, all three raptorial birds (Accipitriformes, Strigiformes, and Falconiformes) show a convergent adaptive enhancement for fat digestion and absorption, while non-raptorial birds tend to exhibit a promoted capability for protein and carbohydrate digestion and absorption. Using this as a molecular marker, our results show relatively strong support for the raptorial lifestyle of the common ancestor of core landbirds, consequently suggesting a single origin of raptors, followed by two secondary losses of raptorial lifestyle within core landbirds. In addition to the dietary niche, we find at temporal niche that diurnal birds tend to exhibit an adaptive enhancement in bright-light vision, while nocturnal birds show an increased adaption in dim-light vision, in line with previous findings. CONCLUSIONS: Our molecular phyloecological study reveals the genome-wide adaptive differentiations underlying the ecological diversification of core landbirds.

Analysis of storage compounds and inorganic ions in dimorphic seeds of euhalophyte Suaeda salsa.

Suaeda salsa is an annual euhalophytic herb that produces dimorphic seeds, such as small black seeds and big brown seeds. In the present study, the fatty acid composition, content of total phenols, flavonoids, carotenoid and inorganic ions in dimorphic seeds of the species collected in the field were measured. There was no significant difference in total oil content between black and brown seeds. Seed total oil content was approximately 19% based on dry weight. The most abundant fatty acid was linoleic acid, and the content was 76.3 and 70.5% of total fatty acids in black and brown seeds, respectively. Furthermore, the contents of total phenols, flavonoids, carotenoids and inorganic ions in brown seeds were higher than those in black seeds, which might be the mechanism of higher salt tolerance of brown seeds than black seeds. The ecological, physiological and genetic mechanisms of the different abilities of nutrition accumulation in black and brown seeds of S. salsa are also discussed and worthy to be investigated in the future.

Utilisation of stored lipids during germination in dimorphic seeds of euhalophyte Suaeda salsa.

Utilisation of stored lipids plays an important role in germination of oil seeds. In the present study, key enzyme activity (lipase, isocitrate lyase and malate synthase) in lipid utilisation was determined during germination in dimorphic seeds of euhalophyte Suaeda salsa (L.) Pall. The results revealed that the percentage of germination were highest in intertidal brown seeds, followed by inland brown seeds and then inland black seeds moistened with 0 and 300mM NaCl during early seed germination. The same trend was found in the activity of three enzymes and soluble sugar content when seeds were moistened with 0 and 300mM NaCl for 3h. Salinity reduced the activity of three enzymes in inland brown and black seeds in the initial 3h, except that salinity had no adverse effect on isocitrate lyase activity of brown seeds. Salinity had no adverse effect on three enzymes in inland brown and black seeds in the initial 30h, except that it decreased malate synthase activity of black seeds. Salinity had no effect on three enzymes in intertidal brown seeds in the initial 3h and 30h. In conclusion, high activity of these enzymes in brown seeds may play an important role in utilisation of stored lipids during their rapid seed germination.

Transcriptomic profiling of genes in matured dimorphic seeds of euhalophyte Suaeda salsa.

BACKGROUND: Suaeda salsa (S. salsa) is a euhalophyte with high economic value. S. salsa can produce dimorphic seeds. Brown seeds are more salt tolerant, can germinate quickly and maintain the fitness of the species under high saline conditions. Black seeds are less salt tolerant, may become part of the seed bank and germinate when soil salinity is reduced. Previous reports have mainly focused on the ecophysiological traits of seed germination and production under saline conditions in this species. However, there is no information available on the molecular characteristics of S. salsa dimorphic seeds. RESULTS: In the present study, a total of 5825 differentially expressed genes were obtained; and 4648 differentially expressed genes were annotated based on a sequence similarity search, utilizing five public databases by transcriptome analysis. The different expression of these genes may be associated with embryo development, fatty acid, osmotic regulation substances and plant hormones in brown and black seeds. Compared to black seeds, most genes may relate to embryo development, and various genes that encode fatty acid desaturase and are involved in osmotic regulation substance synthesis or transport are upregulated in brown seeds. A large number of differentially expressed genes related to plant hormones were found in brown and black seeds, and their possible roles in regulating seed dormancy/germination were discussed. CONCLUSIONS: Upregulated genes involved in seed development and osmotic regulation substance accumulation may relate to bigger seed size and rapid seed germination in brown seeds, compared to black seeds. Differentially expressed genes of hormones may relate to seed dormancy/germination and the development of brown and black seeds. The transcriptome dataset will serve as a valuable resource to further understand gene expression and functional genomics in S. salsa dimorphic seeds.