Effect of apigenin on whole transcriptome profile of TNFα-activated MDA-MB-468 triple negative breast cancer cells.

PMID: 

Oncol Lett. 2020 Mar ;19(3):2123-2132. Epub 2020 Jan 22. PMID: 32194710

Abstract Title: 

Effect of apigenin on whole transcriptome profile of TNFα-activated MDA-MB-468 triple negative breast cancer cells.

Abstract: 

The lack of hormone receptors in triple negative breast cancer (TNBC) is associated with the inefficacy of anti-estrogen chemotherapies, leaving fewer options for patient treatment and higher mortality rates. Additionally, as with numerous types of inflammatory breast cancer, infiltration of tumor associated macrophages and other leukocyte sub-populations within the tumor inevitably lead to aggressive, chemo-resistant, metastatic and invasive types of cancer which escape immune surveillance. These processes are orchestrated by the release of potent cytokines, including TNFα, IL-6 and CCL2 from the stroma, tumor and immune cells within the tumor microenvironment. The present study evaluated apigenin modulating effects on the pro-inflammatory activating action of TNFα in TNBC MDA-MB-468 cells, derived from an African American woman. Initially, cell viability was determined to establish an optimal sub-lethal dose of TNFα and apigenin in MDA-MB-468 cells. Subsequently, various treatments effects were evaluated using whole transcriptomic analysis of mRNA and long intergenic non-coding RNA with Affymetrix HuGene-2.1-st human microarrays. Gene level differential expression analysis was conducted on 48,226 genes where TNFα caused significant upregulation of 53 transcripts and downregulation of 11 transcripts. The largest upward differential shift was for CCL2 [+61.86 fold change (FC); false discovery rate (FDR), P

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The genetic basis of high-carbohydrate and high-monosodium glutamate diet related to the increase of likelihood of type 2 diabetes mellitus.

PMID: 

Endocrine. 2020 Mar 14. Epub 2020 Mar 14. PMID: 32172486

Abstract Title: 

The genetic basis of high-carbohydrate and high-monosodium glutamate diet related to the increase of likelihood of type 2 diabetes mellitus: a review.

Abstract: 

Diabetes is one of the most common metabolic diseases. Aside from the genetic factor, previous studies stated that other factors such as environment, lifestyle, and paternal-maternal condition play critical roles in diabetes through DNA methylation in specific areas of the genome. One of diabetic cases is caused by insulin resistance and changing the homeostasis of blood glucose control so glucose concentration stood beyond normal rate (hyperglycemia). High fat diet has been frequently studied and linked to triggering diabetes. However, most Asians consume rice (or food with high carbohydrate) and food with monosodium glutamate (MSG). This habit could lead to pathophysiology of type 2 diabetes mellitus (T2D). Previous studies showed that high-carbohydrate or high-MSG diet could change gene expression or modify protein activity in body metabolism. This imbalanced metabolism can lead to pleiotropic effects of diabetes mellitus. In this study, the authors have attempted to relate various changes in genes expression or protein activity to the high-carbohydrate and high-MSG-induced diabetes. The authors have also tried to relate several genes that contribute to pathophysiology of T2D and proposed several ideas of genes as markers and target for curing people with T2D. These are done by investigating altered activities of various genes that cause or are caused by diabetes. These genes are selected based on their roles in pathophysiology of T2D.

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Medical Martial Law? DOJ Requests Suspension of Certain Constitutional Rights During Coronavirus Emergency

A concerning new report published in Rolling Stone titled, “DOJ Wants to Suspend Certain Constitutional Rights During Coronavirus Emergency,” reveals that the Department of Justice, under the auspices of protecting the public health from the threat of COVID-19, is attempting to suspend some of the most basic protections upon which the United States Constitution and our civil rights are founded. 

As summarized in the Rolling Stone article,

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Vitamin D deficiency aggravates hepatic oxidative stress and inflammation during chronic alcohol-induced liver injury.

PMID: 

Oxid Med Cell Longev. 2020 ;2020:5715893. Epub 2020 Feb 27. PMID: 32184917

Abstract Title: 

Vitamin D Deficiency Aggravates Hepatic Oxidative Stress and Inflammation during Chronic Alcohol-Induced Liver Injury in Mice.

Abstract: 

Vitamin D deficiency has been reported in alcoholics. This study is aimed at evaluating the effects of vitamin D deficiency on chronic alcohol-induced liver injury in mice. Mice were fed with modified Lieber-DeCarli liquid diets for 6 weeks to establish an animal model of chronic alcohol-induced liver injury. In the VDD+EtOH group, mice were fed with modified diets, in which vitamin D was depleted. Vitamin D deficiency aggravated alcohol-induced liver injury. Furthermore, vitamin D deficiency aggravated hepatocyte apoptosis during alcohol-induced liver injury. Although it has a little effect on hepatic TG content, vitamin D deficiency promoted alcohol-induced hepatic GSH depletion and lipid peroxidation. Further analysis showed that vitamin D deficiency further increased alcohol-induced upregulation of hepatic inducible nitric oxide synthase (), two NADPH oxidase subunitsand, and heme oxygenase- (HO-) 1. By contrast, vitamin D deficiency attenuated alcohol-induced upregulation of hepatic antioxidant enzyme genes, such as superoxide dismutase () 1 and. In addition, vitamin D deficiency significantly elevated alcohol-induced upregulation of hepatic proinflammatory cytokines and chemokines. Taken together, these results suggest that vitamin D deficiency aggravates hepatic oxidative stress and inflammation during chronic alcohol-induced liver injury.

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Weekly vitamin D3 supplementation improves aerobic performance in combat sport athletes.

PMID: 

Eur J Sport Sci. 2020 Mar 18:1-19. Epub 2020 Mar 18. PMID: 32188366

Abstract Title: 

Weekly Vitamin DSupplementation Improves Aerobic Performance in Combat Sport Athletes.

Abstract: 

Vitamin Dsupplementation can affect the strength and power of an athlete, however the effect on endurance performance remains unclear. Twenty-seven recreational male combat athletes with at least 12 months experience within combat sports were recruited (age: 24 ± 4 years, stature: 176 ± 6 cm, weight: 77 ± 14 kg). Participants completed baseline testing for blood haemoglobin and haematocrit, upper and lower body VOand upper and lower body Wingate. Following testing participants were stratified to 50000IU (D1), 80000IU (D2) or 110000IU (D3) of vitamin Dper week. They then completed a 6-week placebo period followed by a 6-week supplementation period. Retesting was carried out after the placebo and supplementation period. There was a significant effect for time for haemoglobin and haematocrit, upper and lower body VOand upper body Wingate power (p0.8). Therefore, there is no additional benefit to increasing dose above 500000IU vitamin D per week. Given the endurance adaptations from vitamin D supplementation and the importance of endurance for combat performance, recreational combat athletes should supplement at 50000IU per week for six weeks.

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Cannabidiol is an effective helper compound in combination with bacitracin to kill Gram-positive bacteria.

PMID: 

Sci Rep. 2020 Mar 5 ;10(1):4112. Epub 2020 Mar 5. PMID: 32139776

Abstract Title: 

Cannabidiol is an effective helper compound in combination with bacitracin to kill Gram-positive bacteria.

Abstract: 

The cannabinoid cannabidiol (CBD) is characterised in this study as a helper compound against resistant bacteria. CBD potentiates the effect of bacitracin (BAC) against Gram-positive bacteria (Staphylococcus species, Listeria monocytogenes, and Enterococcus faecalis) but appears ineffective against Gram-negative bacteria. CBD reduced the MIC value of BAC by at least 64-fold and the combination yielded an FIC index of 0.5 or below in most Gram-positive bacteria tested. Morphological changes in S. aureus as a result of the combination of CBD and BAC included several septa formations during cell division along with membrane irregularities. Analysis of the muropeptide composition of treated S. aureus indicated no changes in the cell wall composition. However, CBD and BAC treated bacteria did show a decreased rate of autolysis. The bacteria further showed a decreased membrane potential upon treatment with CBD; yet, they did not show any further decrease upon combination treatment. Noticeably, expression of a major cell division regulator gene, ezrA, was reduced two-fold upon combination treatment emphasising the impact of the combination on cell division. Based on these observations, the combination of CBD and BAC is suggested to be a putative novel treatment in clinical settings for treatment of infections with antibiotic resistant Gram-positive bacteria.

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Purified pharmaceutical CBD may be an effective and safe adjunctive therapy in refractory epileptic spasms.

PMID: 

Epilepsy Behav. 2020 Mar 10 ;106:106988. Epub 2020 Mar 10. PMID: 32169600

Abstract Title: 

Cannabidiol in treatment of refractory epileptic spasms: An open-label study.

Abstract: 

OBJECTIVE: This study aimed to evaluate clinical efficacy and safety of purified pharmaceutical cannabidiol (CBD) as an adjunctive therapy in refractory childhood-onset epileptic spasms (ES).METHODS: Nine patients with ES were enrolled in an Institutional Review Board (IRB)- and Food and Drug Administration (FDA)-approved expanded access investigational new drug trial. Patients received plant-derived highly purified CBD in oral solution in addition to their baseline medications at an initial dosage of 5 mg/kg/day, which was increased by 5 mg/kg/day every week to an initial target dosage of 25 mg/kg/day. Seizure frequency, adverse event, and parents' subjective reports of cognitive and behavioral changes were recorded after 2 weeks and 1, 2, 3, 6, 9, and 12 months of CBD treatment. Responder rates (percent of patients with>50% reduction in ES frequency from baseline) were calculated. Electrographic changes were studied in relation to CBD initiation and clinical response.RESULTS: Overall, the responder rates in 9 patients were 67%, 78%, 67%, 56%, 78%, 78%, and 78% after 2 weeks and 1, 2, 3, 6, 9, and 12 months of CBD treatment, respectively. Three out of nine patients (33%) were ES free after two months of treatment. Parents reported subjective improvements in cognitive and behavioral domains. Side effects, primarily drowsiness, were seen in 89% of patients (n = 8). Eight of the nine (89%) patients had electroencephalographic (EEG) studies prior to and after initiation of CBD. Three out of five patients (60%) had resolution in their hypsarrhythmia pattern.SIGNIFICANCE: Purified pharmaceutical CBD may be an effective and safe adjunctive therapy in refractory ES and may also be associated with improvements in electrographic findings.

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