A Tale of Two Medicines
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Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis

Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis | A Tale of Two Medicines | Scoop.it

Rheumatoid arthritis (RA) is a prevalent systemic autoimmune disease, caused by a combination of genetic and environmental factors. Animal models suggest a role for intestinal bacteria in supporting the systemic immune response required for joint inflammation. Here we performed 16S sequencing on 114 stool samples from rheumatoid arthritis patients and controls, and shotgun sequencing on a subset of 44 such samples. We identified the presence of Prevotella copri as strongly correlated with disease in new-onset untreated rheumatoid arthritis (NORA) patients. Increases in Prevotella abundance correlated with a reduction in Bacteroides and a loss of reportedly beneficial microbes in NORA subjects. We also identified unique Prevotella genes that correlated with disease. Further, colonization of mice revealed the ability of P. copri to dominate the intestinal microbiota and resulted in an increased sensitivity to chemically induced colitis. This work identifies a potential role for P. copri in the pathogenesis of RA.

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A Tale of Two Medicines
Natural Medicine, Pharmaceuticals and GMO’s, the Good, the Bad and the OMG! - (The information provided is not intended to be a substitute for professional medical advice, diagnosis or treatment.  Never disregard professional medical advice, or delay in seeking it, because of something you have read on this scoopit page.)
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Lectin of Abelmoschus esculentus (okra) promotes selective antitumor effects in human breast cancer cells.

Lectin of Abelmoschus esculentus (okra) promotes selective antitumor effects in human breast cancer cells. | A Tale of Two Medicines | Scoop.it
The anti-tumor effects of a newly-discovered lectin, isolated from okra, Abelmoschus esculentus (AEL), were investigated in human breast cancer (MCF7) and skin fibroblast (CCD-1059 sk) cells. AEL induced significant cell growth inhibition (63 %) in MCF7 cells. The expression of pro-apoptotic caspase-3, caspase-9, and p21 genes was increased in MCF7 cells treated with AEL, compared to those treated with controls. In addition, AEL treatment increased the Bax/Bcl-2 ratio in MCF7 cells. Flow cytometry also indicated that cell death (72 %) predominantly occurred through apoptosis. Thus, AEL in its native form promotes selective antitumor effects in human breast cancer cells and may represent a potential therapeutic to combat human breast cancer.
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Randomised clinical trial comparing melatonin 3 mg, amitriptyline 25 mg and placebo for migraine prevention

Randomised clinical trial comparing melatonin 3 mg, amitriptyline 25 mg and placebo for migraine prevention | A Tale of Two Medicines | Scoop.it

Melatonin has been studied in headache disorders. Amitriptyline is efficacious for migraine prevention, but its unfavourable side effect profile limits its use.

A randomised, double-blind, placebo-controlled study was carried out. Men and women, aged 18–65 years, with migraine with or without aura, experiencing 2–8 attacks per month, were enrolled. After a 4-week baseline phase, 196 participants were randomised to placebo, amitriptyline 25 mg or melatonin 3 mg, and 178 took a study medication and were followed for 3 months (12 weeks). The primary outcome was the number of migraine headache days per month at baseline versus last month. Secondary end points were responder rate, migraine intensity, duration and analgesic use. Tolerability was also compared between groups.

Mean headache frequency reduction was 2.7 migraine headache days in the melatonin group, 2.2 for amitriptyline and 1.1 for placebo. Melatonin significantly reduced headache frequency compared with placebo (p=0.009), but not to amitriptyline (p=0.19). Melatonin was superior to amitriptyline in the percentage of patients with a greater than 50% reduction in migraine frequency. Melatonin was better tolerated than amitriptyline. Weight loss was found in the melatonin group, a slight weight gain in placebo and significantly for amitriptyline users.

Melatonin 3 mg is better than placebo for migraine prevention, more tolerable than amitriptyline and as effective as amitriptyline 25 mg.

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Effects of Thymus vulgaris ethanolic extract on chronic toxoplasmosis in a mouse model. - PubMed - NCBI

Effects of Thymus vulgaris ethanolic extract on chronic toxoplasmosis in a mouse model. - PubMed - NCBI | A Tale of Two Medicines | Scoop.it
The current work was undertaken to investigate the potential effectiveness of Thymus vulgaris ethanolic extract (TVE) against Toxoplasma gondii infection in chronic experimental toxoplasmosis. To evaluate prophylactic effects, mice received 500 mg/kg TVE for 5 days before they were infected by an avirulent Me49 T. gondii strain. To investigate the therapeutic effects of the extract postinfection, daily treatment with TVE was initiated at 6 weeks postinfection and continued for 10 days. The following groups of animals were used as controls: uninfected/non-treated, infected/non-treated, and infected/treated with a combination of pyrimethamine and sulfadiazine. Brain cyst count and histopathological changes using H&E and Feulgen stains were used to evaluate the efficacy of TVE. The mean number of brain cysts was significantly decreased by 24 % in mice treated prophylactically with TVE. TVE also significantly reduced the mean number of brain cysts when administered to animals already chronically infected with T. gondii. The effect of TVE was comparable to that of treatment with a mixture of sulfadiazine and pyrimethamine (46 and 51 % reduction, respectively). Moreover, considerable amelioration of the pathological lesions in the brain and retina was observed. The results demonstrate the potential efficacy of T. vulgaris as a new natural therapeutic and prophylactic agent for use in the treatment of chronic toxoplasmosis.
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Whole plant based treatment of hypercholesterolemia with Crataegus laevigata in a zebrafish model

Whole plant based treatment of hypercholesterolemia with Crataegus laevigata in a zebrafish model | A Tale of Two Medicines | Scoop.it
The results of this study demonstrate that HLF are a promising treatment for hypercholesterolemia. We have created a vertebrate model system to test plant-based dietary intervention of hypercholesterolemia using the zebrafish. We utilized this model to demonstrate that HLF decrease intravascular CH levels and interact with cholesterol to improve CO in diseased fish. These results indicate that the cardiotonic action of hawthorn may depend on diet. Further work is needed to understand the detailed mechanism of how HLF exerts its influence. While hawthorn is not currently a recommended treatment for hypercholesterolemia, our research indicates it may be an effective treatment for this disease.
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Optimization of pulsed ultrasound-assisted technique for extraction of phenolics from pomegranate peel of Malas variety: Punicalagin and hydroxyben...

Optimization of pulsed ultrasound-assisted technique for extraction of phenolics from pomegranate peel of Malas variety: Punicalagin and hydroxyben... | A Tale of Two Medicines | Scoop.it
Pomegranate peel is a rich source of phenolic compounds (such as punicalagin and hydroxybenzoic acids). However, the content of such bioactive compounds in the peel extract can be affected by extraction type and condition. It was hypothesized that the optimization of a pulsed ultrasound-assisted extraction (PUAE) technique could result in the pomegranate peel extract with higher yield and antioxidant activity. The main goal was to optimize PUAE condition resulting in the highest yield and antioxidant activity as well as the highest contents of punicalagin and hydroxybenzoic acids. The operation at the intensity level of 105W/cm(2) and duty cycle of 50% for a short time (10min) had a high efficiency for extraction of phenolics from pomegranate peel. The application of such short extraction can save the energy and cost of the production. Punicalagin and ellagic acid were the most predominant phenolic compounds quantified in the pomegranate peel extract (PPE) from Malas variety. PPE contained a minor content of gallic acid.
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Lactobacillus rossiae, a vitamin B12 producer, represents a metabolically versatile species within the Genus Lactobacillus.

Lactobacillus rossiae is an obligately hetero-fermentative lactic acid bacterium, which can be isolated from a broad range of environments including sourdoughs, vegetables, fermented meat and flour, as well as the gastrointestinal tract of both humans and animals. In order to unravel distinctive genomic features of this particular species and investigate the phylogenetic positioning within the genus Lactobacillus, comparative genomics and phylogenomic approaches, followed by functional analyses were performed on L. rossiae DSM 15814T, showing how this type strain not only occupies an independent phylogenetic branch, but also possesses genomic features underscoring its biotechnological potential. This strain in fact represents one of a small number of bacteria known to encode a complete de novo biosynthetic pathway of vitamin B12 (in addition to other B vitamins such as folate and riboflavin). In addition, it possesses the capacity to utilize an extensive set of carbon sources, a characteristic that may contribute to environmental adaptation, perhaps enabling the strain's ability to populate different niches.
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Long-term oral administration of hop flower extracts mitigates Alzheimer phenotypes in mice.

Coincident with the expanding population of aged people, the incidence of Alzheimer disease (AD) is rapidly increasing in most advanced countries. At present, no effective prophylactics are available. Among several pathological mechanisms proposed for AD, the "amyloid hypothesis" has been most widely accepted, in which accumulation or deposition of Aβ is considered to be the initial event. Thus, prevention of Aβ production would be an ideal strategy for the treatment or prevention of AD. Aβ is produced via the proteolytic cleavage of its precursor protein, APP (amyloid precursor protein), by two different enzymes, β and γ-secretases. Indeed, inhibitors against either or both enzymes have been developed and tested for clinical efficacy. Based on the "amyloid hypothesis", we developed a luciferase-based screening method to monitor γ-secretase activity, screened more than 1,600 plant extracts, most of which have long been used in Chinese medicine, and observed that Hop extracts significantly inhibit Aβ production in cultured cells. A major component of the inhibitory activity was purified, and its chemical identity was determined by NMR to be Garcinielliptone HC. In vivo, oral administration of Hop extracts to AD model mice decreased Aβ depositions in the cerebral cortex of the parietal lobe, hippocampus, and artery walls (amyloid angiopathy) in the brains. In a Morris water maze test, AD model mice that had daily consumed Hop extracts in their drinking water showed significant mitigation of memory impairment at ages of 9 and 12 months. Moreover, in the open field test oral administration of Hop extracts also prevented an emotional disturbance that appeared in the AD mice at 18 months. Despite lifelong consumption of Hop extracts, no deleterious side effects were observed at any age. These results support the "amyloid hypothesis", and indicate that Hop extract is a promising candidate for an effective prophylactic for AD.
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Anti-Inflammatory Effect of Rosa rugosa Flower Extract in Lipopolysaccharide-Stimulated RAW264.7 Macrophages

Anti-Inflammatory Effect of Rosa rugosa Flower Extract in Lipopolysaccharide-Stimulated RAW264.7 Macrophages | A Tale of Two Medicines | Scoop.it
Rosa rugosa Thunb, a deciduous shrub of the genus Rosa, has been widely used to treat stomach aches, diarrhoea, pain, and chronic inflammatory disease in eastern Asia. In recent years, our research team has extensively studied the Rosa rugosa flower extract, and specifically undertook pharmacological experiments which have optimized the extraction process. Our methods have yielded a standard extract enriched in phenolic compounds, named PRE. Herein, we expand our efforts and evaluated the anti-inflammatory activity of PRE on lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophages. PRE significantly inhibited production of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor (TNF)-a, interleukin (IL)-6, and interleukin 1β (IL-1β), as well as expression of their synthesizing enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase2 (COX-2). Furthermore, PRE inhibited activity of mitogen-activated protein kinases (MAPK) as well as nuclear factor-kappa B (NF-κB) signaling pathway. Our findings are the first to explain the anti-inflammatory mechanism by PRE in LPS-stimulated macrophages. Given these results, we propose that PRE has therapeutic potential in the prevention of inflammatory disorders.
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Phytochemical Screening, Antidepressant and Analgesic Effects of Aqueous Extract of Anethum graveolens L. From Southeast of Morocco.

Phytochemical Screening, Antidepressant and Analgesic Effects of Aqueous Extract of Anethum graveolens L. From Southeast of Morocco. | A Tale of Two Medicines | Scoop.it
This study aims to investigate the antidepressant and analgesic properties of the aqueous extract of Anethum graveolens L. from South of Morocco (Rissani-Errachidia region). Extract of plant is obtained by aqueous decoction and administered to Wistar rats orally. The extract has a significant antidepressant and analgesic effects compared with the drug references (sertraline and tramadol) without any adverse effects. The dose of 250 mg/kg, body weight shows the best antidepressant and analgesic effects than 1 g/kg, body weight. Phytochemical study of the aqueous extract of the plant has to show its highlight in polyphenols, flavonoids, and tannins.
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Beneficial bacteria inhibit cachexia

Beneficial bacteria inhibit cachexia | A Tale of Two Medicines | Scoop.it
In conclusion, microbiota may offer novel strategies to reduce muscle wasting and restore good systemic health. Our discovery that edible bacteria have beneficial effects on the muscle mass of mice provides elementary evidence for the presence of a gut microbiota-skeletal muscle axis in mammals. Further research of the mechanisms behind this novel axis and tests for its existence in humans may offer new alternatives for prevention of cancer-associated cachexia and other muscle wasting disorders. Commensurate up-regulation of FoxN1 in thymic epithelia by oral microbe therapy unifies bacteria and immune homeostasis. We have previously shown that sterile microbe preparations are sufficient to inhibit carcinogenesis in mice [44], and therapeutic potential of microbial fractions remains to be examined in the setting of cachexia. Taken together our results suggest that commensal microbiota modulate host resiliency via FoxN1 to regulate host inflammatory tone for effective, yet balanced, immune responses with rapid restoration of homeostasis afterwards. In this way, microbiota offer a tractable target to impart systemic homeostasis lowering risk of inflammation-associated morbidity
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Taraxacum mongolicum extract exhibits a protective effect on hepatocytes and an antiviral effect against hepatitis B virus in animal and human cells

Taraxacum mongolicum extract exhibits a protective effect on hepatocytes and an antiviral effect against hepatitis B virus in animal and human cells | A Tale of Two Medicines | Scoop.it
In order to validate the antiviral effect against hepatitis B virus (HBV) of Taraxacum mongolicum (T. mongolicum), the protective effect on hepatocytes, and antiviral properties against duck hepatitis B virus (DHBV) and HBV of T. mongolicum extract (TME) were evaluated in chemically‑injured neonatal rat hepatocytes, DHBV-infected duck fetal hepatocytes and HBV-transfected HepG2.2.15 cells, respectively. The results demonstrated that TME at 50-100 µg/ml improved D-galactosamine (D-GalN), thioacetamide (TAA) and tert-butyl hydroperoxide (t-BHP)-injured rat hepatocytes, and produced protection rates of 42.2, 34.6 and 43.8% at 100 µg/ml, respectively. Furthermore, TME at 1-100 µg/ml markedly inhibited DHBV DNA replication. Additionally, TME at 25-100 µg/ml reduced HBsAg and HBeAg levels and produced inhibition rates of 91.39 and 91.72% at 100 µg/ml, respectively. TME markedly inhibited HBV DNA replication at 25-100 µg/ml. The results demonstrate the potent antiviral effect of T. mongolicum against HBV effect. The protective of TME effect on hepatocytes may be achieved by its ability to ameliorate oxidative stress. The antiviral properties of TME may contribute to blocking protein synthesis steps and DNA replication. Furthermore, major components of TME were quantificationally analyzed. These data provide scientific evidence supporting the traditional use of TME in the treatment of hepatitis.
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Memory Loss May Be Caused by Common Infections.

Memory Loss May Be Caused by Common Infections. | A Tale of Two Medicines | Scoop.it
Now researchers are finding that common infections also may have an effect on memory as well as other cognitive issues, such as mental processing, abstract thinking, planning as well as reasoning. In this new study out of the University of Miami and Columbia University, researchers followed 588 participants, most of whom were Hispanic. These people, who took part of the Northern Manhattan Study, participated in brain function tests and also had their blood samples taken at the start of the study. At the five-year mark, about half of the participants took another cognitive test. The researchers found that participants who had increased infections in their blood had a decline in cognitive function, even if they never became ill. Researchers are not sure why these infections have an effect on cognitive function.
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Increased chemopreventive effect by combining arctigenin, green tea polyphenol and curcumin in prostate and breast cancer cells.

The low bioavailability of most flavonoids limits their application as anti-carcinogenic agents in humans. A novel approach of treatment with a mixture of bioactive compounds that share molecular anti-carcinogenic targets may enhance the effect on these targets at low concentrations of individual compound, thereby overcoming the limitations of reduced bioavailability. We therefore investigated whether a combination of three natural products arctigenin (Arc), a novel anti-inflammatory lignan from the seeds of Arctium lappa, green tea polyphenol (-)-epigallocatechin gallate (EGCG) and curcumin (Cur) increases the chemopreventive potency of individual compounds. LNCaP prostate cancer and MCF-7 breast cancer cells were treated with 2-4 mg/L (about 5-10μM) Cur, 1μM Arc and 40μM EGCG alone or in combination for 48h. In both cell lines treatment with the mixture of Cur, Arc and EGCG synergistically increased the antiproliferative effect. In LNCaP cells both Arc and EGCG increased the pro-apoptotic effect of Cur. Whereas in MCF-7 cells Arc increased the cell apoptosis of Cur while EGCG enhanced cell cycle arrest of Cur at G0/G1 phase. The strongest effects on cell cycle arrest and apoptosis were achieved by combining all three compounds in both cell lines. The combination treatment significantly increased the ratio of Bax to Bcl-2 proteins, decreased the activation of NFκB, PI3K/Akt and Stat3 pathways and cell migration compared to individual treatment. These results warrant in vivo studies to confirm the efficacy of this novel regimen by combining Arc and EGCG with Cur to enhance chemoprevention in both prostate and breast cancer.
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Respiratory syncytial virus infection increases chlorine-induced airway hyperresponsiveness.

Respiratory syncytial virus infection increases chlorine-induced airway hyperresponsiveness. | A Tale of Two Medicines | Scoop.it
Exposure to chlorine (Cl2) damages airway and alveolar epithelia resulting in acute lung injury and reactive airway hyperresponsiveness (AHR) to methacholine. However, little is known about the effect of preexisting respiratory disease on Cl2-induced lung injury. By using a murine respiratory syncytial virus (RSV) infection model, we found that preexisting RSV infection increases Cl2 (187 ppm for 30 min)-induced lung inflammation and airway AHR at 24 h after exposure (5 days after infection). RSV infection and Cl2 exposure synergistically induced oxygen desaturation and neutrophil infiltration and increased MCP-1, MIP-1β, IL-10, IFN-γ, and RANTES concentrations in the bronchoalveolar lavage fluid (BALF). In contrast, levels of type 2 cytokines (i.e., IL-4, IL-5, IL-9, and IL-13) were not significantly affected by either RSV infection or Cl2 exposure. Cl2 exposure, but not RSV infection, induced AHR to methacholine challenge as measured by flexiVent. Moreover, preexisting RSV infection amplified BALF levels of hyaluronan (HA) and AHR. The Cl2-induced AHR was mitigated by treatment with inter-α-trypsin inhibitor antibody, which inhibits HA signaling, suggesting a mechanism of HA-mediated AHR from exacerbated oxidative injury. Our results show for the first time that preexisting RSV infection predisposes the lung to Cl2-induced injury. These data emphasize the necessity for further research on the effects of Cl2 in vulnerable populations and the development of appropriate treatments.
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Exercise-based Interventions for Non-alcoholic Fatty Liver Disease: a Meta-analysis and Meta-regression.

Exercise-based Interventions for Non-alcoholic Fatty Liver Disease: a Meta-analysis and Meta-regression. | A Tale of Two Medicines | Scoop.it

The burden of non-alcoholic fatty liver disease (NAFLD) is increasing worldwide. We performed a meta-analysis to determine the effectiveness of exercise-based lifestyle interventions on liver-specific endpoints in populations with NAFLD and underlying metabolic disorders such as obesity, type-2 diabetes, or the metabolic syndrome.

We searched PUBMED-MEDLINE, EMBASE, and the Cochrane Central register, through 21st October, 2015 for randomized trials of exercise-based lifestyle interventions on endpoints such as intrahepatic lipid content and blood levels of alanine and aspartate aminotransferases. Effect sizes are reported as standardized mean difference and weighted mean difference values. To investigate heterogeneity, we performed sensitivity and meta-regression analyses. Results were reported according to the PRISMA statement.

We analyzed data from 28 trials. Physical activity, independently from diet change, was associated with a significant reduction in intra-hepatic lipid content (standardized mean difference, -0.69; 95% confidence interval [CI], -0.90 to -0.48) and with reductions in alanine aminotransferase (weighted mean difference, -3.30 IU/l; 95% CI, 5.57 to -1.04) and aspartate aminotransferase (weighted mean difference, -4.85 IU/l; 95% CI, -8.68 to -1.02). By meta-regression, we found individuals with increasing body mass index to be increasingly more likely to benefit from the intervention (beta coefficient = -0.10; P=.037). We recorded no effect modification by variables related to the intensity of the intervention.

In a meta-analysis of randomized trials, we found strong evidence that physical activity reduces intrahepatic lipid content and markers of hepatocellular injury in patients with NAFLD. This effect correlated with baseline body mass index.

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Hydrogen–water enhances 5-fluorouracil-induced inhibition of colon cancer

Hydrogen–water enhances 5-fluorouracil-induced inhibition of colon cancer | A Tale of Two Medicines | Scoop.it
Oxidative stress is involved in cancer development. Hydrogen (H2) is a potent antioxidant and exhibits anti-inflammatory and potentially anticancer-like activities. This study aimed to investigate the role of H2 incombination with 5-fluorouracil (5-FU) in cancer treatment both in vitro and in vivo using the colon 26 cell line. The survival rate was determined using the Kaplan–Meier survival test, and cell viability was assessed using cell viability imaging kit and the MTT assay, and activation of the cell apoptosis pathway (Phosphorylated adenosine monophosphate activated protein kinase (p-AMPK), Apoptosis-inducing factor (AIF) and Caspase 3) were characterized by western blots. Hydrogen water administration improved the survival of mice with colon 26-induced cancer. Furthermore, hydrogen water enhanced cell apoptosis in cancer cells, resulting in a marked increase in the expression of p-AMPK, AIF and Caspase 3 in colon 26 cells. Hydrogen water also increased the inhibitory effect of 5-FU on colon 26 cells with spect to cell survival rate and anticancer functions. Additionally, high-content hydrogen water exhibited stronger antioxidative and anticancer activity than did the natural hydrogen water. In conclusion, high-content hydrogen water can inhibit colon cancer, particularly in combination with 5-fluorouracil.
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Chokeberry (Aronia melanocarpa (Michx.) Elliot) concentrate inhibits NF-κB and synergizes with selenium to inhibit the release of pro-inflammatory mediators in macrophages.

Chokeberry (Aronia melanocarpa (Michx.) Elliot) concentrate inhibits NF-κB and synergizes with selenium to inhibit the release of pro-inflammatory mediators in macrophages. | A Tale of Two Medicines | Scoop.it
Black chokeberry has been known to play a protective role in human health due to its high polyphenolic content including anthocyanins and caffeic acid derivatives. In the present study, we first characterized the polyphenolic content of a commercial chokeberry concentrate and investigated its effect on LPS-induced NF-κB activation and release of pro-inflammatory mediators in macrophages in the presence or the absence of sodium selenite. Examination of the phytochemical profile of the juice concentrate revealed high content of polyphenols (3.3%), including anthocyanins, proanthocyanidins, phenolic acids, and flavonoids. Among them, cyanidin-3-O-galactoside and caffeoylquinic acids were identified as the major compounds. Data indicated that chokeberry concentrate inhibited both the release of TNFα, IL-6 and IL-8 in human peripheral monocytes and the activation of the NF-κB pathway in RAW 264.7 macrophage cells. Furthermore, chokeberry synergizes with sodium selenite to inhibit NF-κB activation, cytokine release and PGE2 synthesis. These findings suggest that selenium added to chokeberry juice enhances significantly its anti-inflammatory activity, thus revealing a sound approach in order to tune the use of traditional herbals by combining them with micronutrients.
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Bisphenol A Exposure in Children With Autism Spectrum Disorders.

The etiology of autism spectrum disorders (ASD) is believed to involve genetic and environmental components. This study focused on the plasticizer, Bisphenol-A (BPA). The major pathway for BPA metabolism and excretion is via glucuronidation. To determine whether there was a relationship between BPA exposure and ASD, urine specimens were collected from 46 children with ASD and 52 controls. Free and total BPA concentrations were determined by mass spectrometry. The fraction glucuronidated was calculated from the difference. A metabolomics study was done to investigate metabolite distribution in the urine. (i) Most of the BPA excreted in the urine was as the glucuronide; (ii) about 20% of the ASD children had BPA levels beyond the 90th percentile (>50 ng/mL) of the frequency distribution for the total sample of 98 children; (iii) Mann–Whitney U tests and multiple regression analyses found significant differences (P |0.30| between metabolite concentrations and total BPA was ∼3 times greater with the ASD group than the controls (P  |0.30| for % bound BPA was ∼15 times higher with ASD (P < 0.001). The results suggest there is an association between BPA and ASD. Autism Res 2015, 8: 272–283.
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Antioxidant Activity and Cytotoxicity Effect of Cocoa Beans Subjected to Different Processing Conditions in Human Lung Carcinoma Cells

Antioxidant Activity and Cytotoxicity Effect of Cocoa Beans Subjected to Different Processing Conditions in Human Lung Carcinoma Cells | A Tale of Two Medicines | Scoop.it
Lung cancer is a common malignancy in men and the second leading cause of cancer-related mortality in men in the western world. Phenolic cocoa ingredients have a strong antioxidative activity and the potential to have a protective effect against cancer. In the present study, we have evaluated the influence of cocoa beans subjected to different processing conditions on cell viability and apoptosis of human lung cancer cells (A549). We measured the viability of lung cells treated with cocoa beans, unroasted slates (US), roasted slates (RS), unroasted well fermented (UWF) cocoa, and roasted well fermented (RWF) cocoa for 24 h. Using an MTT assay, we observed a decrease in the viability of A549 cells after treatment with cocoa bean extracts. Flow cytometer analysis revealed that cocoa beans increased the percentage of cells in sub-G1 phase and promoted up to twofold increase of apoptotic cells when compared to the control group. Taken together, the present study suggests that cocoa beans may have a protective effect against lung cancer.
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Dimethyl trisulfide: A novel cyanide countermeasure.

Dimethyl trisulfide: A novel cyanide countermeasure. | A Tale of Two Medicines | Scoop.it
In the present studies, the in vitro and in vivo efficacies of a novel cyanide countermeasure, dimethyl trisulfide (DMTS), were evaluated. DMTS is a sulfur-based molecule found in garlic, onion, broccoli, and similar plants. DMTS was studied for effectiveness as a sulfur donor-type cyanide countermeasure. The sulfur donor reactivity of DMTS was determined by measuring the rate of the formation of the cyanide metabolite thiocyanate. In experiments carried out in vitro in the presence of the sulfurtransferase rhodanese (Rh) and at the experimental pH of 7.4, DMTS was observed to convert cyanide to thiocyanate with greater than 40 times higher efficacy than does thiosulfate, the sulfur donor component of the US Food and Drug Administration-approved cyanide countermeasure Nithiodote®. In the absence of Rh, DMTS was observed to be almost 80 times more efficient than sodium thiosulfate in vitro. The fact that DMTS converts cyanide to thiocyanate more efficiently than does thiosulfate both with and without Rh makes it a promising sulfur donor-type cyanide antidote (scavenger) with reduced enzyme dependence in vitro. The therapeutic cyanide antidotal efficacies for DMTS versus sodium thiosulfate were measured following intramuscular administration in a mouse model and expressed as antidotal potency ratios (APR = LD50 of cyanide with antidote/LD50 of cyanide without antidote). A dose of 100 mg/kg sodium thiosulfate given intramuscularly showed only slight therapeutic protection (APR = 1.1), whereas the antidotal protection from DMTS given intramuscularly at the same dose was substantial (APR = 3.3). Based on these data, DMTS will be studied further as a promising next-generation countermeasure for cyanide intoxication.
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The Study of Anti-Inflammatory Activity of Oil-Based Dill (Anethum graveolens L.) Extract Used Topically in Formalin-Induced Inflammation Male Rat

Inflammation is one of the symptoms of many common and harmful diseases. As it is incurable through chemical drugs, the study on this ailment using new methods and drugs seems necessary. In addition, the adverse effects of the present anti-inflammatory drugs like NSAIDS and Glucocorticoid appeared in the long time use make such study more demanded. Accordingly, in this study we examined the effects of aerial organs' extract and seed of a plant commonly used in Iranian traditional medicine named Dill on the inflammation caused by plantar injection of formalin in rats and compared them with Diclofenac-gel. One of the methods used for the inflammation assessment is injecting formalin in the rat paw and then measuring the paw volume by the new plethysmometer (weighing method). The assessment is done at a specific time on day for 8 days and then recorded. This study includes 3 groups of 6 male rats: Formalin, Dill-Oil and Diclofenac-gel groups. The Dill-Oil group received 2 g of Dill-Oil, containing 100 mg Dill-extract and the Diclofenac group received 2 g gel containing, 20 mg Diclofenac Na. Data were analyzed with SPSS 17 using ANOVA, Kruskal-Wallis, and Repeated-Measures. The average paw volumes changes in these groups after Formalin-induced inflammation on 1st day, were 0.31 (standard error (SEM) = 0.02), 0.30 (SEM = 0.01) and 0.32 (SEM = 0.05) respectively, with no significant difference. Regarding the peak of inflammation on the 2nd day, it was indicated that the average inflammations in Formalin, Dill-Oil and Diclofenac-gel groups were 0.44 (SEM = 0.03), 0.15 (SEM = 0.04) and 0.36 (SEM = 0.08), respectively. The paw volume changes in groups receiving Dill-oil and Diclofenac-gel, after the daily formalin injection in 8 days compared to the blank group, had a significant decrease (p < 0.001). The Dill group showed even more decrease in the paw volume compared to the Diclofenac one. The results of paw volume measurement analyzed by the Plethysmometer manifest that the Dill-Oil is able to decrease the paw volume significantly.
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Lactobacillus casei Exerts Anti-Proliferative Effects Accompanied by Apoptotic Cell Death and Up-Regulation of TRAIL in Colon Carcinoma Cells.

Probiotic microorganisms such as lactic acid bacteria (LAB) exert a number of strain-specific health-promoting activities attributed to their immunomodulatory, anti-inflammatory and anti-carcinogenic properties. Despite recent attention, our understanding of the biological processes involved in the beneficial effects of LAB strains is still limited. To this end, the present study investigated the growth-inhibitory effects of Lactobacillus casei ATCC 393 against experimental colon cancer. Administration of live Lactobacillus casei (as well as bacterial components thereof) on murine (CT26) and human (HT29) colon carcinoma cell lines raised a significant concentration- and time-dependent anti-proliferative effect, determined by cell viability assays. Specifically, a dramatic decrease in viability of colon cancer cells co-incubated with 109 CFU/mL L. casei for 24 hours was detected (78% for HT29 and 52% for CT26 cells). In addition, live L. casei induced apoptotic cell death in both cell lines as revealed by annexin V and propidium iodide staining. The significance of the in vitro anti-proliferative effects was further confirmed in an experimental tumor model. Oral daily administration of 109 CFU live L. casei for 13 days significantly inhibited in vivo growth of colon carcinoma cells, resulting in approximately 80% reduction in tumor volume of treated mice. Tumor growth inhibition was accompanied by L. casei-driven up-regulation of the TNF-related apoptosis-inducing ligand TRAIL and down-regulation of Survivin. Taken together, these findings provide evidence for beneficial tumor-inhibitory, anti-proliferative and pro-apoptotic effects driven by this probiotic LAB strain.
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Silibinin and its 2,3-dehydro-derivative inhibit basal cell carcinoma growth via suppression of mitogenic signaling and transcription factors activation.

Silibinin and its 2,3-dehydro-derivative inhibit basal cell carcinoma growth via suppression of mitogenic signaling and transcription factors activation. | A Tale of Two Medicines | Scoop.it
Basal cell carcinoma (BCC) is the most common cancer worldwide, and its current treatment options are insufficient and toxic. Surprisingly, unlike several other malignancies, chemopreventive efforts against BCC are almost lacking. Silibinin, a natural agent from milk thistle seeds, has shown strong efficacy against several cancers including ultraviolet radiation-induced skin (squamous) cancer; however, its potential activity against BCC is not yet examined. Herein, for the first time, we report the efficacy of silibinin and its oxidation product 2,3-dehydrosilibinin (DHS) against BCC both in vitro and in vivo using ASZ (p53 mutated) and BSZ (p53 deleted) cell lines derived from murine BCC tumors. Both silibinin and DHS significantly inhibited cell growth and clonogenicity while inducing apoptosis in a dose- and time-dependent manner, with DHS showing higher activity at lower concentrations. Both agents also inhibited the mitogenic signaling by reducing EGFR, ERK1/2, Akt, and STAT3 phosphorylation and suppressed the activation of transcription factors NF-κB and AP-1. More importantly, in an ectopic allograft model, oral administration of silibinin and DHS (200 mg/kg body weight) strongly inhibited the ASZ tumor growth by 44% and 71% (P < 0.05), respectively, and decreased the expression of proliferation biomarkers (PCNA and cyclin D1) as well as NF-κB p50 and c-Fos in the tumor tissues. Taken together, these results provide the first evidence for the efficacy and usefulness of silibinin and its derivative DHS against BCC, and suggest the need for additional studies with these agents in pre-clinical and clinical BCC chemoprevention and therapy models.
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By suppressing the expression of anterior pharynx-defective-1α and -1β and inhibiting the aggregation of β-amyloid protein, magnesium ions inhibit the cognitive decline of amyloid precursor protein...

By suppressing the expression of anterior pharynx-defective-1α and -1β and inhibiting the aggregation of β-amyloid protein, magnesium ions inhibit the cognitive decline of amyloid precursor protein... | A Tale of Two Medicines | Scoop.it
Alzheimer's disease (AD) is associated with a magnesium ion (Mg(2+)) deficit in the serum or brain. However, the mechanisms regulating the roles of Mg(2+) in the pathologic condition of AD remain unknown. We studied whether brain Mg(2+) can decrease β-amyloid (Aβ) deposition and ameliorate the cognitive decline in a model of AD, the APPswe/PS1DE9 transgenic (Tg) mouse. We used a recently developed compound, magnesium-l-threonate (MgT), for a treatment that resulted in enhanced clearance of Aβ in an anterior pharynx-defective (APH)-1α/-1β-dependent manner. To further explore how MgT treatment inhibits cognitive decline in APP/PS1 Tg mice, the critical molecules for amyloid precursor protein (APP) cleavage and signaling pathways were investigated. In neurons, ERK1/2 and PPARγ signaling pathways were activated by MgT treatment, which in turn suppressed (by >80%) the expression of APH-1α/-1β, which is responsible for the deposition of Aβ and potentially contributes to the memory deficit that occurs in AD. More important, Aβ oligomers in the cerebrospinal fluid (CSF) further promoted the expression of APH-1α/-1β (by >2.5-fold), which enhances the γ-cleavage of APP and Aβ deposition during AD progression. These findings provide new insights into the mechanisms of AD progression and are instrumental for developing better strategies to combat the disease.-Yu, X., Guan, P.-P., Guo, J.-W., Wang, Y., Cao, L.-L., Xu, G.-B., Konstantopoulos, K., Wang, Z.-Y., Wang, P. By suppressing the expression of anterior pharynx-defective-1α and -1β and inhibiting the aggregation of β-amyloid protein, magnesium ions inhibit the cognitive decline of amyloid precursor protein/presenilin 1 transgenic mice.
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Morinda citrifolia edible leaf extract enhanced immune response against lung cancer.

Morinda citrifolia edible leaf extract enhanced immune response against lung cancer. | A Tale of Two Medicines | Scoop.it
Lung cancer causes 1.4 million deaths annually. In the search for functional foods as complementary therapies against lung cancer, the immuno-stimulatory properties of the vegetable Morinda citrifolia leaves were investigated and compared with the anti-cancer drug erlotinib. Lung tumour-induced BALB/c mice were fed with 150 mg kg-1 or 300 mg kg-1 body weight of the leaf extract, or erlotinib (50 mg kg-1 body-weight) for 21 days. The 300 mg kg-1 body weight extract significantly (and dose-dependently) suppressed lung tumour growth; the extract worked more effectively than the 50 mg kg-1 body weight erlotinib treatment. The extract significantly increased blood lymphocyte counts, and spleen tissue B cells, T cells and natural killer cells, and reduced the epidermal growth factor receptor (EGFR) which is a lung adenocarcinoma biomarker. The extract also suppressed the cyclooxygenase 2 (COX2) inflammatory markers, and enhanced the tumour suppressor gene (phosphatase and tensin homolog, PTEN). It inhibited tumour growth cellular gene (transformed mouse 3T3 cell double minute 2 (MDM2), V-raf-leukemia viral oncogene 1 (RAF1), and mechanistic target of rapamycin (MTOR)) mRNA expression in the tumours. The extract is rich in scopoletin and epicatechin, which are the main phenolic compounds. The 300 mg kg-1Morinda citrifolia leaf 50% ethanolic extract showed promising potential as a complementary therapeutic dietary supplement which was more effective than the 50 mg kg-1 erlotinib in suppressing lung adenocarcinoma. Part of the mechanisms involved enhancing immune responses, suppressing proliferation and interfering with various tumour growth signalling pathways.
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