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PMID:  Cardiovasc Res. 2019 Feb 8. Epub 2019 Feb 8. PMID: 30753344Abstract Title:  Mesenchymal Stromal Cell-Derived Exosomes Attenuate Myocardial Ischemia-Reperfusion Injury through miR-182-Regulated Macrophage Polarization.Abstract:  Aims: Mesenchymal stem cells (MSCs) gradually become attractive candidates for cardiac inflammation modulation, yet understanding of the mechanism remains elusive. Strikingly, recent studies indicated that exosomes secreted by MSCs might be a novel mechanism for the beneficial effect of MSCs transplantation after myocardial infarction. We therefore explored the role of MSC-derived exosomes (MSC-Exo) in the immunomodulation of macrophages after myocardial ischemia/reperfusion (I/R) and its implications in cardiac injury repair.Methods and Results: Exosomes were isolated from the supernatant of MSCs using gradient centrifugation method. Administration of MSC-Exo to mice through intramyocardial injection after myocardial I/R reduced infarct size and alleviated inflammation level in heart and serum. Systemic depletion of macrophages with clodronate liposomes abolished the curative effects of MSC-Exo. MSC-Exo modified the polarization of M1 macrophages to M2 macrophages both in vivo and in vitro. miRNA-sequencing of MSC-Exo and bioinformatics analysis implicated miR-182 as a potent candidate mediator of macrophage polarization and TLR4 as a downstream target. Diminishing miR-182 in MSC-Exo partially attenuated its modulation of macrophage polarization. Likewise, knock down of TLR4 also conferred cardioprotective efficacy and reduced inflammation level in a mouse model of myocardial I/R.Conclusion: Our data indicates that MSC-Exo attenuates myocardial I/R injury in mice via shuttling miR-182 that modifies the polarization status of macrophages. This study sheds new light on the application of MSC-Exo as a potential therapeutic tool for myocardial I/R injury.

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Posted: February 18, 2019, 3:51 am
PMID:  J Cell Physiol. 2019 Feb 12. Epub 2019 Feb 12. PMID: 30756380Abstract Title:  Exosomes are the novel players involved in the beneficial effects of exercise on type 2 diabetes.Abstract:  Exosomes contain regulatory signals such as lipids, proteins, and nucleic acids which can be transferred to adjacent or remote cells to mediate cell-to-cell communication. Exercise is a positive lifestyle for metabolic health and a nonpharmacological treatment of insulin resistance and metabolic diseases. Moreover, exercise is a stressor that induces cellular responses including gene expression and exosome release in various types of cells. Exosomes can carry the characters of parent cells by their modified cargoes, representing novel mechanisms for the effects of exercise. Here, we present a review of exosomes as the perspective players in mediating exercise's beneficial impacts on type 2 diabetes (T2D).

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Posted: February 18, 2019, 3:23 am
PMID:  Technol Cancer Res Treat. 2019 Jan 1 ;18:1533033818821421. PMID: 30760122Abstract Title:  Exosomes: A Promising Avenue for the Diagnosis of Breast Cancer.Abstract:  Currently, despite the advances in individualized treatment, breast cancer still remains the deadliest form of cancer in women. Diagnostic, prognostic, and therapy-predictive methods are mainly based on the evaluation of tumor tissue samples and are aimed to improve the overall therapeutic level. Therefore, the exploration of a series of circulating biomarkers, which serve as the information source of tumors and could be obtained by peripheral blood samples, represents a high field of interest. Apart from classical biomarkers, exosomes, which are nanovesicles, are emerging as an accessible and efficient source of cell information. The purpose of this review is to summarize the peculiarities of the presently available breast cancer exosomal biomarkers; the review also provides the prediction of a multitude of potential target genes of exosomal microRNAs using 4 databases.

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Posted: February 18, 2019, 3:15 am
PMID:  Crit Care. 2019 Feb 13 ;23(1):44. Epub 2019 Feb 13. PMID: 30760290Abstract Title:  Exosomes from endothelial progenitor cells improve outcomes of the lipopolysaccharide-induced acute lung injury.Abstract:  BACKGROUND: The acute respiratory distress syndrome (ARDS) is characterized by disruption of the alveolar-capillary barrier resulting in accumulation of proteinaceous edema and increased inflammatory cells in the alveolar space. We previously found that endothelial progenitor cell (EPC) exosomes prevent endothelial dysfunction and lung injury in sepsis in part due to their encapsulation of miRNA-126. However, the effects of EPC exosomes in acute lung injury (ALI) remain unknown.METHODS: To determine if EPC exosomes would have beneficial effects in ALI, intratracheal administration of lipopolysaccharide (LPS) was used to induce ALI in mice. Lung permeability, inflammation, and the role of miRNA-126 in the alveolar-epithelial barrier function were examined.RESULTS: The intratracheal administration of EPC exosomes reduced lung injury following LPS-induced ALI at 24 and 48 h. Compared to placebo, intratracheal administration of EPC exosomes significantly reduced the cell number, protein concentration, and cytokines/chemokines in the bronchoalveolar lavage fluid (BALF), indicating a reduction in permeability and inflammation. Further, EPC exosomes reduced myeloperoxidase (MPO) activity, lung injury score, and pulmonary edema, demonstrating protection against lung injury. Murine fibroblast (NIH3T3) exosomes, which do not contain abundant miRNA-126, did not provide these beneficial effects. In human small airway epithelial cells (SAECs), we found that overexpression of miRNA-126-3p can target phosphoinositide-3-kinase regulatory subunit 2 (PIK3R2), while overexpression of miRNA-126-5p inhibits the inflammatory alarmin HMGB1 and permeability factor VEGFα. Interestingly, both miR-126-3p and 5p increase the expression of tight junction proteins suggesting apotential mechanism by which miRNA-126 may mitigate LPS-induced lung injury.CONCLUSIONS: Our data demonstrated that human EPC exosomes are beneficial in LPS-induced ALI mice, in part through the delivery of miRNA-126 into the injured alveolus.

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Posted: February 18, 2019, 3:11 am
PMID:  Stem Cell Res Ther. 2019 Feb 15 ;10(1):60. Epub 2019 Feb 15. PMID: 30770778Abstract Title:  Exosomes from glioma cells induce a tumor-like phenotype in mesenchymal stem cells by activating glycolysis.Abstract:  BACKGROUND: Exosomes are nanoscale membrane vesicles secreted by both normal and cancer cells, and cancer cell-derived exosomes play an important role in the cross-talk between cancer cells and other cellular components in the tumor microenvironment. Mesenchymal stem cells (MSCs) have tropism for tumors and have been used as tumor-tropic vectors for tumor therapy; however, the safety of such therapeutic use of MSCs is unknown. In this study, we investigated the role of glioma cell-derived exosomes in the tumor-like phenotype transformation of human bone marrow mesenchymal stem cells (hBMSCs) and explored the underlying molecular mechanisms.METHODS: The effect of exosomes from U251 glioma cells on the growth of hBMSCs was evaluated with the CCK-8 assay, KI67 staining, and a cell cycle distribution assessment. The migration and invasion of hBMSCs were evaluated with a Transwell assay. A proteomics and bioinformatics approach, together with Western blotting and reverse transcriptase-polymerase chain reaction, was used to investigate the effect of U251 cell-derived exosomes on the proteome of hBMSCs.RESULTS: U251 cell-derived exosomes induced a tumor-like phenotype in hBMSCs by enhancing their proliferation, migration, and invasion and altering the production of proteins involved in the regulation of the cell cycle. Moreover, U251 cell-derived exosomes promoted the production of the metastasis-related proteins MMP-2 and MMP-9, glioma marker GFAP, and CSC markers (CD133 and Nestin). The ten differentially expressed proteins identified participated in several biological processes and exhibited various molecular functions, mainly related to the inactivation of glycolysis. Western blotting showed that U251 cell-derived exosomes upregulated the levels of Glut-1, HK-2, and PKM-2, leading to the induction of glucose consumption and generation of lactate and ATP. Treatment with 2-deoxy-D-glucose significantly reversed these effects of U251 cell-derived exosomes on hBMSCs.CONCLUSIONS: Our data demonstrate that glioma cell-derived exosomes activate glycolysis in hBMSCs, resulting in their tumor-like phenotype transformation. This suggests that interfering with the interaction between exosomes and hBMSCs in the tumor microenvironment has potential as a therapeutic approach for glioma.ᅟ.

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Posted: February 18, 2019, 3:06 am
PMID:  Biomaterials. 2019 Feb 8 ;200:35-47. Epub 2019 Feb 8. PMID: 30771585Abstract Title:  MSC exosomes alleviate temporomandibular joint osteoarthritis by attenuating inflammation and restoring matrix homeostasis.Abstract:  The efficacy of mesenchymal stem cell (MSC) therapies is increasingly attributed to paracrine secretion, particularly exosomes. In this study, we investigated the role of MSC exosomes in the regulation of inflammatory response, nociceptive behaviour, and condylar cartilage and subchondral bone healing in an immunocompetent rat model of temporomandibular joint osteoarthritis (TMJ-OA). We observed that exosome-mediated repair of osteoarthritic TMJs was characterized by early suppression of pain and degeneration with reduced inflammation, followed by sustained proliferation and gradual improvements in matrix expression and subchondral bone architecture, leading to overall joint restoration and regeneration. Using chondrocyte cultures, we could attribute some of the cellular activities during exosome-mediated joint repair to adenosine activation of AKT, ERK and AMPK signalling. Specifically, MSC exosomes enhanced s-GAG synthesis impeded by IL-1β, and suppressed IL-1β-induced nitric oxide and MMP13 production. These effects were partially abrogated by inhibitors of adenosine receptor activation, AKT, ERK and AMPK phosphorylation. Together, our observations suggest that MSC exosomes promote TMJ repair and regeneration in OA through a well-orchestrated mechanism of action that involved multiple cellular processes to restore the matrix and overall joint homeostasis. This study demonstrates the translational potential of a cell-free ready-to-use exosome-based therapeutic for treating TMJ pain and degeneration.

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Posted: February 18, 2019, 3:02 am
PMID:  Cancer Lett. 2019 Feb 13. Epub 2019 Feb 13. PMID: 30771430Abstract Title:  Milk exosomes - Natural nanoparticles for siRNA delivery.Abstract:  Gene-silencing with targeted siRNAs has great potential as a therapeutic approach for various diseases including cancer. However, intracellular delivery of siRNA is challenging. We used bovine milk exosomes as a novel system for siRNA delivery. First, we demonstrated that exosomes can deliver endogenous RNA payloads into recipient cells. Next, we loaded siRNA against specific genes including VEGF, EGFR, AKT, MAPK, and KRAS. We utilized 5'P-labeled siKRAS as a tracer and found exosome loading with siRNA could be variable. We demonstrated that the siRNA of loaded exosomes is stable and resist degradation. Our results indicated that siRNAs against target genes ranged from 2-10-fold knockdown in expression levels in various cancers. Since mutated KRAS has been implicated in the development of various cancers including lung cancer, we tested a mutant-allele specific siRNA against KRAS, in A549 cells. We observed a dose-dependent anti-proliferative activity against A549 cells treated with exosomes carrying siKRAS. We observed significant inhibition of A549 tumor xenografts in animals treated with folic acid-functionalized exosomes carrying siKRAS. In summary, milk-derived exosomes represent a viable natural nano-carrier for the delivery of siRNA for therapeutic application against cancer.

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Posted: February 18, 2019, 2:37 am
This article is copyrighted by GreenMedInfo LLC, 2019
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The idea of “food as medicine” may be a bit hard to swallow, especially if you have a gourmand’s palate. What if you could fight a host of diseases and even increase your longevity, just by adding a few delicious servings of fungus to your diet every day?  

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Posted: February 18, 2019, 2:11 am
PMID:  Mediators Inflamm. 2018 ;2018:3403972. Epub 2018 Dec 17. PMID: 30647533Abstract Title:  Grape Seed Proanthocyanidin Extract Inhibits Human Esophageal Squamous Cancerous Cell Line ECA109 via the NF-B Signaling Pathway.Abstract:  Esophageal squamous cell carcinoma is the most common type of squamous cell carcinoma. Grape seed proanthocyanidin extract (GSPE) is considered to exhibit anticancer activity against several different types of cancer. We aimed to determine whether GSPE inhibited esophageal squamous cancerous cells and the possible involvement of NF-B in this process. The human esophageal squamous cancer cell line ECA109 was treated with GSPE (0-80 g/mL) and BAY11-7082 (10 mol/L) for 12, 24, and 48 h. The MTT assay was used to determine cell proliferation; alterations in cell apoptosis were detected by flow cytometry; levels of inflammatory factors interleukin-6 and cyclooxygenase-2 and apoptotic proteins Bax/Bcl-2 were measured by ELISA; qRT-PCR and western blots were used to examine the activation of caspase-3 and NF-B signaling. GSPE inhibited the proliferation of ECA109 cells and induced cellular apoptosis in a time- and dose-dependent manner. ELISA results showed that GSPE and BAY11-7082 reduced the secretion of inflammatory cytokines interleukin-6 and cyclooxygenase-2. The results of PCR and western blotting indicated that GSPE and BAY11-7082 activated caspase-3 and attenuated the activation of the NF-B signaling pathway. GSPE induced apoptosis in ECA109 cells and inhibited ECA109 cell proliferation via a reduction in the secretion of inflammatory cytokines. This mechanism may be related to the attenuation of NF-B activity and the sensitization of caspase-3.

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Posted: February 16, 2019, 6:26 am
PMID:  Phytother Res. 2019 Jan 17. Epub 2019 Jan 17. PMID: 30653759Abstract Title:  Vitis vinifera (grape) seed extract and resveratrol alleviate bisphenol-A-induced metabolic syndrome: Biochemical and molecular evidences.Abstract:  The mechanisms of bisphenol-A (BPA)-induced metabolic syndrome as well as the protective role of grape seed extract (GSE) and resveratrol were investigated. Rats were treated with BPA (0 and 35 mg·kg·day, gavage) plus resveratrol (25, 50, and 100 mg·kg·day, i.p.) or GSE (3, 6, 12 mg·kg·day, i.p.) or vitamin E (200 IU/kg/every other day, i.p.). After 2 months, mean systolic blood pressure, serum lipid profile, glycaemia, and fat index were examined. By enzyme-linked immunosorbent assay, the serum concentrations of insulin, leptin, adiponectin, and paraoxonase 1, and by real-time polymerase chain reaction aswell as western blotting, key liver elements in cholesterol hemostasis (LDLR, CYP7A1, ABCG5 and 8) and insulin signaling (p-Akt/Akt and p-PI3K/PI3K) were measured. BPA increased mean systolic blood pressure, total cholesterol, and low-density lipoprotein cholesterol and reduced paraoxonase1 and thehepatic expression of both ABCG5 and ABCG8. It increased the body fat index, leptin, adiponectin, insulin, and glycaemia level and decreased the hepatic protein expression of p-Akt/Akt and p-PI3K/PI3k. GSE, resveratrol, or vitamin E coadministration along with BPA restored the detrimental effects of BPA in some levels. Herein, the predisposing effects of BPA-induced metabolic syndrome were restored by GSE and resveratrol, linked to the regulation of insulin signaling, ABCG8 expression, and their antioxidant properties.

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Posted: February 16, 2019, 5:59 am
PMID:  Food Environ Virol. 2019 Mar ;11(1):90-95. Epub 2019 Jan 25. PMID: 30684236Abstract Title:  Antiviral Activity of Essential Oils Against Hepatitis A Virus in Soft Fruits.Abstract:  Berries have repeatedly been associated with outbreaks of hepatitis A virus (HAV) infection. The fruits are usually minimally processed in the food industry due to their delicate nature. While washing treatments partially remove enteric viruses, the commonly used chemical additives produce toxic by-products. A valid alternative to preserve the food safety of these products could be the use of essential oils (EOs). EOs exert antimicrobial activity and do not interfere with the nutritional characteristics of food products. We investigated the efficacy of four essential oils, lemon (Citrus limon), sweet orange (Citrus sinensis), grapefruit (Citrus paradisi), and rosemary cineole (Rosmarinus officinalis chemotype 1.8 cineole) in reducing viral loads of HAV in soft fruits. Mixed fruit berries were inoculated with 10TCID/ml of HAV, and treated with four different EOs (0.5% lemon, 0.1% sweet orange and grapefruit, and 0.05% rosemary) for 1 h at room temperature. Virus infectivity was then assessed by titration assays for its ability to grow on cell cultures. A statistically significant reduction in HAV titer on the fruit surface was observed after treating the berries with EOs of lemon (2.84 log TCID/ml), grapefruit (2.89 log TCID/ml), and rosemary cineole (2.94 log TCID/ml). Rosemary cineole was the most effective EO in reducing viral titer on berries, followed by grapefruit EO. These results improve our knowledge about the antiviral activity of these EOs and highlight their potential use in fresh produce sanitation.

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Posted: February 16, 2019, 5:54 am
PMID:  J Vet Med Sci. 2019 Feb 4. Epub 2019 Feb 4. PMID: 30713281Abstract Title:  Inhibitory effect of grapefruit seed extract (GSE) on avian pathogens.Abstract:  The inhibitory activities of grapefruit seed extract (GSE) on avian influenza virus (AIV), Newcastle disease virus (NDV), infectious bursal disease virus (IBDV), Salmonella Infantis (SI) and Escherichia coli (EC) were evaluated. Original GSE contained 0.24% benzalkonium chloride (BZC), however, 0.0025% BZC solution could not inactivate bacteria. The activity of diluted GSE (×100, ×500 and ×1,000 with redistilled water) against selected viruses and bacteria was evaluated in this study. The GSE solutions were incubated with the pathogens over a period of time after which the remaining viruses were titrated and the bacterial colonies were counted. In the presence of organic material-5% fetal bovine serum (FBS), the test solutions were sprayed at 1 cm and 30 cm distances to test the efficacy of GSE in a spray form. Furthermore, the efficacy of GSE against bacteria on clothes was tested using non-woven cloth. GSE×100 reduced the viral titer of both AIV and NDV even in 5% FBS condition. IBDV showed high resistance to GSE. GSE×1,000 inactivated both SI and EC within 5 sec, even in the presence of 5% FBS. The disinfectant was able to maintain its efficacy in the spray form at 30 cm distance. GSE was also effective against SI and EC inoculated on fabric. GSE isa potential novel disinfectant against viruses and bacteria, effective even within a short contact time.

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Posted: February 16, 2019, 5:45 am
PMID:  Epilepsia. 2019 Feb 12. Epub 2019 Feb 12. PMID: 30747999Abstract Title:  Curcumin reduces development of seizurelike events in the hippocampal-entorhinal cortex slice culture model for epileptogenesis.Abstract:  OBJECTIVE: Inhibition of the mammalian target of rapamycin (mTOR) pathway could be antiepileptogenic in temporal lobe epilepsy (TLE), possibly via anti-inflammatory actions. We studied effects of the mTOR inhibitor rapamycin and the anti-inflammatory compound curcumin-also reported to inhibit the mTOR pathway-on epileptogenesis and inflammation in an in vitro organotypic hippocampal-entorhinal cortex slice culture model.METHODS: Brain slices containing hippocampus and entorhinal cortex were obtained from 6-day-old rat pups and maintained in culture for up to 3 weeks. Rapamycin or curcumin was added to the culture medium from day 2 in vitro onward. Electrophysiological recordings revealed epileptiformlike activity that developed over 3 weeks.RESULTS: In week 3, spontaneous seizurelike events (SLEs) could be detected using whole cell recordings from CA1 principal neurons. The percentage of recorded CA1 neurons displaying SLEs was lower in curcumin-treated slice cultures compared to vehicle-treated slices (25.8% vs 72.5%), whereas rapamycin did not reduce SLE occurrence significantly (52%). Western blot for phosphorylated-S6 (pS6) and phosphorylated S6K confirmed that rapamycin inhibited the mTOR pathway, whereas curcumin only lowered pS6 expression at one phosphorylation site. Real-time quantitative polymerase chain reaction results indicated a trend toward lower expression of inflammatory markers IL-1β and IL-6 and transforming growth factor β after 3 weeks of treatment with rapamycin and curcumin compared to vehicle.SIGNIFICANCE: Our results show that curcumin suppresses SLEs in the combined hippocampal-entorhinal cortex slice culture model and suggest that its antiepileptogenic effects should be further investigated in experimental models of TLE.

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Posted: February 16, 2019, 5:38 am
PMID:  Curr Cancer Drug Targets. 2019 Feb 12. Epub 2019 Feb 12. PMID: 30747066Abstract Title:  Anti-cancer effects of curcumin on myelodysplastic syndrome through the inhibition of enhancer of zeste homolog-2 (EZH2).Abstract:  Enhancer of zeste homolog-2 (EZH2), a histone methyltransferase that regulates histone H3 methylation of lysine27 (H3K27me3), is involved in the pathogenesis of myelodysplastic syndrome (MDS). Targeting epigenetic regulators has been identified as a potential treatment target in MDS chemotherapy. Curcumin, a natural compound extracted from turmeric, was found to possess a wide range of anticancer activities in various tumors. This study was designed to investigate the inhibitory effect and action mechanism of curcumin in myelodysplastic syndrome (MDS) in vitro and in vivo. Our results showed that curcumin can significantly suppress cell proliferation and induce cell apoptosis and cell cycle arrest in human MDS-derived cell lines. It reduced EZH2, DNA methyltransferase 3A(DNMT3a), ASXL1 and downstream H3K4me3, H3K27me3 and HOXA9 expression and inhibited EZH2 and H3K27me3 nuclear translocation. Curcumin also showed anti-cancer effects in a xenograft mouse model and reduced EZH2, H3K4me3 and H3K27me3 in vivo. EZH2 knockdown can reduce the H3K27me3 levels and induce curcumin resistance in vitro but attenuates leukemic transformation in vivo. These findings provide the potential molecular mechanism of curcumin as a therapeutic agent for MDS.

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Posted: February 16, 2019, 5:27 am
n/aPMID:  Cad Saude Publica. 2019 Feb 11 ;35(2):e00091618. Epub 2019 Feb 11. PMID: 30758455Abstract Title:  Human exposure to mercury and its hematological effects: a systematic review.Abstract:  Mercury is a metal found in the environment from natural and anthropogenic sources. It is highly toxic to ecosystems and living beings. Most human exposures come from ingestion of contaminated seafood, outgassing from dental amalgam or occupational exposure (e.g. gold mining), among other cases. Large populations are exposed to mercury, making it a very important issue from the public health perspective. Adverse health effects are commonly seen in the nervous system, but every organ is a potential target, such as the bone marrow. The main goal of this study was to assess the available evidence on human exposure to mercury and its hematological effects. A search strategy was constructed, including key terms (MeSH, text word and equivalents) for querying 2 repositories of master dissertation and PhD thesis (Fiocruz/ARCA and University of São Paulo) and 4 different electronic databases: BVS/LILACS, MEDLINE/PubMed, Scopus and TOXLINE/NIH, for articles published from 1950 to February 2018. There was no language restriction and a tool (EPHPP) was used to assess the quality of included studies. According to pre-established criteria, 80 studies were retrieved, all of them observational (48 case reports, 24 cross-sectional, 6 case series and 2 cohorts), comprising 9,284 people. Despite the fact that most exposed ones (6,012) had normal blood cell count and mercury hematological effects did not seem very usual (1,914 cases: 14 severeand 29 deaths), three studies reported association (β) for anemia, lymphopenia, neutrophilia and basophilia. We concluded that the gathered information pointed to mercury hematotoxic effects, some of them may be serious and even fatal.
Posted: February 16, 2019, 5:19 am
PMID:  Radiology. 2018 09 ;288(3):799-803. Epub 2018 Jun 26. PMID: 29944087Abstract Title:  Ex Vivo Mercury Release from Dental Amalgam after 7.0-T and 1.5-T MRI.Abstract:  Purpose To evaluate ex vivo mercury release from dental amalgam after 7.0-T and 1.5-T MRI. Materials and Methods The authors evaluated 60 caries-free molar or premolar teeth that had been extracted for clinical indications. Two-sided cavities were opened in each tooth and amalgam fillings applied. After 9 days, two groups of 20 randomly selected teeth were placed in 20 mL of artificial saliva immediately followed by 20 minutes of MRI exposure at 1.5 or 7.0 T. A control group of teeth was placed in artificial saliva without undergoing MRI exposure. The teeth were removed from the artificial saliva 24 hours later, and the saliva was analyzed for mercury content by using inductively coupled plasma mass spectrometry. One-way analysis of variance was used to compare the mean mercury values among the three independent groups, and the Tukey test was used for multiple comparisons of the mean values. Results The mean mercury content of the artificial saliva was 673μg/L ± 179 in the 7.0-T MRI group, 172 μg/L ± 60 in the 1.5-T MRI group, and 141 μg/L ± 152 in the control group. The mercury content in the 7.0-T group was greater than that in both the 1.5-T group (P

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Posted: February 16, 2019, 5:17 am
PMID:  Eur J Case Rep Intern Med. 2018 ;5(5):000844. Epub 2018 May 25. PMID: 30756034Abstract Title:  Statin-related Lichenoid Dermatosis: An Uncommon Adverse Reaction to a Common Treatment.Abstract:  : 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are generally safe and well-tolerated drugs that are extensively used for the primary and secondary prevention of atherosclerotic cardiovascular events. Muscle and liver adverse reactions are the best recognized, while cutaneous side effects are exceedingly rare. We present the case of a 65-year-old woman with severe hypercholesterolemia, who developed generalized erythematous cutaneous lesions with pruritus, resembling lichen planus, months after starting treatment with simvastatin. The symptoms disappeared on withdrawal of simvastatin and reappeared within 3 months upon rechallenge with rosuvastatin. In addition to describing a rare adverse effect of statins, the authors also discuss the nutraceutical approach to the management of a statin-intolerant patient.LEARNING POINTS: Lichenoid drug eruption is an uncommon cutaneous adverse effect of several drugs, with very few cases associated with statins.A temporal relationship, dechallenge/rechallenge information, and the lack of confounding factors or alternative explanations support the suggestion of causality.Due to the lack of optimized alternative treatment options for statin-intolerant patients, the nutraceutical approach should be considered.

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Posted: February 16, 2019, 5:10 am
PMID:  Phytomedicine. 2018 Dec 1 ;51:233-240. Epub 2018 Oct 10. PMID: 30466622Abstract Title:  Effect of Artemisia annua and Artemisia afra tea infusions on schistosomiasis in a large clinical trial.Abstract:  BACKGROUND AND OBJECTIVE: Schistosomiasis (bilharzia), a serious neglected tropical disease affecting millions, has few cost-effective treatments, so two Artemisia wormwood species, A. annua and A. afra, were compared with the current standard praziquantel (PZQ) treatment in an 800 patient clinical trial, August-November of 2015.METHODS: The double blind, randomized, superiority clinical trial had three treatment arms: 400 for PZQ, 200 for A. annua, and 200 for A. afra. PZQ-treated patients followed manufacturer posology. Artemisia-treated patients received 1 l/d of dry leaf/twig tea infusions divided into 3 aliquots daily, for 7 days with 28-day follow-up.RESULTS: Of 800 enrolled patients having an average of>700 Schistosoma mansoni eggs per fecal sample, 780 completed the trial. Within 14 days of treatment, all Artemisia-treated patients had no detectable eggs in fecal smears, a result sustained 28 days post treatment. Eggs in fecal smears of PZQ-treated patients were undetectable after D21. More males than females who entered the trial had melena, but both genders responded equally well to treatment; by D28 melena disappeared in all patients. In all arms, eosinophil levels declined by about 27% from D0 to D28. From D0 to D28 hemoglobin increases were greater in PZQ and A. afra-treated patients than in A. annua-treated patients. Hematocrit increases were greater from D0 to D28 for patients treated with either PZQ or A. annua compared to those treated with A. afra. Gender comparison showed that A. afra-treated males had significantly greater hemoglobin and hematocrit increases by D28 than either PZQ or A. annua-treated males. In contrast, PZQ and A. afra-treated females had greater hemoglobin and hematocrit increases than A. annua-treated females. Both adults and pediatric patients treated with A. annua responded better compared to PZQ treatment.CONCLUSION: Both A. annua and A. afra provided faster effective treatment of schistosomiasis and should be considered for implementation on a global scale.

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Posted: February 16, 2019, 5:04 am
PMID:  Biomed Pharmacother. 2019 Jan ;109:744-750. Epub 2018 Nov 5. PMID: 30551527Abstract Title:  Comparison of antidiabetic effects of saponins and polysaccharides from Momordica charantia L. in STZ-induced type 2 diabetic mice.Abstract:  Saponins as small organic molecules and polysaccharides as biomacromolecules are the main bioactive substances of Momordica charantia L. (M. charantia) with anti-hyperglycemic activities. This study was aimed to fully compare the antidiabetic effects and the potential mechanism of saponins (SMC) and polysaccharides (PMC) from M. charantia in STZ-induced type 2 diabetic mice with high-fat diet. Three dosages of SMC (L-SMC: 20 mg/kg, M-SMC: 40 mg/kg, H-SMC: 80 mg/kg) have a certain of therapeutic effect on type 2 diabetic mice, and M-SMC (40 mg/kg) is the optimal dosage for the prevention and treatment of diabetes. The results showed that oral administration of SMC, especially M-SMC (40 mg/kg) compared to PMC (500 mg/kg), could significantly restore the body weight, reduce fasting blood glucose levels, ameliorate insulin resistance and increase the proportion of hepatic phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK)/total protein. The above results proved that hypoglycemic mechanism of SMC might involve in the AMPK/NF-κB signal pathway by activating AMPK phosphorylation and regulating the energy metabolism of the body. However, oral administration of PMC could significant improve the antioxidant capacity by increasing the level of SOD and decreasing the level of MDA, andalleviate the STZ-induced organ tissues (kidney and pancreas), which proved that the hypoglycemic mechanism of PMC might by repairing the pancreatic β cells damaged by STZ.

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Posted: February 16, 2019, 4:54 am
PMID:  Food Funct. 2019 Jan 22 ;10(1):448-457. PMID: 30628614Abstract Title:  Polysaccharides from fermented Momordica charantia ameliorate obesity in high-fat induced obese rats.Abstract:  Momordica charantia (M. charantia) has been widely used to treat obesity due to its bioactive ingredients. This research aimed to investigate the anti-obesity effect of polysaccharides (FP) from fermented M. charantia with Lactobacillus plantarum NCU116 on high-fat induced obese rats. We found that FP could effectively lower the body weight gain, Lee's index, insulin resistance and cell sizes of epididymal adipose tissues in obese rats compared with polysaccharides from non-fermented M. charantia (NFP). FP treatments decreased the total cholesterol, triacylglycerols, and low-density lipoprotein cholesterol, leptin, whereas they elevated the high-density lipoprotein cholesterol, adiponectin, significantly in the serum of obese rats. Furthermore, administrations of FP notably improved oxidative balance in obese rats. Lipidomics results indicated that 24 potential biomarkers have been identified in serum. Additionally, 21 lipids were considerably altered by FP and NFP intakes, such as fatty acyls, glycerolipids, sphingolipids, sterol lipids and glycerophospholipids. The anti-obesity properties of FP were revealed via relieving insulin resistance and fat accumulation of obese rats, which was associated with the regulation of lipid metabolism. Overall, FP exerted more favourable impacts on the anti-obesity effect than NFP, which may be attributed to fermentation.

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Posted: February 16, 2019, 4:47 am
PMID:  Front Pharmacol. 2017 ;8:228. Epub 2017 Apr 27. PMID: 28496409Abstract Title:  Rapid Screening forα-Glucosidase Inhibitors fromby Affinity Ultrafiltration-HPLC-MS.Abstract:  R. Br. (Asclepiadaceae) has been known to posses potential anti-diabetic activity, and the gymnemic acids were reported as the main bioactive components in this plant species. However, the specific components responsible for the hypoglycemic effect still remain unknown. In the present study, thestudy revealed that the extract ofexhibited significant inhibitory activity againstα-glucosidase with ICat 68.70± 1.22 μg/mL compared to acarbose (positive control) at 59.03 ± 2.30 μg/mL, which further indicated the potential anti-diabetic activity. To this end, a method based on affinity ultrafiltration coupled with liquid chromatography mass spectrometry (UF-HPLC-MS) was established to rapidly screen and identify the α-glucosidase inhibitors from. In this way, 9 compounds with higher enrichment factors (EFs) were identified according to their MS/MS spectra. Finally, the structure-activity relationships revealed that glycosylation could decrease the potential antisweet activity of sapogenins, and other components except gymnemic acids incould also be goodα-glucosidase inhibitors due to their synergistic effects. Taken together, the proposed method combing α-glucosidase and UF-HPLC-MS presents high efficiency for rapidly screening and identifying potential inhibitors of α-glucosidase from complex natural products, and could be further explored asa valuable high-throughput screening (HTS) platform in the early anti-diabetic drug discovery stage.

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Posted: February 16, 2019, 4:42 am
PMID:  Am J Chin Med. 2017 ;45(4):813-832. Epub 2017 May 18. PMID: 28514906Abstract Title:  The Effects of Gymnema sylvestre in High-Fat Diet-Induced Metabolic Disorders.Abstract:  This study used an integrated approach to investigate the effects of Gymnema sylvestre (GS) extract as a functional dietary supplement with a high-fat diet. This approach examined insulin resistance, the dysfunction of adipose tissue, and liver steatosis. Male C57BL/6J mice were fed a normal chow or high-fat diet (HFD) for the acute and chronic study, in addition to GS in different doses (100, 250 and 500[Formula: see text]mg/kg body weight). Their body composition changes, serum lipid and glucose parameters, adipose and liver tissue histology, and gene expression were measured. It was found that GS significantly suppressed the increase of body weight, serum levels of lipid, insulin and leptin, and adipose tissue, and liver inflammation. GS also demonstrated hypoglycemic effects due to the amylase inhibition activity. Our results support the existence of a relationship between the HFD induced insulin resistance, adipose dysfunction and liver steatosis. In conclusion, GS works as a functional dietary supplement with preventative effects against metabolic disorder.

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Posted: February 16, 2019, 4:38 am
PMID:  Evid Based Complement Alternat Med. 2019 ;2019:7523159. Epub 2019 Jan 6. PMID: 30723516Abstract Title:  Chromatography Based Metabolomics andScreening ofLeaf Extract for Its Antidiabetic Potential.Abstract:  , popularly known as gurmar, is extensively used in traditional systems of medicine for diabetes, stomach ailments, liver diseases, and cardiac disorders. Dried leaf powder ofwas extracted through soxhlation using 70% (v/v) alcohol. The hydroalcoholic extract was concentrated to 1/4th of its volume and basified to isolate gymnemic acid enriched extract using chloroform. The isolated extract was checked for its antioxidant potential against 1, 1-diphenyl-2-picryl-hydrazyl (DPPH), which showed scavenging activity of 82.31% at 80 g/mL of extract. Quality control analysis of the extract was carried out by TLC. Chloroform and methanol (9.5:0.5, v/v) were used as a solvent system and separated compounds were detected at 254 and 366 nm. A total of 13 metabolites were separated. However, major peaks were at R0.12, 0.69, 0.79, and 0.85. Further, UPLC-MS fingerprinting of the extract was done using acetonitrile and 0.5% formic acid in water as mobile phase in gradient elution mode. A total of 21 metabolites were separated and tentatively identified from the database. Deacyl gymnemic acid and quercetin are the two major metabolites found in the extract. Gymnemic acid, deacyl gymnemic acid, and quercetin were docked with ten different proteins associated with glucose metabolism, transport, and glucose utilization. It has been observed that gymnemic acid was more potent than deacyl gymnemic acid in terms of binding affinity towards proteins and showed a favorable interaction with amino acid residues at the active site. Thus, the present study gives an insight of identified metabolites with protein interaction and a reason for the hypoglycemic potential of deacyl gymnemic acid enriched extract, which can be further explored forandstudies to establish its phytopharmacological and therapeutic effect.

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Posted: February 16, 2019, 4:29 am
PMID:  J Ayurveda Integr Med. 2019 Jan 17. Epub 2019 Jan 17. PMID: 30661947Abstract Title:  Ayurvedic polyherbal combination (PDBT) for prediabetes: A randomized double blind placebo controlled study.Abstract:  BACKGROUND: Increasing prevalence of type 2 diabetes mellitus (DM) has become alarming, burdening health care systems throughout the world. Prediabetes is an intermediate step before manifestation of full blown DM. Effective intervention at this step would help stop/slow progression to DM.OBJECTIVE: This study aimed at use of a polyherbal combination (PDBT - constituted of Tinospora cordifolia, Pterocarpus marsupium, Gymnema sylvestre, Zingiber officinale and Momordica charantia) along with life style modification compared to a placebo in prevention of DM among prediabetic individuals.MATERIALS AND METHODS: The study was a double blinded, placebo controlled randomized clinical trial. Participants were divided in to a group on PDBT and life style management (LSM) and second on placebo and LSM. Participants in the intervention group received 2 gm/day of PDBT. All participants received the intervention for a period of 6 months.RESULTS: One hundred and fourteen participants were enrolled in the study, 57 each in intervention and control group. At the end of the study, 8 participants from the intervention group, compared to 15 participants in the control group had converted to DM. There was a 47% risk reduction in the intervention group. Participants in the intervention group showed statistically significant decrease in their blood glucose level (fasting and PP), HbA1c, fasting serum insulin and HOMA-IR values. There was no significant change in BMI. No adverse effects were reported by any participants.CONCLUSION: PDBT along with LSM in prediabetic participants was associated with reduction in conversion to DM than placebo along with LSM without any adverse effects.

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Posted: February 16, 2019, 4:20 am
PMID:  Nutr Cancer. 2018 Feb-Mar;70(2):297-305. Epub 2018 Jan 4. PMID: 29300111Abstract Title:  Elaeagnus angustifolia Plant Extract Inhibits Angiogenesis and Downgrades Cell Invasion of Human Oral Cancer Cells via Erk1/Erk2 Inactivation.Abstract:  Oral cancer is a common malignancy in both men and women worldwide; this cancer is characterized by a marked propensity for invasion and spreading to local lymph nodes. On the other hand, Elaeagnus angustifolia (EA) is a medicinal plant that has been used for centuries for treating many human diseases in the Middle East. However, the effect of EA plant extract on human cancers especially oral has not been investigated yet. Thus, first we examined the outcome of EA flower extract on angiogenesis, using the chorioallantoic membrane (CAM) of the chicken embryo; we found that EA extract reduces blood vessel development of the CAM. Then, we investigated the effect of EA flower extract on selected parameters in FaDu and SCC25 oral cancer cell lines. Our results show that EA extract inhibits cell proliferation and colony formation, in addition to the initiation of S cell cycle arrest and reduction of G1/G2 phase. In parallel, EA extract provokes differentiation to an epithelial phenotype"mesenchymal-to-epithelial transition: MET"which is the opposite of"epithelial-to-mesenchymal transition, EMT": an important event in cell invasion and metastasis. Thus, EA plant extract causes a dramatic decrease in cell invasion and motility abilities of FaDu and SCC25 cancer cells in comparison with their controls. These changes are accompanied by an upregulation of E-cadherin expression. The molecular pathway analysis of the EA flower extract reveals that it can inhibit the phosphorylation of Erk1/Erk2, which could be behind the inhibition of angiogenesis, the initiation of MET event, and the overexpression of E-cadherin. Our findings indicate that EA plant extract can reduce human oral cancer progression by the inhibition of angiogenesis and cell invasion via Erk1/Erk2 signaling pathways.

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Posted: February 16, 2019, 3:25 am
Content Was Refreshed: 18 Feb 2019 | 12:47:07

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