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Three Cancer Drugs Don't Work Properly Without Gut Bacteria

Three Cancer Drugs Don't Work Properly Without Gut Bacteria | A Tale of Two Medicines | Scoop.it

Your gut is home to tens of trillions of bacteria. Collectively, they act as another organ, one with many different roles. They influence your body weight, your ability to digest your food, your risk of catching infectious diseases, your chances of resisting infections or autoimmune diseases, the development of your brain, and more.

 

Now, we can add an entry to this growing list. At least in mice, gut bacteria can influence whether cancer treatments work.

 

Working independently, two teams of scientists showed that three cancer treatments rely on gut bacteria to mobilise the immune system and kill tumour cells—not just in the gut, but also in the blood (lymphomas) and skin (melanomas). Remove the bacteria with antibiotics, and you also neuter the drugs.

 

“It was a surprise,” says Romina Goldszmid from the National Cancer Institute, who led one of the studies. “Nobody would ever have thought we should worry about gut bacteria when thinking about treating cancer.”

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Christian Yamashiba Kasongo's curator insight, January 28, 2014 12:29 AM

Three Cancer Drugs Don't Work Properly Without Gut Bacteria

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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Garlic could aid cystic fibrosis fight

Garlic could aid cystic fibrosis fight | A Tale of Two Medicines | Scoop.it

A chemical in garlic kills bacteria that cause deadly infections in people with cystic fibrosis, University research shows.

 

The study reveals that the chemical - known as allicin - could be an effective treatment against infectious bacteria that are highly resistant to most antibiotics.

 

Allicin is produced naturally by garlic bulbs to ward off a closely-related group of plant pathogens found in soil and water habitats.

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Effect of green tea (matcha) on gastrointestinal tract absorption of polychlorinated biphenyls, polychlorinated dibenzofurans and polychlorinated dibenzo-p-dioxins in rats.

This paper presents the liver distribution and fecal excretion of polychlorinated biphenyls (PCB), polychlorinated dibenzofurans (PCDF) congeners and polychlorinated dibenzo-p-dioxins (PCDD) congeners, in male rats fed with powdered green tea (matcha). The rats were given a treatment diet containing 10% matcha for the first five days. Then, the animals were administered 4 g of 10% matcha diet containing 0.5 ml of the casual rice-bran oil of Yusho that had occurred in the Southwest part of Japan in 1968 and kept on the same diet for another five days. The fecal excretion of PCB, PCDF and PCDD in the group fed with 10% matcha were 4.4, 2.4-9.1 and 2.5-4.7 times higher (p < 0.01), respectively, than that in the control group. The liver distribution of PCB, PCDF and PCDD in the same groups were 79%, 20-75% and 26-67% of the control group, respectively. These findings suggest that administration of matcha is useful as a treatment of Yusho patients exposed to PCB, PCDF and PCDD.

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Four types of fatty acids exert differential impact on pancreatic cancer growth

Four types of fatty acids exert differential impact on pancreatic cancer growth | A Tale of Two Medicines | Scoop.it

Increased fatty acids (FAs) regulate pancreatic cancer progression, however, the detailed mechanism is not clear, and different forms of FAs may play diversified roles in pancreatic cancer. To elucidate the underlying mechanism, we compared the effects of four major types of FAs on pancreatic cancer growth both in cell culture and in a mouse model. HPAF pancreatic cancer cells were implanted in nude mice for 14 weeks, and the mice were fed with four different high-fat/high-energy diets (15% fat, 4 kcal/g), an iso-caloric diet (5% fat, 4 kcal/g) and a normal diet (4% fat, 3 kcal/g). The high fat diets were rich in saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and n-6 and n-3 polyunsaturated fatty acids (n6- and n3PUFAs), respectively. Whilst n3PUFA diet decreased tumor viability, the other high fat diets stimulated tumor viability by apparently different mechanisms. For instance, xenografts whose carriers were fed with SFA diet had marked expression of cancer-related proteins and lipid droplets. Although mice that were fed with MUFA- and n6PUFA diets had pancreatic tumors of similar size, liver metastasis occurred more frequently in those with the n6PUFA diet. In experiments in vitro, HPAF-cell population was increased by SFAs and MUFAs, decreased by n3PUFAs and not changed by n6PUFAs. In conclusion, different fatty acids have different impact on pancreatic cancer cells. The effects of fatty acids on pancreatic cancer cells were consistent in vivo and in vitro except that n6PUFAs only had regulatory effects in vivo.

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Food-derived polyphenols inhibit pancreatic cancer growth through mitochondrial cytochrome C release and apoptosis.

Food-derived polyphenols inhibit pancreatic cancer growth through mitochondrial cytochrome C release and apoptosis. | A Tale of Two Medicines | Scoop.it

There is increasing evidence that food-derived polyphenols have a beneficial effect for cancers. Our purpose was to determine the effect and mechanism of action of these compounds on pancreatic cancer. We measured effects of quercetin on pancreatic cancer in a nude mouse model. We also investigated the effects of quercetin, rutin, trans-resveratrol and genistein on apoptosis and underlying signaling in pancreatic carcinoma cells in vitro. Quercetin decreased primary tumor growth, increased apoptosis and prevented metastasis in a model of pancreatic cancer. In vitro quercetin and trans-resveratrol, but not rutin, markedly enhanced apoptosis, causing mitochondrial depolarization and cytochrome c release followed by caspase-3 activation. In addition, the effect of a combination of quercetin and trans-resveratrol on mitochondrial cytochrome c release and caspase-3 activity was greater than the expected additive response. The inhibition of mitochondrial permeability transition prevented cytochrome c release, caspase-3 activation and apoptosis caused by polyphenols. Nuclear factor-κB activity was inhibited by quercetin and trans-resveratrol, but not genistein, indicating that this transcription factor is not the only mediator of the polyphenols' effects on apoptosis. The results suggest that food-derived polyphenols inhibit pancreatic cancer growth and prevent metastasis by inducing mitochondrial dysfunction, resulting in cytochrome c release, caspase activation and apoptosis.

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Efficacy of Garcinia kola 0.5% Aqueous Eye Drops in Patients with Primary Open-Angle Glaucoma or Ocular Hypertension

Efficacy of Garcinia kola 0.5% Aqueous Eye Drops in Patients with Primary Open-Angle Glaucoma or Ocular Hypertension | A Tale of Two Medicines | Scoop.it

To evaluate the intraocular pressure (IOP) lowering efficacy of Garcinia kola 0.5% aqueous solution eye drops in patients with newly diagnosed primary open-angle glaucoma or ocular hypertension (POAG/OH).

 

A randomized, double-masked, multicenter, active-controlled prospective study. Patients who met the inclusion criteria were randomly assigned in equal numbers to receive Timolol 0.5% eye drops as a control medication (A = Group 1 eyes) or Garcinia kola 0.5% eye drops as the study medication (B = Group 2 eyes). All drops were instilled at 6 am and 6 pm daily. Goldman applanation tonometry was performed at 9 am, 12 pm and 3 pm at baseline, week-6, week-12 and week-24 visits. Voluntary and actively elicited reports of adverse events were documented. The mean change in IOP over 24 weeks was the primary outcome measure. Both groups were compared for statistically significant differences at all visits. A P < 0.05 was considered statistically significant.

 

A total of 178 patients were randomly assigned to G. kola and Timolol groups. At baseline there were no differences in mean IOP between groups, based on age, sex, or diagnosis. At the end of the study period (24th week), the mean (± SD) reduction in IOP was 12.93 ± 2.3 mmHg (47.8% ± 0.8% reduction) in G. Kola group and 13.09 ± 2.8 mm Hg (48.2% ± 1.03% reduction) in the Timolol group (P > 0.05). Adverse events were mild in nature with no statistically significant differences between groups (P > 0.05).


Garcinia kola ophthalmic solution significantly reduces IOP as compared to baseline. The IOP lowering effect of both treatments was equivalent.

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Nutritional medicine as mainstream in psychiatry.

Psychiatry is at an important juncture, with the current pharmacologically focused model having achieved modest benefits in addressing the burden of poor mental health worldwide. Although the determinants of mental health are complex, the emerging and compelling evidence for nutrition as a crucial factor in the high prevalence and incidence of mental disorders suggests that diet is as important to psychiatry as it is to cardiology, endocrinology, and gastroenterology. Evidence is steadily growing for the relation between dietary quality (and potential nutritional deficiencies) and mental health, and for the select use of nutrient-based supplements to address deficiencies, or as monotherapies or augmentation therapies. We present a viewpoint from an international collaboration of academics (members of the International Society for Nutritional Psychiatry Research), in which we provide a context and overview of the current evidence in this emerging field of research, and discuss the future direction. We advocate recognition of diet and nutrition as central determinants of both physical and mental health.

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The Epigenetic Impact of Cruciferous Vegetables on Cancer Prevention.

Many studies have contributed to the incorporation of dietary agents as forms of cancer remediation. Cruciferous vegetables are enriched with several chemical components that have tremendous negative effects on multiple pathways of cancer cells due to their anti-proliferative and anti-tumorigenic properties. The consumption of these vegetables is beneficial in the sense that they are precursors to glucosinolates which give rise to isothiocyanates such as sulforaphane and indoles such as indole-3-carbinol. Most cancers are characterized by the overexpression of HDAC and DNMT and the mis-expression of miRNAs. Both I3C and SFN are inhibitors and regulators of these processes and the incorporation of these compounds causes cancerous cell lines to take on a healthier and more normalized appearance. In addition, significant decreases in uncontrolled cell growth as well as increases in programed cell death are noticed with the incorporation of SFN and I3C. Many studies reveal that cruciferous vegetables are key instruments in advancing progress toward the prevention of cancer. Future studies will undoubtedly be directed toward further deciding the epigenetic events impacted by the bioactive components of cruciferous vegetables and their significance with respect to not only cancer prevention but also many other biological processes.

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Tannic acid inhibited norovirus binding to HBGA receptors, a study of 50 Chinese medicinal herbs

Noroviruses (NoVs) are the leading cause of viral acute gastroenteritis affecting people of all ages worldwide. The disease is difficult to control due to its widespread nature and lack of an antiviral or vaccine. NoV infection relies on the interaction of the viruses with histo-blood group antigens (HBGAs) as host receptors. Here we investigated inhibition effects of Chinese medicinal herbs against NoVs binding to HBGAs for potential antivirals against NoVs. Blocking assays was performed using the NoV protrusion (P) protein as NoV surrogate and saliva as HBGAs. Among 50 clinically effective Chinese medicinal herbs against gastroenteritis diseases, two herbs were found highly effective. Chinese Gall blocked NoV P dimer binding to type A saliva at IC50 = 5.35 μg/ml and to B saliva at IC50 = 21.7 μg/ml. Similarly, Pomegranate blocked binding of NoV P dimer to type A saliva at IC50 = 15.59 μg/ml and B saliva at IC50 = 66.67 μg/ml. Literature data on preliminary biochemistry analysis showed that tannic acid is a common composition in the extracts of the two herbs, so we speculate that it might be the effective compound and further studies using commercially available, highly purified tannic acid confirmed the tannic acid as a strong inhibitor in the binding of NoV P protein to both A and B saliva (IC50 ≈ 0.1 μM). In addition, we tested different forms of hydrolysable tannins with different alkyl esters, including gallic acid, ethyl gallate, lauryl gallate, octyl gallate and propyl gallate. However, none of these tannins-derivatives revealed detectable inhibiting activities. Our data suggested that tannic acid is a promising candidate antiviral against NoVs.

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Meta-analysis of randomized controlled trials on cognitive effects of Bacopa monnieri extract.

Bacopa monnieri has a long history in Ayurvedic medicine for neurological and behavioral defects. To assess its efficacy in improving cognitive function.

 

MEDLINE, EMBASE, CINAHL, AMED, Cochrane Central of clinical trial, WHO registry, Thai Medical Index, Index Medicus Siriraj library and www.clinicaltrial.gov were searched from the inception date of each database to June 2013 using scientific and common synonyms of Bacopa monnieri, cognitive performance or memory. The reference lists of retrieved articles were also reviewed. Randomized, placebo controlled human intervention trials on chronic ≥ 12 weeks dosing of standardized extracts of Bacopa monnieri without any co-medication were included in this study. The methodological quality of studies was assessed using Cochrane's risk of bias assessment and Jadad's quality scales. The weighted mean difference and 95% confidence interval (95% CI) were performed using the random-effects model of the Dersimonian-Laird method.

 

Nine studies met the inclusion criteria using 518 subjects. Overall quality of all included trials was low risk of bias and quality of reported information was high. Meta-analysis of 437 eligible subjects showed improved cognition by shortened Trail B test (-17.9 ms; 95% CI -24.6 to -11.2; p<0.001) and decreased choice reaction time (10.6 ms; 95% CI -12.1 to -9.2; p<0.001).

 

This meta-analysis suggests that Bacopa monnieri has the potential to improve cognition, particularly speed of attention but only a large well designed 'head-to-head' trial against an existing medication will provide definitive data on its efficacy on healthy or dementia patients using a standardized preparation.

 

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Increased sugar uptake promotes oncogenesis via EPAC/RAP1 and O-GlcNAc pathways

There is a considerable resurgence of interest in the role of aerobic glycolysis in cancer; however, increased glycolysis is frequently viewed as a consequence of oncogenic events that drive malignant cell growth and survival. Here we provide evidence that increased glycolytic activation itself can be an oncogenic event in a physiologically relevant 3D culture model. Overexpression of glucose transporter type 3 (GLUT3) in nonmalignant human breast cells activated known oncogenic signaling pathways, including EGFR, β1 integrin, MEK, and AKT, leading to loss of tissue polarity and increased growth. Conversely, reduction of glucose uptake in malignant cells promoted the formation of organized and growth-arrested structures with basal polarity, and suppressed oncogenic pathways. Unexpectedly and importantly, we found that unlike reported literature, in 3D the differences between “normal” and malignant phenotypes could not be explained by HIF-1α/2α, AMPK, or mTOR pathways. Loss of epithelial integrity involved activation of RAP1 via exchange protein directly activated by cAMP (EPAC), involving also O-linked N-acetylglucosamine modification downstream of the hexosamine biosynthetic pathway. The former, in turn, was mediated by pyruvate kinase M2 (PKM2) interaction with soluble adenylyl cyclase. Our findings show that increased glucose uptake activates known oncogenic pathways to induce malignant phenotype, and provide possible targets for diagnosis and therapeutics.

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Vitamin C may alleviate exercise-induced bronchoconstriction: a meta-analysis.

To determine whether vitamin C administration influences exercise-induced bronchoconstriction (EIB).

 

Systematic review and meta-analysis.

 

MEDLINE and Scopus were searched for placebo-controlled trials on vitamin C and EIB. The primary measures of vitamin C effect used in this study were: (1) the arithmetic difference and (2) the relative effect in the postexercise forced expiratory volume in 1 s (FEV1) decline between the vitamin C and placebo periods. The relative effect of vitamin C administration on FEV1 was analysed by using linear modelling for two studies that reported full or partial individual-level data. The arithmetic differences and the relative effects were pooled by the inverse variance method. A secondary measure of the vitamin C effect was the difference in the proportion of participants suffering from EIB on the vitamin C and placebo days.

 

3 placebo-controlled trials that studied the effect of vitamin C on EIB were identified. In all, they had 40 participants. The pooled effect estimate indicated a reduction of 8.4 percentage points (95% CI 4.6 to 12) in the postexercise FEV1 decline when vitamin C was administered before exercise. The pooled relative effect estimate indicated a 48% reduction (95% CI 33% to 64%) in the postexercise FEV1 decline when vitamin C was administered before exercise. One study needed imputations to include it in the meta-analyses, but it also reported that vitamin C decreased the proportion of participants who suffered from EIB by 50 percentage points (95% CI 23 to 68); this comparison did not need data imputations.

 

Given the safety and low cost of vitamin C, and the positive findings for vitamin C administration in the three EIB studies, it seems reasonable for physically active people to test vitamin C when they have respiratory symptoms such as cough associated with exercise. Further research on the effects of vitamin C on EIB is warranted.

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Quantification of epigenetic biomarkers: an evaluation of established and emerging methods for DNA methylation analysis

DNA methylation is an important epigenetic mechanism in several human diseases, most notably cancer. The quantitative analysis of DNA methylation patterns has the potential to serve as diagnostic and prognostic biomarkers, however, there is currently a lack of consensus regarding the optimal methodologies to quantify methylation status. To address this issue we compared five analytical methods: (i) MethyLight qPCR, (ii) MethyLight digital PCR (dPCR), methylation-sensitive and -dependent restriction enzyme (MSRE/MDRE) digestion followed by (iii) qPCR or (iv) dPCR, and (v) bisulfite amplicon next generation sequencing (NGS). The techniques were evaluated for linearity, accuracy and precision.

 

Methylight qPCR displayed the best linearity across the range of tested samples. Observed methylation measured by Methylight- and MSRE/MDRE-qPCR and -dPCR were not significantly different to expected values whilst bisulfite amplicon NGS analysis over-estimated methylation content. Bisulfite amplicon NGS showed good precision, whilst the lower precision of qPCR and dPCR analysis precluded discrimination of differences of <25% in methylation status. A novel dPCR Methylight assay is also described as a potential method for absolute quantification that simultaneously measures both sense and antisense DNA strands following bisulfite treatment.

 

Our findings comprise a comprehensive benchmark for the quantitative accuracy of key methods for methylation analysis and demonstrate their applicability to the quantification of circulating tumour DNA biomarkers by using sample concentrations that are representative of typical clinical isolates.

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Plant extract trumps nicotine patches to quit smoking.

Plant extract trumps nicotine patches to quit smoking. | A Tale of Two Medicines | Scoop.it

If quitting smoking is one of your New Year's resolutions, we might have just the thing. Cytisine, a plant extract commonly used in eastern Europe to wean people off cigarettes, appears to be much better at the task than nicotine replacement patches and gums.

Not to be confused with the DNA building block cytosine, cytisine is an alkaloid extract from the laburnum or golden rain tree (Laburnum anagyroides), which grows all over Europe. It works by blocking nicotine's access to the brain's pleasure receptors.

Like nicotine, cytisine is toxic when ingested in large amounts but is safe at low doses. It is produced commercially mainly in Bulgaria and Poland, and has been used as a quitting aid in eastern European countries since the 1960s but is largely unknown elsewhere. Clinical trials carried out in the 60s and 70s did not meet US and European standards so did not lead to wider adoption.

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Efficacy of Dragon's blood cream on wound healing: A randomized, double-blind, placebo-controlled clinical trial

The blood-red sap of Dragon's blood has been used in folk medicine for fractures, wounds, inflammation, gastrointestinal disorders, rheumatism, blood circulation dysfunctions, and cancer. Existing in vitro and in vivo bioactivity of this herb on different mechanisms of healing shows strong potential of this sap in wound healing. This clinical trial study was designated to evaluate the wound healing effect of Dragon's blood on human wounds. Sixty patients, between the ages of 14–65 years, who were referred to remove their skin tag, were assigned to this double-blind, placebo-controlled, randomized clinical trial and received either Dragon's blood or a placebo cream. They were visited on the 3rd, 5th, 7th, 10th, 14th, and 20th day of the trial to check the process of healing and to measure the wound's surface. At the end of trial, there was a significant difference in the mean duration of wound healing between the two groups (p = 0.0001). The phenolic compounds and the alkaloid taspine, which exist in Dragon's-blood resin, are probably the main reasons for the wound healing property of this plant. Being natural accessible, safe, and affordable makes Dragon's blood cream, a good choice for addition to the wound healing armamentarium. Further studies on wounds with different causes and among larger populations are suggested to ensure the effectiveness and safety of Dragon's blood.

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Drinking green tea before taking supplements may offer protection from toxicity.

Drinking green tea before taking supplements may offer protection from toxicity. | A Tale of Two Medicines | Scoop.it

As high doses of green tea extract supplements for weight loss become more popular, potential liver toxicity becomes a concern. In the last decade, dozens of people have been diagnosed with the condition. However, drinking green tea in the weeks before taking supplements likely reduces risk, according to researchers in Penn State's College of Agricultural Sciences.

 

Researchers gave mice high doses of the green tea polyphenol epigallocatechin-3-gallate (EGCG). The dosage was equivalent to the amount of the polyphenol found in some dietary supplements taken by humans.

 

One group of mice was pretreated with a diet containing a low level of ECGC for two weeks prior to receiving high doses of the polyphenol. Another group was fed a diet that did not include EGCG prior to receiving the high, supplement-like doses. After three days of high doses, the scientists tested the blood of the mice to determine how their livers handled the EGCG. Pretreated mice had a 75 percent reduction in liver toxicity compared to untreated mice.

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The Food and Drug Administration Covers Up Evidence of Fraud, Fabrication, and Scientific Misconduct

The Food and Drug Administration Covers Up Evidence of Fraud, Fabrication, and Scientific Misconduct | A Tale of Two Medicines | Scoop.it

Agents of the Food and Drug Administration know better than anyone else just how bad scientific misbehavior can get. Reading the FDA’s inspection files feels almost like watching a highlights reel from a Scientists Gone Wild video. It’s a seemingly endless stream of lurid vignettes—each of which catches a medical researcher in an unguarded moment, succumbing to the temptation to do things he knows he really shouldn’t be doing. Faked X-ray reports. Forged retinal scans. Phony lab tests. Secretly amputated limbs. All done in the name of science when researchers thought that nobody was watching.

 

That misconduct happens isn’t shocking. What is: When the FDA finds scientific fraud or misconduct, the agency doesn’t notify the public, the medical establishment, or even the scientific community that the results of a medical experiment are not to be trusted. On the contrary. For more than a decade, the FDA has shown a pattern of burying the details of misconduct. As a result, nobody ever finds out which data is bogus, which experiments are tainted, and which drugs might be on the market under false pretenses. The FDA has repeatedly hidden evidence of scientific fraud not just from the public, but also from its most trusted scientific advisers, even as they were deciding whether or not a new drug should be allowed on the market. Even a congressional panel investigating a case of fraud regarding a dangerous drug couldn't get forthright answers. For an agency devoted to protecting the public from bogus medical science, the FDA seems to be spending an awful lot of effort protecting the perpetrators of bogus science from the public.

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Dried whole-plant Artemisia annua slows evolution of malaria drug resistance and overcomes resistance to artemisinin

Pharmaceutical monotherapies against human malaria have proven effective, although ephemeral, owing to the inevitable evolution of resistant parasites. Resistance to two or more drugs delivered in combination will evolve more slowly; hence combination therapies have become the preferred norm in the fight against malaria. At the forefront of these efforts has been the promotion of Artemisinin Combination Therapy, but despite these efforts, resistance to artemisinin has begun to emerge. In 2012, we demonstrated the efficacy of the whole plant (WP)—not a tea, not an infusion—as a malaria therapy and found it to be more effective than a comparable dose of pure artemisinin in a rodent malaria model. Here we show that WP overcomes existing resistance to pure artemisinin in the rodent malaria Plasmodium yoelii. Moreover, in a long-term artificial selection for resistance in Plasmodium chabaudi, we tested resilience of WP against drug resistance in comparison with pure artemisinin (AN). Stable resistance to WP was achieved three times more slowly than stable resistance to AN. WP treatment proved even more resilient than the double dose of AN. The resilience of WP may be attributable to the evolutionary refinement of the plant’s secondary metabolic products into a redundant, multicomponent defense system. Efficacy and resilience of WP treatment against rodent malaria provides compelling reasons to further explore the role of nonpharmaceutical forms of AN to treat human malaria.

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Evidence Shows Some Sugars Are Worse Than Others; Fructose Tops the List.

Evidence Shows Some Sugars Are Worse Than Others; Fructose Tops the List. | A Tale of Two Medicines | Scoop.it

Are all sugars created equal, or are some more likely to cause obesity and related diseases, including type 2 diabetes?

 

A study published in the American Journal of Clinical Nutrition in 2004 proposed that the growing use of high-fructose corn syrup as a sweetener in processed foods could be linked to ballooning rates of obesity. It launched a long, contentious scientific debate.

 

A recently published paper in the Mayo Clinic Proceedings won’t settle the issue, but it does pose a significant new challenge to those who believe that a sugar is a sugar is a sugar.

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Nicotinamide sensitizes human breast cancer cells to the cytotoxic effects of radiation and cisplatin

Nicotinamide sensitizes human breast cancer cells to the cytotoxic effects of radiation and cisplatin | A Tale of Two Medicines | Scoop.it
Poly(ADP-ribose) polymerase (PARP) inhibitors enhance the effect of DNA alkylating agents on BRCA1‑ and BRCA2-deficient cell lines. The aim of this study was to analyze the effect of the PARP inhibitor nicotinamide (NAM) on breast cancer cells with different BRCA1 expression or function, such as BRCA1‑deficient MDA-MB-436 cells, low expression BRCA1 MCF-7 cells, and the BRCA1 wild‑type MDA-MB-231 cells, to demonstrate its effects as a chemo‑ or radiosensitizing agent. PARP activity was analyzed in MDA-MB-436, MCF-7 and MDA-MB-231 breast cancer cells subjected or not to NAM. Inhibition of PARP by NAM in the presence of DNA damage was examined by Alexa Fluor 488 immunofluorescence. Crystal violet assays were used to test growth inhibition and the chemo‑ and radiosensitization effects of NAM were investigated using clonogenic assays. Significant differences among data sets were determined using two-tailed ANOVA and Bonferroni tests. We demonstrated that NAM reduces PARP activity in vitro, and in cells subjected or not to DNA damage, it also reduces the viability of breast cancer cell lines and synergyzes the cytotoxicity of cisplatin in MDA-MB-436 and MCF-7 cells. Downregulation of PARP1 with siRNA led to modest growth inhibition, which was further increased by cisplatin. Nicotinamide also induced radiosensitization in MDA-MB-436 and MDA-MB-231 cells. In conclusion, NAM may be used as a chemo‑ or radiosensitizing agent regardless of the BRCA1 status in breast cancer.
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Krishan Maggon 's curator insight, January 28, 2:30 AM
Nicotinamide sensitizes human breast cancer cells to the cytotoxic effects of radiation and cisplatinAuthors: G. Domínguez-Gómez J. Díaz-Chávez A. Chávez-Blanco A. Gonzalez-FierroJ. E. Jiménez-Salazar P. Damián-Matsumura L. E. Gómez-Quiroz A. Dueñas-GonzálezCorresponding author: A. Dueñas-González [

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Published online on: Tuesday, December 9, 2014Pages: 721-728DOI: 10.3892/or.2014.3661
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A push-pull treatment for strengthening the ‘lazy eye’ in amblyopia

Almost all individuals exhibit sensory eye dominance, one neural basis of which is unequal interocular inhibition. Sensory eye dominance can impair binocular functions that depend on both excitatory and inhibitory mechanisms 1, 2 and 3. We developed a ‘push-pull’ perceptual learning protocol that simultaneously affects the excitatory and inhibitory networks to reduce sensory eye dominance and improve stereopsis in adults with otherwise normal vision [4]. The push-pull protocol provides a promising clinical paradigm for treating the extreme sensory eye dominance in amblyopia (‘lazy eye’). The prevailing standard of care does not directly treat sensory eye dominance; instead, selected excitatory functions in the amblyopic eye are stimulated while the strong eye is patched, on the assumption that recovery of the weak eye’s excitatory functions rebalances the eyes. Patching the strong eye does not directly address interocular inhibition; in contrast, the push-pull protocol by design excites the weak eye, while completely inhibiting the strong eye’s perception to recalibrate the interocular balance of excitatory and inhibitory interactions. Here, we show that three adult amblyopes who trained on the push-pull protocol gained longstanding improvements in interocular balance and stereopsis. Our findings provide a proof-of-concept and evidence that push-pull learning leads to long-term plasticity.

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Role of diet in prostate cancer: the epigenetic link

Role of diet in prostate cancer: the epigenetic link | A Tale of Two Medicines | Scoop.it

Diet is hypothesized to be a critical environmentally related risk factor for prostate cancer (PCa) development, and specific diets and dietary components can also affect PCa progression; however, the mechanisms underlying these associations remain elusive. As for a maturing organism, PCa’s epigenome is plastic and evolves from the pre-neoplastic to the metastatic stage. In particular, epigenetic remodeling relies on substrates or cofactors obtained from the diet. Here we review the evidence that bridges dietary modulation to alterations in the prostate epigenome. We propose that such diet-related effects offer a mechanistic link between the impact of different diets and the course of PCa development and progression.

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Serum glucose and risk of cancer: a meta-analysis

Raised serum glucose has been linked to increased risk of many solid cancers. We performed a meta-analysis to quantify and summarise the evidence for this link.

 

Pubmed and Embase were reviewed, using search terms representing serum glucose and cancer. Inclusion and exclusion criteria focused on epidemiological studies with clear definitions of serum glucose levels, cancer type, as well as well-described statistical methods with sufficient data available. We used 6.1 mmol/L as the cut-off for high glucose, consistent with the WHO definition of metabolic syndrome. Random effects analyses were performed to estimate the pooled relative risk (RR).

 

Nineteen studies were included in the primary analysis, which showed a pooled RR of 1.32 (95% CI: 1.20 – 1.45). Including only those individuals with fasting glucose measurements did not have a large effect on the pooled RR (1.32 (95% CI: 1.11-1.57). A stratified analysis showed a pooled RR of 1.34 (95% CI: 1.02-1.77) for hormonally driven cancer and 1.21 (95% CI: 1.09-1.36) for cancers thought to be driven by Insulin Growth Factor-1.

 

A positive association between serum glucose and risk of cancer was found. The underlying biological mechanisms remain to be elucidated but our subgroup analyses suggest that the insulin- IGF-1 axis does not fully explain the association. These findings are of public health importance as measures to reduce serum glucose via lifestyle and dietary changes could be implemented in the context of cancer mortality.

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Life Extension Foundation supported trial finds 7,000 IU vitamin D improves immunological parameters in HIV-positive individuals

Dr. Virginia A. Stallings and colleagues from the Children's Hospital of Philadelphia published a double-blind, randomized, placebo-controlled trial in which treatment with a 7,000 IU vitamin D3 product benefited HIV-positive children and young adults. The vitamin D supplements used in the trial were provided by the Life Extension Foundation. The publication, titled "High-Dose Vitamin D3 Supplementation in Children and Young Adults with HIV: A Randomized, Placebo-Controlled Trial," was published in The Pediatric Infectious Disease Journal.

 

Over a 12-month period, 50 HIV-positive individuals aged 5 to 24.9 years were given 7,000 IU of vitamin D3 or placebo daily. Blood tests showed that 95% of study participants had suboptimal vitamin D blood levels at baseline.  Vitamin D3 supplementation increased average serum 25-hydroxyvitamin D3 levels from 18 ng/mL at baseline to 32 ng/mL at three months. After the 12-month study period, vitamin D3 subjects maintained a 12 ng/mL increase in 25-hydroxyvitamin D blood levels compared to placebo. The supplement dosage was also observed to be safe in this population.

 

Several measures of immune function improved with vitamin D3 supplementation compared with placebo. There was an increase in the percentage of naïve T helper cells, CD4+ cells, and a reduction in RNA viral load at several time points during the study.

 

"It's encouraging to see that high-dose vitamin D3 improved important aspects of immune function in these HIV-positive study participants without causing any major side effects. This study certainly supports further research into the use of high-dose vitamin D3 supplementation for individuals with HIV," says Dr. Steven Hirsh, director of clinical research for Life Extension.

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Anti-Inflammatory Activity of Fruit Fractions in Vitro, Mediated through Toll-Like Receptor 4 and 2 in the Context of Inflammatory Bowel Disease

Anti-Inflammatory Activity of Fruit Fractions in Vitro, Mediated through Toll-Like Receptor 4 and 2 in the Context of Inflammatory Bowel Disease | A Tale of Two Medicines | Scoop.it

Pattern recognition receptors such as Toll-Like Receptor 2 (TLR2) and 4 (TLR4) are important in detecting and responding to stress and bacterial stimuli. Defect or damage in the TLR2 and TLR4 pathways can lead to sustained inflammation, characteristic of inflammatory bowel disease (IBD). The goal of this study was to identify fruit fractions that can be tested further to develop them as complementary therapies for IBD. In order to do this, we identified fruit fractions that mediate their anti-inflammatory response through the TLR4 and TLR2 pathway. Human Embryonic Kidney (HEK)-hTLR4 and hTLR2 cells were stimulated with their respective ligands to induce inflammation. These cells were treated with one of the 12 fractionated fruits and the inflammatory effect measured. 10 of the fruits came up as anti-inflammatory in the hTLR4 assay and nine in the hTLR2 assays. Many of the fruit fractions mediated their anti-inflammatory actions either mainly in their hydrophobic fractions (such as elderberry) or hydrophilic fractions (such as red raspberry), or both. The strongest anti-inflammatory effects were seen for feijoa and blackberry. This study shows that fruits can have multiple fractions eliciting anti-inflammatory effects in a pathway specific manner. This suggests that the compounds found in fruits can act together to produce health benefits by way of reducing inflammation. Exploiting this property of fruits can help develop complimentary therapies for inflammatory diseases.

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Potential of epigenetic therapies in non-cancerous conditions.

There has been an explosion of knowledge in the epigenetics field in the past 20 years. The first epigenetic therapies have arrived in the clinic for cancer treatments. In contrast, much of the promise of epigenetic therapies for non-cancerous conditions remains in the laboratories. The current review will focus on the recent progress that has been made in understanding the pathogenic role of epigenetics in immune and inflammatory conditions, and how the knowledge may provide much needed new therapeutic targets for many autoimmune diseases. Dietary factors are increasingly recognized as potential modifiers of epigenetic marks that can influence health and diseases across generations. The current epigenomics revolution will almost certainly complement the explosion of personal genetics medicine to help guide treatment decisions and disease risk stratification.

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