E-cigarettes: unstandardized, under-regulated, understudied, and unknown health and cancer risks.

PMID: 

Cancer Res. 2019 Dec 15 ;79(24):6079-6083. Epub 2019 Oct 28. PMID: 31658978

Abstract Title: 

E-Cigarettes: Unstandardized, Under-Regulated, Understudied, and Unknown Health and Cancer Risks.

Abstract: 

E-cigarettes have the ability to deliver nicotine in a manner that is similar to, and, theoretically, safer than, combusted tobacco. However, these devices are extremely heterogeneous and regulation has struggled to keep up with their rapid evolution. A compilation of early data suggest that e-cigarettes may contain numerous toxic substances, including known carcinogens. However, there are few data available on the short- and long-term health effects of e-cigarettes, including any potential effect on cancer risk. Until more is known, e-cigarettes should not be considered a safe alternative to combusted tobacco use.

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Unusual cadinane-type sesquiterpene glycosides with α-glucosidase inhibitory activities from the fruit of Cornus officinalis.

PMID: 

Bioorg Chem. 2019 02 ;82:1-5. Epub 2018 Sep 20. PMID: 30267969

Abstract Title: 

Unusual cadinane-type sesquiterpene glycosides withα-glucosidase inhibitory activities from the fruit of Cornus officinalis Sieb. et Zuuc.

Abstract: 

Five novel and rare cadinane-type sesquiterpene glycosides, cornucadinoside A-E (1-5) were isolated from water extract of the fruit of Cornus officinalis Sieb. et Zuuc.. The new chemical structures, together with their absolute configurations, were elucidated on the basis of extensive spectroscopic analysis, including a comparison of their experimental and calculated electronic circular dichroism (ECD) spectra. Their structures, which possess a naphthalene skeleton, are the first report on the occurrence of cadinane sesquiterpene glycosides in Cornus. Additionally, all the compounds exhibited markedα-glucosidase inhibitory activity except for 3in vitro.

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New iridoid derivatives from the fruits of Cornus officinalis and their neuroprotective activities.

PMID: 

Molecules. 2019 Feb 11 ;24(3). Epub 2019 Feb 11. PMID: 30754635

Abstract Title: 

New Iridoid Derivatives from the Fruits ofand Their Neuroprotective Activities.

Abstract: 

Three previously undescribed iridoids, cornusfurals A⁻C, were isolated from the ethanolic extracts of fruits of. Their structures were elucidated by spectroscopic methods, including one-dimensional and two-dimensional nuclear magnetic resonance, ultraviolet spectroscopy, infrared spectroscopy, and mass spectrometry. The neuroprotective activity was evaluated by measuring corticosterone-induced damage in PC12 cells. The results showed that cornusfural B decreased corticosterone-induced PC12 cell damage compared with that in model cells.

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Compositional analysis and biological characterization of Cornus officinalis on human 1.1B4 pancreatic β cells.

PMID: 

Mol Cell Endocrinol. 2019 08 20 ;494:110491. Epub 2019 Jun 27. PMID: 31255730

Abstract Title: 

Compositional analysis and biological characterization of Cornus officinalis on human 1.1B4 pancreaticβ cells.

Abstract: 

Type 1 diabetes (T1D) is an autoimmune disease resulting from the loss of pancreaticβ cells and subsequent insulin production. Novel interventional therapies are urgently needed that can protect existing β cells from cytokine-induced death and enhance their function before symptomatic onset. Our initial evidence is suggesting that bioactive ingredients within Cornus officinalis (CO) may be able to serve in this function. CO has been extensively used in Traditional Chinese Medicine (TCM) and reported to possess both anti-inflammatory and pro-metabolic effects. We hypothesize that CO treatment may provide a future potential candidate for interventional therapy for early stageT1D prior to significant β cell loss. Our data demonstrated that CO can inhibit cytokine-mediated β cell death, increase cell viability and oxidative capacity, and increase expression of NFATC2 (Nuclear Factor of Activated T Cells, Cytoplasmic 2). We have also profiled the bioactive components inCO from multiple sources by HPLC/MS (High Performance Liquid Chromatography/Mass Spectrometry) analysis. Altogether, CO significantly increases the energy metabolism of β cells while inducing the NFAT pathway to signal for increased proliferation and endocrine function.

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Neuroprotective effects of Cornus officinalis on stress-induced hippocampal deficits.

PMID: 

Antioxidants (Basel). 2019 Dec 26 ;9(1). Epub 2019 Dec 26. PMID: 31888114

Abstract Title: 

Neuroprotective Effects ofon Stress-Induced Hippocampal Deficits in Rats and HO-Induced Neurotoxicity in SH-SY5Y Neuroblastoma Cells.

Abstract: 

Oxidative stress plays a vital role in neurodegenerative diseases.(CC) has a wide range of pharmacological activities (e.g., antioxidant, neuroprotective, and anti-inflammatory). The present study was undertaken to elucidate the neuroprotective mechanism of CC and fermented CC (FCC) on stress and HO-induced oxidative stress damage in rats and SH-SY5Y cells. A dose of 100 mg/kg CC or FCC was orally administered to rats 1 h prior to immobilization 2 h per day for 14 days. CC, especially FCC administration decreased immobility time in forced swim test (FST), effectively alleviated the oxidative stress, and remarkably decreased corticosterone,β-endorphin and increased serotonin levels, respectively. In cells, CC and FCC significantly inhibited reactive oxygen species (ROS) generation, lactate dehydrogenase (LDH) release and significantly increased the genes expression of antioxidant and neuronal markers, such as superoxide dismutase (SOD), catalase (CAT), and brain-derived neurotrophic factor (BDNF). Moreover, the pro-apoptotic factor Bax and anti-apoptotic factor Bcl-2 (Bax/Bcl-2) ratio was regulated by CC and FCC pretreatment. Both in rats and cells, CC and FCC downregulated mitogen-activated protein kinase (MAPK) phosphorylation. Taken together, these results demonstrated that CC and particularly FCC ameliorated oxidative stress and may be used on the neuroprotection.

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Growth inhibitory efficacy of Cornus officinalis in a cell culture model for triple-negative breast cancer.

PMID: 

Oncol Lett. 2019 Jun ;17(6):5261-5266. Epub 2019 Mar 21. PMID: 31186742

Abstract Title: 

Growth inhibitory efficacy ofin a cell culture model for triple-negative breast cancer.

Abstract: 

Triple-negative breast cancer (TNBC) lacks the expressions of estrogen receptor-α, progesterone receptor and human epidermal growth factor receptor-2. The treatment options for TNBC include anthracyclin/taxol based conventional chemotherapy and small molecular inhibitor based targeted therapy. However, the therapeutic efficacy is limited by systemic toxicity and acquired tumorresistance; identification of less toxic testable alternatives is urgently required. Non-toxic nutritional herbs are commonly used in traditional Chinese herbal medicine for general health management and may additionally represent a testable therapeutic alternative for TNBC. The present study examined the growth inhibitory efficacy of the nutritional herb(CO) in MDA-MB-231 cells, which represent a cell culture model for TNBC, and identified potential mechanistic leads. In MDA-MB-231 cells, CO induced dose-dependent cytostatic growth arrest [inhibitory concentration (IC), 0.1% and IC, 0.5%], and inhibited anchorage independent colony formation. Mechanistically, CO inhibited Gto S phase transition leading to Garrest and decreased the expression of cyclin D1 and phosphorylated-retinoblastoma proteins. CO additionally altered apoptosis specific BCL-2 associated X protein/B-cell lymphoma-2 expression and upregulated pro-apoptotic caspase-3/7 activity. Collectively, these data provided mechanistic evidence for the efficacy of CO, and validated a mechanism-based approach to prioritize efficacious nutritional herbs as testable alternatives for secondary prevention/treatment of TNBC.

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Comparative study of crude and wine-processing Corni Fructus on chemical composition and antidiabetic effects.

PMID: 

Evid Based Complement Alternat Med. 2019 ;2019:3986964. Epub 2019 Dec 2. PMID: 31885645

Abstract Title: 

Comparative Study of Crude and Wine-Processingon Chemical Composition and Antidiabetic Effects.

Abstract: 

Wine processing is a specialized technology which involves sautéing crude herbal medicine using Chinese rice wine. Herein, we identified the changes in chemical profiles and antidiabetic effects of(CF) after wine processing in high-fat diet (HFD) streptozotocin- (STZ-) induced diabetic mice. A novel high-efficiency method for simultaneously quantifying gallic acid, 5-hydroxymethylfurfural, morroniside, loganin, sweroside, and cornuside by UPLC was developed, and validating crude and wine-processing CF was done for the first time. Mice were randomly divided into the following groups and orally given different solutions for 4 weeks: normal group (NC, 0.4% (w/v) CMC-Na), model group (DM, 0.4% (w/v) CMC-Na), crude CF group (CP, 3.87 g/kg), and wine-processing CF group (PP, 3.87 g/kg) followed by HFD and multiple subcutaneous injection of STZ (40 mg/kg) to induce the diabetes model except the NC group. Biochemical indexes (body weight, fasting blood glucose level, lipid level, insulin, and free fatty acid) and other parameters involving liver toxicity were measured with commercial kits and immunohistochemical method. Comparative studies on pharmacology showed that the crude extracts possess higher efficacy on hypoglycemia and hypolipidemia, while wine-processing products exhibit better effects on liver preservation.Our data suggested that wine processing was recommended when CF was used for protecting the liver; however, crude products should be used as antidiabetic drugs.

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No animal models have been adequately standardized and validated to predict the risk of allergy and autoimmunity associated with vaccines.

PMID: 

Toxicology. 2002 May 15 ;174(1):45-51. PMID: 11972991

Abstract Title: 

Vaccines: predicting the risk of allergy and autoimmunity.

Abstract: 

The field of vaccines is markedly evolving with the introduction and development of many new concepts and formulations, as well as new indications. Based on the current clinical experience, vaccines can be considered safe in most cases. Nevertheless, allergy and, to a lesser extent, autoimmunity have repeatedly been described or suspected as rare adverse consequences of human vaccines. The mechanisms of these adverse reactions are ill-elucidated, if at all. No animal models have been adequately standardized and validated to predict the risk of allergy and autoimmunity associated with vaccines. However, a number of existing models can be considered for use, but need refinement to be applied to vaccine evaluation. Finally, because the preclinical safety evaluation has not received much attention in the past, efforts should be paid to design specific and cost-effective procedures to meet the current expectations.

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Preliminary testing of cancer vaccines caused mice to develop vitiligo.

PMID: 

Cancer Res. 2004 Feb 15 ;64(4):1509-14. PMID: 14973051

Abstract Title: 

Vaccination-induced autoimmune vitiligo is a consequence of secondary trauma to the skin.

Abstract: 

A major concern for cancer vaccines targeting self-tumor antigens is the risk of autoimmune sequelae. Although antitumor immunity correlates with autoimmune disease in some preclinical models, the mechanism(s) linking antitumor immunity and subsequent autoimmune pathology remain(s) to be determined. In the current study, we demonstrated that intradermal (i.d.) immunization with a recombinant adenovirus (Ad) expressing the murine melanoma antigen tyrosinase-related protein 2 (AdmTrp-2) results in a moderate level of tumor protection against the B16F10 murine melanoma without any vitiligo. Similar immunization with an Ad encoding human Trp-2 (AdhTrp-2) resulted in 50-fold greater protective immunity and produced vitiligo in all of the mice, suggesting that the development of autoimmunity may reflect the potency of the vaccine. Interestingly, delivery of AdhTrp-2 by i.m. injection generated protective immunity comparable with that seen in mice that received the vaccine by the i.d. route, but none of the recipients in the i.m. group developed vitiligo. The cellular and humoral responses in the i.m. immunized mice were greater than in the i.d. group; therefore, the lack of vitiligo was not caused by reduced efficacy of the vaccine. These results led us to hypothesize that vaccine-induced vitiligo was associated with local inflammatory responses. Mice immunized i.m. with AdhTrp-2 did develop vitiligo when they subsequently were injected i.d. with either a control Ad vector or complete Freund's adjuvant, suggesting that vitiligo is initiated by some form of trauma within the skin. Our data demonstrated that autoimmune pathology is not an unavoidable outcome of effective cancer vaccines directed against self-tumor antigens.

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