PMID: 

Am J Obstet Gynecol. 2012 Jul ;207(1):59.e1-7. Epub 2012 May 14. PMID: 22727350

Abstract Title: 

Adverse event reports after tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccines in pregnant women.

Abstract: 

OBJECTIVE: We sought to characterize reports to the Vaccine Adverse Event Reporting System (VAERS) of pregnant women who received tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap).STUDY DESIGN: We searched VAERS for reports of pregnant women who received Tdap from Jan. 1, 2005, through June 30, 2010. We conducted a clinical review of reports and available medical records.RESULTS: We identified 132 reports of Tdap administered to pregnant women; 55 (42%) described no adverse event (AE). No maternal or infant deaths were reported. The most frequent pregnancy-specific AE was spontaneous abortion in 22 (16.7%) reports. Injection site reactions were the most frequent non-pregnancy-specific AE found in 6 (4.5%) reports. One report with a major congenital anomaly (gastroschisis) was identified.CONCLUSION: During a time when Tdap was not routinely recommended in pregnancy, review of reports to VAERS in pregnant women after Tdap did not identify any concerning patterns in maternal, infant, or fetal outcomes.

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PMID: 

J Int Med Res. 2018 May ;46(5):1717-1733. Epub 2018 Mar 8. PMID: 29517941

Abstract Title: 

Polysaccharide from Angelica sinensis protects H9c2 cells against oxidative injury and endoplasmic reticulum stress by activating the ATF6 pathway.

Abstract: 

Objectives Angelica sinensis exerts various pharmacological effects, such as antioxidant and anti-apoptotic activity. This study aimed to investigate the active ingredients in A. sinensis with antioxidant properties and whether A. sinensis polysaccharide (ASP) protects H9c2 cells against oxidative and endoplasmic reticulum (ER) stress. Methods The ingredients of A. sinensis and their targets and related pathways were determined using web-based databases. Markers of oxidative stress, cell viability, apoptosis, and ER stress-related signalling pathways were measured in H9c2 cells treated with hydrogen peroxide (HO) and ASP. Results The ingredient-pathway-disease network showed that A. sinensis exerted protective effects against oxidative injury through its various active ingredients on regulation of multiple pathways. Subsequent experiments showed that ASP pretreatment significantly decreased HO-induced cytotoxicity and apoptosis in H9c2 cells. ASP pretreatment inhibited HO-induced reactive oxygen species generation, lactic dehydrogenase release, and malondialdehyde production. ASP exerted beneficial effects by inducing activating transcription factor 6 (ATF6) and increasing ATF6 target protein levels, which in turn attenuated ER stress and increased antioxidant activity. Conclusions Our findings indicate that ASP, a major water-soluble component of A. sinensis, exerts protective effects against HO-induced injury in H9c2 cells by activating the ATF6 pathway, thus ameliorating ER and oxidative stress.

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PMID: 

Cell Biol Int. 2018 Jul ;42(7):867-876. Epub 2018 Mar 24. PMID: 29465760

Abstract Title: 

Angelica sinensis polysaccharide inhibits proliferation, migration, and invasion by downregulating microRNA-675 in human neuroblastoma cell line SH-SY5Y.

Abstract: 

Neuroblastoma is the most common tumor diagnosed in children and infants, with high recurrence and poor prognosis. Angelica sinensis polysaccharide (AP) whose average molecular weight is 72,900 Da possesses various bioactivities. We aimed to explore the effects of AP on neuroblastoma SH-SY5Y cells as well as the underlying mechanisms. Effects of AP on cell viability, proliferation, apoptosis, migration, invasion, and expressions of long noncoding RNA H19 (lncRNA-H19), microRNA (miR)-675, and CD44 were assessed. Then, effects of miR-675 overexpression on AP-treated cells were analyzed. Next, expression of key kinases in the PI3K/AKT and JAK/ STAT pathways was detected. The possible target gene of miR-675 was finally explored. Cell viability was reduced by 200-500 µg/mL AP. Meanwhile, AP repressed cell proliferation, migration, and invasion, but induced apoptosis. Expressions of lncRNA-H19 and miR-675 were upregulated in neuroblastoma cells, and were downregulated by AP. AP was also identified to upregulate CD44. We next found AP affected SH-SY5Y cells through downregulating miR-675. Key kinases in the PI3K/AKT and JAK/STAT pathways were downregulated by AP stimulation, while these downregulations were abrogated by miR-675 overexpression. KIF1B isoform β (KIF1Bβ) is proved to be a target of miR-675. In conclusion, AP was first identified to inhibit proliferation, migration, and invasion but induce apoptosis. Furthermore, AP might repress tumorigenesis of SH-SY5Y cells through miR-675-mediated inactivation of the PI3K/AKT and JAK/STAT pathways. Besides, KIF1Bβ might be a target of miR-675.

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PMID: 

Cell Physiol Biochem. 2018 ;47(3):1084-1094. Epub 2018 May 25. PMID: 29843136

Abstract Title: 

The Effects of Angelica Sinensis Polysaccharide on Tumor Growth and Iron Metabolism by Regulating Hepcidin in Tumor-Bearing Mice.

Abstract: 

BACKGROUND/AIMS: Iron plays a fundamental role in cell biology and its concentration must be precisely regulated. It is well documented that excess iron burden contributes to the occurrence and progression of cancer. Hepcidin secreted by liver plays an essential role in orchestrating iron metabolism. In the present study, we aimed to investigate the ability of angelica sinensis polysaccharide (ASP) to decrease iron burden in tumor-bearing mice and the mechanism of ASP regulation hepcidin expression.METHODS: Western blot, RT-PCR, immunohistochemistry (IHC), and enzyme-linked immunosorbent assay (ELISA) were used to detect the regulation of hepcidin and related cytokines by ASP. The role of ASP in tumor proliferation was investigated using in vivo assays. Iron depositions and iron concentrations in organs were determined by hematoxylin-eosin (H&E) staining and atomic absorption spectrophotometer.RESULTS: We found that ASP could inhibit tumor growth in mice xenografted with 4T1 and H22 cancer cells. In vivo experiments also showed that ASP could potently regulate hepcidin expression in liver and serum and decrease iron burden in liver, spleen and grafted tumors in mouse model. Treatment with ASP in hepatic cell lines reproduced comparable results in decreasing hepcidin as in mouse liver. Furthermore, we found that ASP markedly suppressed the expression of interleukin-6 (IL-6), JAK2, p-STAT3, and p-SMAD1/5/8 in liver, suggesting that JAK/STAT and BMP-SMAD pathways were involved in the regulation of hepcidin expression by ASP. We also found down-regulation of iron-related cytokines in ASP treated mice.CONCLUSION: The present study provides new evidence that ASP decreases hepcidin expression, which can reduce iron burden and inhibit tumor proliferation. These findings might aid ASP developed as a potential candidate for cancer treatment in patients with iron overload.

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PMID: 

Proc Natl Acad Sci U S A. 2014 Jan 14 ;111(2):787-92. Epub 2013 Nov 25. PMID: 24277828

Abstract Title: 

Acellular pertussis vaccines protect against disease but fail to prevent infection and transmission in a nonhuman primate model.

Abstract: 

Pertussis is a highly contagious respiratory illness caused by the bacterial pathogen Bordetella pertussis. Pertussis rates in the United States have been rising and reached a 50-y high of 42,000 cases in 2012. Although pertussis resurgence is not completely understood, we hypothesize that current acellular pertussis (aP) vaccines fail to prevent colonization and transmission. To test our hypothesis, infant baboons were vaccinated at 2, 4, and 6 mo of age with aP or whole-cell pertussis (wP) vaccines and challenged with B. pertussis at 7 mo. Infection was followed by quantifying colonization in nasopharyngeal washes and monitoring leukocytosis and symptoms. Baboons vaccinated with aP were protected from severe pertussis-associated symptoms but not from colonization, did not clear the infection faster than naïve animals, and readily transmitted B. pertussis to unvaccinated contacts. Vaccination with wP induced a more rapid clearance compared with naïve and aP-vaccinated animals. By comparison, previously infected animals were not colonized upon secondary infection. Although all vaccinated and previously infected animals had robust serum antibody responses, we found key differences in T-cell immunity. Previously infected animals and wP-vaccinated animals possess strong B. pertussis-specific T helper 17 (Th17) memory and Th1 memory, whereas aP vaccination induced a Th1/Th2 response instead. The observation that aP, which induces an immune response mismatched to that induced by natural infection, fails to prevent colonization or transmission provides a plausible explanation for the resurgence of pertussis and suggests that optimal control of pertussis will require the development of improvedvaccines.

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PMID: 

Nutrients. 2018 May 21 ;10(5). Epub 2018 May 21. PMID: 29883374

Abstract Title: 

Anti-Inflammatory Effects of(Oliv.) Diels Water Extract on RAW 264.7 Induced with Lipopolysaccharide.

Abstract: 

The dry root of(Oliv.) Diels, also known as“female ginseng”, is a popular herbal drug amongst women, used to treat a variety of health issues and cardiovascular diseases. The aim of this study is to evaluate the detailed molecular mechanism for anti-inflammatory effects ofroot water extract (ASW). The anti-inflammatory effect of ASW on lipopolysaccharide (LPS)-induced RAW 264.7 mouse macrophages was evaluated by the tetrazolium-based colorimetric assay (MTT), Griess reagent assay, multiplex cytokine assay, real time reverse transcription polymerase chain reaction (RT-PCR), and Fluo-4 calcium assay. ASW restored cell viability in RAW 264.7 at concentrations of up to 200µg/mL. ASW showed notable anti-inflammatory effects. ASW exhibited IC= 954.3, 387.3, 191.7, 317.8, 1267.0, 347.0, 110.1, 573.6, 1171.0, 732.6, 980.8, 125.0, and 257.0µg/mL for interleukin (IL)-6, tumor necrosis factor (TNF)-α, monocyte chemotactic activating factor (MCP)-1, regulated on activation, normal T cell expressed and secreted (RANTES), granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), lipopolysaccharide-induced CXC chemokine (LIX), macrophage inflammatory protein (MIP)-1α, MIP-1β, MIP-2, IL-10, and intracellular calcium, respectively. Additionally, ASW inhibited the LPS-induced production of nitric oxide and the LPS-induced mRNA expression of CHOP (GADD153), Janus kinase 2 (JAK2), signal transducers and activators of transcription 1 (STAT1), first apoptosis signal receptor (FAS), and c-Fos, NOS2, and PTGS2 (COX2) in RAW 264.7 significantly (

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PMID: 

Fitoterapia. 2018 Sep ;129:102-107. Epub 2018 Jun 21. PMID: 29935258

Abstract Title: 

Phthalide dimers from Angelica sinensis and their COX-2 inhibition activity.

Abstract: 

Four new dimeric phthalides, angesinenolides C-F (1-4), along with three known ones, were isolated from the roots of Angelica sinensis. Their structures were determined by means of HRMS and NMR experiments. The structures of compounds 1 and 3 were confirmed using X-ray crystallographic data. All isolated compounds were tested for activities on the inhibition of COX-2 enzyme in vitro. Compounds 1-6 exhibited inhibitory activity against COX-2 with ICvalues ranging from 29.32 ± 0.07 to 137.91 ± 0.24 μM.

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PMID: 

N Engl J Med. 2003 Jan 30 ;348(5):460-3. Epub 2002 Dec 19. PMID: 12496354

Abstract Title: 

A different view of smallpox and vaccination.

Abstract: 

[No Abstract Available]

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PMID: 

Biomed Pharmacother. 2018 Oct ;106:225-231. Epub 2018 Jun 28. PMID: 29960169

Abstract Title: 

Angelica sinensis polysaccharide protects rat cardiomyocytes H9c2 from hypoxia-induced injury by down-regulation of microRNA-22.

Abstract: 

BACKGROUND: The cardioprotective role of Angelica sinensis has been proven in previous studies. However, the effects of Angelica sinensis polysaccharide (ASP, major bioactive component of Angelica sinensis) on myocardial infarction (MI) remain unclear. This study aimed to investigate the effects of ASP on hypoxia-induced H9c2 cell injury as well as the underlying mechanisms.METHODS: We constructed in vitro hypoxic model to mimic MI. Cell viability, proliferation and apoptosis were respectively measured by using CCK-8 assay, Western blot analysis, and flow cytometry assay/Western blot analysis, to evaluate cell injury after treatments. The effects of ASP pretreatment on hypoxia-induced injury were explored. Expression of miR-22 after treatments was determined by stem-loop RT-PCR, and whether ASP affected H9c2 cells via miR-22 was studied. Involvements of the PI3K/AKT and JAK1/STAT3 pathways were finally explored.RESULTS: Hypoxia-induced decreases of cell viability and proliferation as well as increase of apoptosis were attenuated by ASP pretreatments. Hypoxia treatment up-regulated miR-22 expression, and the up-regulation was mitigated by ASP pretreatment. Effects of ASP pretreatment on hypoxia-treated H9c2 cells were mitigated by miR-22 overexpression while were augmented by miR-22 inhibition. Phosphorylation levels of PI3K, AKT, JAK1 and STAT3 were increased by ASP through down-regulating miR-22 in hypoxia-treated H9c2 cells.CONCLUSION: ASP pretreatment attenuated hypoxia-induced H9c2 cell injury, possibly through down-regulating miR-22 expression. The PI3K/AKT and JAK1/STAT3 pathways were activated by ASP pretreatment via miR-22 in hypoxia-treated cells.

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PMID: 

J Med Food. 2018 Sep ;21(9):887-898. Epub 2018 Aug 15. PMID: 30109956

Abstract Title: 

Angelica sinensis Supercritical Fluid COExtract Attenuates D-Galactose-Induced Liver and Kidney Impairment in Mice by Suppressing Oxidative Stress and Inflammation.

Abstract: 

Angelica sinensis (AS, Danggui in Chinese) is an important herbal component of various traditional formulae for the management of asthenia and its tonic effects. Although AS has been shown to ameliorate cognitive damage and nerve toxicity in D-galactose (D-gal)-elicited senescent mice brain, its effects on liver and kidney injury have not yet been explored. In this work, mice were subjected to hypodermic injection with D-gal (200 mg/kg) and orally gavaged with AS (20, 40, or 80 mg/kg) once a day for 8 successive weeks. Results revealed that AS significantly improved liver and kidney function as assessed by organ index and functional parameters. In addition, AS pretreatment effectively ameliorated the histological deterioration. AS attenuated the MDA level and markedly enhanced the activities and gene expressions of antioxidative enzymes, namely Cu, Zn-SOD, CAT, and GPx. Furthermore, AS markedly inhibited the D-gal-mediated increment of expressions of inflammatory cytokines iNOS, COX-2, IκBα, p-IκBα, and p65 and promoted the IκBα expression level in both hepatic and renal tissues. In sum, AS pretreatment could effectively guard the liver and kidney of mice from D-gal-induced injury, and the underlying mechanism was deemed to be intimately related to attenuating oxidative response and inflammatory stress.

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