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Assessment of the Psychotherapeutic Effects of Ritual Ayahuasca Use on Drug Dependency: A Pilot Study.

Assessment of the Psychotherapeutic Effects of Ritual Ayahuasca Use on Drug Dependency: A Pilot Study. | A Tale of Two Medicines | Scoop.it

Using personality, psychopathology, and neuropsychological assessment instruments, our team assessed the therapeutic effects of an ayahuasca ritual treatment. Data was collected at the Institute of Applied Amazonian Ethnopsychology (IDEAA), in the Brazilian Amazon Basin. Psychological assessments were obtained both before and at the end of the treatment. The ayahuasca treatment lasted between 3 and 9 months and included biweekly ayahuasca consumption. The sample consisted of 13 patients (8 men, 5 women) with a mean age of 35 years. Nine had a diagnosis of drug abuse and/or dependence; one of borderline personality disorder, and 3 were at IDEAA for personal growth. Results showed that the “Impulsiveness,” “Disorderliness,” “Anticipatory Worry,” and “Shyness with Strangers” subscales of the Temperament and Character Inventory presented statistically significant reductions after treatment, while the “Self-Directedness,” “Responsibility,” “Purposefulness,” and “Congruent Second Nature” subscales presented significant increases. The psychopathology subscales “Positive Symptoms,” “Obsessive–Compulsive,” and “Anxiety” of the Symptom Check-List-90-Revised, were significantly diminished after treatment, as well as all subscales of the Frontal Systems Behavior Scale: “Total,” “Apathy,” “Disinhibition,” and “Executive Dysfunction.” In addition, the “Resistance to Interference” measure of the Stroop Color and Word Test, the Purpose in Life Test, and the “Transcendent Dimension,” “Meaning and Purpose in Life,” “Mission in Life,” and “Material Values” subscales of the Spiritual Orientation Inventory presented statistically significant increases after treatment. Despite important limitations, such as the small sample size and the lack of a control group, the present pilot study provides preliminary evidence suggesting psychotherapeutic effects of ritual ayahuasca treatment in drug-related disorders.

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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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The Neuroprotective Properties of Hericium erinaceus in Glutamate-Damaged Differentiated PC12 Cells and an Alzheimer's Disease Mouse Model.

Hericium erinaceus, an edible and medicinal mushroom, displays various pharmacological activities in the prevention of dementia in conditions such as Parkinson's and Alzheimer's disease. The present study explored the neuroprotective effects of H. erinaceus mycelium polysaccharide-enriched aqueous extract (HE) on an l-glutamic acid (l-Glu)-induced differentiated PC12 (DPC12) cellular apoptosis model and an AlCl₃ combined with d-galactose-induced Alzheimer's disease mouse model. The data revealed that HE successfully induced PC12 cell differentiation. A 3 h HE incubation at doses of 50 and 100 µg/mL before 25 mM of l-Glu effectively reversed the reduction of cell viability and the enhancement of the nuclear apoptosis rate in DPC12 cells. Compared with l-Glu-damaged cells, in PC12 cells, HE suppressed intracellular reactive oxygen species accumulation, blocked Ca2+ overload and prevented mitochondrial membrane potential (MMP) depolarization. In the Alzheimer's disease mouse model, HE administration enhanced the horizontal and vertical movements in the autonomic activity test, improved the endurance time in the rotarod test, and decreased the escape latency time in the water maze test. It also improved the central cholinergic system function in the Alzheimer's mice, demonstrated by the fact that it dose-dependently enhanced the acetylcholine (Ach) and choline acetyltransferase (ChAT) concentrations in both the serum and the hypothalamus. Our findings provide experimental evidence that HE may provide neuroprotective candidates for treating or preventing neurodegenerative diseases.
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Fasting selectively blocks development of acute lymphoblastic leukemia via leptin-receptor upregulation.

Fasting selectively blocks development of acute lymphoblastic leukemia via leptin-receptor upregulation. | A Tale of Two Medicines | Scoop.it
New therapeutic approaches are needed to treat leukemia effectively. Dietary restriction regimens, including fasting, have been considered for the prevention and treatment of certain solid tumor types. However, whether and how dietary restriction affects hematopoietic malignancies is unknown. Here we report that fasting alone robustly inhibits the initiation and reverses the leukemic progression of both B cell and T cell acute lymphoblastic leukemia (B-ALL and T-ALL, respectively), but not acute myeloid leukemia (AML), in mouse models of these tumors. Mechanistically, we found that attenuated leptin-receptor (LEPR) expression is essential for the development and maintenance of ALL, and that fasting inhibits ALL development by upregulation of LEPR and its downstream signaling through the protein PR/SET domain 1 (PRDM1). The expression of LEPR signaling-related genes correlated with the prognosis of pediatric patients with pre-B-ALL, and fasting effectively inhibited B-ALL growth in a human xenograft model. Our results indicate that the effects of fasting on tumor growth are cancer-type dependent, and they suggest new avenues for the development of treatment strategies for leukemia.
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Chronic Ethanol Exposure Effects on Vitamin D Levels Among Subjects with Alcohol Use Disorder.

Chronic Ethanol Exposure Effects on Vitamin D Levels Among Subjects with Alcohol Use Disorder. | A Tale of Two Medicines | Scoop.it
Vitamin D has been previously recognized to play important roles in human immune system and function. In the pulmonary system, vitamin D regulates the function of antimicrobial peptides, especially cathelicidin/LL-37. Human cathelicidin/LL-37 is a bactericidal, bacteriostatic, and antiviral endogenous peptide with protective immune functions. Chronic exposure to excessive alcohol has the potential to reduce levels of vitamin D (inactive vitamin D [25(OH)D3] and active vitamin D [1, 25(OH)2D3]) and leads to downregulation of cathelicidin/LL-37. Alcohol-mediated reduction of LL-37 may be partly responsible for increased incidence of more frequent and severe respiratory infections among subjects with alcohol use disorder (AUD). The objective of this study was to investigate the mechanisms by which alcohol exerts its influence on vitamin D metabolism. In addition, the aim was to establish associations between chronic alcohol exposures, levels of pulmonary vitamin D, and cathelicidin/LL-37 using broncho-alveolar lavage fluid samples of subjects with AUD and healthy controls. Findings from the experiment showed that levels of inactive vitamin D (25(OH)D3), active vitamin D (1, 25(OH)2D3), cathelicidin/LL-37, and CYP27B1 proteins were significantly reduced (P < 0.05) when compared with the matched healthy control group. However, CYP2E1 was elevated in all the samples examined. Chronic exposure to alcohol has the potential to reduce the levels of pulmonary vitamin D and results in subsequent downregulation of the antimicrobial peptide, LL-37, in the human pulmonary system.
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The circadian clock modulates anti-cancer properties of curcumin.

The circadian clock modulates anti-cancer properties of curcumin. | A Tale of Two Medicines | Scoop.it


Curcuminoids of the spice turmeric and their enhanced derivatives have much potential as cancer treatments. They act on a wide variety of biological pathways, including those regulating cell division and circadian rhythms. It is known that circadian clocks can modify cancer therapy effectiveness, according to studies aimed at optimizing treatments based on the circadian cycle. It is therefore important to determine whether treatments with curcumin or similar chemotherapeutic agents are regulated by circadian timing. Similarly, it is important to characterize any effects of curcumin on timing abilities of the circadian clocks within cancer cells.

We examined the circadian clock's impact on the timing of cell death and cell division in curcumin-treated C6 rat glioma cells through continuous video microscopy for several days. To evaluate its persistence and distribution in cancer cells, curcumin was localized within cell compartments by imaging its autofluorescence. Finally, HPLC and spectroscopy were used to determine the relative stabilities of the curcumin congeners demethoxycurcumin and bisdemethoxycurcumin that are present in turmeric.

Circadian rhythms in cell death were observed in response to low (5 μM) curcumin, reaching a peak several hours before the peak in rhythmic expression of mPER2 protein, a major circadian clock component. These results revealed a sensitive phase of the circadian cycle that could be effectively targeted in patient therapies based on curcumin or its analogs. Curcumin fluorescence was observed in cell compartments at least 24 h after treatment, and the two congeners displayed greater stability than curcumin in cell culture medium.

We propose a mechanism whereby curcuminoids act in a sustained manner, over several days, despite their tendency to degrade rapidly in blood and other aqueous media. During cancer therapy, curcumin or its analogs should be delivered to tumor cells at the optimal phase for highest efficacy after identifying the circadian phase of the cancer cells. We confirmed the greater stability of the curcumin congeners, suggesting that they may produce sustained toxicity in cancer cells and should be considered for use in patient care.

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Rosa canina Extracts Have Antiproliferative and Antioxidant Effects on Caco-2 Human Colon Cancer

The in vitro antiproliferative and antioxidant effects of different fractions of Rosa canina hips on human colon cancer cell lines (Caco-2) was studied. The compounds tested were total extract (fraction 1), vitamin C (fraction 2), neutral polyphenols (fraction 3) and acidic polyphenols (fraction 4). All the extracts showed high cytotoxicity after 72 h, both low and high concentrations. The flow cytometric analysis revealed that all the fractions produce disturbances in the cell cycle resulting in a concomitant cell death by an apoptotic pathway. Changes in the redox status of Caco-2 cells in response to Rosa canina hips were determined. Cells were exposed to hydrogen peroxide in presence of plant fractions and the production of Reactive Oxygen Species (ROS) was significantly decreased. Therefore, our data demonstrate that rosehip extracts are a powerful antioxidant that produces an antiproliferative effect in Caco-2 cells. Therefore, these results predict a promising future for Rosa canina as a therapeutic agent. Thus, this natural plant could be an effective component of functional foods addressed towards colorectal carcinoma.
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The microbiota of breast tissue and its association with tumours.

The microbiota of breast tissue and its association with tumours. | A Tale of Two Medicines | Scoop.it
This study shows that different bacterial profiles in breast tissue exist between healthy women and those with breast cancer. Higher relative abundances of bacteria, that had the ability to cause DNA damage in vitro, were detected in breast cancer patients, as well as a decrease in some lactic acid bacteria, known for their beneficial health effects, including anti-carcinogenic properties. This study raises the important question as to the role of the mammary microbiome in modulating the risk of breast cancer development.
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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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The Green Tea Catechin Epigallocatechin Gallate Ameliorates Graft-versus-Host Disease

The Green Tea Catechin Epigallocatechin Gallate Ameliorates Graft-versus-Host Disease | A Tale of Two Medicines | Scoop.it
Allogeneic hematopoetic stem cell transplantation (allo-HSCT) is a standard treatment for leukemia and other hematologic malignancies. The major complication of allo-HSCT is graft-versus-host-disease (GVHD), a progressive inflammatory illness characterized by donor immune cells attacking the organs of the recipient. Current GVHD prevention and treatment strategies use immune suppressive drugs and/or anti-T cell reagents these can lead to increased risk of infections and tumor relapse. Recent research demonstrated that epigallocatechin gallate (EGCG), a component found in green tea leaves at a level of 25–35% at dry weight, may be useful in the inhibition of GVHD due to its immune modulatory, anti-oxidative and anti-angiogenic capacities. In murine allo-HSCT recipients treated with EGCG, we found significantly reduced GVHD scores, reduced target organ GVHD and improved survival. EGCG treated allo-HSCT recipients had significantly higher numbers of regulatory T cells in GVHD target organs and in the blood. Furthermore, EGCG treatment resulted in diminished oxidative stress indicated by significant changes of glutathione blood levels as well as glutathione peroxidase in the colon. In summary, our study provides novel evidence demonstrating that EGCG ameliorates lethal GVHD and reduces GVHD-related target organ damage. Possible mechanisms are increased regulatory T cell numbers and reduced oxidative stress.
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Vitamin C induces apoptosis in AGS cells via production of ROS of mitochondria.

Vitamin C induces apoptosis in AGS cells via production of ROS of mitochondria. | A Tale of Two Medicines | Scoop.it
It has been demonstrated that vitamin C exhibits anti-cancer activity in various tumor cell lines; however, its specific mechanism of action remains unknown. Although the diagnosis and therapy of cancer patients have markedly improved in recent years, safer and more cost-effective treatments are still required. Therefore, the present study examined the effect of vitamin C on the induction of cell death in gastric cancer and its underlying mechanism of action. It was observed that the cytotoxicity of vitamin C on the human gastric cancer cell line AGS is dependent on the apoptotic pathway, including caspase cascades, but not on the necroptotic pathway. It was demonstrated that the vitamin C-induced calcium influx and ROS generation have critical roles in the induction of apoptosis. Furthermore, vitamin C treatment depleted adenosine triphosphate (ATP) production in AGS cells, and the autophagy pathway may be involved in this process. Taken together, the current study suggests that a high dose of vitamin C may induce gastric cancer cell apoptosis through the dysfunction of mitochondria, including calcium influx, reactive oxygen species generation and ATP depletion.
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Synergistic Protective Activity of Deuterium Depleted Water (DDW) and Satureja rechingeri Essential Oil on Hepatic Oxidative Injuries Induced by Acetaminophen in Rats

Synergistic Protective Activity of Deuterium Depleted Water (DDW) and Satureja rechingeri Essential Oil on Hepatic Oxidative Injuries Induced by Acetaminophen in Rats | A Tale of Two Medicines | Scoop.it
Therefore, it was concluded from the current results that DDW alone and in combination with E.O provided a synergistic effects in prevention of acetaminophen induced hepatotoxicity in rat. This protection may involve the reduction of oxidative stresses.
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Potent SIRT1 enzyme-stimulating and anti-glycation activities of polymethoxyflavonoids from Kaempferia parviflora.

Potent SIRT1 enzyme-stimulating and anti-glycation activities of polymethoxyflavonoids from Kaempferia parviflora. | A Tale of Two Medicines | Scoop.it
The SIRT1 enzyme-stimulating and anti-glycation activities of Kaempferia parviflora extract and its main polymethoxyflavonoids were evaluated in vitro. K. parviflora extract elevated SIRT1 catalytic activity by eight- and 17-fold at 20 μg/mL and 100 μg/mL, respectively, compared with vehicle only. Two major polymethoxyflavonoids, 3,5,7,3',4'-pentamethoxyflavone (4) and 5,7,4'-trimethoxyflavone (5), were isolated from this extract and are four- and fivefold more potent than resveratrol, hitherto the strongest known natural SIRT1 activator. In addition, the anti-glycation activity of K. parviflora extract was observed to be seven times more effective than aminoguanidine, a clinical anti-diabetes drug. 3,5,7,3',4'-Pentamethoxyflavone (4) and 5,7,4'-trimethoxyflavone (5) showed the strongest anti-glycation activity among the tested polymethoxyflavonoids. Further comparison of the activity of these structurally related polymethoxyflavonoids revealed a possible structure-activity relationship, in particular, for the contribution of methoxy moieties.
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Aqueous Extract of Anethum Graveolens L. has Potential Antioxidant and Antiglycation Effects

Aqueous Extract of Anethum Graveolens L. has Potential Antioxidant and Antiglycation Effects | A Tale of Two Medicines | Scoop.it
The aim of this study was to assess the antiglycation and antioxidant properties of aqueous extract of Anethum graveolens (dill). In the in vivo and in vitro experiments, antioxidant properties, blood glucose, and AGEs formation were determined. Dill extract was given orally to healthy and diabetic rats. Our results illustrated that different concentrations of dill extract (0.125, 0.25, 0.5, and 1 mg/ml) have potential antiradical and antioxidant activity. Aqueous extract of dill significantly reduced AGEs formation and fructosamine levels, protein carbonyl and also thiol group’s oxidation, amyloid cross-β and fragmentation. After 2 months, blood glucose levels (P=0.006) and AGEs formation (P=0.003) significantly reduced in dill treated group compared with untreated diabetic animals. In conclusion, dill can be recommended as herbal medicine for the control and prevention of diabetic complications.
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Potassium increases the antitumor effects of ascorbic acid in breast cancer cell lines in vitro

Potassium increases the antitumor effects of ascorbic acid in breast cancer cell lines in vitro | A Tale of Two Medicines | Scoop.it
Ascorbic acid (A) has been demonstrated to exhibit anti-cancer activity in association with chemotherapeutic agents. Potassium (K) is a regulator of cellular proliferation. In the present study, the biological effects of A and K bicarbonate, alone or in combination (A+K), on breast cancer cell lines were evaluated. The survival of cancer cells was determined by sulforhodamine B cell proliferation assay, while analysis of the cell cycle distribution was conducted via fluorescence-activated cell sorting. In addition, the expression of signaling proteins was analyzed upon treatment. The results indicated that there was a heterogeneous response of the different cell lines to A and K, and the best effects were achieved by A+K and A treatment. The interaction between A+K indicated an additive or synergistic effect. In addition, A+K increased the percentage of cells in the sub-G1 phase of the cell cycle, and was the most effective treatment in activating the degradation of poly(adenosine diphosphate-ribose) polymerase-1. In the breast cancer cell line MCF-7, A+K induced the appearance of the 18 kDa isoform of B-cell lymphoma-2-associated X protein (Bax), which is a more potent inducer of apoptosis than the full-length Bax-p21. The effects of A and K on the phosphorylation of extracellular signal-regulated kinase (ERK)1 and ERK2 were heterogeneous. In addition, treatment with K, A and A+K inhibited the expression of nuclear factor-κB. Overall, the results of the present study indicated that K potentiated the anti-tumoral effects of A in breast cancer cells in vitro.
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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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