The ethanol extract from Artemisia princeps Pampanini induces p53-mediated G1 phase arrest in A172 human neuroblastoma cells.

PMID: 

J Med Food. 2008 Jun ;11(2):237-45. PMID: 18598164

Abstract Title: 

The ethanol extract from Artemisia princeps Pampanini induces p53-mediated G1 phase arrest in A172 human neuroblastoma cells.

Abstract: 

In the present study, the antiproliferative effects of the ethanol extract of Artemisia princeps Pampanini (EAPP) and the mechanism involved were investigated. Of the various cancer cells examined, human neuroblastoma A172 cells were most sensitive to EAPP, and their proliferation was dose- and time-dependently inhibited by EAPP. DNA flow cytometry analysis indicated that EAPP notably induced the G(1) phase arrest in A172 cells. Of the G(1) phase cycle-related proteins examined, the expressions of cyclin-dependent kinase (CDK) 2, CDK4, and CDK6 and of cyclin D(1), D(2), and D(3) were found to be markedly reduced by EAPP, whereas cyclin E was unaffected. Moreover, the protein and mRNA levels of the CDK inhibitors p16(INK4a), p21(CIP1/WAF1), and p27(KIP1) were increased, and the activities of CDK2, CDK4, and CDK6 were reduced. Furthermore, the expressions of E2F-1 and of phosphorylated pRb were also decreased, and the protein levels of p53 and pp53 (Ser15) were increased. Up-regulation of p21(CIP1/WAF1) was found to be mediated by a p53-dependent pathway in EAPP-induced G(1)-arrested A172 cells. When these data are taken together, the EAPP was found to potently inhibit the proliferation of human neuroblastoma A172 cells via G(1) phase cell cycle arrest.

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This report details acute disseminated encephalomyelitis following seasonal influenza vaccination in an elderly patient.

PMID: 

Clin Vaccine Immunol. 2013 Sep ;20(9):1485-6. Epub 2013 Jul 24. PMID: 23885031

Abstract Title: 

Acute disseminated encephalomyelitis following seasonal influenza vaccination in an elderly patient.

Abstract: 

Although such occurrences are rare, it should be recognized that certain vaccines might trigger serious neurological immune phenomena such as Guillain-Barre syndrome, seizures, cranial neuropathy, and acute disseminated encephalomyelitis (ADEM). Here we report on an elderly woman with ADEM following seasonal influenza vaccination who recovered after plasma exchange.

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This report describes a case of acute disseminated encephalomyelitis with severe neurological outcomes following a seasonal influenza vaccine.

PMID: 

Hum Vaccin Immunother. 2014 ;10(7):1969-73. PMID: 25424806

Abstract Title: 

Acute disseminated encephalomyelitis with severe neurological outcomes following virosomal seasonal influenza vaccine.

Abstract: 

Acute disseminated encephalomyelitis (ADEM) is an inflammatory, usually monophasic, immune mediate, demyelinating disease of the central nervous system which involves the white matter. ADEM is more frequent in children and usually occurs after viral infections, but may follow vaccinations, bacterial infections, or may occur without previous events. Only 5% of cases of ADEM are preceded by vaccination within one month prior to symptoms onset. The diagnosis of ADEM requires both multifocal involvement and encephalopathy and specific demyelinating lesions of white matter. Overall prognosis of ADEM patients is often favorable, with full recovery reported in 23% to 100% of patients from pediatric cohorts, and more severe outcome in adult patients. We describe the first case of ADEM occurred few days after administration of virosomal seasonal influenza vaccine. The patient, a 59-year-old caucasic man with unremarkable past medical history presented at admission decreased alertness, 10 days after flu vaccination. During the 2 days following hospitalization, his clinical conditions deteriorated with drowsiness and fever until coma. The magnetic resonance imaging of the brain showed multiple and symmetrical white matter lesions in both cerebellar and cerebral hemispheres, suggesting demyelinating disease with inflammatory activity, compatible with ADEM. The patient was treated with high dose of steroids and intravenous immunoglobulin with relevant sequelae and severe neurological outcomes.

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Sequential systemic immune activation by immunological agents like vaccines can activate the brain immune system, leading to immunoexcitotoxicity which is exacerbated by fluoride and aluminum.

PMID: 

Surg Neurol Int. 2018 ;9:74. Epub 2018 Apr 9. PMID: 29721353

Abstract Title: 

Immunoexcitotoxicity as the central mechanism of etiopathology and treatment of autism spectrum disorders: A possible role of fluoride and aluminum.

Abstract: 

Our review suggests that most autism spectrum disorder (ASD) risk factors are connected, either directly or indirectly, to immunoexcitotoxicity. Chronic brain inflammation is known to enhance the sensitivity of glutamate receptors and interfere with glutamate removal from the extraneuronal space, where it can trigger excitotoxicity over a prolonged period. Neuroscience studies have clearly shown that sequential systemic immune stimulation can activate the brain's immune system, microglia, and astrocytes, and that with initial immune stimulation, there occurs CNS microglial priming. Children are exposed to such sequential immune stimulation via a growing number of environmental excitotoxins, vaccines, and persistent viral infections. We demonstrate that fluoride and aluminum (Al) can exacerbate the pathological problems by worsening excitotoxicity and inflammation. While Alappears among the key suspicious factors of ASD, fluoride is rarely recognized as a causative culprit. A long-term burden of these ubiquitous toxins has several health effects with a striking resemblance to the symptoms of ASD. In addition, their synergistic action in molecules of aluminofluoride complexes can affect cell signaling, neurodevelopment, and CNS functions at several times lower concentrations than either Alor fluoride acting alone. Our review opens the door to a number of new treatment modes that naturally reduce excitotoxicity and microglial priming.

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A. princeps has potential to be utilized as a source of anti-obesity compounds.

PMID: 

Prev Nutr Food Sci. 2019 Sep ;24(3):299-307. Epub 2019 Sep 30. PMID: 31608255

Abstract Title: 

Inhibits Adipogenic Differentiation of 3T3-L1 Pre-Adipocytes via Downregulation of PPARγ and MAPK Pathways.

Abstract: 

, the Korean mugwort, is an edible plant that has various beneficial effects on health, and which has been used as a part of traditional folk medicine. The current study investigated the possible effects of solvent (HO,-BuOH, 85% aq. MeOH, and-hexane) partitioned fractions ofcrude extract (APE) on adipogenic differentiation of 3T3-L1 mouse pre-adipocytes. Characteristics of the differentiated adipocytes were evaluated by Oil red O staining of intracellular lipid droplets, analyzing mRNA and protein levels of peroxisome proliferator-activated receptor (PPAR)γ, CCAAT/enhancer-binding protein (C/EBP) α, and sterol regulatory element-binding protein (SREBP)-1c, and immunoblotting of phosphorylated mitogen-activated protein kinase (MAPK) pathway proteins such as p38, extracellular-signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK). Introduction of APE fractions to differentiating adipocytes resulted in lowered lipid accumulation and downregulation of the PPARγ pathway. APE fractions significantly decreased mRNA and protein expression of PPARγ, C/EBPα, and SREBP-1c. Analysis of MAPK pathway activation showed similar results since treatment with the APE fraction treatment decreased levels of phosphorylated p38, ERK, and JNK. Overall, the-BuOH and-hexane fractions were observed to be the most active fractions to suppress adipogenesis-related signaling in 3T3-L1 cells. The promising ability of APE fractions to inhibit adipocyte differentiation of 3T3-L1 cells suggest thathas potential to be utilized as a source of anti-obesity compounds.

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This study concludes that the measles vaccine plays a part in the development of Crohn’s disease and ulcerative colitis.

PMID: 

Lancet. 1995 Apr 29 ;345(8957):1071-4. PMID: 7715338

Abstract Title: 

Is measles vaccination a risk factor for inflammatory bowel disease?

Abstract: 

Measles virus may persist in intestinal tissue, particularly that affected by Crohn's disease, and early exposure to measles may be a risk factor for the development of Crohn's disease. Crohn's disease and ulcerative colitis occur in the same families and may share a common aetiology. In view of the rising incidence of inflammatory bowel disease (Crohn's disease and ulcerative colitis), we examined the impact of measles vaccination upon these conditions. Prevalences of Crohn's disease, ulcerative colitis, coeliac disease, and peptic ulceration were determined in 3545 people who had received live measles vaccine in 1964 as part of a measles vaccine trial. A longitudinal birth cohort of 11,407 subjects was one unvaccinated comparison cohort, and 2541 partners of those vaccinated was another. Compared with the birth cohort, the relative risk of developing Crohn's disease in the vaccinated group was 3.01 (95% CI 1.45-6.23) and of developing ulcerative colitis was 2.53 (1.15-5.58). There was no significant difference between these two groups in coeliac disease prevalence. Increased prevalence of inflammatory bowel disease, but not coeliac disease or peptic ulceration, was found in the vaccinated cohort compared with their partners. These findings suggest that measles virus may play a part in the development not only of Crohn's disease but also of ulcerative colitis.

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The autonomic nervous system and the immune system interface with each other.

PMID: 

Pharmacol Rev. 2000 Dec ;52(4):595-638. PMID: 11121511

Abstract Title: 

The sympathetic nerve–an integrative interface between two supersystems: the brain and the immune system.

Abstract: 

The brain and the immune system are the two major adaptive systems of the body. During an immune response the brain and the immune system"talk to each other"and this process is essential for maintaining homeostasis. Two major pathway systems are involved in this cross-talk: the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS). This overview focuses on the role of SNS in neuroimmune interactions, an area that has received much less attention than the role of HPA axis. Evidence accumulated over the last 20 years suggests that norepinephrine (NE) fulfills the criteria for neurotransmitter/neuromodulator in lymphoid organs. Thus, primary and secondary lymphoid organs receive extensive sympathetic/noradrenergic innervation. Under stimulation, NE is released from the sympathetic nerve terminals in these organs, and the target immune cells express adrenoreceptors. Through stimulation of these receptors, locally released NE, or circulating catecholamines such as epinephrine, affect lymphocyte traffic, circulation, and proliferation, and modulate cytokine production and the functional activity of different lymphoid cells. Although there exists substantial sympathetic innervation in the bone marrow, and particularly in the thymus and mucosal tissues, our knowledge about the effect of the sympathetic neural input on hematopoiesis, thymocyte development, and mucosal immunity is extremely modest. In addition, recent evidence is discussed that NE and epinephrine, through stimulation of the beta(2)-adrenoreceptor-cAMP-protein kinase A pathway, inhibit the production of type 1/proinflammatory cytokines, such as interleukin (IL-12), tumor necrosis factor-alpha, and interferon-gamma by antigen-presenting cells and T helper (Th) 1 cells, whereas they stimulate the production of type 2/anti-inflammatory cytokines such as IL-10 and transforming growth factor-beta. Through this mechanism, systemically, endogenous catecholamines may cause a selective suppression of Th1 responses and cellular immunity, and a Th2 shift toward dominance of humoral immunity. On the other hand, in certain local responses, and under certain conditions, catecholamines may actually boost regional immune responses, through induction of IL-1, tumor necrosis factor-alpha, and primarily IL-8 production. Thus, the activation of SNS during an immune response might be aimed to localize the inflammatory response, through induction of neutrophil accumulation and stimulation of more specific humoral immune responses, although systemically it may suppress Th1 responses, and, thus protect the organism from the detrimental effects of proinflammatory cytokines and other products of activated macrophages. The above-mentioned immunomodulatory effects of catecholamines and the role of SNS are also discussed in the context of their clinical implication in certain infections, major injury and sepsis, autoimmunity, chronic pain and fatigue syndromes, and tumor growth. Finally, the pharmacological manipulation of the sympathetic-immune interface is reviewed with focus on new therapeutic strategies using selective alpha(2)- and beta(2)-adrenoreceptor agonists and antagonists and inhibitors of phosphodiesterase type IV in the treatment of experimental models of autoimmune diseases, fibromyalgia, and chronic fatigue syndrome.

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Recent clinical trials suggest that vitamin A supplementation reduces morbidity and mortality in different infectious diseases, such as measles, diarrhoeal disease, measles-related pneumonia, human immunodeficiency virus infection and malaria.

PMID: 

Proc Nutr Soc. 1999 Aug ;58(3):719-27. PMID: 10604208

Abstract Title: 

Vitamin A and immunity to viral, bacterial and protozoan infections.

Abstract: 

Studies in animal models and cell lines show that vitamin A and related retinoids play a major role in immunity, including expression of mucins and keratins, lymphopoiesis, apoptosis, cytokine expression, production of antibody, and the function of neutrophils, natural killer cells, monocytes or macrophages, T lymphocytes and B lymphocytes. Recent clinical trials suggest that vitamin A supplementation reduces morbidity and mortality in different infectious diseases, such as measles, diarrhoeal disease, measles-related pneumonia, human immunodeficiency virus infection and malaria. Immune responses vary considerably during different infections, and the available data suggest that the modulation of immune function by vitamin A may also vary widely, depending on the type of infection and immune responses involved.

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