PMID: 

Plant Physiol. 2019 03 ;179(3):969-985. Epub 2018 Nov 5. PMID: 30397021

Abstract Title: 

Identification and Microbial Production of the Raspberry Phenol Salidroside that Is Active against Huntington's Disease.

Abstract: 

Edible berries are considered to be among nature's treasure chests as they contain a large number of (poly)phenols with potentially health-promoting properties. However, as berries contain complex (poly)phenol mixtures, it is challenging to associate any interesting pharmacological activity with a single compound. Thus, identification of pharmacologically interesting phenols requires systematic analyses of berry extracts. Here, raspberry (, var Prestige) extracts were systematically analyzed to identify bioactive compounds against pathological processes of neurodegenerative diseases. Berry extracts were tested on differentstrains expressing disease proteins associated with Alzheimer's, Parkinson's, or Huntington's disease, or amyotrophic lateral sclerosis. After identifying bioactivity against Huntington's disease, the extract was fractionated and the obtained fractions were tested in the yeast model, which revealed that salidroside, a glycosylated phenol, displayed significant bioactivity. Subsequently, a metabolic route to salidroside was reconstructed inandThe best-performingstrain was capable of producing 2.1 mm (640 mg L) salidroside from Glc in shake flasks, whereas an engineeredstrain could efficiently convert the precursor tyrosol to salidroside, accumulating up to 32 mm (9,700 mg L) salidroside in bioreactor cultivations (yield: 0.81 mol mol). Targeted yeast assays verified that salidroside produced by both organisms has the same positive effects as salidroside of natural origin.

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PMID: 

Altern Ther Health Med. 2006 Jul-Aug;12(4):16-7. PMID: 16862738

Abstract Title: 

Are mercury amalgam fillings safe for children? An evaluation of recent research results.

Abstract: 

Two recent clinical trials on the safety of amalgam fillings in children found no evidence of harmful effects from mercury-containing dental fillings after following children for 5-7 years. This review suggests the studies' results are limited by (1) sample sizes that were too small to allow detection of genetic variations in mercury toxicity at a rate of 1 in 100 or lower, (2) a lack of control for other sources of mercury, and (3) a population that may have been skewed by excluding children with autism during a time when autism was escalating due, in part, to increased frequency of thimerosal-containing vaccine use.

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PMID: 

Food Chem Toxicol. 2019 Jan ;123:443-452. Epub 2018 Nov 5. PMID: 30408537

Abstract Title: 

Evaluation of Rubus grandifolius L. (wild blackberries) activities targeting management of type-2 diabetes and obesity using in vitro models.

Abstract: 

Rubus grandifolius Lowe (wild blackberries) is an endemic species from Madeira Archipelago (Portugal) used in folk medicine for alleviating diabetic complications. In this work, R. grandifolius methanolic extracts were analysed for in vitro inhibitory effect on digestive enzymes linked to type-2 diabetes, as well as aldose reductase activity and protein glycation. The phenolic composition, antioxidant and cytotoxic activities were also determined. Methanolic extracts exhibited strong inhibition of glucosidases (α- and β), but were less potent for α-amylase and pancreatic lipase when compared to current pharmaceutical drugs. The total phenolic content determined by HPLC-DAD varied between 92.96 – 97.47 and 118.01-137.41 mg gof dry extract for berries and leaves, respectively. Fifty polyphenols were quantified, anthocyanins and ellagitannins being the main compounds. Cyanidin-3-glucoside was identified as one of the main hypoglycaemic and hypolipidemic agents in all extracts. R. grandifolius also prevented glycation of bovine-serum albumin (BSA) and showed strong radical scavenging activity against tested free radicals. At low concentration, the extracts were not cytotoxic against Caco-2 cells. Based on the results of this study, wild blackberry extracts demonstrated a potential beneficial effect on the control/management of type-2 diabetes mellitus, validating their use in folk medicine.

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Google is simply not ranking any sites that are not on their “approved” list. Whether they did this through algorithm or manually is irrelevant, as the results are the same

PMID: 

J Appl Toxicol. 2006 Nov-Dec;26(6):536-9. PMID: 17080402

Abstract Title: 

Comparison of organic and inorganic mercury distribution in suckling rat.

Abstract: 

Thiomersal is used as a preservative in vaccines given to small children. The metabolic product of thiomersal is ethylmercury and its distribution and kinetics are still not known, especially at this early age. The purpose of this study was to compare the body distribution of two forms of mercury: organic (thiomersal) and inorganic (mercury(2+) chloride) in very young, suckling rats. Mercury was applied subcutaneously three times during the suckling period on days 7, 9 and 11 of pups age, imitating the vaccination of infants. A single dose of mercury was equimolar in both exposed groups, i.e. 0.81 micromol Hg kg(-1). At 14 days of age the animals were killed and the total mercury analysed in blood and organs (kidney, liver and brain). The analytical method applied was total decomposition, amalgamation, atomic absorption spectrometry. The results showed that the level of mercury was higher in the liver and kidney of the inorganic mercury group than in the thiomersal exposed group. However, the brain and blood concentrations of mercury were higher in the thiomersal exposed group. These results need to be clarified by additional data on the kinetic pathways of ethylmercury compared with inorganic mercury.

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PMID: 

Biol Trace Elem Res. 2019 Aug 24. Epub 2019 Aug 24. PMID: 31446563

Abstract Title: 

Boron, a Trace Mineral, Alleviates Gentamicin-Induced Nephrotoxicity in Rats.

Abstract: 

The present study was considered to assess the protective effects of boron (B) on gentamicin-induced oxidative stress, proinflammatory cytokines, and histopathological changes in rat kidneys. Rats were split into eight equal groups which were as follows: control (fed with low-boron diet); gentamicin group (100 mg/kg, i.p.); B, B, and B(5, 10, and 20 mg/kg B, i.p.) groups; gentamicin (100 mg/kg, i.p.) plus B, B, and B(5, 10, and 20 mg/kg B, i.p.) groups. B was given to rats 4 days before the gentamicin treatment and B administration was completed on the 14th day. Gentamicin administration was started on the 4th day and finished on the 12th day. Gentamicin increased malondialdehyde levels, while reduced glutathione levels in the blood and kidney. Furthermore, superoxide dismutase and catalase activities of erythrocyte were decreased. Besides, serum and kidney nitric oxide and 8-dihydroxyguanidine levels were increased by gentamicin. Additionally, serum levels and kidney mRNA expressions of TNF-α, NFκB, IL-1β, and IFN-γ were found to be the highest in the gentamicin group. Histopathologically, interstitial hemorrhage and tubular necrosis were detected in the kidneys of the gentamicin group. Nonetheless, B administration reversed gentamicin-induced lipid peroxidation, antioxidant status, and inflammation. In conclusion, B has a preventive effect against gentamicin-induced nephrotoxicity and ameliorates kidney tissues of the rat.

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PMID: 

Arch Toxicol. 2019 Jul 30. Epub 2019 Jul 30. PMID: 31363819

Abstract Title: 

Aluminum affects neural phenotype determination of embryonic neural progenitor cells.

Abstract: 

Aluminum (Al) is a neurotoxin and is associated with the etiology of neurodegenerative diseases, such as Alzheimer's disease (AD). The Al-free ion (Al) is the biologically reactive and toxic form. However, the underlying mechanisms of Al toxicity in the brain remain unclear. Here, we evaluated the effects of Al(in the chloride form-AlCl) at different concentrations (0.1-100 µM) on the morphology, proliferation, apoptosis, migration and differentiation of neural progenitor cells (NPCs) isolated from embryonic telencephalons, cultured as neurospheres. Our results reveal that Alat 100 µM reduced the number and diameter of neurospheres. Cell cycle analysis showed that Alhad a decisive function in proliferation inhibition of NPCs during neural differentiation and induced apoptosis on neurospheres. In addition, 1 µM Alresulted in deleterious effects on neural phenotype determination. Flow cytometry and immunocytochemistry analysis showed that Alpromoted a decrease in immature neuronal markerβ3-tubulin expression and an increase in co-expression of the NPC marker nestin and glial fibrillary acidic protein. Thus, our findings indicate that Alcaused cellular damage and reduced proliferation and migration, resulting in global inhibition of NPC differentiation and neurogenesis.

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PMID: 

Toxicol Sci. 2005 Jul ;86(1):132-40. Epub 2005 Apr 20. PMID: 15843506

Abstract Title: 

Effects of thimerosal on NGF signal transduction and cell death in neuroblastoma cells.

Abstract: 

Signaling through neurotrophic receptors is necessary for differentiation and survival of the developing nervous system. The present study examined the effects of the organic mercury compound thimerosal on nerve growth factor signal transduction and cell death in a human neuroblastoma cell line (SH-SY5Y cells). Following exposure to 100 ng/ml NGF and increasing concentrations of thimerosal (1 nM-10 microM), we measured the activation of TrkA, MAPK, and PKC-delta. In controls, the activation of TrkA MAPK and PKC-delta peaked after 5 min of exposure to NGF and then decreased but was still detectable at 60 min. Concurrent exposure to increasing concentrations of thimerosal and NGF for 5 min resulted in a concentration-dependent decrease in TrkA and MAPK phosphorylation, which was evident at 50 nM for TrkA and 100 nM for MAPK. Cell viability was assessed by the LDH assay. Following 24-h exposure to increasing concentrations of thimerosal, the EC50 for cell death in the presence or absence of NGF was 596 nM and 38.7 nM, respectively. Following 48-h exposure to increasing concentrations of thimerosal, the EC50 for cell death in the presence and absence of NGF was 105 nM and 4.35 nM, respectively. This suggests that NGF provides protection against thimerosal cytotoxicity. To determine if apoptotic versus necrotic cell death was occurring, oligonucleosomal fragmented DNA was quantified by ELISA. Control levels of fragmented DNA were similar in both the presence and absence of NGF. With and without NGF, thimerosal caused elevated levels of fragmented DNA appearing at 0.01 microM (apoptosis) to decrease at concentrations>1 microM (necrosis). These data demonstrate that thimerosal could alter NGF-induced signaling in neurotrophin-treated cells at concentrations lower than those responsible for cell death.

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PMID: 

Oxid Med Cell Longev. 2019 ;2019:9529676. Epub 2019 Jan 6. PMID: 30723535

Abstract Title: 

Red Raspberry Extract Protects the Skin against UVB-Induced Damage with Antioxidative and Anti-inflammatory Properties.

Abstract: 

Extensive exposure to UVB (280-320 nm) is the major risk responsible for various skin injuries. Numerous reports have shown that natural products could demonstrate photochemopreventive efficacy against UVB damage. We investigated the preventive effects and associated molecular mechanisms of red raspberry extract upon UVB-caused damage in human epidermal keratinocytes and a nude mouse model. The protein profiles and immunohistological study on a nude mouse skin indicated that red raspberry extract could prevent UVB-caused cell death and protect the skin against UVB-exposed injury manifested by wrinkling, scaling, tanning, andwater loss as well as epidermal thickening. In addition, red raspberry extract application effectively abolished oxidative damage in DNA and attenuated the carbonylation level of proteins, which attributed to the activation of SOD, Nrf2 and its target genes, and HO-1. Red raspberry extract also altered the cells' apoptotic signaling pathways including caspase-3 as well as the inflammatory cascade such as c-jun and attenuated UVB-induced activation of NF-B and COX-2. Red raspberry extract could alleviate direct photodamage to the skin caused by UVB exposure through the ROS scavenger and protection against inflammatory responses, which may allow the development of novel strategies in protecting the skin subjected to UVB radiation.

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PMID: 

Int J Toxicol. 2009 May-Jun;28(3):190-206. PMID: 19546257

Abstract Title: 

Calcium and calmodulin regulate mercury-induced phospholipase D activation in vascular endothelial cells.

Abstract: 

Earlier, we reported that mercury, the environmental risk factor for cardiovascular diseases, activates vascular endothelial cell (EC) phospholipase D (PLD). Here, we report the novel and significant finding that calcium and calmodulin regulated mercury-induced PLD activation in bovine pulmonary artery ECs (BPAECs). Mercury (mercury chloride, 25 microM; thimerosal, 25 microM; methylmercury, 10 microM) significantly activated PLD in BPAECs. Calcium chelating agents and calcium depletion of the medium completely attenuated the mercury-induced PLD activation in ECs. Calmodulin inhibitors significantly attenuated mercury-induced PLD activation in BPAECs. Despite the absence of L-type calcium channels in ECs, nifedipine, nimodipine, and diltiazem significantly attenuated mercury-induced PLD activation and cytotoxicity in BPAECs. This study demonstrated the importance of calcium and calmodulin in the regulation of mercury-induced PLD activation and the protective action of L-type calcium channel blockers against mercury cytotoxicity in vascular ECs, suggesting mechanisms of mercury vasculotoxicity and mercury-induced cardiovascular diseases.

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