Source-specific ecological and health risks of polycyclic aromatic hydrocarbons in the adjacent coastal area of the Yellow River Estuary, China.

Industrialization and urbanization have led to increasing levels of PAH pollution in highly urbanized estuaries and their adjacent coastal areas globally. This study focused on the adjacent coastal area of the Yellow River Estuary (YRE) and collected surface seawater, surface sediment, and clams Ruditapes philippinarum and Mactra veneriformis at four sites (S1 to S4) in May, August, and October 2021 to analyze the source-specific ecological and health risks and bioeffects. The findings revealed that the main sources of PAHs were traffic emission (25.2% to 28.5%), petroleum sources (23.3% to 29.5%), coal combustion (24.7% to 27.5%), and biomass combustion (19.8% to 20.7%). Further, the PMF-RQ and PMF-ILCR analyses indicated that traffic emission was the primary contributor to ecological risks in seawater and health risks in both clam species, while coal combustion was the major contributor in sediment. Taken together, it is recommended to implement control strategies for PAH pollution following the priority order: traffic > coal > petroleum > biomass, to reduce the content and risk of PAHs in the YRE.

Isoliquiritin promote angiogenesis by recruiting macrophages to improve the healing of zebrafish wounds.

Licorice is a widely used herbal medicine for the treatment of various diseases in southern Europe and parts of Asia. It has been reported that the isoliquiritin (ISL) from Glycyrrhiza root has the activity of promoting angiogenesis. The purpose of this study was to investigate the effect of ISL on the wound healing activity of zebrafish and its mechanism. 6-month-old zebrafish were injured in the skin (2 mm in diameter) and then treated with ISL. By measuring wound size and by histological examination, we found that ISL improved wound healing. In addition, 4-day-old zebrafish embryos of double transgenic line [Tg(fli-1:EGFP)]/[Tg(mpeg:mCherry)] were suffered from tissue traumas and then treated with ISL. Through fluorescent microscopy, we found that ISL promoted macrophage recruitment and angiogenesis in the wound area. Through qPCR analysis, we found that ISL up-regulated the expression of genes related to inflammation and angiogenesis in zebrafish embryos. These results showed that ISL could promote inflammatory response and angiogenesis, which played key roles in promoting wound healing. Therefore, ISL can be used as a promising candidate to promote wound healing.

Pro-angiogenic activity of isoliquiritin on HUVECs in vitro and zebrafish in vivo through Raf/MEK signaling pathway.

AIMS: Liquorice is a widely used herbal medicine for treating various diseases native to southern Europe and parts of Asia. Isoliquiritin (ISL), a licorice root-derived flavonoid, has been reported to exhibit antioxidant, anti-inflammatory, anti-genotoxic activity and anti-depression activities. This study was aimed to explore the pro-angiogenic activity of ISL and explicate the underlying mechanism. MAIN METHODS: In vitro, ISL-treated human umbilical vein endothelial cells (HUVECs) were analyzed for cell viability, cell migration and tube formation. In vivo, pro-angiogenic effects were evaluated for the intersegmental vessels (ISVs) formation in transgenic zebrafish embryos [Tg(fli-1: EGFP)]. Furthermore, a blocking assay with eight pathways-specific kinase inhibitors were also used to determine the potential pro-angiogenic mechanism of ISL. KEY FINDINGS: ISL counteracted tyrosine kinase inhibitor II (VRI)-induced endothelial cell apoptosis and promoted cell migration and tube formation in HUVECs. ISL markedly rescued ISVs loss induced by VRI in zebrafish embryos, probably by activating vascular endothelial growth factor receptor-2 (VEGFR-2), phosphoinositide 3-kinase (PI3K), Raf and mitogen-activated protein kinase (MEK)-dependent signaling pathways. SIGNIFICANCE: Our study first discovered and confirmed the pro-angiogenic activity of ISL both in HUVECs and zebrafish. Thus, ISL could be developed as a potential therapeutic agent by the role of pro-angiogenic activity for the treatment of cardiovascular diseases, cerebrovascular diseases and other vascular diseases.

Low iodine diet in differentiated thyroid cancer: a review.

Radioactive iodine (RAI) ablation is a beneficial, adjuvant therapy for the management of differentiated thyroid cancer (DTC) after thyroidectomy. The goal of RAI is to destroy remnant thyroid and microscopic cancerous tissue. Radioactive iodine uptake is enhanced by elevating TSH levels and initiating a low iodine diet (LID) prior to ablation. An ideal LID should preferably not exceed 50 mcg/day of dietary iodine for 1-2 weeks, although the duration may be shortened to a week with a structured patient education programme. A pre-ablation spot urinary iodine concentration (UIC) of <100 mcg/l and/or a urinary iodine to creatinine ratio (UICR) of <100 mcg/gCr would support an adequate LID preparation. Hyponatraemia, most likely due to iatrogenic hypothyroidism, is a potential side effect associated with LID and occurs during and a few days after the LID. Although the overall incidence of hyponatraemia is low, patients at high risk (older age, female sex, use of thiazide diuretics) may benefit from serum sodium monitoring. The existing evidence on the impact of LID on RAI ablation has been largely inconsistent due to retrospective study designs and the lack of an objective measurement of urinary iodine levels. Future large prospective randomized control trials are needed to elucidate and confirm the crucial role of LID in achieving successful RAI ablation and greater disease-free survival in DTC.

A transgenic platform for testing drugs intended for reversal of cardiac remodeling identifies a novel 11ßHSD1 inhibitor rescuing hypertrophy independently of re-vascularization.

RATIONALE: Rescuing adverse myocardial remodeling is an unmet clinical goal and, correspondingly, pharmacological means for its intended reversal are urgently needed. OBJECTIVES: To harness a newly-developed experimental model recapitulating progressive heart failure development for the discovery of new drugs capable of reversing adverse remodeling. METHODS AND RESULTS: A VEGF-based conditional transgenic system was employed in which an induced perfusion deficit and a resultant compromised cardiac function lead to progressive remodeling and eventually heart failure. Ability of candidate drugs administered at sequential remodeling stages to reverse hypertrophy, enlarged LV size and improve cardiac function was monitored. Arguing for clinical relevance of the experimental system, clinically-used drugs operating on the Renin-Angiotensin-Aldosterone-System (RAAS), namely, the ACE inhibitor Enalapril and the direct renin inhibitor Aliskerin fully reversed remodeling. Remodeling reversal by these drugs was not accompanied by neovascularization and reached a point-of-no-return. Similarly, the PPARγ agonist Pioglitazone was proven capable of reversing all aspects of cardiac remodeling without affecting the vasculature. Extending the arsenal of remodeling-reversing drugs to pathways other than RAAS, a specific inhibitor of 11ß-hydroxy-steroid dehydrogenase type 1 (11ß HSD1), a key enzyme required for generating active glucocorticoids, fully rescued myocardial hypertrophy. This was associated with mitigating the hypertrophy-associated gene signature, including reversing the myosin heavy chain isoform switch but in a pattern distinguishable from that associated with neovascularization-induced reversal. CONCLUSIONS: A system was developed suitable for identifying novel remodeling-reversing drugs operating in different pathways and for gaining insights into their mechanisms of action, exemplified here by uncoupling their vascular affects.

Antiangiogenic effects and mechanisms of trans-ethyl p-methoxycinnamate from Kaempferia galanga L.

Kaempferia galanga L. (Zingiberaceae) is an aromatic herb and a popular spice used as a condiment in Asian cuisine. The ethanol extract of the dried plant and its successive four subfractions were investigated on zebrafish model by quantitative endogenous alkaline phosphatase assay. Both n-hexane and ethyl acetate fractions had antiangiogenic activity, and two major active components (trans-ethyl p-methoxycinnamate and kaempferol) showed potent antiangiogenic effects on wild-type zebrafish. Because of its much stronger effect and no antiangiogenic activity reported, trans-ethyl p-methoxycinnamate was further investigated for its action mechanism. It dose dependently inhibited vessel formation on both wild- and Tg(fli1a:EGFP)y1-type zebrafish embryos. The semiquantitative reverse transcription polymerase chain reaction assay suggested that trans-ethyl p-methoxycinnamate affects multiple molecular targets related to angiogenesis. In vitro, it specifically inhibited the migration and tube formation of human umbilical vein endothelial cells. In vivo, it could block bFGF-induced vessel formation on Matrigel plug assay.

Anti-angiogenic effect and mechanism of rhein from Rhizoma Rhei.

PURPOSE: Rhein is a major bioactive component in rhubarb (Dahuang), a famous traditional Chinese medicine derived from the rhizome of Rheum palmatum and related species. It was reported to have antitumor and anti-inflammatory properties. Our previous studies found rhein displaying potent anti-angiogenic activities in a zebrafish embryo model. Its action mechanisms need further elucidation. METHODS: The inhibition effect of vessel formation was checked by microscopic imaging on Tg(fli1a:EGFP)y1 zebrafish embryos. Then the action mechanism of rhein was investigated by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) on wild type zebrafish embryos and further tested on human umbilical vein endothelial cells. RESULTS: At 20µM, rhein could almost completely block intersegmental blood vessels formation at both 48 and 72hpf, and completely inhibit subintestinal vessel plexus formation at 72hpf. Rhein affected multiple molecular targets related to angiogenesis, particularly angpt2 and tie2, and also inhibited endothelial cell migration. CONCLUSION: Rhein could inhibit angiogenesis, which may play a role in antitumor and anti-inflammatory actions.

Anti-angiogenic effects of the fruit of Alpinia oxyphylla.

AIM OF STUDY: The fruit of Alpinia oxyphylla, an herb commonly used in East Asian medicine, is variously used for the treatment of cancer and inflammatory conditions, which may possibly be mediated through anti-angiogenesis. This study aims to check for anti-angiogenic functions in the herb. MATERIALS AND METHODS: The 95% ethanol extract and four subsequent fractions (n-hexane, ethyl acetate, n-butanol and aqueous fractions) of the fruit of A. oxyphylla were tested on zebrafish model by quantitative endogenous alkaline phosphatase assay; then the active fractions were further tested on wild type and Tg(fli1a:EGFP)y1 zebrafish embryos and human umbilical vein endothelial cells and tumor cell lines for the anti-angiogenic effects. RESULTS: The n-hexane and ethyl acetate fractions showed anti-angiogenic potentials in both in vivo and in vitro models. CONCLUSIONS: The use of A. oxyphylla for cancer and inflammation diseases may be partly due to its effects against vessel formation.

Anti-angiogenic effects of rhubarb and its anthraquinone derivatives.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhubarb root (Dahuang) is often included as an ingredient in traditional Chinese compound prescriptions for the treatment of inflammatory diseases. This application may possibly be mediated through anti-angiogensis and thus would shed light on its potential value in cancer therapy. AIM OF THE STUDY: To elucidate the anti-angiogenic properties of rhubarb root, we tested the inhibitory effects of different fractions and a series of anthraquinone derivatives against vessel formation in zebrafish embryos. MATERIALS AND METHODS: The 95% ethanol extract and four subsequent fractions (n-hexane, ethyl acetate, n-butanol and aqueous fractions) of rhubarb root and five anthraquinone derivatives were investigated on zebrafish model by quantitative endogenous alkaline phosphatase assay and staining assay. RESULTS: Ethyl acetate fraction showed the strongest inhibition of vessel formation by 52%. Three anthraquinones (aloe-emodin, emodin and rhein) displayed potent anti-angiogenic activities. CONCLUSIONS: The angiogenic properties of rhubarb root may partly account for its use in inflammatory diseases. The anthraquinones with acidic or polar, hydrophilic substitution at C-6 or C-3 positions played a substantial role in inhibiting angiogenesis. The value of the zebrafish angiogenic model is further supported.

2-aryl benzofurans and their derivatives from seeds of Styrax macranthus.

Two new 2-aryl benzofuran derivatives, 3-[7-methoxy-2-(3,4-methylenedioxyphenyl) benzofuran-5-yl]propyl 3-[7-methoxy-2-(3,4-methylenedioxyphenyl)benzofuran-5-yl]propanoate (1) and demethoxy egonol gentiobioside (2), were isolated from the aqueous ethanolic extract of the seeds of Styrax macranthus, together with 7-methoxy-2-(3,4-methylenedioxyphenyl)benzofuran-5-carbaldehyde, egonol, demethoxy egonol, demethyl egonol, egonol glucoside, egonol gentiobioside, egonol gentiotrioside, stigmasterol, 2,3-dihydroxypropyl tetracosoate, and daucosterol. Their structures were elucidated on the basis of spectral and chemical evidence.