Elucidating the mechanism of action of Radix Angelica sinensis (Oliv.) Diels and Radix Astragalus mongholicus Bunge ultrafiltration extract on radiation-induced myocardial fibrosis based on network pharmacology and experimental research.

Myocardial fibrosis can induce cardiac dysfunction and remodeling. Great attention has been paid to traditional chinese medicine (TCM) 's effectiveness in treating MF. Radix Angelica sinensis (Oliv.) Diels and Radix Astragalus mongholicus Bunge ultrafiltration extract (RAS-RA), which is a key TCM compound preparation, have high efficacy in regulating inflammation. However, studies on its therapeutic effect on radiation-induced myocardial fibrosis (RIMF) are rare. In this study, RAS-RA had therapeutic efficacy in RIMF and elucidated its mechanism of action. First, we formulated the prediction network that described the relation of RAS-RA with RIMF according to data obtained in different databases. Then, we conducted functional enrichment to investigate the functions and pathways associated with potential RIMF targets for RAS-RA. In vivo experiments were also performed to verify these functions and pathways. Second, small animal ultrasound examinations, H&E staining, Masson staining, transmission electron microscopy, Enzyme-linked immunosorbent assay (ELISA), Western-blotting, Immunohistochemical method and biochemical assays were conducted to investigate the possible key anti-RIMF pathway in RAS-RA. In total, 440 targets were detected in those 21 effective components of RAS-RA; meanwhile, 1,646 RIMF-related disease targets were also discovered. After that, PPI network analysis was conducted to identify 20 key targets based on 215 overlap gene targets. As indicated by the gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analysis results, inflammation and PI3K/AKT/mTOR pathways might have important effects on the therapeutic effects on RIMF. Molecular docking analysis revealed high binding of effective components to targets (affinity < -6 kcal/mol). Based on experimental verification results, RAS-RA greatly mitigated myocardial fibrosis while recovering the cardiac activity of rats caused by X-rays. According to relevant protein expression profiles, the PI3K/AKT/mTOR pathway was important for anti-fibrosis effect of RAS-RA. Experimental studies showed that RAS-RA improved cardiac function, decreased pathological damage and collagen fiber deposition in cardiac tissues, and improved the mitochondrial structure of the heart of rats. RAS-RA also downregulated TNF-α, IL-6, and IL-1ß levels. Additionally, RAS-RA improved the liver and kidney functions and pathological injury of rat kidney and liver tissues, enhanced liver and kidney functions, and protected the liver and kidneys. RAS-RA also increased PI3K, AKT and mTOR protein levels within cardiac tissues and downregulated α-SMA, Collagen I, and Collagen III. The findings of this study suggested that RAS-RA decreased RIMF by suppressing collagen deposition and inflammatory response by inhibiting the PI3K/AKT/mTOR pathway. Thus, RAS-RA was the potential therapeutic agent used to alleviate RIMF.

Therapeutic potential of Angelica sinensis in addressing organ fibrosis: A comprehensive review.

Fibrosis-related diseases (FRD) include conditions like myocardial fibrosis, pulmonary fibrosis, hepatic fibrosis, renal fibrosis, and others. The impact of fibrosis can be severe, causing organ dysfunction, reduced functionality, and even organ failure, leading to significant health issues. Currently, there is a lack of effective modern anti-fibrosis drugs in clinical practice. However, Chinese medicine has a certain beneficial effect on the treatment of such diseases. Angelica sinensis, with its considerable medicinal value, has garnered attention for its anti-fibrosis properties in recent investigations. In the past few years, there has been a growing number of experimental inquiries into the impact of angelica polysaccharide (ASP), angelica water extract, angelica injection, and angelica compound preparation on fibrosis-associated ailments, piquing the interest of researchers. This paper aims to consolidate recent advances in the study of Angelica sinensis for the treatment of fibrosis-related disorders, offering insights for prospective investigations. Literature retrieval included core electronic databases, including Baidu Literature, CNKI, Google-Scholar, PubMed, and Web of Science. The applied search utilized specified keywords to extract relevant information on the pharmacological and phytochemical attributes of plants. The investigation revealed that Angelica sinensis has the potential to impede the advancement of fibrotic diseases by modulating inflammation, oxidative stress, immune responses, and metabolism. ASP, Angelica sinensis extract, Angelica sinensis injection, and Angelica sinensis compound preparation were extensively examined and discussed. These constituents demonstrated significant anti-fibrosis activity. In essence, this review seeks to gain a profound understanding of the role of Angelica sinensis in treating fiber-related diseases. Organ fibrosis manifests in nearly all tissues and organs, posing a critical challenge to global public health due to its widespread occurrence, challenging early diagnosis, and unfavorable prognosis. Despite its prevalence, therapeutic options are limited, and their efficacy is constrained. Over the past few years, numerous studies have explored the protective effects of traditional Chinese medicine on organ fibrosis, with Angelica sinensis standing out as a multifunctional natural remedy. This paper provides a review of organ fibrosis pathogenesis and summarizes the recent two decades' progress in treating fibrosis in various organs such as the liver, lung, kidney, and heart. The review highlights the modulation of relevant signaling pathways through multiple targets and channels by the effective components of Angelica sinensis, whether used as a single medicine or in compound prescriptions.

NO enhances the adaptability to high-salt environments by regulating osmotic balance, antioxidant defense, and ion homeostasis in eelgrass based on transcriptome and metabolome analysis.

Introduction: Eelgrass is a typical marine angiosperm that exhibits strong adaptability to high-salt environments. Previous studies have shown that various growth and physiological indicators were significantly affected after the nitrate reductase (NR) pathway for nitric oxide (NO) synthesis in eelgrass was blocked. Methods: To analyze the molecular mechanism of NO on the adaptability to high-salt environment in eelgrass, we treated eelgrass with artificial seawater (control group) and artificial seawater with 1 mM/L Na2WO4 (experimental group). Based on transcriptomics and metabolomics, we explored the molecular mechanism of NO affecting the salt tolerance of eelgrass. Results: We obtained 326, 368, and 859 differentially expressed genes (DEGs) by transcriptome sequencing in eelgrass roots, stems, and leaves, respectively. Meanwhile, we obtained 63, 52, and 36 differentially accumulated metabolites (DAMs) by metabolomics in roots, stems, and leaves, respectively. Finally, through the combined analysis of transcriptome and metabolome, we found that the NO regulatory mechanism of roots and leaves of eelgrass is similar to that of terrestrial plants, while the regulatory mechanism of stems has similar and unique features. Discussion: NO in eelgrass roots regulates osmotic balance and antioxidant defense by affecting genes in transmembrane transport and jasmonic acid-related pathways to improve the adaptability of eelgrass to high-salt environments. NO in eelgrass leaves regulates the downstream antioxidant defense system by affecting the signal transduction of plant hormones. NO in the stems of eelgrass regulates ion homeostasis by affecting genes related to ion homeostasis to enhance the adaptability of eelgrass to high-salt environments. Differently, after the NO synthesis was inhibited, the glyoxylate and dicarboxylate metabolism, as well as the tricarboxylic acid (TCA) cycle, was regulated by glucose metabolism as a complementary effect to cope with the high-salt environment in the stems of eelgrass. These are studies on the regulatory mechanism of NO in eelgrass, providing a theoretical basis for the study of the salt tolerance mechanism of marine plants and the improvement of terrestrial crop traits. The key genes discovered in this study can be applied to increase salt tolerance in terrestrial crops through cloning and molecular breeding methods in the future.

Development and validation of a nomogram to predict cardiac death after radiotherapy for esophageal cancer.

Background: Patients frequently die from cardiac causes after radiotherapy for esophageal cancer. Early detection of cardiac death risk in these patients is crucial to improve clinical decision-making and prognosis. Thus, we modeled the risk of cardiac death after irradiation for esophageal cancer. Methods: A retrospective analysis of 37,599 esophageal cancer cases treated with radiotherapy in the SEER database between 2000 and 2018 was performed. The selected cases were randomly assigned to the model development group (n = 26,320) and model validation group (n = 11,279) at a ratio of 7:3. We identified the risk factors most commonly associated with cardiac death by least absolute shrinkage and selection operator regression analysis (LASSO). The endpoints for model development and validation were 5- and 10-year survival rates. The net clinical benefit of the models was evaluated by decision curve analysis (DCA) and concordance index (C-index). The performance of the models was further assessed by creating a receiver operating characteristic curve (ROC) and calculating the area under the curve (AUC). Kaplan-Meier (K-M) survival analysis was performed on the probability of death. Patients were classified according to death probability thresholds. Five- and ten-year survival rates for the two groups were shown using K-M curves. Results: The major risk factors for cardiac death were age, surgery, year of diagnosis, sequence of surgery and radiotherapy, chemotherapy and a number of tumors, which were used to create the nomogram. The C-indexes of the nomograms were 0.708 and 0.679 for the development and validation groups, respectively. DCA showed the good net clinical benefit of nomograms in predicting 5- and 10-year risk of cardiac death. The model exhibited moderate predictive power for 5- and 10-year cardiac mortality (AUC: 0.833 and 0.854, respectively), and for the development and validation cohorts (AUC: 0.76 and 0.813, respectively). Conclusions: Our nomogram may assist clinicians in making clinical decisions about patients undergoing radiotherapy for esophageal cancer based on early detection of cardiac death risk.

Development and Validation of a Nomogram Model for the Risk of Cardiac Death in Patients Treated with Chemotherapy for Esophageal Cancer.

The primary cause of mortality in esophageal cancer survivors is cardiac death. Early identification of cardiac mortality risk during chemotherapy for esophageal cancer is crucial for improving the prognosis. We developed and validated a nomogram model to identify patients with high cardiac mortality risk after chemotherapy for esophageal cancer for early screening and clinical decision-making. We randomly allocated 37,994 patients with chemotherapy-treated esophageal cancer into two groups using a 7:3 split ratio: model training (n = 26,598) and validation (n = 11,396). 5- and 10-year survival rates were used as endpoints for model training and validation. Decision curve analysis and the consistency index (C-index) were used to evaluate the model's net clinical advantage. Model performance was evaluated using receiver operating characteristic curves and computing the area under the curve (AUC). Kaplan-Meier survival analysis based on the prognostic index was performed. Patient risk was stratified according to the death probability. Age, surgery, sex, and year were most closely related to cardiac death and used to plot the nomograms. The C-index for the training and validation datasets were 0.669 and 0.698, respectively, indicating the nomogram's net clinical advantage in predicting cardiac death risk at 5 and 10 years. The 5- and 10-year AUCs were 0.753 and 0.772 for the training dataset and 0.778 and 0.789 for the validation dataset, respectively. The accuracy of the model in predicting cardiac death risk was moderate. This nomogram can identify patients at risk of cardiac death after chemotherapy for esophageal cancer at an early stage.

Pharmacological action of Hedysarum polysaccharides: a review.

Hedysarum, a traditional Chinese herbal medicine and food with a long history of clinical application, is used to improve health conditions and treat various diseases. Hedysarum polysaccharides (HPS), flavonoids, saponins, and alkaloids, are the primary components of Hedysarum. HPS is the most important natural active ingredient of Hedysarum, which has many pharmacological effects. Currently, HPS exhibits significant promise in drug development for various ailments such as tumors, diabetes, cardiovascular diseases, Alzheimer's disease, and fibrosis. This review paper discusses the extraction, separation, and content determination techniques of HPS, along with the investigation of its chemical constituents. More importantly, we reviewed the anti-inflammatory pharmacological effects of HPS, such as inhibition of inflammatory factors and NF-κB signaling pathway; antitumor activity through apoptosis induction in tumor cells and blocking tumor cell proliferation and metastasis; antioxidant effects; regulation of various cytokines and immune cells; regulation of blood sugar levels, such as in type I and type II diabetes and in diabetic complications; improvement in symptoms of Alzheimer disease; anti-aging and anti-fibrosis properties; and improvement in cerebral ischemia-reperfusion injury. This review paper establishes the theoretical foundation for future studies on the structure, mechanism, and clinical use of HPS.

Early diagnostic value of high-sensitivity cardiac troponin T for cancer treatment-related cardiac dysfunction: a meta-analysis.

Early diagnosis of cancer treatment-related cardiac dysfunction (CTRCD) is important as cancer therapy increases the risk of cardiac dysfunction. High-sensitivity cardiac troponin T (hs-cTnT) is a highly specific marker of myocardial injury. However, its diagnostic value for CTRCD has not been systematically evaluated. This meta-analysis aimed to evaluate whether hs-cTnT could be used as an early diagnostic biomarker for CTRCD. We systematically surveyed PubMed, Embase, Cochrane Library, and Web of Science databases for studies of hs-cTnT for the diagnosis of CTRCD before 1 April 2022. Patients of all ages and all cancer types who underwent echocardiographic left ventricular ejection fraction assessment and blood hs-cTnT and received anticancer therapy (including chemotherapy, radiotherapy, targeted therapy, immune checkpoint inhibitors, and other treatments) were included in this study, resulting in a total of eight studies with 1294 patients. The occurrence of CTRCD was associated with elevated hs-cTnT [sensitivity: 0.78, 95% confidence interval (CI): 0.64-0.88; specificity: 0.75, 95% CI: 0.59-0.86; area under the curve (AUC): 0.83, 95% CI: 0.80-0.86]. We further performed subgroup analysis and found that the AUC of hs-cTnT elevation for the diagnosis of CTRCD increased from 0.83 to 0.90 (95% CI: 0.87-0.92) at 3-6 months, suggesting a higher early diagnostic value of hs-cTnT compared with echocardiography for CTRCD. In terms of clinical applicability, the Fagan plot showed pre-test and post-test probabilities of 51% and 9%, respectively, indicating that hs-cTnT testing can improve the accuracy of clinical diagnosis of CTRCD. However, it was not possible to determine the optimal cut-off value for early diagnosis of CTRCD with hs-cTnT. The Deeks funnel plot was largely symmetrical (P = 0.74); hence, publication bias was not observed. Hs-cTnT allowed early CTRCD diagnosis at 3-6 months. However, further high-quality research is needed to determine the optimal cut-off value for early CTRCD diagnosis with this biomarker.

Corrigendum: Global research trends in catheter ablation and surgical treatment of atrial fibrillation: A bibliometric analysis and science mapping.

[This corrects the article DOI: 10.3389/fsurg.2022.1048454.].

A potential application for life-related organics detection on Mars by diffuse reflectance infrared spectroscopy.

Life information searching is a hot point for Mars exploration. Ancient Mars was very likely to reach a habitable environment, and there was a real possibility of arising life on Mars. However, the current Mars has a harsh environment. Under such conditions, life materials on Mars are supposed to have taken the form of relatively primitive microbial or organic residues, which might be preserved in some mineral matrices. Detection of these remnants is of great significance for understanding the origin and evolution of life on Mars. The best detection method is in-situ detection or sample return. Herein, diffuse reflectance infrared spectroscopy (DRIFTS) was used to detect characteristic spectra and the limit of detection (LOD) of potential representative organic compounds with associated minerals. In view of high oxidation due to the electrostatic discharge (ESD) during dust actives on Martian surface. The degradation of organic matter by ESD process was studied under simulated Mars conditions. Our results show that the spectral characteristics of organic matter are significantly different from that of associated minerals. The different organic samples have different mass loss and color change after ESD reaction. And the signal intensity of infrared diffuse reflection spectrum can also reflect the changes of organic molecules after ESD reaction. Our results indicated that the degradation products of organics rather than organic itself are most likely to be founded on current Martian surface.

Research progress of natural medicine Astragalus mongholicus Bunge in treatment of myocardial fibrosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Myocardial fibrosis (MF) is a common pathological manifestation of many cardiovascular diseases at a certain stage, with excessive accumulation of collagen fibers, excessive increase in collagen content, and a significant increase in collagen volume as the main pathological changes. There are currently no effective drugs for the treatment of myocardial fibrosis. Traditional Chinese medicine (TCM), the main component of the medical practice used for more than 5000 years, especially in China, often exerts a wider action spectrum than previously attempted options in treating human diseases. In recent times, the great potential of TCM in the treatment of MF has received much attention. Especially many experimental studies on the treatment of MF by Astragalus mongholicus Bunge have been conducted, and the effect is remarkable, which may provide more comprehensive database and theoretical support for the application of Astragalus mongholicus Bunge in the treatment of MF and could be considered a promising candidate drug for preventing MF. AIM OF THE REVIEW: This review summarizes the chemical components of Astragalus mongholicus Bunge, Astragalus mongholicus Bunge extract, Astragalus mongholicus Bunge single prescription, and Astragalus mongholicus Bunge compound preparation in the treatment of MF, and provides comprehensive information and a reliable basis for the exploration of new treatment strategies of botanical drugs in the therapy of MF. METHODS: The literature information was obtained from the scientific databases on ethnobotany and ethnomedicines (up to August 2022), mainly from the PubMed, Web of Science, and CNKI databases. The experimental studies on the anti-myocardial fibrosis role of the effective active components of Astragalus mongholicus Bunge and the utility of its compound preparation and the involved mechanisms were identified. The search keywords for such work included: "myocardial fibrosis" or "Cardiac fibrosis ", and "Astragalus mongholicus Bunge", "extract," or "herb". RESULTS: Several studies have shown that the effective active components of Astragalus mongholicus Bunge and its formulas, particularly Astragaloside IV, Astragalus polysaccharide, total saponins of Astragalus mongholicus Bunge, triterpenoid saponins of Astragalus mongholicus Bunge, and cycloastragenol, exhibit potential benefits against MF, the mechanisms of which appear to involve the regulation of inflammation, oxidant stress, and pro-fibrotic signaling pathways, etc. Conclusion: These research works have shown the therapeutic benefits of Astragalus mongholicus Bunge in the treatment of MF. However, further research should be undertaken to clarify the unconfirmed chemical composition and regulatory mechanisms, conduct standard clinical trials, and evaluate the possible side effects. The insights in the present review provided rich ideas for developing new anti-MF drugs. THESIS: Myocardial fibrosis (MF) with excessive accumulation of collagen fibers, excessive increase in collagen content, and a significant increase in collagen volume as the main pathological changes is a common pathological manifestation of many cardiovascular diseases at a certain stage, which seriously affects cardiac function. At present, there is still a lack of effective drugs for the treatment of MF. Traditional Chinese medicine (TCM), the main component of the medical practice used for more than 5000 years especially in China, often exerts wider action spectrum than previously attempted options in treating human diseases. In recent times, the great potential of TCM in the treatment of MF has received much attention. Especially many experimental studies on the treatment of MF by Astragalus mongholicus Bunge have been conducted, and the effect is remarkable, which may provide more comprehensive data base and theoretical support for the application of Astragalus mongholicus Bunge in the treatment of MF and could be considered a promising candidate drug for preventing MF.

Role and molecular mechanism of traditional Chinese medicine in preventing cardiotoxicity associated with chemoradiotherapy.

Cardiotoxicity is a serious complication of cancer therapy. It is the second leading cause of morbidity and mortality in cancer survivors and is associated with a variety of factors, including oxidative stress, inflammation, apoptosis, autophagy, endoplasmic reticulum stress, and abnormal myocardial energy metabolism. A number of studies have shown that traditional Chinese medicine (TCM) can mitigate chemoradiotherapy-associated cardiotoxicity via these pathways. Therefore, this study reviews the effects and molecular mechanisms of TCM on chemoradiotherapy-related cardiotoxicity. In this study, we searched PubMed for basic studies on the anti-cardiotoxicity of TCM in the past 5 years and summarized their results. Angelica Sinensis, Astragalus membranaceus Bunge, Danshinone IIA sulfonate sodium (STS), Astragaloside (AS), Resveratrol, Ginsenoside, Quercetin, Danggui Buxue Decoction (DBD), Shengxian decoction (SXT), Compound Danshen Dripping Pill (CDDP), Qishen Huanwu Capsule (QSHWC), Angelica Sinensis and Astragalus membranaceus Bunge Ultrafiltration Extract (AS-AM),Shenmai injection (SMI), Xinmailong (XML), and nearly 60 other herbs, herbal monomers, herbal soups and herbal compound preparations were found to be effective as complementary or alternative treatments. These preparations reduced chemoradiotherapy-induced cardiotoxicity through various pathways such as anti-oxidative stress, anti-inflammation, alleviating endoplasmic reticulum stress, regulation of apoptosis and autophagy, and improvement of myocardial energy metabolism. However, few clinical trials have been conducted on these therapies, and these trials can provide stronger evidence-based support for TCM.

Correlation Between the MTHFR C677T Genotype and Coronary Heart Disease in Populations from Gansu, China.

This study was designed to evaluate the relationship between polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene and coronary heart disease (CHD) in populations from the Gansu region of China. The MTHFR C677T polymorphism genotypes from 209 patients with CHD, as confirmed by coronary angiography, and 212 non-CHD control patients were identified using PCR gold magnetic particle chromatography. We simultaneously evaluated homocysteine (Hcy) and folate levels in these samples using biochemical methods. The TT genotype of the MTHFR C677T locus was significantly more frequent in the CHD group than in the control, while the CC genotype was significantly less frequent in CHD patients than in non-CHD patients (p < 0.05). In addition, biochemical analysis revealed that the serum Hcy levels increased, and folate levels decreased in the TT genotype. Logistic regression analysis showed that this correlation was independent of nationality, sex, age, body mass index, medical history, and blood lipid level (p < 0.05). The occurrence of the TT genotype at the MTHFR C677T locus was closely associated with CHD in the Gansu population and may serve as a biomarker of increased risk for this disease.

Research Progress of Traditional Chinese Medicine in Treatment of Myocardial fibrosis.

Effective drugs for the treatment of myocardial fibrosis (MF) are lacking. Traditional Chinese medicine (TCM) has garnered increasing attention in recent years for the prevention and treatment of myocardial fibrosis. This Article describes the pathogenesis of myocardial fibrosis from the modern medicine, along with the research progress. Reports suggest that Chinese medicine may play a role in ameliorating myocardial fibrosis through different regulatory mechanisms such as reduction of inflammatory reaction and oxidative stress, inhibition of cardiac fibroblast activation, reduction in extracellular matrix, renin-angiotensin-aldosterone system regulation, transforming growth Factor-ß1 (TGF-ß1) expression downregulation, TGF-ß1/Smad signalling pathway regulation, and microRNA expression regulation. Therefore, traditional Chinese medicine serves as a valuable source of candidate drugs for exploration of the mechanism of occurrence and development, along with clinical prevention and treatment of MF.

Global research trends in catheter ablation and surgical treatment of atrial fibrillation: A bibliometric analysis and science mapping.

Introduction: To evaluate the global research results of the catheter ablation and surgical treatment of atrial fibrillation in the past 40 years by bibliometrics, and to explore the hotspots and prospects for future development. Methods: Relevant literatures were selected from the Web of Science Core Collection. VOSviewer 1.6.17, SciMAT 1.1.04, and CiteSpace 5.8.R1 were used to analyze the data objectively, deeply and comprehensively. Results: As of July 14, 2021, 11,437 studies for the catheter ablation and surgical treatment of atrial fibrillation have been identified from 1980 to 2021. The Journal of Cardiovascular Electrophysiology and Circulation respectively ranked first in terms of the number of publications and the number of co-citations. A total of 6,631 institutions from 90 countries participated in the study, with USA leading the way with 3,789 documents. Cryoablation, atrial fibrosis, substrate modification, minimally invasive and access surgery will still be the research focus and frontier in the next few years. Conclusions: The publication information for the catheter ablation and surgical treatment of atrial fibrillation were reviewed, including country, institution, author, journal publications, and so on. Developed countries had the advantage in this research areas, and cooperation with low-income countries should be improved. The former research hotspots in the field of catheter ablation and surgical treatment of atrial fibrillation were analyzed, and the future research direction was predicted.

GDF15 Promotes Cardiac Fibrosis and Proliferation of Cardiac Fibroblasts via the MAPK/ERK1/2 Pathway after Irradiation in Rats.

Ionizing radiation exposure is associated with a risk of cardiac fibrosis; however, the underlying molecular mechanism remains unclear. Growth/differentiation factor-15 (GDF15), a fibroblast factor, is a divergent member of the transforming growth factor ß superfamily. Next-generation sequencing analyses has revealed that Gdf15 is increased in cardiac fibroblasts during radiation-induced fibrosis. However, the role of Gdf15 in cardiac fibrosis remains unclear. In this study, we demonstrated that the upregulated expression of GDF15 in newborn rat cardiac fibroblasts and adult rats after irradiation could induce fibrosis, which was confirmed by the increased cell proliferation rate and the increased expression of fibrosis markers (Col1α and αSMA) in newborn rat cardiac fibroblasts after transfection with Gdf15 in vitro. Conversely, the downregulation of GDF15 inhibited cardiac fibrosis, as confirmed by G2/M-cell cycle arrest, suppression of cell proliferation, and low levels of Col1α and αSMA expression. We also found that suppressing the expression of Gdf15 in cardiac fibroblasts could lead to a decrease in CDK1 and inhibit phosphorylation of ERK1/2. Thus, GDF15 might promote cardiac fibroblast fibrosis through the MAPK/ERK1/2 pathway and thus contribute to the pathogenesis of radiation-induced heart disease.

miR-21 is upregulated, promoting fibrosis and blocking G2/M in irradiated rat cardiac fibroblasts.

BACKGROUND: Radiation exposure of the thorax is associated with a greatly increased risk of cardiac morbidity and mortality even after several decades of advancement in the field. Although many studies have demonstrated the damaging influence of ionizing radiation on cardiac fibroblast (CF) structure and function, myocardial fibrosis, the molecular mechanism behind this damage is not well understood. miR-21, a small microRNA, promotes the activation of CFs, leading to cardiac fibrosis. miR-21 is overexpressed after irradiation; however, the relationship between increased miR-21 and myocardial fibrosis after irradiation is unclear. This study was conducted to investigate gene expression after radiation-induced CF damage and the role of miR-21 in this process in rats. METHODS: We sequenced irradiated rat CFs and performed weighted correlation network analysis (WGCNA) combined with differentially expressed gene (DEG) analysis to observe the effect on the expression profile of CF genes after radiation. RESULTS: DEG analysis showed that the degree of gene changes increased with the radiation dose. WGCNA revealed three module eigengenes (MEs) associated with 8.5-Gy-radiation-the Yellow, Brown, Blue modules. The three module eigengenes were related to apoptosis, G2/M phase, and cell death and S phase, respectively. By blocking with the cardiac fibrosis miRNA miR-21, we found that miR-21 was associated with G2/M blockade in the cell cycle and was mainly involved in regulating extracellular matrix-related genes, including Grem1, Clu, Gdf15, Ccl7, and Cxcl1. Stem-loop quantitative real-time PCR was performed to verify the expression of these genes. Five genes showed higher expression after 8.5 Gy-radiation in CFs. The target genes of miR-21 predicted online were Gdf15 and Rsad2, which showed much higher expression after treatment with antagomir-miR-21 in 8.5-Gy-irradiated CFs. Thus, miR-21 may play the role of fibrosis and G2/M blockade in regulating Grem1, Clu, Gdf15, Ccl7, Cxcl1, and Rsad2 post-irradiation.

Transcriptomic analysis reveals the molecular adaptation to NaCl stress in Zostera marina L.

The seagrass Zostera marina L. shows optimal growth in marine water and reduced growth under low salinity conditions. However, little is known about the molecular mechanisms underlying its adaptation to high salinity in Z. marina. In this study, transcriptomic analyses were performed using RNA-seq of the following two groups with different NaCl content: the CK group (seagrasses grown in the absence of NaCl) and the NaCl group (seagrasses grown in the presence of 400 mM NaCl for 6 h). Approximately 316 million high-quality reads were generated, and 87.9% of the data were mapped to the reference genome. Moreover, differentially expressed genes between the CK and NaCl groups were identified. According to a functional analysis, the up-regulated genes after the NaCl treatment were significantly enriched in nitrogen metabolism, calcium signalling and DNA replication while the down-regulated genes were significantly enriched in photosynthesis. A comparative transcriptomic analysis detected many differentially expressed genes and pathways required for adaptation to NaCl stress, providing a foundation for future studies investigating the molecular mechanisms of salt adaptation in Z. marina. We discuss how molecular changes in these processes may have contributed to the NaCl adaptation.

The nearly complete mitochondrial genome of Chinese pygmy dormouse Typhlomys cinereus (Rodentia: Platacanthomyidae).

In this study, we report the nearly complete mitochondrial genome of a Chinese pygmy dormouse Typhlomys cinereus (Rodentia: Platacanthomyidae). The 15,011 bp genome is consisted of 13 protein-coding genes, 16S rRNA, 21 tRNAs, partial 12S rRNA and control region. A phylogenetic tree was built using 12 protein-coding genes of 19 species from Dipodoidea and Muroidea. Our result shows that T. cinereus represents the earliest split within Muroidea. The genome would contribute to further study of phylogeny in Muroidea and Rodentia.

Arabidopsis histone methylase CAU1/PRMT5/SKB1 acts as an epigenetic suppressor of the calcium signaling gene CAS to mediate stomatal closure in response to extracellular calcium.

Elevations in extracellular calcium ([Ca(2+)]o) are known to stimulate cytosolic calcium ([Ca(2+)]cyt) oscillations to close stomata. However, the underlying mechanisms regulating this process remain largely to be determined. Here, through the functional characterization of the calcium underaccumulation mutant cau1, we report that the epigenetic regulation of CAS, a putative Ca(2+) binding protein proposed to be an external Ca(2+) sensor, is involved in this process. cau1 mutant plants display increased drought tolerance and stomatal closure. A mutation in CAU1 significantly increased the expression level of the calcium signaling gene CAS, and functional disruption of CAS abolished the enhanced drought tolerance and stomatal [Ca(2+)]o signaling in cau1. Map-based cloning revealed that CAU1 encodes the H4R3sme2 (for histone H4 Arg 3 with symmetric dimethylation)-type histone methylase protein arginine methytransferase5/Shk1 binding protein1. Chromatin immunoprecipitation assays showed that CAU1 binds to the CAS promoter and modulates the H4R3sme2-type histone methylation of the CAS chromatin. When exposed to elevated [Ca(2+)]o, the protein levels of CAU1 decreased and less CAU1 bound to the CAS promoter. In addition, the methylation level of H4R3sme2 decreased in the CAS chromatin. Together, these data suggest that in response to increases in [Ca(2+)]o, fewer CAU1 protein molecules bind to the CAS promoter, leading to decreased H4R3sme2 methylation and consequent derepression of the expression of CAS to mediate stomatal closure and drought tolerance.

Arabidopsis NRT1.5 is another essential component in the regulation of nitrate reallocation and stress tolerance.

Nitrate reallocation to plant roots occurs frequently under adverse conditions and was recently characterized to be actively regulated by Nitrate Transporter1.8 (NRT1.8) in Arabidopsis (Arabidopsis thaliana) and implicated as a common response to stresses. However, the underlying mechanisms remain largely to be determined. In this study, characterization of NRT1.5, a xylem nitrate-loading transporter, showed that the mRNA level of NRT1.5 is down-regulated by salt, drought, and cadmium treatments. Functional disruption of NRT1.5 enhanced tolerance to salt, drought, and cadmium stresses. Further analyses showed that nitrate, as well as Na(+) and Cd(2+) levels, were significantly increased in nrt1.5 roots. Important genes including Na(+)/H(+) exchanger1, Salt overly sensitive1, Pyrroline-5-carboxylate synthase1, Responsive to desiccation29A, Phytochelatin synthase1, and NRT1.8 in stress response pathways are steadily up-regulated in nrt1.5 mutant plants. Interestingly, altered accumulation of metabolites, including proline and malondialdehyde, was also observed in nrt1.5 plants. These data suggest that NRT1.5 is involved in nitrate allocation to roots and the consequent tolerance to several stresses, in a mechanism probably shared with NRT1.8.