A Woman with Klippel-Trenaunay Syndrome Reproductive Tract Bleeding Case Report and Review of the Literature.

Klippel-Trenaunay syndrome (KTS) is a rare congenital vascular disorder characterized by wine stains, abnormal tissue and bone growth, and vascular malformations. Genital involvement is uncommon. We report a case of a 12-year-old female with KTS who experienced recurrent profuse vaginal bleeding and provide a comprehensive literature review on KTS cases with genital involvement. The literature reports 7 cases, mainly in individuals aged 25 to 45, presenting with uncontrollable vaginal bleeding and anemia. Endovascular interventions were the primary treatment, although surgery was necessary in some cases. Recent studies have identified a potential association between KTS and the PIK3CA gene mutation, offering insights for pharmacological treatment.

Double-contrast barium enema is no longer justified as a backup examination for colonoscopy in the population screening program: Population study in an organized fecal immunochemical test-based screening program.

BACKGROUND AND AIM: Currently, some countries still acknowledge double-contrast barium enema (DCBE) as a backup confirmatory examination when colonoscopy is not feasible or incomplete in colorectal cancer (CRC) screening programs. This study aims to compare the performance of colonoscopy and DCBE in terms of the risk of incident CRC after negative results in the fecal immunochemical test (FIT)-based Taiwan Colorectal Cancer Screening Program. METHODS: Subjects who had positive FITs and received confirmatory exams, either colonoscopy or DCBE, without the findings of neoplastic lesions from 2004 to 2013 in the screening program comprised the study cohort. Both the colonoscopy and DCBE subcohorts were followed until the end of 2018 and linked to the Taiwan Cancer Registry to identify incident CRC cases. Multivariate analysis was conducted to compare the risk of incident CRC in both subcohorts after controlling for potential confounders. RESULTS: A total of 102 761 colonoscopies and 5885 DCBEs were performed after positive FITs without neoplastic findings during the study period. By the end of 2018, 2113 CRCs (2.7 per 1000 person-years) and 368 CRCs (7.6 per 1000 person-years) occurred in the colonoscopy and DCBE subcohorts, respectively. After adjusting for major confounders, DCBE had a significantly higher risk of incident CRC than colonoscopy, with an adjusted HR of 2.81 (95% CI = 2.51-3.14). CONCLUSIONS: In the FIT screening program, using DCBE as a backup examination was associated with a nearly threefold risk of incident CRC compared with colonoscopy, demonstrating that it is no longer justified as a backup examination for incomplete colonoscopy.

Efficacy and mechanism study of cordycepin against brain metastases of small cell lung cancer based on zebrafish.

BACKGROUND: Small cell lung cancer (SCLC) is an aggressive tumor with high brain metastasis (BM) potential. There has been no significant progress in the treatment of SCLC for more than 30 years. Cordycepin has shown the therapeutic potential for cancer by modulating multiple cellular signaling pathways. However, the effect and mechanism of cordycepin on anti-SCLC BM remain unknown. PURPOSE: In this study, we focused on the anti-SCLC BM effect of cordycepin in the zebrafish model and its potential mechanism. STUDY DESIGN AND METHODS: A SCLC xenograft model based on zebrafish embryos and in vitro cell migration assay were established. Cordycepin was administrated by soaking and microinjection in the zebrafish model. RNA-seq assay was performed to analyze transcriptomes of different groups. Geno Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were performed to reveal the underlying mechanism. Real-time qPCR was used to verify the effects of cordycepin on the key genes. RESULTS: Cordycepin showed lower cytotoxicity in vitro compared with cisplatin, anlotinib and etoposide, but showed comparable anti-proliferation and anti-BM effects in zebrafish SCLC xenograft model. Cordycepin showed significant anti-SCLC BM effects when administrated by both soaking and microinjection. RNA-seq demonstrated that cordycepin was involved in vitamin D metabolism, lipid transport, and proteolysis in cellular protein catabolic process pathways in SCLC BM microenvironment in zebrafish, and was involved in regulating the expressions of key genes such as cyp24a1, apoa1a, ctsl. The anti-BM effect of cordycepin in SCLC was mediated by reversing the expression of these genes. CONCLUSION: Our work is the first to describe the mechanism of cordycepin against SCLC BM from the perspective of regulating the brain microenvironment, providing new evidence for the anti-tumor effect of cordycepin.

Efficacy of traditional Chinese medicine combined with anti-vascular endothelial growth factor in the treatment of wet age-related macular degeneration: A systematic review and network Meta-analysis / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To evaluate the clinical efficacy of traditional Chinese medicine(TCM)combined with intravitreal injection of anti-vascular endothelial growth factor(VEGF)or anti-VEGF medicines alone in the treatment of wet age-related macular degeneration(wAMD).METHODS:A total of eight databases were searched for relevant literatures in English and Chinese, including Chinese National Knowledge Infrastructure(CNKI), Wanfang, CQVIP, SinoMed, PubMed, Web of Science, Cochrane Library, Embase. Taking patients with wAMD as research objects, the Chinese and English clinical randomized controlled trials(RCTs)published from the databases' inception to April 20, 2022, which compared TCM combined with anti-VEGF drugs with anti-VEGF drugs alone were selected. The outcome indicators were best corrected visual acuity(BCVA)and central macular thickness(CMT). Traditional Meta and network Meta analysis were used to examine the data.RESULTS:There were 39 eligible studies among the 617 retrieved articles, involving 28 oral administration of Chinese herbal medicines and 2 757 participants. For BCVA improvement, results of TCM combination therapy were more favorable than anti-VEGF alone(MD=0.07, 95%CI: 0.05～0.09). Sheng Puhuang Decoction(SPD)ranked highest in 1 and 2mo after treatment, and Xuefu Zhuyu Capsule(XZC)ranked highest in 3mo after treatment. In terms of reducing CMT, TCM combination therapy were better(MD=-25.32 μm, 95%CI: -30.06～-20.57). Danggui Mingmu Decoction(DMD)ranked the highest in 1mo after treatment. Bushen Huoxue Decoction(BHD)ranked the highest in 2mo. Erchen Erhuang Decoction(EED)ranked the highest in 3mo.CONCLUSIONS: Compared with anti-VEGF treatment alone, TCM combination therapy led to improved BCVA and reduced CMT. However, most of the included literature is small-sample, single-center, single-blind RCTs with an overall low quality.

Research progress of Shegan Mahuang Decoction and predictive analysis on its Q-markers / 中国中药杂志

Shegan Mahuang Decoction has been used in clinical practice for thousands of years, and is a classical formula for treating asthma and other respiratory diseases, with the effects of ventilating lung, dispersing cold, and relieving cough and asthma. This paper summarized the history, clinical application and mechanism of Shegan Mahuang Decoction, and predicted its quality markers(Q-markers) based on the "five principles" of Q-markers. The results suggested that irisflorentin, tectoridin, tectorigenin, irigenin, ephedrine, pseudoephedrine, asarinin, methyleugenol, shionone, epifriedelanol, tussilagone, 6-gingerol, trigonelline, cavidine, schizandrin, and schizandrin B could be used as Q-markers of Shegan Mahuang Decoction, which provided a basis for the quality control and subsequent research and development of Shegan Mahuang Decoction.

Chromosome-level genome assembly of bunching onion illuminates genome evolution and flavor formation in Allium crops.

The Allium genus is cultivated globally as vegetables, condiments, or medicinal plants and is characterized by large genomes and strong pungency. However, the genome evolution and genomic basis underlying their unique flavor formation remain poorly understood. Herein, we report an 11.27-Gb chromosome-scale genome assembly for bunching onion (A. fistulosum). The uneven bursts of long-terminal repeats contribute to diversity in genome constituents, and dispersed duplication events largely account for gene expansion in Allium genomes. The extensive duplication and differentiation of alliinase and lachrymatory factor synthase manifest as important evolutionary events during flavor formation in Allium crops. Furthermore, differential selective preference for flavor-related genes likely lead to the variations in isoalliin content in bunching onions. Moreover, we reveal that China is the origin and domestication center for bunching onions. Our findings provide insights into Allium genome evolution, flavor formation and domestication history and enable future genome-assisted breeding of important traits in these crops.

[Effectiveness of induction therapy with exclusive enteral nutrition in pediatric Crohn's disease]. / å ¨è‚ å† è¥å »å¯¹å„¿ç«¥å ‹ç½—æ©ç— è¯±å¯¼ç¼“è§£ç–—æ•ˆç ”ç©¶.

OBJECTIVES: To evaluate the effectiveness of induction therapy with exclusive enteral nutrition (EEN) in pediatric Crohn's disease (CD). METHODS: A retrospective analysis was performed on the medical data of 62 children with CD who received EEN in Children's Hospital, Zhejiang University School of Medicine, from March 2013 to August 2021. The medical data included general information and height, weight, Pediatric Crohn's Disease Activity Index (PCDAI), Crohn's Disease Endoscopic Index of Severity, C-reactive protein, erythrocyte sedimentation rate, and serum albumin level before treatment and after 8 weeks of treatment. The changes in the above indicators were compared before and after treatment. RESULTS: Among the 62 children with CD, there were 39 boys (63%) and 23 girls (37%), with a mean age of (11.9±3.0) years at diagnosis. Among the 55 children who completed EEN treatment for at least 8 weeks, 48 (87%) achieved clinical remission at week 8. PCDAI at week 8 was significantly lower than that before treatment (P<0.001). Except for 17 children with involvement of the small intestine alone and 3 children with involvement of the colon who did not receive colonoscopy reexamination, the remaining 35 children with involvement of the colon received colonoscopy reexamination after the 8-week EEN treatment. Of the 35 children, 29 (83%) achieved mucosal healing. As for the 48 children who achieved clinical remission at week 8, there were significant improvements in height-for-age Z-score and body mass index-for-age Z-score at week 8 (P<0.01). As for the 7 children who did not achieve clinical remission at week 8, there were no significant changes in height-for-age Z-score and body mass index-for-age Z-score at week 8 (P>0.05). CONCLUSIONS: The 8-week EEN treatment has a good effect on clinical remission and mucosal healing in children with CD. For the children with CD achieving clinical remission, EEN can improve their height and body mass index.

Effectiveness of induction therapy with exclusive enteral nutrition in pediatric Crohn's disease / 中国当代儿科杂志

OBJECTIVES@#To evaluate the effectiveness of induction therapy with exclusive enteral nutrition (EEN) in pediatric Crohn's disease (CD).@*METHODS@#A retrospective analysis was performed on the medical data of 62 children with CD who received EEN in Children's Hospital, Zhejiang University School of Medicine, from March 2013 to August 2021. The medical data included general information and height, weight, Pediatric Crohn's Disease Activity Index (PCDAI), Crohn's Disease Endoscopic Index of Severity, C-reactive protein, erythrocyte sedimentation rate, and serum albumin level before treatment and after 8 weeks of treatment. The changes in the above indicators were compared before and after treatment.@*RESULTS@#Among the 62 children with CD, there were 39 boys (63%) and 23 girls (37%), with a mean age of (11.9±3.0) years at diagnosis. Among the 55 children who completed EEN treatment for at least 8 weeks, 48 (87%) achieved clinical remission at week 8. PCDAI at week 8 was significantly lower than that before treatment (P<0.001). Except for 17 children with involvement of the small intestine alone and 3 children with involvement of the colon who did not receive colonoscopy reexamination, the remaining 35 children with involvement of the colon received colonoscopy reexamination after the 8-week EEN treatment. Of the 35 children, 29 (83%) achieved mucosal healing. As for the 48 children who achieved clinical remission at week 8, there were significant improvements in height-for-age Z-score and body mass index-for-age Z-score at week 8 (P<0.01). As for the 7 children who did not achieve clinical remission at week 8, there were no significant changes in height-for-age Z-score and body mass index-for-age Z-score at week 8 (P>0.05).@*CONCLUSIONS@#The 8-week EEN treatment has a good effect on clinical remission and mucosal healing in children with CD. For the children with CD achieving clinical remission, EEN can improve their height and body mass index.

Research Progress on Dysemenorrhea of Essential Oils of Traditional Chinese Medicine： A Review / 中国实验方剂学杂志

Dysmenorrhea is a common gynecological disease in clinic， with primary dysmenorrhea and secondary dysmenorrhea. Primary dysmenorrhea is usually not accompanied by organic lesions in genital organs， which is mainly related to the increase of prostaglandin content in endometrium during menstruation. Secondary dysmenorrhea is accompanied by organic lesions of reproductive organs， often associated with local lesions of reproductive organs， but also with patients' mental factors and neuroendocrine factors.The incidence of dysmenorrhea is as high as 73.8%， and there is no radical cure method， which has a great impact on the life， work and learning of patients. Chinese medicine essential oil widely exists in aromatic Chinese medicine， with antibacterial， antioxidant and anticancer activities. It can regulate neuroendocrine function， anti-inflammatory and analgesic effects， and improve mood by regulating the levels of prostaglandins， oxytocin and other hormones in the body and regulating the emotions of patients， there by alleviating dysmenorrhea to a certain extent. In recent years， many scholars have made more in-depth research on Chinese medicine essential oil in alleviating dysmenorrhea， but there is a lack of comprehensive collation of such studies. In this regard， the author has systematically sorted out the generation and classification of dysmenorrhea， the mechanism of action of essential oil of traditional Chinese medicine to alleviate dysmenorrhea and the application of essential oil of traditional Chinese medicine in the field of dysmenorrhea by consulting relevant literature in Chinese and foreign languages in recent years， so as to provide reference for the treatment of dysmenorrhea.

Mechanism of Combination of Pungent Dispersing Bitter Evacuant in Treatment of Asthma Based on Theory of Five Flavor Compatibility / 中国实验方剂学杂志

Bronchial asthma， a chronic inflammatory airway disease， belongs to the category of wheezing disease in the system of traditional Chinese medicine （TCM）. The wheezing symptom of this disease is mainly caused by the imbalance of lung Qi. According to the theory of five flavor compatibility， the Chinese medicinal materials with five different flavors （pungent， bitter， sour， sweet， and salty） can be combined to produce new functions. The pungent medicinal materials have dispersing effect and the bitter medicinal materials have discharging effect， which are important components in the theory of five flavor compatibility. Pungent herbs and bitter herbs can relieve the adverse lung Qi， occupying an important position in the current medication for the treatment of asthma. However， there is still a lack of in-depth analysis of the TCM theory and mechanism of the compatibility of pungent herbs and bitter herbs in the treatment of asthma. The molecular mechanisms of action of pungent herbs and bitter herbs are closely related to transient receptor potential （TRP） channels and bitter taste receptors （TAS2Rs）， respectively. Ca2+ signaling has been recognized in the process of asthma and is involved in the development of multiple symptoms of asthma. The TRP channels and TAS2Rs located on the cell membrane have been proved to directly regulate the intracellular Ca2+ signal and play a role in the treatment of asthma. Therefore， the dispersing effect of pungent herbs and the discharging effect of bitter herbs may be realized through the Ca2+ signaling pathway mediated by TRPs/TAS2Rs. We summarized the theoretical understanding and modern studies of pungent herbs dispersing lung Qi and bitter herbs discharging lung Qi， aiming to explain the internal relationship and mechanism of the compatibility of pungent herbs and bitter herbs in the treatment of asthma from the perspective of TCM theory and modern medicine. The compatibility of pungent herbs and bitter herbs based on the theory of five flavor compatibility for the treatment of asthma has a solid theoretical basis of TCM， and its mechanism can be verified by modern research. Therefore， it may be a main research direction in the treatment of asthma by Chinese medicinal herbs in the future.

Clinical effect of alfacalcidol in children with Henoch-Schönlein purpura: a prospective randomized controlled trial. / é˜¿æ³•éª¨åŒ–é†‡æ²»ç–—å„¿ç«¥è¿‡æ•æ€§ç´«ç™œçš„å‰çž»æ€§éšæœºå¯¹ç §ç ”ç©¶.

OBJECTIVES: To study the effects of alfacalcidol on serum 25-(OH)D3 level, cellular immune function, and inflammatory factors in children with Henoch-Schönlein purpura (HSP). METHODS: A total of 200 children with HSP were prospectively enrolled from June 2018 to June 2020. According to the random number table method, they were divided into an observation group and a control group (n=100 each). The control group was treated with vitamin C, rutin tablets, dipyridamole, cimetidine, calcium supplements, and glucocorticoids. In addition to the treatment for the control group, the observation group received alfacalcidol capsules (0.25 µg/d) orally before bed for 4 weeks. The two groups were compared in terms of the level of 25-(OH)D3, the percentages of T lymphocyte subsets (CD3+, CD4+, and CD8+) and NK cells, and the levels of inflammatory factors, interleukin-6 (IL-6), interleukin-17 (IL-17), interleukin-21 (IL-21), and tumor necrosis factor-α (TNF-α), before treatment and after 4 weeks of treatment. The children were followed up for 6 months to determine the recurrence rate and the incidence of renal damage. RESULTS: After treatment, the observation group showed a significantly higher serum 25-(OH)D3 level, significantly higher percentages of CD3+T cells, CD4+T cells, and NK cells, and significantly lower levels of IL-6, IL-17, IL-21, and TNF-α compared with the control group (P<0.05). After 6 months of follow-up, the recurrence rate and the incidence of renal damage in the observation group were significantly lower than those in the control group (P<0.05). CONCLUSIONS: Alfacalcidol can increase the serum 25-(OH)D3 level, improve cellular immune function, decrease inflammatory factor levels, and reduce recurrence and renal damage in children with HSP.

Isoliquiritin exert protective effect on telencephalon infarction injury by regulating multi-pathways in zebrafish model of ischemic stroke.

BACKGROUND: Ischemic stroke is a multifactorial disease contributing to mortality and neurological dysfunction. Isoliquiritin (ISL) has been reported to possess a series of pharmacological activities including antioxidant, anti-inflammatory, antifungal, anti-depression, anti-neurotoxicity and pro-angiogenesis activities but whether it can be used for ischemic stroke treatment remains unknown. PURPOSE: The goal of this study is to explore its therapeutic effect on ischemic stroke and demonstrated the potential mechanism of ISL in zebrafish model. METHODS: Using the photothrombotic-induced adult zebrafish model of ischemic stroke, we visualized the telencephalon (Tel) and optic tectum (OT) infarction injury at 24 h post-light exposure for 30 min by TTC and H&E staining. The effect of ISL on neurological deficits was analyzed during open tank swimming by video tracking. The antioxidant activity against ischemia injury was quantified by SOD, GSH-Px and MDA assay. Transcriptome analysis of zebrafish Tel revealed how ISL regulating gene expression to exert protective effect, which were also been validated by real-time quantitative PCR assays. RESULTS: We found for the first time that the Tel tissue was the first damaged site of the whole brain and it showed more sensitivity to the brain ischemic damage compared to the OT. ISL reduced the rate of Tel injury, ameliorated neurological deficits as well as counteracted oxidative damages by increasing SOD, GSH-Px and decreasing MDA activity. GO enrichment demonstrated that ISL protected membrane and membrane function as well as initiate immune regulation in the stress response after ischemia. KEGG pathway analysis pointed out that immune-related pathways, apoptosis as well as necroptosis pathways were more involved in the protective mechanism of ISL. Furthermore, the log2 fold change in expression pattern of 25 genes detected by qRT-PCR was consistent with that by RNA-seq. CONCLUSIONS: Tel was highly sensitive to the brain ischemia injury in zebrafish model of ischemic stroke. ISL significantly exerted protective effect on Tel injury, neurological deficits and oxidative damages. ISL could regulate a variety of genes related to immune, apoptosis and necrosis pathways against complex cascade reaction after ischemia. These findings enriched the study of ISL, making it a novel multi-target agent for ischemic stroke treatment.

Green and efficient biosynthesis of pectin-based copper nanoparticles and their antimicrobial activities.

Herein, we reported a green biosynthesis method of copper nanoparticles (CuNPs) at microwave irradiation condition by using pectin as a stabilizer and ascorbic acid as a reducing agent. Under the optimum conditions, CuNPs1 and 2 were synthesized under microwave times 0 and 3 min, respectively. Transmission electron microscope and scanning electron microscope (SEM) tests showed that CuNPs1 and 2 had irregular polygon particles with average diameters of 61.9 ± 19.4 and 40.9 ± 13.6 nm, respectively. Zeta potentials of CuNPs1 and 2 were -45.2 and -48.7 mV, respectively. X-ray diffraction, Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and X-ray photoelectron spectroscopy techniques were used to characterize the properties of CuNPs. Furthermore, inhibition zone tests showed that CuNPs2 exhibited higher antimicrobial activities against Escherichia coli, Staphylococcus aureus, and Aspergillus japonicus than CuNPs1. The antibacterial activities were also studied by the bacterial growth kinetics in broth media, and CuNPs2 exhibited lower minimum bactericidal concentrations than CuNPs1.

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 Tongnao decoction on HUVECs in vitro and zebrafish in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Tongnao Decoction (TND) is a Chinese decoction approved and used in Jiangsu Province Hospital for the treatment of ischemic stroke. It shows conclusive efficiency in the improvement of neurologic impairment and activities of daily living of the patients. AIM OF THE STUDY: Recently, angiogenesis has been recognized as a potential therapeutic strategy for treating cerebral ischemia. This study was aimed to provide comprehensive evidence for the pro-angiogenic effect of TND and characterize the underlying mechanism. MATERIALS AND METHODS: We firstly established the chemical fingerprinting of TND. Then, the in vitro pro-angiogenic activities of TND were tested on human umbilical vein endothelial cells (HUVECs) through cell viability, wound healing and tube formation assays. The in vivo pro-angiogenic effects were evaluated on transgenic zebrafish embryos [Tg (fli-1: EGFP)] through the formation of intersegmental vessels (ISVs), subintestinal vessels (SIVs) and central arteries (CtAs). Lastly, the potential mechanisms of TND were analyzed by a blocking assay with eight pathways-specific kinase inhibitors. RESULTS: TND promoted the proliferation, migration and tube formation of HUVECs. TND also rescued the impairment of ISVs, SIVs and CtAs caused by VRI in a dose-dependent manner in zebrafish embryos. TND could activate vascular endothelial growth factor receptor-2 (VEGFR-2), phosphoinositide 3-kinase (PI3K) - protein kinase B (Akt) and Raf - mitogen-activated protein kinase1/2 (MEK1/2) - extracellular regulated kinase 1/2 (ERK1/2) signaling pathways. CONCLUSION: Our study firstly demonstrated the pro-angiogenic activities of TND. Our work provided evidences for the clinical usage of TND in restoring neurovascular function through promoting angiogenesis in the ischemic cerebral microvascular.

Antifatigue Activity and Exercise Performance of Phenolic-Rich Extracts from Calendula officinalis, Ribes nigrum, and Vaccinium myrtillus.

Calendula officinalis, Ribes nigrum, and Vaccinium myrtillus (CRV) possess a high phenolic compound content with excellent antioxidant activity. Dietary antioxidants can reduce exercise-induced oxidative stress. Consumption of large amounts of phenolic compounds is positively correlated with reduction in exercise-induced muscle damage. Research for natural products to improve exercise capacity, relieve fatigue, and accelerate fatigue alleviation is ongoing. Here, CRV containing a large total phenolic content (13.4 mg/g of CRV) demonstrated antioxidant activity. Ultra-performance liquid chromatography quantification revealed 1.95 ± 0.02 mg of salidroside in 1 g of CRV. In the current study, CRV were administered to mice for five weeks, and the antifatigue effect of CRV was evaluated using the forelimb grip strength test; weight-loaded swimming test; and measurement of fatigue-related biochemical indicators, such as blood lactate, ammonia, glucose, blood urea nitrogen (BUN), and creatine kinase (CK) activity; and muscle and liver glycogen content. The results indicated that in CRV-treated mice, the forelimb grip strength significantly increased; weight-loaded swimming time prolonged; their lactate, ammonia, BUN, and CK activity decreased, and muscle and liver glucose and glycogen content increased compared with the vehicle group. Thus, CRV have antifatigue activity and can increase exercise tolerance.

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.

Effects of Ganoderma lucidum and 'Essence of Chicken' on Physical Fatigue Recovery and Exercise Performance Improvement.

A fast-paced lifestyle, pressure from the environment and a heavy work load often cause extreme tiredness in modern life. Different kinds of nutritional supplements in the form of functional foods or traditional Chinese medicine, such as 'essence of chicken' and Ganoderma lucidum have been claimed to benefit physical performance and promote health. Previous studies have revealed that 'essence of chicken' or G. lucidum have a wide spectrum of biological activities. In this study, we combined these two ingredients together (designated as CEG) to evaluate their synergistic effects on physiological adaption on exercise fatigue and physical activities. The ICR strain mice were allocated as 0, 833, 1666, and 4165 mg/kg dose groups and administrated by oral gavage consecutively for 4 weeks. Physical activities including grip strength and aerobic endurance were evaluated. Various fatigue-associated biochemical variables such as lactate, BUN or CK were also evaluated. The levels of liver and muscle glycogen were measured as an indicator of energy storage at the end of the experiment. Safety assessments for supplementation were also evaluated. CEG supplementation significantly increased the endurance and grip strength and demonstrated beneficial effects on lactate production and clearance rate after an acute exercise challenge. The CEG supplementation significantly mitigated the BUN and CK indexes after extended exercise and elevated the glycogen content in the liver and muscle tissues. According to body composition, biochemical and histopathological data, daily administration of CEG for over 28 days (subacute toxicity) also demonstrated reasonable safety results for supplementation. Combined G. lucidum and 'essence of chicken' can significantly increase the exercise performance and improve fatigue recovery. It may also provide a viable alternative nutritional supplement for health promotion.

1-Methoxycarbony-ß-carboline from Picrasma quassioides exerts anti-angiogenic properties in HUVECs in vitro and zebrafish embryos in vivo.

Angiogenesis is a crucial process in the development of inflammatory diseases, including cancer, psoriasis and rheumatoid arthritis. Recently, several alkaloids from Picrasma quassioides had been screened for angiogenic activity in the zebrafish model, and the results indicated that 1-methoxycarbony-ß-carboline (MCC) could effectively inhibit blood vessel formation. In this study, we further confirmed that MCC can inhibit, in a concentration-dependent manner, the viability, migration, invasion, and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro, as well as the regenerative vascular outgrowth of zebrafish caudal fin in vivo. In the zebrafish xenograft assay, MCC inhibited the growth of tumor masses and the metastatic transplanted DU145 tumor cells. The proteome profile array of the MCC-treated HUVECs showed that MCC could down-regulate several angiogenesis-related self-secreted proteins, including ANG, EGF, bFGF, GRO, IGF-1, PLG and MMP-1. In addition, the expression of two key membrane receptor proteins in angiogenesis, TIE-2 and uPAR, were also down-regulated after MCC treatment. Taken together, these results shed light on the potential therapeutic application of MCC as a potent natural angiogenesis inhibitor via multiple molecular targets.

Anti-angiogenic activity of para-coumaric acid methyl ester on HUVECs in vitro and zebrafish in vivo.

BACKGROUND: Para-coumaric acid methyl ester (pCAME) is one of the bioactive components of Costus speciosus (Koen) Sm. (Zingiberaceae). This plant is traditionally used in Asia to treat catarrhal fevers, worms, dyspepsia, and skin diseases. PURPOSE: To investigate the anti-angiogenic activity of pCAME and its molecular mechanism of action. STUDY DESIGN: We investigated the anti-angiogenic activity of pCAME on human umbilical vein endothelial cells (HUVECs) in vitro and zebrafish (Danio rerio) in vivo. METHODS: In vitro cell proliferation, would healing, migration and tube formation assays were used, along with in vivo physiological angiogenic vessel formation, tumor-induced angiogenic vessel formation assays on zebrafish model. qRT-PCR and RNA-seq were also used for the target investigation. RESULTS: pCAME could inhibit the proliferation, would healing, migration and tube formation of HUVECs, disrupt the physiological formation of intersegmental vessels (ISVs) and the subintestinal vessels (SIVs) of zebrafish embryos, and inhibit tumor angiogenesis in the zebrafish cell-line derived xenograft (zCDX) model of SGC-7901 in a dose-dependent manner. Mechanistic studies revealed that pCAME inhibited vegf/vegfr2 and ang/tie signaling pathways in zebrafish by quantitative RT-PCR analysis, and regulated multi-signaling pathways involving immune, inflammation and angiogenesis in SGC-7901 zCDX model by RNA-seq analysis. CONCLUSION: pCAME may be a multi-target anti-angiogenic drug candidate and hold great potential for developing novel therapeutic strategy for cancer treatment.