Research hotspots and emerging trends of mesenchymal stem cells in cardiovascular diseases: a bibliometric-based visual analysis.

Background: Mesenchymal stem cells (MSCs) have important research value and broad application prospects in cardiovascular diseases (CVDs). However, few bibliometric analyses on MSCs in cardiovascular diseases are available. This study aims to provide a thorough review of the cooperation and influence of countries, institutions, authors, and journals in the field of MSCs in cardiovascular diseases, with the provision of discoveries in the latest progress, evolution paths, frontier research hotspots, and future research trends in the regarding field. Methods: The articles related to MSCs in cardiovascular diseases were retrieved from the Web of Science. The bibliometric study was performed by CiteSpace and VOSviewer, and the knowledge map was generated based on data obtained from retrieved articles. Results: In our study, a total of 4,852 publications launched before August 31, 2023 were accessed through the Web of Science Core Collection (WoSCC) database via our searching strategy. Significant fluctuations in global publications were observed in the field of MSCs in CVDs. China emerged as the nation with the largest number of publications, yet a shortage of high-quality articles was noted. The interplay among countries, institutions, journals and authors is visually represented in the enclosed figures. Importantly, current research trends and hotspots are elucidated. Cluster analysis on references has highlighted the considerable interest in exosomes, extracellular vesicles, and microvesicles. Besides, keywords analysis revealed a strong emphasis on myocardial infarction, therapy, and transplantation. Treatment methods-related keywords were prominent, while keywords associated with extracellular vesicles gathered significant attention from the long-term perspective. Conclusion: MSCs in CVDs have become a topic of active research interest, showcasing its latent value and potential. By summarizing the latest progress, identifying the research hotspots, and discussing the future trends in the advancement of MSCs in CVDs, we aim to offer valuable insights for considering research prospects.

Research trends and hotspots of circular RNA in cardiovascular disease: A bibliometric analysis.

From a global perspective, cardiovascular diseases (CVDs), the leading factor accounting for population mortality, and circRNAs, RNA molecules with stable closed-loop structures, have been proven to be closely related. The latent clinical value and the potential role of circRNAs in CVDs have been attracting increasing, active research interest, but bibliometric studies in this field are still lacking. Thus, in this study, we conducted a bibliometric analysis by using software such as VOSviewer, CiteSpace, Microsoft Excel, and the R package to determine the current research progress and hotspots and ultimately provide an overview of the development trends and future frontiers in this field. In our study, based on our search strategy, a total of 1206 publications published before July 31, 2023 were accessed from the WOSCC database. According to our findings, there is a notable increasing trend in global publications in the field of circRNA in CVDs. China was found to be the dominant country in terms of publication number, but a lack of high-quality articles was a significant fault. A cluster analysis on the co-cited references indicated that dilated cardiomyopathy, AMI, and cardiac hypertrophy are the greatest objects of concern. In contrast, a keywords analysis indicated that high importance has been ascribed to MI, abdominal aortic aneurysm, cell proliferation, and coronary artery diseases.

Recent pharmacological advances in the treatment of cardiovascular events with Astragaloside IV.

Cardiovascular disease (CVD) remains the leading cause of death and disability globally. A wide range of CVDs have been reported, each of which diverges significantly, exhibiting sophisticated types of pathogenesis (e.g., inflammatory, oxidative stress, and disorders in cardiomyocyte metabolism). Compared with conventional treatments in modern medicine, traditional Chinese medicine (TCM) can exhibit comparative advantages in the treatment of CVDs. TCM can be utilized to develop effective strategies for addressing the challenges of CVD, with fewer side effects and higher therapeutic efficiency. Astragaloside IV (AS-IV) has been confirmed as one of the major active ingredients found in Astragalus membranaceus (a Chinese herbal medicine that has been extensively employed clinically for the treatments of CVDs). Since recent studies have shown that AS-IV in CVD treatments has achieved promising results, the substance has aroused great attention and further discussions in the field. The present review aims to summarize the recent pharmacological advances in employing AS-IV in the treatment of CVDs.

Genetic adaptations of sea anemone to hydrothermal environment.

Hydrothermal vent habitats are characterized by high hydrostatic pressure, darkness, and the continuous release of toxic metal ions into the surrounding environment where sea anemones and other invertebrates thrive. Nevertheless, the understanding of metazoan metal ion tolerances and environmental adaptations remains limited. We assembled a chromosome-level genome for the vent sea anemone, Alvinactis idsseensis sp. nov. Comparative genomic analyses revealed gene family expansions and gene innovations in A. idsseensis sp. nov. as a response to high concentrations of metal ions. Impressively, the metal tolerance proteins MTPs is a unique evolutionary response to the high concentrations of Fe2+ and Mn2+ present in the environments of these anemones. We also found genes associated with high concentrations of polyunsaturated fatty acids that may respond to high hydrostatic pressure and found sensory and circadian rhythm-regulated genes that were essential for adaptations to darkness. Overall, our results provide insights into metazoan adaptation to metal ions, high pressure, and darkness in hydrothermal vents.

Sapanisertib attenuates pulmonary fibrosis by modulating Wnt5a/mTOR signalling.

Sapanisertib is an orally bioavailable ATP-dependent high-potential raptor-mTOR (TORC1) inhibitor with antineoplastic activity. Here, the impact of sapanisertib was assessed on transforming growth factor-ß1 (TGF-ß1)-treated L929 and A549 cells and on a rat model of bleomycin pulmonary fibrosis. First, in A549 cells treated with TGF-ß1, sapanisertib significantly suppressed the TGF-ß1-induced epithelial-mesenchymal transition, with elevated and reduced E-cadherin and vimentin expression, respectively. In L929 cells treated with TGF-ß1, sapanisertib significantly blocked the TGF-ß1-induced cell proliferation, with decreases in the extracellular matrix-related proteins collagens I and III and smooth muscle actin and in the mechanism-related proteins hypoxia-inducing factor, mTOR, p70S6K, and Wnt5a. Compared with bleomycin alone, continuous gavage administration of sapanisertib for 14 days reduced pathological scores in bleomycin-induced pulmonary fibrosis rats, with decreases in collagen deposition and in the same proteins as in L929 and A549 cells. Accordingly, our findings show that sapanisertib can ameliorate experimental pulmonary fibrosis by inhibiting Wnt5a/mTOR/HIF-1α/p70S6K.

Paritaprevir ameliorates experimental acute lung injury in vitro and in vivo.

Paritaprevir is a potent inhibitor of the NS3/4A protease used to treat chronic hepatitis C virus infection. However, its therapeutic effect on acute lung injury (ALI) remains to be elucidated. In this study, we investigated the effect of paritaprevir on a lipopolysaccharide (LPS)-induced two-hit rat ALI model. The anti-ALI mechanism of paritaprevir was also studied in human pulmonary microvascular endothelial (HM) cells following LPS-induced injury in vitro. Administration of 30 mg/kg paritaprevir for 3 days protected rats from LPS-induced ALI, as reflected by the changes in the lung coefficient (from 0.75 to 0.64) and lung pathology scores (from 5.17 to 5.20). Furthermore, the levels of the protective adhesion protein VE-cadherin and tight junction protein claudin-5 increased, and the cytoplasmic p-FOX-O1 and nuclear ß-catenin and FOX-O1 levels decreased. Similar effects were observed in vitro with LPS-treated HM cells, including decreased nuclear ß-catenin and FOX-O1 levels and higher VE-cadherin and claudin-5 levels. Moreover, ß-catenin inhibition resulted in higher p-FOX-O1 levels in the cytoplasm. These results suggested that paritaprevir could alleviate experimental ALI via the ß-catenin/p-Akt/ FOX-O1 signaling pathway.

A molecular atlas reveals the tri-sectional spinning mechanism of spider dragline silk.

The process of natural silk production in the spider major ampullate (Ma) gland endows dragline silk with extraordinary mechanical properties and the potential for biomimetic applications. However, the precise genetic roles of the Ma gland during this process remain unknown. Here, we performed a systematic molecular atlas of dragline silk production through a high-quality genome assembly for the golden orb-weaving spider Trichonephila clavata and a multiomics approach to defining the Ma gland tri-sectional architecture: Tail, Sac, and Duct. We uncovered a hierarchical biosynthesis of spidroins, organic acids, lipids, and chitin in the sectionalized Ma gland dedicated to fine silk constitution. The ordered secretion of spidroins was achieved by the synergetic regulation of epigenetic and ceRNA signatures for genomic group-distributed spidroin genes. Single-cellular and spatial RNA profiling identified ten cell types with partitioned functional division determining the tri-sectional organization of the Ma gland. Convergence analysis and genetic manipulation further validated that this tri-sectional architecture of the silk gland was analogous across Arthropoda and inextricably linked with silk formation. Collectively, our study provides multidimensional data that significantly expand the knowledge of spider dragline silk generation and ultimately benefit innovation in spider-inspired fibers.

The protective role of raltegravir in experimental acute lung injury in vitro and in vivo.

Disruption of pulmonary endothelial permeability and associated barrier integrity increase the severity of acute respiratory distress syndrome (ARDS). This study investigated the potential ability of the human immunodeficiency virus-1 (HIV-1) integrase inhibitor raltegravir to protect against acute lung injury (ALI) and the underlying mechanisms. Accordingly, the impact of raltegravir treatment on an in vitro lipopolysaccharide (LPS)-stimulated human pulmonary microvascular endothelial cell (HPMEC) model of ALI and an in vivo LPS-induced two-hit ALI rat model was examined. In the rat model system, raltegravir treatment alleviated ALI-associated histopathological changes, reduced microvascular permeability, decreased Evans blue dye extravasation, suppressed the expression of inflammatory proteins including HMGB1, TLR4, p-NF-κB, NLRP3, and MPO, and promoted the upregulation of protective proteins including claudin 18.1, VE-cadherin, and aquaporin 5 as measured via western blotting. Immunohistochemical staining further confirmed the ability of raltegravir treatment to reverse LPS-induced pulmonary changes in NLRP3, claudin 18.1, and aquaporin 5 expression. Furthermore, in vitro analyses of HPMECs reaffirmed the ability of raltegravir to attenuate LPS-induced declines in VE-cadherin and claudin 18.1 expression while simultaneously inhibiting NLRP3 activation and reducing the expression of HMGB1, TLR4, and NF-kB, thus decreasing overall vascular permeability. Overall, our findings suggested that raltegravir may represent a viable approach to treating experimental ALI that functions by maintaining pulmonary microvascular integrity.

Adaptation and evolution of the sea anemone Alvinactis sp. to deep-sea hydrothermal vents: A comparison using transcriptomes.

Sea anemones are diverse and ecologically successful members of Anthozoa. They are often found in intertidal and shallow waters, although a few of them inhabit harsher living conditions, such as deep-sea hydrothermal vents. Here, we sequenced the transcriptome of the vent sea anemone Alvinactis sp., which was collected from Edmond vent along the central Indian Ocean ridge at a depth of 3275 m, to explore the molecular mechanisms related to adaptation to vents. Compared with another deep-sea anemone (Paraphelliactis xishaensis) and five shallow water sea anemones, a total of 117 positively selected genes and 46 significantly expanded gene families were found in Alvinactis sp. specifically that may be related to its vent-specific aspect of adaptation. In addition, 127 positively selected genes and 23 significantly expanded gene families that were found in both Alvinactis sp. and P. xishaensis. Among these, vent-specific adaptations of Alvinactis sp. may involve genetic alterations in peroxisome, ubiquitin-mediated protein degradation, oxidative phosphorylation, and endocytosis, and its deep-sea adaptation may involve changes in genetic information processing. Differentially expressed genes between Alvinactis sp. and the deep-sea anemone P. xishaensis were enriched in a variety of pathways related to adaptation, such as energy metabolism, genetic information processing, endocytosis, and peroxisomes. Overall, we provided the first transcriptome of sea anemones that inhabit vents, which enriches our knowledge of deep-sea hydrothermal vent adaptation and the diversity of sea anemones.

Verdiperstat attenuates acute lung injury by modulating MPO/µ-calpain/ß-catenin signaling.

Verdiperstat, a myeloperoxidase (MPO) inhibitor, is a well-known drug used for the treatment of multisystem atrophy. However, its therapeutic effect on acute lung injury (ALI) remains to be elucidated. In this study, the effect of verdiperstat on lipopolysaccharide (LPS)-induced two-hit rat ALI model was studied in vivo. Subsequently, to explore the anti-ALI mechanism of verdiperstat, an LPS-induced injury in human pulmonary microvascular endothelial cells (HMs) was studied in vitro. The continuous administration of verdiperstat at 120 mg/kg for 3 days exerted a protective effect on the LPS-induced two-hit rat ALI model, as reflected by the change in the lung coefficient and lung pathology scores from 0.72 to 0.61 and 6.08 to 4.37, respectively. Furthermore, the values of protective adhesion protein VE-cadherin and tight junction protein claudin 5 changed from 0.42 to 0.97 and 0.25 to 0.72, but MPO, the ratio of N-µ-calpain to µ-calpain, and the distribution of ß-catenin in the nucleus changed from 3.04 to 2.17, 0.62 to 0.38 and 2.25 to 0.76, respectively. LPS-induced HMs in vitro also showed similar results, including lower MPO and the distribution of ß-catenin in the nucleus, but higher VE-cadherin claudin 5 and N-µ-calpain. Moreover, MPO inhibition resulted in lower µ-calpain activation and lower ß-catenin in the nucleus. Our cumulative results suggest that verdiperstat alleviates ALI by strengthening VE-cadherin and claudin 5 through the inhibition of MPO/µ-calpain/ß-catenin activation.

The protective role of raltegravir in experimental acute lung injury in vitro and in vivo

Disruption of pulmonary endothelial permeability and associated barrier integrity increase the severity of acute respiratory distress syndrome (ARDS). This study investigated the potential ability of the human immunodeficiency virus-1 (HIV-1) integrase inhibitor raltegravir to protect against acute lung injury (ALI) and the underlying mechanisms. Accordingly, the impact of raltegravir treatment on an in vitro lipopolysaccharide (LPS)-stimulated human pulmonary microvascular endothelial cell (HPMEC) model of ALI and an in vivo LPS-induced two-hit ALI rat model was examined. In the rat model system, raltegravir treatment alleviated ALI-associated histopathological changes, reduced microvascular permeability, decreased Evans blue dye extravasation, suppressed the expression of inflammatory proteins including HMGB1, TLR4, p-NF-κB, NLRP3, and MPO, and promoted the upregulation of protective proteins including claudin 18.1, VE-cadherin, and aquaporin 5 as measured via western blotting. Immunohistochemical staining further confirmed the ability of raltegravir treatment to reverse LPS-induced pulmonary changes in NLRP3, claudin 18.1, and aquaporin 5 expression. Furthermore, in vitro analyses of HPMECs reaffirmed the ability of raltegravir to attenuate LPS-induced declines in VE-cadherin and claudin 18.1 expression while simultaneously inhibiting NLRP3 activation and reducing the expression of HMGB1, TLR4, and NF-kB, thus decreasing overall vascular permeability. Overall, our findings suggested that raltegravir may represent a viable approach to treating experimental ALI that functions by maintaining pulmonary microvascular integrity.

Tirbanibulin Attenuates Pulmonary Fibrosis by Modulating Src/STAT3 Signaling.

Tirbanibulin (KX-01) is the first clinical Src inhibitor of the novel peptidomimetic class that targets the peptide substrate site of Src providing more specificity toward the Src kinase. This study assessed the impact of KX-01 on cobalt chloride (CoCl2)-treated L929 cells and bleomycin (BLM)-induced pulmonary fibrosis in rats to evaluate the efficacy of this compound in vitro and in vivo, respectively. In CoCl2-treated L929 cells, KX-01 significantly reduced the expression of smooth muscle actin (α-SMA), collagen I, collagen III, hypoxia inducing factor (HIF-1α), signal transducers and transcriptional activators (p-STAT3), and p-Src. In BLM-induced pulmonary fibrosis rats, KX-01 reduced pathological scores, collagen deposition, α-SMA, collagen I, collagen III, p-Src, HIF-1α, and p-STAT3. Overall, these findings revealed that KX-01 can alleviate experimental pulmonary fibrosis via suppressing the p-SRC/p-STAT3 signaling pathways.

Analysis of rare thalassemia caused by HS-40 regulatory site deletion.

ABSTRACT Objectives: To investigate the effect of HS-40 regulatory site deletion on α-globin gene expression and its clinical significance. Methods: Venous blood samples of subjects were analyzed using a hematology analyzer and high- performance liquid chromatography; fetal cord blood was analyzed by a capillary electrophoresis analyzer. Gap-polymerase chain reaction (PCR), reverse dot blot (RDB), and multiple-link-dependent probe amplification (MLPA) were used for genotyping of thalassemia. Results: The proband was POLR3 K, HS-40 heterozygous deletion; the proband's wife was -SEA/αα; the fetus was POLR3 K, HS-40 heterozygous deletion combined with -SEA deletion; all of them had microcytic hypochromic anemia. Fetal umbilical cord blood electrophoresis revealed a suspected Hb Bart's band to be 88.4%, and the fetus was, thus, diagnosed as Hb Bart's fetus. The red blood cell parameters of the sporadic case showed that he had microcytic hypochromic anemia. Hemoglobin (Hb) electrophoresis analysis showed Hb H to be 5.3%, leading to a diagnosis of Hb H disease. Gap-PCR and RDB identified the genotype to be -α3.7/αα, ßA/ßA. MLPA detected heterozygous deletion or -α3.7 deletion on one allele and deletion of the HS-40 regulatory site on the other allele. Conclusion: The deletion of HS-40 regulatory site reduced expression of α-globin. HS-40 heterozygous deletion manifested as mild anemia, which was of microcytic hypochromic type. When compounded with -α3.7/αα, it manifested as Hb H disease; and when compounded with -SEA/αɑ, it manifested as Hb Bart's fetus.

Analysis of Hb levels and degree of anemia in relation to genotype in 615 patients with hemoglobin H disease.

OBJECTIVES: We analyzed hemoglobin (Hb) levels and degree of anemia in relation to genotype in patients with hemoglobin H (Hb H) disease, thereby providing a scientific basis for the prevention and treatment of Hb H disease in the Guangxi region of China. METHODS: Hb analysis was conducted in 615 patients using high performance liquid chromatography. Seven α-thalassemia and 17 ß-thalassemia genotypes commonly found in the Chinese population were detected by Gap-polymerase chain reaction and reverse dot hybridization. Multiple ligation-dependent probe amplification and sequencing were used to detect α-globin gene. RESULTS: On analyzing the degree of anemia, we found that the proportion of severe and moderate anemia was the highest among cases with - SEA/αCSα genotype, followed by - SEA/αQSα. When Hb H disease was present in combination with ß-thalassemia, the clinical symptoms of most patients were milder than those with simple Hb H disease. CONCLUSION: The clinical manifestations of various types of Hb H disease are heterogeneous; the Hb levels of patients with deletional Hb H are generally higher than those with non-deletional Hb H (P < 0.05). In-depth knowledge of the gene mutation spectrum of thalassemia in Guangxi can provide a basis for genetic counseling of couples and enable prenatal diagnosis.

[Analysis of beta-globin gene variants in Liuzhou area of Guangxi].

OBJECTIVE: To determine the composition and distribution of beta-thalassemia-associated genotypes in Liuzhou area of Guangxi, China. METHODS: From January to December 2017, 13 847 individuals who came for premarital examination, maternity examination or health check were recruited with informed consent. The subjects were analyzed by reverse dot blotting (RDB) for 17 common beta-thalassemia-associated variants among the Chinese population. Individuals with inconsistent results by blood test, electrophoresis, and RDB were subjected to Sanger sequencing to detect rare variants of the beta globin gene. RESULTS: In total 2098 individuals were found to harbor beta-thalassemia-associated variants, which included 2075 heterozygotes (98.90%), 12 compound heterozygotes (0.57%) and 11 homozygotes (0.52%). CD41-42 (48.43%) and CD17 (31.45%) were the most common variants. Three hundred and thirty eight-individuals were found to also carry heterozygous variants of the alpha globin gene, with the most common types being --SEA/aa, -a3.7/aa, aCSa/aa, -a4.2/aa. Through Sanger sequencing, rare genotypes such as beta-32/betaN, betaCD41-42/betaIVS-II-5 and betaCD30/betaN were detected. CONCLUSION: Liuzhou area has a high incidence of beta-thalassemia, but with a complex variant spectrum and clinical phenotypes different from other regions. Genetic counseling and prenatal diagnosis for the carrier population is crucial for the reduction of the related birth defects. Our result may provide valuable information for the prevention and control of beta-thalassemia in this area.

Application of Copy Number Variation Sequencing in Genetic Analysis of Miscarriages in Early and Middle Pregnancy.

High-throughput sequencing based on copy number variation (CNV-seq) is commonly used to detect chromosomal abnormalities. This study identifies chromosomal abnormalities in aborted embryos/fetuses in early and middle pregnancy and explores the application value of CNV-seq in determining the causes of pregnancy termination. High-throughput sequencing was used to detect chromosome copy number variations (CNVs) in 116 aborted embryos in early and middle pregnancy. The detection data were compared with the Database of Genomic Variants (DGV), the Database of Chromosomal Imbalance and Phenotype in Humans using Ensemble Resources (DECIPHER), and the Online Mendelian Inheritance in Man (OMIM) database to determine the CNV type and the clinical significance. High-throughput sequencing results were successfully obtained in 109 out of 116 specimens, with a detection success rate of 93.97%. In brief, there were 64 cases with abnormal chromosome numbers and 23 cases with CNVs, in which 10 were pathogenic mutations and 13 were variants of uncertain significance. An abnormal chromosome number is the most important reason for embryo termination in early and middle pregnancy, followed by pathogenic chromosome CNVs. CNV-seq can quickly and accurately detect chromosome abnormalities and identify microdeletion and microduplication CNVs that cannot be detected by conventional chromosome analysis, which is convenient and efficient for genetic etiology diagnosis in miscarriage.