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.

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.

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.

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.

[Study on the mechanism of paeonol in improving low-density lipoprotein-induced human vascular endothelial cell injury].

OBJECTIVE: To investigate the effects of paeonol on low-density lipoprotein-induced human vascular endothelial cell injury and its molecular mechanisms. METHODS: Human umbilical vein endothelial cells (HUVECs) were divided into 9 groups, normal control (NC) group, ox-LDL group (100 ng/L ox-LDL), low, medium, and high-dose paeonol groups (60 µmol/L, 120 µmol/L, 240 µmol/L paeonol+100 ng/L ox-LDL), ox-LDL+small interfering RNA negative control (si-NC) group, ox-LDL+circ_0003204 small interfering RNA (si-circ_0003204) group, middle dose group+ox-LDL+circ_0003204 overexpression negative control (pcDNA-NC) group, middle dose group+ox-LDL+circ_0003204 overexpression (pcDNA-circ_0003204) group, three replicate wells in each group. MTT flow cytometry, and Western blot were used to detect cell proliferation, apoptosis and protein (CDK2, Bcl2, p27, Bax) expressions, respectively. Malondialdehyde (MDA) and superoxide dismutase (SOD) kit were used to detect MDA content and SOD activity; real-time quantitative PCR (RT-qPCR) was used to detect the expression of circ_0003204. RESULTS: Compared with the NC group, the proliferation activity, protein expressions of CDK2 and Bcl2, and SOD activity of HUVECs in the ox-LDL group were decreased significantly (P＜0.05), and the apoptosis rate, protein expressions of p27 and Bax, MDA content, and circ_0003204 expression were increased significantly (P＜ 0.05). Compared with the ox-LDL group, the proliferation activity, protein (CDK2, Bcl2) expressions and SOD activity of HUVECs in the low, medium and high dose paeonol groups were increased significantly (P＜0.05), and the apoptosis rate, protein (p27, Bax) expressions, MDA content And circ_0003204 expression were decreased significantly (P＜ 0.05). Compared with ox-LDL+si-NC group, the proliferation activity, protein (CDK2, Bcl2) expressions, SOD activity of HUVECs in ox-LDL+si-circ_0003204 group were increased significantly (P＜0.05), the apoptosis rate, protein (p27, Bax) expressions, and the content of MDA were decreased significantly (P＜0.05). Compared with the middle-dose+ox-LDL+pcDNA-NC group, the HUVECs proliferation activity, protein (CDK2, Bcl2) expressions, and SOD activity in the middle-dose+ox-LDL+pcDNA-circ_0003204 group were decreased significantly (P＜0.05), and the levels of circ_0003204, apoptosis rate, protein (p27, Bax) expressions and MDA content were increased significantly (P＜0.05). CONCLUSION: Paeonol can inhibit ox-LDL-induced apoptosis and oxidative stress of human umbilical vein endothelial cells, and alleviate human umbilical vein endothelial cell injury. The mechanism of action may be related to the down-regulation of circ_0003204 expression.

Combined use of low T3 syndrome and NT-proBNP as predictors for death in patients with acute decompensated heart failure.

BACKGROUND: In patients with established HF, low triiodothyronine syndrome (LT3S) is commonly present, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a useful marker for predicting death. This study was aimed to evaluate the prognostic value of LT3S in combination with NT-proBNP for risk of death in patients with heart failure (HF). METHODS: A total of 594 euthyroid patients hospitalized with acute decompensated HF were enrolled by design. Of these patients, 27 patients died during hospitalization and 100 deaths were identified in patients discharged alive during one year follow-up. Patients were divided into 2 groups on the base of the reference ranges of free T3 (FT3) levels: LT3S group (FT3 < 2.3pg/mL, n = 168) and non-LT3S group (FT3 ≥ 2.3pg/mL, n = 426). RESULTS: In multivariable Cox regression, LT3S was significantly associated with 1 year all-cause mortality (adjusted hazard ratio, 1.85; 95 % confidence interval [CI], 1.21 to 2.82; P = 0.005), but not significant for in-hospital mortality (adjusted hazard ratio, 1.58; 95 % CI, 1.58 to 2.82; P = 0.290) after adjustment for clinical variables and NT-proBNP. Addition of LT3S and NT-proBNP to the prediction model with clinical variables significantly improved the C statistic for predicting 1 year all-cause mortality. CONCLUSIONS: In patients with acute decompensated HF, the combination of LT3S and NT-proBNP improved prediction for 1 year all-cause mortality beyond established risk factors, but was not strong enough for in-hospital mortality.

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.