PMID: 

Arch Biochem Biophys. 2018 11 1 ;657:65-73. Epub 2018 Sep 15. PMID: 30222954

Abstract Title: 

Nicotine enhances alcoholic fatty liver in mice: Role of CYP2A5.

Abstract: 

Tobacco and alcohol are often co-abused. Nicotine can enhance alcoholic fatty liver, and CYP2A6 (CYP2A5 in mice), a major metabolism enzyme for nicotine, can be induced by alcohol. CYP2A5 knockout (cyp2a5) mice and their littermates (cyp2a5) were used to test whether CYP2A5 has an effect on nicotine-enhanced alcoholic fatty liver. The results showed that alcoholic fatty liver was enhanced by nicotine in cyp2a5mice but not in the cyp2a5mice. Combination of ethanol and nicotine increased serum triglyceride in cyp2a5mice but not in the cyp2a5mice. Cotinine, a major metabolite of nicotine, also enhanced alcoholic fatty liver, which was also observed in cyp2a5mice but not in the cyp2a5mice. Nitrotyrosine and malondialdehyde (MDA), markers of oxidative/nitrosative stress, were induced by alcohol and were further increased by nicotine and cotinine in cyp2a5mice but not in the cyp2a5mice. Reactive oxygen species (ROS) production during microsomal metabolism of nicotine and cotinine was increased in microsomes from cyp2a5mice but not in microsomes from cyp2a5mice. These results suggest that nicotine enhances alcoholic fatty liver in a CYP2A5-dependent manner, which is related to ROS produced during the process of CYP2A5-dependent nicotine metabolism.

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Full of inaccuracies and omissions, the New York Times’ recent articles on the safety of the 5G rollout should be viewed more as an opinion piece than factual news reporting

PMID: 

Toxicol Lett. 2018 Dec 15 ;299:40-46. Epub 2018 Sep 15. PMID: 30227238

Abstract Title: 

Tobacco smoke and nicotine suppress expression of activating signaling molecules in human dendritic cells.

Abstract: 

Cigarette smoke has significant toxic effects on the immune system, and increases the risk of developing autoimmune diseases; one immunosuppressive effect of cigarette smoke is that it inhibits the T cell-stimulating, immunogenic properties of myeloid dendritic cells (DCs). As the functions of DCs are regulated by intra-cellular signaling pathways, we investigated the effects of cigarette smoke extract (CSE) and nicotine on multiple signaling molecules and other regulatory proteins in human DCs to elucidate the molecular basis of the inhibition of DC maturation and function by CSE and nicotine. Maturation of monocyte-derived DCs was induced with the TLR3-agonist poly I:C or with the TLR4-agonist lipopolysaccharide, in the absence or presence of CSE or nicotine. Reverse-phase protein microarray was used to quantify multiple signaling molecules and other proteins in cell lysates. Particularly in poly I:C-matured DCs, cigarette smoke constituents and nicotine suppressed the expression of signaling molecules associated with DC maturation and T cell stimulation, cell survival and cell migration. In conclusion, constituents of tobacco smoke suppress the immunogenic potential of DCs at the signaling pathway level.

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PMID: 

Arthritis Rheumatol. 2016 12 ;68(12):2878-2888. PMID: 27337150

Abstract Title: 

Suppression of Inflammatory Arthritis by Human Gut-Derived Prevotella histicola in Humanized Mice.

Abstract: 

OBJECTIVE: The gut microbiome regulates host immune homeostasis. Rheumatoid arthritis (RA) is associated with intestinal dysbiosis. This study was undertaken to test the ability of a human gut-derived commensal to modulate immune response and treat arthritis in a humanized mouse model.METHODS: We isolated a commensal bacterium, Prevotella histicola, that is native to the human gut and has systemic immune effects when administered enterally. Arthritis-susceptible HLA-DQ8 mice were immunized with type II collagen and treated with P histicola. Disease incidence, onset, and severity were monitored. Changes in gut epithelial proteins and immune response as well as systemic cellular and humoral immune responses were studied in treated mice.RESULTS: When treated with P histicola in prophylactic or therapeutic protocols, DQ8 mice exhibited significantly decreased incidence and severity of arthritis compared to controls. The microbial mucosal modulation of arthritis was dependent on regulation by CD103+ dendritic cells and myeloid suppressors (CD11b+Gr-1+ cells) and by generation of Treg cells (CD4+CD25+FoxP3+) in the gut, resulting in suppression of antigen-specific Th17 responses and increased transcription of interleukin-10. Treatment with P histicola led to reduced intestinal permeability by increasing expression of enzymes that produce antimicrobial peptides as well as tight junction proteins (zonula occludens 1 and occludin). However, the innate immune response via Toll-like receptor 4 (TLR-4) and TLR-9 was not affected in treated mice.CONCLUSION: Our results demonstrate that enteral exposure to P histicola suppresses arthritis via mucosal regulation. P histicola is a unique commensal that can be explored as a novel therapy for RA and may have few or no side effects.

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PMID: 

Int J Mol Med. 2018 Nov ;42(5):2447-2458. Epub 2018 Sep 6. PMID: 30226534

Abstract Title: 

Sulforaphane regulates apoptosis- and proliferation‑related signaling pathways and synergizes with cisplatin to suppress human ovarian cancer.

Abstract: 

Ovarian cancer is currently the most life‑threatening type of gynecological malignancy with limited treatment options. Therefore, improved targeted therapies are required to combat ovarian cancer across the world. Sulforaphane is found in raw cruciferous vegetables. The chemotherapeutic and anti‑carcinogenic properties of sulforaphanehave been demonstrated, however, the underlying mechanisms remain to be fully elucidated, particularly in ovarian cancer. In the present study, the possibility of repurposing sulforaphane as an anti‑ovarian cancer agent was examined. Cell viability and colony formation assay were used to test theanticancer efficiency of sulforaphane. Then wound healing assay, migration assay, cell cycle and apoptosis assays were used to detect how the drug worked on the cells. The mechanism of sulforaphane was investigated by western blot analysis. It was found that sulforaphane effectively suppressed the progression of human ovarian cancer cell proliferation, migration and cell cycle, and promoted apoptosis. Sulforaphane inhibited multiple cancer‑associated signaling pathways, including B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein, cytochrome c, Caspase‑3, phosphorylated AKT,phosphorylated nuclear factor‑κB, P53, P27, Cyclin‑D1 and cMyc, and reduced the expression levels of human epidermal growth factor receptor 2 in human ovarian cancer cells. Sulforaphane synergized with cisplatin to suppress the cancer cell proliferation and enhance ovarian cancer cell apoptosis. Xenograft experiments in vivo confirmed that sulforaphane effectively suppressed tumor growth by inhibiting ovarian cancer cell proliferation through targeting tumor‑related signals. The results indicated that sulforaphane may be repurposed as an effective anti‑ovarian cancer agent, with further preclinical or clinical investigations required.

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PMID: 

Brain Circ. 2019 Apr-Jun;5(2):74-83. Epub 2019 Jun 27. PMID: 31334360

Abstract Title: 

The neuroprotective mechanisms and effects of sulforaphane.

Abstract: 

Sulforaphane (SFN) is a phytochemical found in cruciferous vegetables. It has been shown to have many protective effects against many diseases, including multiple types of cancer. SFN is a potent activator of the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant response element (ARE) genetic pathway. Upregulation of Nrf2-ARE increases the availability of multiple antioxidants. A substantial amount of preclinical research regarding the ability of SFN to protect the nervous system from many diseases and toxins has been done, but only a few small human trials have been completed. Preclinical data suggest that SFN protects the nervous system through multiple mechanisms and may help reduce the risk of many diseases and reduce the burden of symptoms in existing conditions. This review focuses on the literature regarding the protective effects of SFN on the nervous system. A discussion of neuroprotective mechanisms is followed by a discussion of the protective effects elicited by SFN administration in a multitude of neurological diseases and toxin exposures. SFN is a promising neuroprotective phytochemical which needs further human trials to evaluate its efficacy in preventing and decreasing the burden of many neurological diseases.

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PMID: 

J Korean Med Sci. 2019 Jul 22 ;34(28):e197. Epub 2019 Jul 22. PMID: 31327180

Abstract Title: 

The Anti-Inflammatory Effect of Sulforaphane in Mice with Experimental Autoimmune Encephalomyelitis.

Abstract: 

BACKGROUND: Multiple sclerosis (MS) is an immune-associated inflammatory disorder of the central nervous system and results in serious disability. Although many disease-modifying therapy drugs have been developed, these drugs have shown limited clinical efficacy and some adverse effects in previous studies, therefore, there has been reasonable need for less harmful and cost-effective therapeutics. Herein, we tested the anti-inflammatory effect of sulforaphane (SFN) in a mouse model of experimental autoimmune encephalomyelitis (EAE).METHODS: The EAE mice were randomly assigned into two experimental groups: the phosphate-buffered saline (PBS)-treated EAE group and SFN-treated EAE group. After EAE mice induction by auto-immunization against the myelin oligodendrocyte glycoprotein peptide, we evaluated EAE symptom scores and biochemical analyses such as infiltration of inflammatory cells and demyelination of the spinal cord. Furthermore, western blotting was performed using the spinal cords of EAE mice.RESULTS: In the behavioral study, the SFN-treated EAE mice showed favorable clinical scores compared with PBS-treated EAE mice at the 13th day (1.30± 0.15 vs. 1.90 ± 0.18;= 0.043) and 14th day (1.80± 0.13 vs. 2.75 ± 0.17;= 0.003). Additionally, the biochemical studies revealed that SFN treatment inhibited the inflammatory infiltration, demyelinating injury of the spinal cords, and the up-regulation of inducible nitric oxide synthase in the EAE mice.CONCLUSION: The SFN treatment showed anti-inflammatory and anti-oxidative effects in the EAE mice. Conclusively, this study suggests that SFN has neuroprotective effects via anti-inflammatory processing, so it could be a new therapeutic or nutritional supplement for MS.

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PMID: 

Neuroscience. 2019 Jul 9 ;414:228-244. Epub 2019 Jul 9. PMID: 31299349

Abstract Title: 

Neonatal Monosodium Glutamate Administration Disrupts Place Learning and Alters Hippocampal-Prefrontal Learning-Related Theta Activity in the Adult Rat.

Abstract: 

Neonatal treatment with monosodium glutamate causes profound deficits in place learning and memory in adult rats evaluated in the Morris maze. Theta activity has been related to hippocampal learning, and increased high-frequency theta activity occurs through efficient place learning training in the Morris maze. We wondered whether the place learning deficits observed in adult rats that had been neonatally treated with monosodium glutamate (MSG), were related to altered theta patterns in the hippocampus and prelimbic cortex, which were recorded during place learning training in the Morris maze. The MSG-treated group had a profound deficit in place learning ability, with a marginal reduction in escape latencies during the final days of training. Learning-related changes were observed in the relative power distribution in control and MSG-treated groups in the hippocampal EEG, but not in the prelimbic cortex. Increased prefrontal and reduced hippocampal absolute power that appeared principally during the final days of training, and reduced coherence between regions throughout the training (4-12 Hz), were observed in the MSG-treated rats, thereby suggesting a misfunction of the circuits rather than a hyperexcitable general state. In conclusion, neonatal administration of MSG, which caused a profound deficit in place learning at the adult age, also altered the theta pattern both in the hippocampus and prelimbic cortex.

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