PMID: 

Int J Oncol. 2018 Jun ;52(6):2119-2129. Epub 2018 Mar 23. PMID: 29620169

Abstract Title: 

Lutein inhibits proliferation, invasion and migration of hypoxic breast cancer cells via downregulation of HES1.

Abstract: 

An intratumoral hypoxic microenvironment is frequently observed in solid tumors, including breast cancer. Lutein, a plant-derived compound and non-vitamin A carotenoid, has been demonstrated to possess multiple protective properties including anti-inflammation, anti-oxidative stress and antitumor effects. The main objective of the present research was to elucidate the involvement of lutein in the production of reactive oxygen species (ROS) under hypoxia, the activation of hairy and enhancer of split 1 (HES1), and the proliferation, invasion and migration of breast cancer cells. The human breast cancer cell lines MDA‑MB‑157 and MCF‑7 were exposed to hypoxic conditions and various concentrations of lutein. An MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay was performed to examine cell proliferation, and Annexin V-fluorescein isothiocyanate/propidium iodide staining was performed to analyze the apoptosis ratio. The levels of hypoxia inducible factor-1α (HIF‑1α), NOTCH signaling molecules, HES1 and epithelial-mesenchymal transition (EMT)-associated factors were examined by reverse transcription-quantitative polymerase chain reaction and western blot analysis. Wound healing and Transwell invasion assays were used to detect the invasion and migration of breast cancer cells. Intracellular ROS levels were examined using 2,7-dichlorodihydrofluorescein-diacetate and flow cytometry. The results revealed that cell proliferation was inhibited by lutein in a dose-dependent manner, and the apoptosis ratio gradually increased with lutein treatment under hypoxia as evident from flow cytometry-based analysis. Exposure to lutein inhibited hypoxia-mediated activation of HIF‑1α, NOTCH signaling and HES1 expression, and suppressed the hypoxia-induced expression of EMT-associated factors. Lutein markedly inhibited the invasion and migration of breast cancer cells under hypoxia. Hypoxia-induced production of ROS was also decreased by lutein. Furthermore, the ROS scavenger N‑acetylcysteine also suppressed hypoxia inducible factor 1α and HES1 expression in breast cancer cells during hypoxia, but hydrogen peroxide (H2O2) levels were increased. Taken together, the results of the present study suggested that lutein may be a novel candidate for the chemoprevention of breast cancer. Furthermore, HES1 may be crucial in mediating the involvement of lutein in the suppression of hypoxia-driven ROS-induced breast cancer progression.

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PMID: 

Inflammopharmacology. 2019 Apr 29. Epub 2019 Apr 29. PMID: 31037573

Abstract Title: 

Neuroprotective and anti-inflammatory effects of isoliquiritigenin in kainic acid-induced epileptic rats via the TLR4/MYD88 signaling pathway.

Abstract: 

Epileptogenesis is a complex pathological process that occurs after an initial brain injury and involves a series of molecular events. Isoliquiritigenin (ISL), a flavonoid in licorice, is reported to have anti-inflammatory and antioxidant effects in various experimental models, but its specific roles and molecular mechanisms in the epileptogenic process following kainic acid (KA) treatment remain unclear. The purpose of this study was to explore the effects of ISL pretreatment in KA-induced epileptic rats and the underlying mechanisms. Our findings show that ISL pretreatment significantly attenuated the KA-induced expression of ionized calcium-binding adapter molecule 1 (IBα1)-labeled microglia (F = 97.29, p 

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PMID: 

BMC Neurosci. 2019 08 6 ;20(1):41. Epub 2019 Aug 6. PMID: 31387531

Abstract Title: 

Isoliquiritigenin attenuates lipopolysaccharide-induced cognitive impairment through antioxidant and anti-inflammatory activity.

Abstract: 

BACKGROUND: Oxidative stress and neuroinflammation are central pathogenic mechanisms common to many neurological diseases. Isoliquiritigenin (ISL) is a flavonoid in licorice with multiple pharmacological properties, including anti-inflammatory activity, and has demonstrated protective efficacy against acute neural injury. However, potential actions against cognitive impairments have not been examined extensively. We established a rat model of cognitive impairment by intracerebroventricular injection of lipopolysaccharide (LPS), and examined the effects of ISL pretreatment on cognitive function, hippocampal injury, and hippocampal expression of various synaptic proteins, antioxidant enzymes, pro-inflammatory cytokines, and signaling factors controlling anti-oxidant and pro-inflammatory responses.RESULTS: Rats receiving LPS alone demonstrated spatial learning deficits in the Morris water maze test as evidenced by longer average escape latency, fewer platform crossings, and shorter average time in the target quadrant than untreated controls. ISL pretreatment reversed these deficits as well as LPS-induced decreases in the hippocampal expression levels of synaptophysin, postsynaptic density-95, brain-derived neurotrophic factor, superoxide dismutase, glutathione peroxidase, and BCL-2. ISL pretreatment also reversed LPS-induced increases in TUNEL-positive (apoptotic) cells, BAX/BCL-2 ratio, and expression levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and C-C motif chemokine ligand 3. Pretreatment with ISL increased the expression levels of phosphorylated (p)-GSK-3β, nuclear NRF2, HO-1 mRNA, and NQO1 mRNA, and reversed LPS-induced nuclear translocation of nuclear factor (NF)-κB.CONCLUSIONS: ISL protects against LPS-induced cognitive impairment and neuronal injury by promoting or maintaining antioxidant capacity and suppressing neuroinflammation, likely through phosphorylation-dependent inactivation of GSK-3β, enhanced expression of NRF2-responsive antioxidant genes, and suppression of NF-κB-responsive pro-inflammatory genes.

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PMID: 

Cancers (Basel). 2019 Aug 7 ;11(8). Epub 2019 Aug 7. PMID: 31394829

Abstract Title: 

Isoliquiritigenin Suppresses E2-Induced Uterine Leiomyoma Growth through the Modulation of Cell Death Program and the Repression of ECM Accumulation.

Abstract: 

Uterine leiomyomas, also known as fibroids, are common and prevalent in women of reproductive age. In this study, the effect of Isoliquiritigenin (ISL), a licorice flavonoid, on the anti-proliferation of uterine leiomyoma was investigated. We found that the survival of uterine leiomyoma ELT3 cells and primary uterine smooth muscle (UtSMC) cells was reduced by treatment with ISL alone or with ISL plus estradiol (E2). Cell cycles were arrested through the reduction of G2/M- and S-phase populations in ELT3 and UtSMC cells, respectively. Furthermore, increased sub-G1 phase and nucleus condensation were observed in ELT3 cells but not in UtSMC cells. Co-treatment of ELT3 cells with E2 and ISL inhibited ERK1/2 activation, whereas p38 and c-Jun N-terminal kinase (JNK) activation was enhanced. Moreover, ISL-induced apoptosis and autophagy cell death in ELT3 cells were observed. Serum E2 and P4 levels were reduced in a E2-enhanced uterine myometrium hyperplasia mouse model by ISL treatment, which contributed to the downregulation of the expression of extracellular matrix (ECM) associated proteins and matrix metalloproteinase (MMPs). Taken together, these results showed that ISL exerted a higher effect on the inhibition of estrogen-induced uterine leiomyoma growth for both in vitro and in vivo ECM accumulation, demonstrating its potential as a new option for treatment of uterine leiomyoma.

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PMID: 

Saudi J Biol Sci. 2015 Jan ;22(1):75-84. Epub 2014 Aug 6. PMID: 25561888

Abstract Title: 

Experimental model for ELF-EMF exposure: Concern for human health.

Abstract: 

Low frequency (LF) electromagnetic fields (EMFs) are abundantly present in modern society and in the last 20 years the interest about the possible effect of extremely low frequency (ELF) EMFs on human health has increased progressively. Epidemiological studies, designed to verify whether EMF exposure may be a potential risk factor for health, have led to controversial results. The possible association between EMFs and an increased incidence of childhood leukemia, brain tumors or neurodegenerative diseases was not fully elucidated. On the other hand, EMFs are widely used, in neurology, psychiatry, rheumatology, orthopedics and dermatology, both in diagnosis and in therapy. In vitro studies may helpto evaluate the mechanism by which LF-EMFs affect biological systems. In vitro model of wound healing used keratinocytes (HaCaT), neuroblastoma cell line (SH-SY5Y) as a model for analysis of differentiation, metabolism and functions related to neurodegenerative processes, and monocytic cell line (THP-1) was used as a model for inflammation and cytokines production, while leukemic cell line (K562) was used as a model for hematopoietic differentiation. MCP-1, a chemokine that regulates the migration and infiltration of memory T cells, natural killer (NK), monocytes and epithelial cells, has beendemonstrated to be induced and involved in various diseases. Since, varying the parameters of EMFs different effects may be observed, we have studied MCP-1 expression in HaCaT, SH-SY5Y, THP-1 and K562 exposed to a sinusoidal EMF at 50 Hz frequency with a flux density of 1 mT (rms). Our preliminary results showed that EMF-exposure differently modifies the expression of MCP-1 in different cell types. Thus, the MCP-1 expression needs to be better determined, with additional studies, with different parameters and times of exposure to ELF-EMF.

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PMID: 

J Cutan Pathol. 2001 Nov ;28(10):513-9. PMID: 11737520

Abstract Title: 

Cutaneous mast cells are altered in normal healthy volunteers sitting in front of ordinary TVs/PCs–results from open-field provocation experiments.

Abstract: 

BACKGROUND: Considerable controversy has surrounded the question of possible biological responses to electromagnetic fields (EMFs) generated from visual display terminals (VDTs), such as personal computers (PCs) and ordinary television sets (TVs). The cellular and molecular mechanisms for such potential harmful health hazards have not yet been understood, although clues from the literature include mast cells and histamine. The aim of this study was therefore to investigate possible biological mast cell responses to TV/PC screens.METHODS: Using the indirect immunofluorescence technique, we studied the presence of histamine-containing mast cells in the dermis of healthy volunteers. Cutaneous biopsies taken before and after exposure to ordinary TV/PC screens for 2 or 4 h were investigated in 13 healthy subjects.RESULTS: Our present in vivo study indicates that normal cutaneous mast cells could be altered by exposure from ordinary TV/PC screens. To our great surprise, we found the number of mast cells in the papillary and reticular dermis to increase, to varying degrees, in 5 out the 13 subjects after such an exposure. A migration of mast cells towards the uppermost dermis appeared as the most important event. Thus, the normally upper"empty zone"of the dermis disappeared, and instead, a higher density of mast cells were found in this zone. These cells also seemed to have a tendency to increase in number towards the epidermal-dermal junctional zone and some of them lost their granular content and the cytoplasm shrunk (=degranulation). These findings could only be seen in the exposed skin. Two of the 13 cases instead showed a decrease in mast cell number, but the shift in mast cells towards the upper dermis was still visible. Twenty-four h after the provocation, the cellular number and location were normalized in all subjects.CONCLUSIONS: By definition, normal healthy volunteers are assumed not to react to a TV/PC screen provocation. To our great surprise, this proved not to be true. The present results might lay a foundation to understand the underlying cause of so-called"screen dermatitis"with special reference to mast cells. However, blind or double-blind experiments using patients ought to be further investigated in order to find out the exact cause for the observed changes. Such causes include the effects of surrounding airborne chemicals, stress factors, etc.

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PMID: 

Life Sci Space Res. 1970 ;8:177-87. PMID: 11826883

Abstract Title: 

The effects of electric fields on circadian rhythmicity in men.

Abstract: 

In an underground bunker built for the study of human circadian rhythms, one of the two experimental rooms is shielded against natural magnetic and electric fields. So far, autonomous rhythms of 82 subjects have been measured. As a result, the mean period value is lower in the non-shielded room than in the shielded room (significant with p

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PMID: 

PLoS One. 2017 ;12(5):e0175136. Epub 2017 May 4. PMID: 28472042

Abstract Title: 

Mobile phone use and glioma risk: A systematic review and meta-analysis.

Abstract: 

OBJECTIVE: Many studies have previously investigated the potential association between mobile phone use and the risk of glioma. However, results from these individual studies are inconclusive and controversial. The objective of our study was to investigate the potential association between mobile phone use and subsequent glioma risk using meta-analysis.METHODS: We performed a systematic search of the Science Citation Index Embase and PubMed databases for studies reporting relevant data on mobile phone use and glioma in 1980-2016. The data were extracted and measured in terms of the odds ratio (OR) and 95% confidence interval (CI) using the random effects model. Subgroup analyses were also carried out. This meta-analysis eventually included 11 studies comprising a total 6028 cases and 11488 controls.RESULTS: There was a significant positive association between long-term mobile phone use (minimum, 10 years) and glioma (OR = 1.44, 95% CI = 1.08-1.91). And there was a significant positive association between long-term ipsilateral mobile phone use and the risk of glioma (OR = 1.46, 95% CI = 1.12-1.92). Long-term mobile phone use was associated with 2.22 times greater odds of low-grade glioma occurrence (OR = 2.22, 95% CI = 1.69-2.92). Mobile phone use of any duration was not associated with the odds of high-grade glioma (OR = 0.81, 95% CI = 0.72-0.92). Contralateral mobile phone use was not associated with glioma regardless of the duration of use. Similarly, this association was not observed when the analysis was limited to high-grade glioma.CONCLUSIONS: Our results suggest that long-term mobile phone use may be associated with an increased risk of glioma. There was also an association between mobile phone use and low-grade glioma in the regular use or long-term use subgroups. However, current evidence is of poor quality and limited quantity. It is therefore necessary to conduct large sample, high quality research or better characterization of any potential association between long-term ipsilateral mobile phone use and glioma risk.

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PMID: 

Mol Pharmacol. 2019 Aug 28. Epub 2019 Aug 28. PMID: 31462456

Abstract Title: 

Isoliquiritigenin, an orally available natural FLT3 inhibitor from licorice, exhibits selective anti-AML efficacy in vitro and in vivo.

Abstract: 

Licorice is a medicinal herb widely used to treat inflammation-related diseases in china. Isoliquiritigenin (ISL) is an important constituent of Licorice, and possesses multiple bioactivitys. In this study, we examined the selective anti-AML (Acute myeloid leukemia) property of ISL via targeting FLT3, a certified valid target for the treatment of AML. In vitro, ISL potently inhibited FLT3 kinase with an IC50 of 115.1± 4.2 nM, selectively inhibited the viability of FLT3-ITD or FLT3-ITD/F691L mutant AML cells, and showed very weak activity towards other tested cell lines or kinases.Western blotting detection revealed that ISL potently inhibited the activation of FLT3/Erk1/2/STAT5 signal in AML cells. Meanwhile,Molecular docking study indicated that ISL could stably form aromatic interactions and hydrogen bonds within the kinase domain of FLT3. In vivo, oral administration of ISL significantly inhibited the MV4-11 tumor growth and prolonged the survival time of bone marrow engraftment AML mice via decreasing the expression of Ki67, and induced apoptosis. Taken together, the present study identified a novel function of ISL as a selective FLT3 inhibitor to be a promising novel potential natural bioactive compound for the treatment of AML with FLT3-ITD or FLT3-ITD/F691L mutations. Thus, ISL and licoricemight posess potential therapeutic effects in the treatment of AML, and combining with other drugs maight provide more effective treatment strategy. SIGNIFICANCE STATEMENT: Isoliquiritigenin selectively inhibited the viability of FLT3-ITD mutant AML cells via targeting FLT3 Oral administration of Isoliquiritigenin could significantly inhibit in vivo tumor growth of AML cells in xenograft tumor model and bone marrow model with well tolerance. Isoliquiritigenin is an orally available natural FLT3 inhibitor from licorice. Isoliquiritigenin still retained a good inhibitory activity against FLT3-ITD/F691L mutation, a resistance kinase domain mutation against sorafenib and AC220.

I am a parent member of a diversity, equity and inclusion committee at the Portland Waldorf school in Oregon. We agreed to read “White Fragility: Why It’s So Hard for White People to Talk About Racism”, by Robin DiAngelo,[i]^⁠ which I found to be penetratingly accurate and helpful.

It helped me to understand better how to minimize my own defensiveness and sensitivity to racism so that I can actively participate in its undoing through better self-awareness of my own education, socialization, and biases, and that of my children. In other words, the task presented by this book is a fundamentally spiritual task: to know myself.

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