PMID: 

Sci Rep. 2017 07 14 ;7(1):5376. Epub 2017 Jul 14. PMID: 28710377

Abstract Title: 

Antiangiogenic activity of phthalides-enriched Angelica Sinensis extract by suppressing WSB-1/pVHL/HIF-1α/VEGF signaling in bladder cancer.

Abstract: 

The hypoxia-inducible factor-1α (HIF-1α) plays a critical role in tumor angiogenesis. It has been reported that the acetone extract of Angelica sinensis (AE-AS) rich in phthalides is able to inhibit cancer cell proliferation. However, whether AE-AS reduces cancer angiogenesis remains unknown. In this study, we demonstrated that AE-AS significantly inhibited the angiogenesis in vitro and in vivo evidenced by attenuation of the tube formation in hypoxic human umbilical vascular endothelial cells (HUVECs), and the vasculature generation in Matrigel plug, the chicken chorioallantoic membrane, and tumors. Treatment with AE-ASmarkedly decreased the protein accumulation and transcriptional activity of HIF-1α, vascular endothelial growth factor (VEGF) expression/secretion, and VEGFR2 phosphorylation in hypoxic human bladder cancer (T24) cells and tumor tissues accompanied by a reduction of tumor growth. Notably, AE-AS-induced HIF-1α protein degradation may, at least partly, attribute to inhibition of WSB-1-dependent pVHL degradation. Moreover, VEGFR2-activated PI3K/AKT/mTOR signaling pathway in hypoxic T24 cells was greatly inhibited by AE-AS. Collectively, AE-AS may be a potential anticancer agent by attenuatingcancer angiogenesis via suppression of WSB-1/pVHL/HIF-1α/VEGF/VEGFR2 cascade.

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PMID: 

Int J Mol Sci. 2017 Aug 11 ;18(8). Epub 2017 Aug 11. PMID: 28800083

Abstract Title: 

Effect of Angelica sinensis Root Extract on Cancer Prevention in Different Stages of an AOM/DSS Mouse Model.

Abstract: 

root (ASR) extract was obtained to investigate its effects on colorectal carcinogenesis in different stages of an Azoxymethane/Dextran sodium sulphate (AOM/DSS) model. In this study, we showed that ASR extract administration in the initial stage of the AOM/DSS model had cancer preventive effects with decreasing tumor incidence and a high-grade of intraepithelial neoplasia incidence. With respect to DNA damage, the amounts of 8-oxoguanine andγ-H2AX were suppressed in colon tissue. The balance of apoptosis and proliferation was approaching the normal state. In contrast, ASR extract administration in the promotion stage of the AOM/DSS model accelerated the progression of carcinogenesis. The maximum tumor size reached 49.85 ± 25.04 mm³.High-grade pathological changes were significantly increased. Decreased DNA damage and P53 level reflected the disrupted reactive oxygen species (ROS) concentration in colorectal tissue, which led to an imbalance of proliferative and apoptotic relationships. These findings suggested that the cancer-preventive effect of ASR extract may be stage-dependent in the process of carcinogenesis.

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PMID: 

Phytomedicine. 2017 Sep 15 ;33:21-27. Epub 2017 Jul 8. PMID: 28887916

Abstract Title: 

Angelica polysaccharides inhibit the growth and promote the apoptosis of U251 glioma cells in vitro and in vivo.

Abstract: 

BACKGROUND: Angelica sinensis (Oliv) Diels (Apiaceae) is a traditional medicine that has been used for more than 2000 years in China. It exhibits various therapeutic effects including neuroprotective, anti-oxidant, anti-inflammatory, and immunomodulatory activities. Angelica polysaccharides (APs), bioactive constituents of Angelica have been shown to be responsible for these effects; however, the utility of APs for the treatment of glioma and their mechanism of action remain to be elucidated.PURPOSE: In this study, we investigated the inhibitory effects of APs on a glioma cell line and their molecular mechanism of action.STUDY DESIGN: U251 cells were utilized to confirm the effects of APs on glioma.METHODS: The human glioblastoma cell line U251 was utilized for both in vitro and in vivo models, in which we tested the effects of APs. Flow cytometry, gene expression analysis, western blotting, and MTT assays were used to elucidate the effects of APs on cell proliferation, cell cycle, and apoptosis.RESULTS: The results demonstrated that APs significantly inhibited the growth and proliferation of U251 cells and induced their apoptosis. Furthermore, APs effectively reduced the expression of several cell cycle regulators: cyclins D1, B, and E. The apoptosis suppressor protein Bcl-2 was also downregulated, and the expression of pro-apoptotic proteins Bax and cleaved-caspase-3 increased. Additionally, APs inhibited the transforming growth factor (TGF)-β signaling pathway and stimulated the expression of E-cadherin, thus prohibiting cell growth.CONCLUSION: In conclusion, the results indicate that APs attenuate the tumorigenicity of glioma cells and promote their apoptosis by suppressing the TGF-β signaling pathway. The present study therefore provides evidence of the inhibitory effects of APs against glioma progression, and proposes their potential application as alternative therapeutic agents for glioma.

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PMID: 

Biomed Res Int. 2017 ;2017:6280972. Epub 2017 Sep 20. PMID: 29098158

Abstract Title: 

Suppresses Body Weight Gain and Alters Expression of theGene in High-Fat-Diet Induced Obese Mice.

Abstract: 

The root of(RAS) is a traditional Chinese medicine used for preventing and treating various diseases. In this study, we assessed RAS supplementation effects on body weight and thegene expression and methylation status in a high-fat-diet (HFD) induced obese mouse model. Female obese mice were divided into groups according to RAS dosage in diet as follows: normal diet, HFD diet (HC), HFD with low-dosage RAS (DL), HFD with medium-dosage RAS (DM), and HFD with high-dosage RAS (DH). After RAS supplementation for 4 weeks, body weight suppression andexpression in DH mice were significantly higher than in HC mice, whereas no significant change inexpression was detected between DM and DL mice or in their offspring. Bisulfite sequencing PCR (BSP) revealed that the CpG island in thepromoter was hypermethylated up to 95.44% in the HC group, 91.67% in the DH group, and 90.00% in the normal diet group. Histological examination showed that adipocytes in the DH group were smaller than those in the HC group, indicating a potential role of RAS in obesity. This study indicated that RAS could ameliorate obesity induced by HFD and that the molecular mechanism might be associated with the expression of thegene.

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PMID: 

Am J Chin Med. 2017 ;45(8):1683-1708. Epub 2017 Nov 9. PMID: 29121798

Abstract Title: 

Angelica sinensis Exerts Angiogenic and Anti-apoptotic Effects Against Cerebral Ischemia-Reperfusion Injury by Activating p38MAPK/HIF-1[Formula: see text]/VEGF-A Signaling in Rats.

Abstract: 

This study evaluated the effects of Angelica sinensis extract [Dang Gui (DG)] administered before 60[Formula: see text]min of middle cerebral artery occlusion followed by 3[Formula: see text]d of reperfusion and investigated the involvement of mitogen-activated protein kinase (MAPK)/hypoxia-inducible factor (HIF)-1[Formula: see text] signaling in the cortical ischemic penumbra. DG was intraperitoneally administered at a dose of 0.25[Formula: see text]g/kg (DG-0.25g), 0.5[Formula: see text]g/kg (DG-0.5g), or 1[Formula: see text]g/kg (DG-1g) 30[Formula: see text]min before the onset of cerebral ischemia. Our study results revealed that DG-0.5g and DG-1g pretreatment effectively attenuated cerebral infarct and improved neurological deficits. DG-0.5g and DG-1g pretreatment significantly downregulated glial fibrillary acidic protein (GFAP), cytochrome c, and cleaved caspase-3 expression and upregulated phospho-p38 MAPK (p-p38 MAPK)/p38 MAPK, phospho-cAMP response element-binding protein (p-CREB)/CREB, cytosolic and mitochondrial phospho-Bad (p-Bad)/Bad ratios, and HIF-1[Formula: see text], vascular endothelial growth factor-A (VEGF-A), phospho-90 kDa ribosomal S6 kinase (p-p90RSK), and von Willebrand factor (vWF) expression in the cortical ischemic penumbra. Pretreatment with SB203580, a p38 MAPK inhibitor, dramatically abrogated the upregulating effects of DG-1g on p-p38 MAPK/p38 MAPK, p-CREB/CREB, and p-Bad/Bad ratios and HIF-1[Formula: see text], VEGF-A, and vWF expression and the downregulating effects of DG-1g on GFAP, cytochrome c, cleaved caspase-3, and cerebral infarction. DG-0.5g and DG-1g pretreatment provided neuroprotective effects against astrocyte-mediated cerebral infarction by activating angiogenic and anti-apoptotic signaling. Moreover, the angiogenic and anti-apoptotic effects of DG pretreatment can be attributed to the activation of p38 MAPK/HIF-1[Formula: see text]/VEGF-A/vWF signaling and p38 MAPK/HIF-1[Formula: see text]/VEGF-A/p-Bad-related regulation of cytochrome c/caspase-3 signaling, respectively, in the cortical ischemic penumbra 3[Formula: see text]d after reperfusion.

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PMID: 

Int J Mol Sci. 2017 Oct 28 ;18(11). Epub 2017 Oct 28. PMID: 29143796

Abstract Title: 

Angelica sinensis Polysaccharides Ameliorate Stress-Induced Premature Senescence of Hematopoietic Cell via Protecting Bone Marrow Stromal Cells from Oxidative Injuries Caused by 5-Fluorouracil.

Abstract: 

Myelosuppression is the most common complication of chemotherapy. Decline of self-renewal capacity and stress-induced premature senescence (SIPS) of hematopoietic stem cells (HSCs) induced by chemotherapeutic agents may be the cause of long-term myelosuppression after chemotherapy. Whether the mechanism of SIPS of hematopoietic cells relates to chemotherapeutic injury occurred in hematopoietic microenvironment (HM) is still not well elucidated. This study explored the protective effect ofpolysaccharide (ASP), an acetone extract polysaccharide found as the major effective ingredients of a traditional Chinese medicinal herb named Chinese Angelica (Dong Quai), on oxidative damage of homo sapiens bone marrow/stroma cell line (HS-5) caused by 5-fluorouracil (5-FU), and the effect of ASP relieving oxidative stress in HM on SIPS of hematopoietic cells. Tumor-suppressive doses of 5-FU inhibited the growth of HS-5 in a dose-dependent and time-dependent manner. 5-FU induced HS-5 apoptosis and also accumulated cellular hallmarks of senescence including cell cycle arrest and typical senescence-associatedβ-galactosidase positive staining. The intracellular reactive oxygen species (ROS) was increased in 5-FU treated HS-5 cells and coinstantaneous with attenuated antioxidant capacity marked by superoxide dismutase and glutathione peroxidase. Oxidative stress initiated DNA damage indicated by increased γH2AX and 8-OHdG. Oxidative damage of HS-5 cells resulted in declined hematopoietic stimulating factors including stem cell factor (SCF), stromal cell-derived factor (SDF), and granulocyte-macrophage colony-stimulating factor (GM-CSF), however, elevated inflammatory chemokines such as RANTES. Inaddition, gap junction channel protein expression and mediated intercellular communications were attenuated after 5-FU treatment. Significantly, co-culture on 5-FU treated HS-5 feeder layer resulted in less quantity of human umbilical cord blood-derived hematopoietic cells and CD34⁺ hematopoieticstem/progenitor cells (HSPCs), and SIPS of hematopoietic cells. However, it is noteworthy that ASP ameliorated SIPS of hematopoietic cells by the mechanism of protecting bone marrow stromal cells from chemotherapeutic injury via mitigating oxidative damage of stromal cells and improving their hematopoietic function. This study provides a new strategy to alleviate the complication of conventional cancer therapy using chemotherapeutic agents.

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PMID: 

Lancet Infect Dis. 2002 Feb ;2(2):103-10. PMID: 11901641

Abstract Title: 

What is the evidence for a causal link between hygiene and infections?

Abstract: 

Even in an era in which access to personal"cleanliness"and a public health infrastructure are readily available in developed countries, illnesses associated with day care centres and homes continue to be a problem. The inhabitants of less developed countries, on the other hand, must contend with an inadequate public health infrastructure, lack of education programmes, and economic limitations in obtaining hygiene products. Therefore, less developed countries carry a greater burden of morbidity and mortality from infectious illnesses. The objective of this review is to examine and assess the epidemiological evidence for a causal relation between hygiene practices and infections. The Medline database was searched from January 1980 to June 2001 and studies were included if the outcome(s) was infection or symptoms of infection, and if the independent variable(s) was one or more hygiene measures. The strength of the association as measured by the relative reduction in risk of illness was appreciable and generally greater than 20%. Despite methodological strengths and limitations of the studies assessed, the weight of evidence collectively suggests that personal and environmental hygiene reduces the spread of infection. The results from this review demonstrate that there is a continued, measurable, positive effect of personal and community hygiene on infections.

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PMID: 

Vaccine. 2016 Apr 4 ;34(15):1800-5. Epub 2016 Feb 26. PMID: 26921782

Abstract Title: 

Adverse events following HPV vaccination, Alberta 2006-2014.

Abstract: 

BACKGROUND: In Canada, private purchase of human papilloma virus (HPV) vaccines has been possible since 2006. In Alberta, Canada, a publicly funded quadrivalent HPV vaccine program began in the 2008/2009 school year. There have been concerns about adverse events, including venous thromboembolism (VTE) associated with HPV vaccines. We describe the frequencies of adverse events following HPV vaccination among Alberta females aged 9 years or older and look at VTE following HPV vaccination.
METHODS: We used the Alberta Immunization and Adverse Reaction to Immunization (Imm/ARI) repository (publicly funded vaccine), the population-based Pharmaceutical Information Network (PIN) information system (dispensing of a vaccine), and the Alberta Morbidity and Ambulatory Care Abstract reporting system (MACAR) for June 1, 2006-November 19, 2014. Deterministic data linkage used unique personal identifiers. We identified all reported adverse events following immunization (AEFI) and all emergency department (ED) utilization or hospitalizations within 42 days of immunization. We calculated the frequency of AEFI by type, rates per 100,000 doses of HPV vaccine administered and the frequencies of ICD-10-CA codes for hospitalizations and emergency department visits.
RESULTS: Over the period 195,270 females received 528,913 doses of HPV vaccine. Of those receiving at least one dose, 192 reported one or more AEFI events (198 AEFI events), i.e., 37.4/100,000 doses administered (95% CI 32.5-43.0). None were consistent with VTE. Of the women who received HPV vaccine 958 were hospitalized and 19,351 had an ED visit within 42 days of immunization. Four women who had an ED visit and hospitalization event were diagnosed with VTE. Three of these had other diagnoses known to be associated with VTE; the fourth woman had VTE among ED diagnoses but not among those for the hospitalization.
CONCLUSIONS: Rates of AEFI after HPV immunization in Alberta are low and consistent with types of events seen elsewhere.

PMID: 

Int J Biol Macromol. 2018 May ;111:1133-1139. Epub 2018 Feb 19. PMID: 29415408

Abstract Title: 

Angelica sinensis polysaccharide protects against acetaminophen-induced acute liver injury and cell death by suppressing oxidative stress and hepatic apoptosis in vivo and in vitro.

Abstract: 

Acetaminophen (APAP)-induced hepatic damage is prevalent in western countries. The present study aimed to investigate the hepatoprotective effects of Angelica sinensis polysaccharide (ASP), an active constituent derived from a water extract of Angelica sinensis, in rats exposed to an APAP overdose. The mechanisms underlying the activity of this compound were also considered. Specifically, serum and hepatic biochemical parameters including alanine aminotransferase (ALT), aspartate transaminase (AST), glutathione (GSH), malondialdehyde (MDA) and superoxide dismutase (SOD) were evaluated, and key proteins involved in hepatic apoptosis, including cleaved caspase-3, Bax and Bcl-2 were quantified. In vivo, H&E staining reveals that ASP reduces the degeneration of hepatocytes and the amount of cytoplasmic vacuolation in rats exposed to an overdose of APAP. ASP markedly alleviated liver injury via an increase in GSH levels and the inhibition of hepatic apoptosis. In vitro, ASP significantly elevated the survival rate of rat primary hepatocytes exposed to an overdose of APAP. The beneficial effect might be, at least in part, due to the amelioration of lipid peroxidation and oxidative stress, along with the inhibition of apoptosis. Taken together, our findings reveal that ASP has potential to be used as a hepatoprotective agent for the management of APAP-induced liver injury.

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PMID: 

Int J Biol Macromol. 2018 Aug ;115:281-286. Epub 2018 Apr 16. PMID: 29673954

Abstract Title: 

Oxidative stress in osteoarthritis and antioxidant effect of polysaccharide from angelica sinensis.

Abstract: 

This study aimed to investigate the oxidative stress in human osteoarthritis (OA) chondrocytes and the antioxidant effect of angelica sinensis polysaccharide (ASP) on it. Human OA chondrocytes and human normal chondrocytes induced by hydrogen peroxide (HO) alone or treated with ASP were cultured, then they were measured with cell viability, levels of reactive oxygen species (ROS), nitric oxide (NO) and malondialdehyde (MDA) production, activities of inducible nitric oxide synthase (iNOS), superoxide dismutase (SOD) and catalase (CAT), expression of related genes, such as collagen type II (Col2a1), Aggrecan, iNOS, SOD, CAT and peroxisome proliferator-activated receptor gamma (PPARγ). We found that the production of ROS, NO, and MDA and the activity of iNOS, SOD and CAT were significantly increased in OA chondrocytes compared with human normal chondrocytes. When treated with HO, human chondrocytes exhibited acute oxidative stress injure, which was similar to OA chondrocytes. Pretreatment with ASP before HOalleviated oxidative stress and protected human chondrocytes. The activity of PPARγ was decreased in OA chondrocytes and increased when treated with ASP. In conclusion, oxidative stress is an important pathogenesis of OA, and ASP inhibits HO-mediated injury in human chondrocytes. Our data also suggest that PPARγ participates in oxidation and anti-oxidation of OA.

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