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Smokers with BRCA2 gene mutation 'have increased lung cancer risk'

Smokers with BRCA2 gene mutation 'have increased lung cancer risk' | A Tale of Two Medicines | Scoop.it

It is well known that mutations in the BRCA genes increase the risk of female breast and ovarian cancers. But for the first time, researchers from The Institute of Cancer Research in the UK have discovered a link between smokers with a BRCA2 gene mutation and increased risk of lung cancer.


According to the American Cancer Society, approximately 224,201 Americans will receive a lung cancer diagnosis this year.

It is common knowledge that smoking is the leading risk factor for lung cancer, causing at least 80% of deaths from the disease.

 

But the researchers of this latest study, led by Richard Houlston, professor of molecular population and genetics at The Institute of Cancer Research (ICR), say past studies have indicated that genetic factors may also increase lung cancer risk.

 

To investigate further, the research team compared the DNA of 11,348 European individuals who had lung cancer with the DNA of 15,861 Europeans who were free of the disease.

 

Their findings, recently published in the journal Nature Genetics, revealed that smokers who had mutations in the BRCA2 gene had a 25% chance of developing lung cancer during their lifetime. Smokers in general have around a 13-15% chance of lung cancer, so the study results show that a BRCA2 gene mutation can increase lung cancer risk even further.

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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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Mushroom extract, AHCC, helpful in treating HPV

Mushroom extract, AHCC, helpful in treating HPV | A Tale of Two Medicines | Scoop.it

A Japanese mushroom extract appears to be effective for the eradication of human papillomavirus (HPV), according to a pilot clinical trial at The University of Texas Health Science Center at Houston (UTHealth) Medical School.

 

The results were presented at the 11th International Conference of the Society for Integrative Oncology in Houston today by principal investigator Judith A. Smith, Pharm.D., associate professor in the Department of Obstetrics, Gynecology and Reproductive Sciences at the UTHealth Medical School.

 

Ten HPV-positive women were treated orally with the extract, AHCC (active hexose correlated compound) once daily for up to six months. Five achieved a negative HPV test result -- three with confirmed eradication after stopping AHCC -- with the remaining two responders continuing on the study.

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Olea europaea leaf extract improves the treatment response of GBM stem cells by modulating miRNA expression

Olea europaea leaf extract improves the treatment response of GBM stem cells by modulating miRNA expression | A Tale of Two Medicines | Scoop.it

The stem-like cells of Glioblastoma multiforme (GBM) tumors (GSCs) are one of the important determinants of recurrence and drug resistance. The aims of the current study were to evaluate the anticancer effect of Olea europaea leaf extract (OLE) on GBM cell lines, the association between OLE and TMZ responses, and the effect of OLE and the OLE-TMZ combination in GSCs and to clarify the molecular mechanism of this effect on the expression of miRNAs related to cell death. The anti-proliferative activity of OLE and the effect of the OLE-TMZ combination were tested in the T98G, U-138MG and U-87MG GBM cell lines using WST-1 assay. The mechanism of cell death was analyzed with Annexin V/FITC and TUNEL assays. The effects of OLE on the expression levels of miR-181b, miR-153, miR-145 and miR-137 and potential mRNA targets were analyzed in GSCs using RT-qPCR. OLE exhibited anti-proliferative effects via apoptosis and necrosis in the GBM cell lines. In addition, OLE significantly induced the expression of miR-153, miR-145, and miR-137 and decreased the expression of the target genes of these miRNAs in GSCs (p < 0.05). OLE causes cell death in GBM cells with different TMZ responses, and this effect is synergistically increased when the cells are treated with a combination of OLE and TMZ. This is the first study to indicate that OLE may interfere with the pluripotency of GSCs by modulating miRNA expression. Further studies are required, but we suggest that OLE may have a potential for advanced therapeutic cancer drug studies in GBM.

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Anti-Neuroinflammatory effects of the extract of Achillea fragrantissima

Anti-Neuroinflammatory effects of the extract of Achillea fragrantissima | A Tale of Two Medicines | Scoop.it

The neuroinflammatory process plays a central role in the initiation and progression of neurodegenerative diseases such as Parkinson's and Alzheimer's diseases, and involves the activation of brain microglial cells. During the neuroinflammatory process, microglial cells release proinflammatory mediators such as cytokines, matrix metalloproteinases (MMP), Reactive oxygen species (ROS) and nitric oxide (NO). In the present study, extracts from 66 different desert plants were tested for their effect on lipopolysaccharide (LPS) - induced production of NO by primary microglial cells. The extract of Achillea fragrantissima (Af), which is a desert plant that has been used for many years in traditional medicine for the treatment of various diseases, was the most efficient extract, and was further studied for additional anti-neuroinflammatory effects in these cells.

 

In the present study, the ethanolic extract prepared from Af was tested for its anti-inflammatory effects on lipopolysaccharide (LPS)-activated primary cultures of brain microglial cells. The levels of the proinflammatory cytokines interleukin1β (IL-1β) and tumor necrosis factor-α (TNFα) secreted by the cells were determined by reverse transcriptase-PCR and Enzyme-linked immunosorbent assay (ELISA), respectively. NO levels secreted by the activate cells were measured using Griess reagent, ROS levels were measured by 2'7'-dichlorofluorescein diacetate (DCF-DA), MMP-9 activity was measured using gel zymography, and the protein levels of the proinflammatory enzymes cyclooxygenase-2 (COX-2) and induced nitric oxide synthase (iNOS) were measured by Western blot analysis. Cell viability was assessed using Lactate dehydrogenase (LDH) activity in the media conditioned by the cells or by the crystal violet cell staining.

 

We have found that out of the 66 desert plants tested, the extract of Af was the most efficient extract and inhibited ~70% of the NO produced by the LPS-activated microglial cells, without affecting cell viability. In addition, this extract inhibited the LPS - elicited expression of the proinflammatory mediators IL-1β, TNFα, MMP-9, COX-2 and iNOS in these cells.

 

Thus, phytochemicals present in the Af extract could be beneficial in preventing/treating neurodegenerative diseases in which neuroinflammation is part of the pathophysiology.

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Cancer cells can ‘infect’ normal neighbours

Cancer cells can ‘infect’ normal neighbours | A Tale of Two Medicines | Scoop.it

When a cancer cell throws out its trash, it can turn healthy neighbours into fellow tumour cells, researchers have found.

 

Many cells, including cancerous ones, shed thousands of tiny membrane-bound vesicles called exosomes that contain proteins, DNA and RNA. The process is thought to be a waste-management system, but it may also facilitate cell-to-cell communication: some of these vesicles can then merge with other cells and dump their payload inside.

 

In a study published online on 23 October in Cancer Cell1, researchers show that when human breast-cancer exosomes can cause tumours when mixed with normal cells then injected into mice. The results could pave the way to finding markers to monitor the progression of cancer, and possibly even point to targets for therapies.

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Lycopene and Beta-carotene Induce Cell-Cycle Arrest and Apoptosis in Human Breast Cancer Cell Lines

Lycopene and Beta-carotene Induce Cell-Cycle Arrest and Apoptosis in Human Breast Cancer Cell Lines | A Tale of Two Medicines | Scoop.it

Lycopene and beta-carotene are carotenoids widely distributed in fruits and vegetables, with potential anticancer activity. Epidemiological trials rarely provide evidence for the mechanisms of action of these compounds, and their biological effects at different times of treatment are still unclear. The aim of the present study was to determine the effect of carotenoids on the cell cycle and cell viability in human breast cancer cell lines. Human breast cell lines were treated with carotenoids (0.5-10 μM) for 48 and 96 h. Cell viability was monitored using the MTT method (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide; thiazolyl blue). The cell cycle was analyzed by flow cytometry, and apoptotic cells were identified by annexin/propidium iodide (PI) biomarkers. Our data showed a significant decrease in the number of viable breast cancer cells on treatment with carotenoids. Carotenoids also promoted cell-cycle arrest followed by decreased cell viability in the majority of cell lines after 96 h, compared to controls. Furthermore, an increase in apoptosis was observed in cell lines when cells were treated with carotenoids. Our findings show the capacity of lycopene and beta-carotene to inhibit cell proliferation, arrest the cell cycle in different phases, and increase apoptosis. These findings indicate that the effect was cell type-dependent and that carotenoids are potential agents for biological interference with cancer.

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Cytotoxicity of dietary flavonoids on different human cancer types

Cytotoxicity of dietary flavonoids on different human cancer types | A Tale of Two Medicines | Scoop.it

Flavonoids are ubiquitous in nature. They are also in food, providing an essential link between diet and prevention of chronic diseases including cancer. Anticancer effects of these polyphenols depend on several factors: Their chemical structure and concentration, and also on the type of cancer. Malignant cells from different tissues reveal somewhat different sensitivity toward flavonoids and, therefore, the preferences of the most common dietary flavonoids to various human cancer types are analyzed in this review. While luteolin and kaempferol can be considered as promising candidate agents for treatment of gastric and ovarian cancers, respectively, apigenin, chrysin, and luteolin have good perspectives as potent antitumor agents for cervical cancer; cells from main sites of flavonoid metabolism (colon and liver) reveal rather large fluctuations in anticancer activity probably due to exposure to various metabolites with different activities. Anticancer effect of flavonoids toward blood cancer cells depend on their myeloid, lymphoid, or erythroid origin; cytotoxic effects of flavonoids on breast and prostate cancer cells are highly related to the expression of hormone receptors. Different flavonoids are often preferentially present in certain food items, and knowledge about the malignant tissue-specific anticancer effects of flavonoids could be purposely applied both in chemoprevention as well as in cancer treatment.

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Circadian control of xenobiotic carcinogenesis and cancer pharmacology

Circadian control of xenobiotic carcinogenesis and cancer pharmacology | A Tale of Two Medicines | Scoop.it
Xenobiotic metabolism and detoxification, as well as cell cycle events, DNA repair, apoptosis and angiogenesis are rhythmically controlled by the Circadian Timing System (CTS), a hierarchical and coordinated network of cellular clocks. Interwoven transcription/translation feedback loops involving 15 clock genes rhythmically moderate metabolism and effects of carcinogenic xenobiotics and anticancer drugs. Anatomic, physiologic or molecular CTS disruption accelerates cancer processes, including initiation, promotion and progression in experimental models, while, CTS reinforcement halts these processes. These experimental data support a role for the CTS in the increased cancer risk associated to shift work. Chronotherapeutics aims at improving outcomes through the delivery of medicines according to circadian rhythms. Indeed, circadian timing can modify 2- to 10-fold the tolerability of anticancer medications in experimental models and in cancer patients. Improved efficacy is also seen when drugs are given near their respective times of best tolerability. These findings support a paradigm for cancer therapy that is specific to chronotherapy,i.e. "the lesser the toxicity, the better the efficacy" (Lévi et al. Annu Rev Pharm Toxicol 2010). While most chronopharmacologic effects have been shown in light-dark synchronized mammals, the relevance of clock robustness and drug timing for cancer chronotherapeutics is now systematically studied in synchronized cell cultures, using clock gene silencing with RNA interference. Recent studies reveal the molecular clock dependency of irinotecan bioactivation, detoxification, transport, and molecular target interactions. They further enable a precise quantification and mathematical modeling of chronoPK-PD relations at cell population levels (Dulong et al. submitted). Stochastic modeling of mouse and human chronoPKPD reveals that optimal chronotherapeutic effects require circadian entrainment to be robust in healthy cells and weak in cancer cells, a finding supported by experimental data. Moreover host clocks differ according to sex and genetic background, and can further be altered with xenobiotics as a function of dose and circadian timing. We find that the combined circadian expressions of core clock genes Rev- Erbα and Bmal1 are proper predictors of optimal drug timing in mice from different strains and sex, using irinotecan as a model (Li et al. Cancer Res 2013). Current studies support the relevance of the physiological rhythms that reset both clock genes as clinically relevant CTS biomarkers both for the detection of cancer risk and the prediction of optimal chronotherapeutics schedule. Support: C5SYS project (ANR and ERASysBio+ initiative, an EU ERA-NET in FP7); Ca
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Revealed -- how genes control 24-hour circadian rhythm in humans

Revealed -- how genes control 24-hour circadian rhythm in humans | A Tale of Two Medicines | Scoop.it

A new study published in the journal Genes and Development has revealed how genes involved in circadian clock in humans control them in a proper rhythm within 24-hour period. This study reveals the actual involvement of genes almost 16 years after scientists after their discovery.


According to the researchers, it was known that there are four proteins involved in maintaining the circadian rhythm but how exactly they reset the cells was not known. The findings of this study gives a better idea about how the genes function to set the cells rhythm.

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Vitamin D improves kids’ winter dermatitis

Vitamin D improves kids’ winter dermatitis | A Tale of Two Medicines | Scoop.it

A new study conducted in more than 100 Mongolian schoolchildren found that daily treatment with a vitamin D supplement significantly reduced the symptoms of winter-related atopic dermatitis, a type of eczema.

 

The report in the  the Journal of Allergy and Clinical Immunology supports the results of a small preliminary study that showed similar results in a small group of children in Boston.

“While we don’t know the exact proportion of patients with atopic dermatitis whose symptoms worsen in the winter, the problem is common,” says Carlos Camargo, MD, DrPH, of Massachusetts General Hospital.

 

“In this large group of patients, who probably had low levels of vitamin D, taking daily vitamin D supplements – which are inexpensive, safe and widely available – proved to be quite helpful.”

Camargo led both the earlier 2008 Boston pilot study and the current investigation, which was performed in collaboration with investigators from the Health Sciences University of Mongolia.

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Efficacy of Yun Zhi (Coriolus versicolor) on Survival in Cancer Patients: Systematic Review and Meta-Analysis

Efficacy of Yun Zhi (Coriolus versicolor) on Survival in Cancer Patients: Systematic Review and Meta-Analysis | A Tale of Two Medicines | Scoop.it
Aim: Patients with cancer frequently use herbs along with the conventional medical treatment, hoping to enhance recovery. Mushrooms have an established history of use in traditional oriental therapies. In Asian cultures, mushrooms are combined with herbal mixtures to treat cancer. This systematic review and meta-analysis draw from randomized, placebo-controlled, double-blind trials to assess the efficacy of Yun Zhi (YZ) for survival in cancer patients. Material & Methods: Systematic review and meta-analysis technique were used to aggregate and analyze the efficacy of Yun Zhi on survival in cancer patients from 13 clinical trials using computerized database and manual search. Results: The findings show that Yun Zhi results in a significant survival advantage compared with standard conventional anti-cancer treatment alone. Of patient randomized to Yun Zhi, there was a 9% absolute reduction in 5-year mortality, resulting in one additional patient alive for every 11 patients treated. In patients with breast cancer, gastric cancer, or colorectal cancer treated with chemotherapy, the effects of the combination of Yun Zhi preparation on the overall 5-year survival rate was more evident, but not in esophageal cancer and nasophayngeal carcinoma. However, subgroup analysis could not conclude which type of anti-cancer treatment may maximize the benefit from Yun Zhi. Conclusion: This meta-analysis has provided strong evidence that Yun Zhi would have survival benefit in cancer patients, particularly in carcinoma of breast, gastric and colorectal. Nevertheless, the findings highlight the need for further evidence from prospective studies of outcome to guide future potential modifications of treatment regimes. Recent patents on the use of mushrooms for the treatment of cancer are also summarized in this review.
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Effects of topical Kiwifruit on healing of neuropathic diabetic foot ulcer

Effects of topical Kiwifruit on healing of neuropathic diabetic foot ulcer | A Tale of Two Medicines | Scoop.it

Kiwifruit (Actindia Deliciosa) is demonstrated to have antibacterial and pro-angiogenic effects. It also contains proteolytic enzymes (actinidin) and ascorbic acid. In this study, the effects of Kiwifruit on neuropathic diabetic foot ulcer healing in clinical settings were evaluated.

 

In this randomized clinical trial of 37 patients (17 in experimental and 20 in control groups) with neuropathic diabetic foot ulcer were studied in Isfahan-Iran. Patients of the control group received just the standard treatments. In the experimental group, in addition to the standard treatments, ulcers were dressed with pure extract of kiwifruit twice daily for 21 days. The ulcers were examined and evaluated based on macroscopic, microscopic and microbiological status. Pre- and post-interventions, biopsies were taken from the ulcers to perform microbiological and histological studies.

 

Mean reduction in surface area of foot ulcer in the experimental group was significantly higher than the control group (168.11 ± 22.31 vs. 88.80 ± 12.04 mm2 respectively, P < 0.0001). The amount of collagen and granulation tissues was significantly higher in the experimental groups than the control group (P value < 0.0001). Significantly higher levels of angiogenesis and vascularization were found in the kiwifruit treated patients (P value < 0.0001). No significant antibacterial effect was observed for kiwifruit.

 

Natural compounds in the kiwifruit including protein-dissolving enzymes (Actinidin) improved different aspects of the wound healing process. Based on these benefits and safety aspects, we conclude that using kiwifruit is a simple, applicable and effective way for treatment of neuropathic diabetic foot ulcer.

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Effect of Light Irradiation by Light Emitting Diode on Colon Cancer Cells

Effect of Light Irradiation by Light Emitting Diode on Colon Cancer Cells | A Tale of Two Medicines | Scoop.it

Recent studies have demonstrated the efficacy of irradiation from light emitting diodes (LED) for wound healing, anti-inflammation and anticancer therapies. However, little is known about the effects of visible light in colon cancer cells. The purpose of this study was to evaluate the biological response (including gene expression changes) of human colon cancer cells to different wavelengths of LED irradiation. Materials and Methods: Human colon cancer cells (HT29 or HCT116) were seeded onto laboratory dishes that were then put on LED irradiation equipment with a 465 nm-, 525 nm-, or 635 nm-LED. Irradiation at 15 or 30 mW was performed 10 min/day, each day for 5 days. The cell counting kit8 was then used to measure cell viability. Apoptosis and expression of several mRNAs (caspase, MAPK and autophagy pathway) in HT29 cultures irradiated with 465 nm LED were evaluated via AnnexinV/PI and RT-PCR, respectively. Results: Viability of HT29 and HCT116 cells was lower in 465 nm-LED irradiated cultures than in control cultures, but viability of HT29 cells did not differ between control cultures and 525 nm-LED or 635 nm-LED irradiated cultures. Moreover, the expression of FAS, caspase-3, capase-8, and JUK were significantly higher in 465 nm-LED irradiated cultures than in control cultures, and expression of ERK1/2 and LC3 was lower in blue-irradiated cells. Conclusion: LED irradiation at 465 nm inhibited the proliferation of HT29 cells and of HCT116 cells. Notably, LED irradiation at 465 nm promoted apoptosis inHT29 cultures via the extrinsic apoptosis pathway and the MAPK pathway.

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Wogonin induces apoptosis by suppressing E6 and E7 expressions and activating intrinsic signaling pathways in HPV-16 cervical cancer cells.

Wogonin is a flavonoid compound extracted from Scutellaria baicalensis and is well known as a benzodiazepine receptor ligand with anxiolytic effects. Many recent studies have demonstrated that wogonin modulates angiogenesis, proliferation, invasion, and tumor progress in various cancer tissues. We further explored the mechanism of action of wogonin on cervical cancer cells that contain or lack human papillomavirus (HPV) DNA. Wogonin was cytotoxic to HPV 16 (+) cervical cancer cells, SiHa and CaSki, but not to HPV-negative cells. We demonstrated that wogonin induced apoptosis by suppressing the expressions of the E6 and E7 viral oncogenes in HPV-infected cervical cancer CaSki and SiHa cells. The modulation of p53 and protein retinoblastoma (pRb) were also triggered by the suppression of E6 and E7 expressions. However, p53 was not altered in HPV-negative cervical cancer C33A cells. Moreover, wogonin modulated the mitochondrial membrane potential and the expression of pro- and anti-apoptotic factors such as Bax and Bcl-2. Wogonin also provoked the cleavage of caspase-3, caspase-9, and poly ADP ribose polymerase. After transfection of siRNAs to target E6 and E7, additional restoration of p53 and pRb was not induced, but processing of caspases and PARP was increased compared with wogonin treatment alone. Together, our findings demonstrated that wogonin effectively promotes apoptosis by downregulating E6 and E7 expressions and promoting intrinsic apoptosis in human cervical cancer cells.

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Suppression of Tumor Growth by Pleurotus ferulae Ethanol Extract through Induction of Cell Apoptosis, and Inhibition of Cell Proliferation and Migration

Suppression of Tumor Growth by Pleurotus ferulae Ethanol Extract through Induction of Cell Apoptosis, and Inhibition of Cell Proliferation and Migration | A Tale of Two Medicines | Scoop.it

Cancer is the second leading cause of death worldwide. Edible medicinal mushrooms have been used in traditional medicine as regimes for cancer patients. Recently anti-cancer bioactive components from some mushrooms have been isolated and their anti-cancer effects have been tested. Pleurotus ferulae, a typical edible medicinal mushroom in Xinjiang China, has also been used to treat cancer patients in folk medicine. However, little studies have been reported on the anti-cancer components of Pleurotus ferulae. This study aims to extract bioactive components from Pleurotus ferulae and to investigate the anti-cancer effects of the extracts. We used ethanol to extract anti-cancer bioactive components enriched with terpenoids from Pleurotus ferulae. We tested the anti-tumour effects of ethanol extracts on the melanoma cell line B16F10, the human gastric cancer cell line BGC 823 and the immortalized human gastric epithelial mucosa cell line GES-1 in vitro and a murine melanoma model in vivo. Cell toxicity and cell proliferation were measured by MTT assays. Cell cycle progression, apoptosis, caspase 3 activity, mitochondrial membrane potential (MMP), migration and gene expression were studied in vitro. PFEC suppressed tumor cell growth, inhibited cell proliferation, arrested cells at G0/G1 phases and was not toxic to non-cancer cells. PFEC also induced cell apoptosis and necrosis, increased caspase 3 activity, reduced the MMP, prevented cell invasion and changed the expression of genes associated with apoptosis and the cell cycle. PFEC delayed tumor formation and reduced tumor growth in vivo. In conclusion, ethanol extracted components from Pleurotus ferulae exert anti-cancer effects through direct suppression of tumor cell growth and invasion, demonstrating its therapeutic potential in cancer treatment.

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The “Aged Garlic Extract”(AGE) and One of its Active Ingredients S-Allyl-L-Cysteine (SAC) as Potential Preventive and Therapeutic Agents for Alzheimer’s Disease (AD)

Alzheimer’s disease (AD) is the most common form of dementia in the older people and 6th leading cause of death in the United States. Deposition of amyloid-beta (Aβ) plaques, hyperphosphorylation of microtubule associated protein tau (MAPT), neuroinflammation and cholinergic neuron loss are the major hallmarks of AD. Deposition of Aβ peptides, which takes place years before the clinical onset of the disease can trigger hyperphophorylation of tau proteins and neuroinflammation, and the latter is thought to be primarily involved in neuronal and synaptic damage seen in AD. To date, four cholinesterase inhibitors or ChEI (tacrine, rivastigmine, donepezil and galantamine) and a partial NMDA receptor antagonist (memantine) are the only approved treatment options for AD. However, these drugs fail to completely cure the disease, which warrants a search for newer class of targets that would eventually lead to effective drugs for the treatment of AD. In addition to selected pharmacological agents, botanical and medicinal plant extracts are also being investigated. Apart from its culinary use, garlic (Allium sativum) is being used to treat several ailments like cancer and diabetes. Herein we have discussed the effects of a specific ‘Aged Garlic Extract’ (AGE) and one of its active ingredients, S-allyl-L-cysteine (SAC) in restricting several pathological cascades related to the synaptic degeneration and neuroinflammatory pathways associated with AD. Thus, based on the reported positive preliminary results reviewed herein, further research is required to develop the full potential of AGE and/or SAC into an effective preventative strategy for AD.

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Extremely low frequency electromagnetic field exposure causes cognitive impairment associated with alteration of the glutamate level, MAPK pathway activation and decreased CREB phosphorylation in m...

Lotus seedpod procyanidins (LSPCs) could effectively prevent learning and memory damage and oxidative damage caused by extremely low frequency electromagnetic field (ELF-EMF) exposure. However, LSPCs protect neurons from ELF-EMF-induced damage by mechanisms currently not clear. An excessive release of glutamate is considered to be one of the molecular mechanisms of neuronal damage in several neurological diseases. In this study we determined whether the ELF-EMF (50 Hz, 8 mT, 28 days) exposure induced alterations of glutamate release in mice hippocampus and explored the possible mechanism, and if LSPC treatment normalized its alterations. The results showed that ELF-EMF exposure induced the increased contents of glutamate, GABA, excessively activated NMDA receptors, increasing the number of NMDA receptor 2B (NR2B) and intracellular Ca2+ concentration [Ca2+]i in hippocampus. In addition, ELF-EMF exposure decreased the ERK1/2 and CREB phosphorylation, which suggested that the Ca2+ influx induced by the ELF-EMF exposure stimulated activity of the ERK, in turn, influences the expression of downstream proteins in this signaling pathway. Besides, ELF-EMF exposure also increased JNK1/2 phosphorylation through the activated ASK1, which plays a pivotal role in hippocampal neuronal cell death. However, oral administration of LSPCs (especially 60 and 90 mg kg−1) markedly improved expressions of p-CREB, p-ERK1/2 and p-JNK1/2, accompanied by decreased levels of glutamate, GABA, [Ca2+]i and NR2B. Thus, the results from the present study suggest that p-ERK1/2, p-JNK1/2, [Ca2+]i and p-CREB expression normalized, possibly via a NMDA receptor-channel through the changes of GABA, glutamate and NR2B, which might be responsible for the neuroprotective or memory enhancing effects of LSPCs.

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Finally: A missing link between vitamin D and prostate cancer

Finally: A missing link between vitamin D and prostate cancer | A Tale of Two Medicines | Scoop.it

A University of Colorado Cancer Center study recently published in the journal Prostate offers compelling evidence that inflammation may be the link between Vitamin D and prostate cancer. Specifically, the study shows that the gene GDF-15, known to be upregulated by Vitamin D, is notably absent in samples of human prostate cancer driven by inflammation.

 

"When you take Vitamin D and put it on prostate cancer cells, it inhibits their growth. But it hasn't been proven as an anti-cancer agent. We wanted to understand what genes Vitamin D is turning on or off in prostate cancer to offer new targets," says James R. Lambert, PhD, investigator at the CU Cancer Center and associate research professor in the CU School of Medicine Department of Pathology.

 

Since demonstrating that Vitamin D upregulates the expression of GDF-15, Lambert and colleagues, including Scott Lucia, MD, wondered if this gene might be a mechanism through which Vitamin D works in prostate cancer. Initially it seemed as if the answer was no.

 

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Montmorency Cherries Reduce the Oxidative Stress and Inflammatory Responses to Repeated Days High-Intensity Stochastic Cycling

Montmorency Cherries Reduce the Oxidative Stress and Inflammatory Responses to Repeated Days High-Intensity Stochastic Cycling | A Tale of Two Medicines | Scoop.it

This investigation examined the impact of Montmorency tart cherry concentrate (MC) on physiological indices of oxidative stress, inflammation and muscle damage across 3 days simulated road cycle racing. Trained cyclists (n = 16) were divided into equal groups and consumed 30 mL of MC or placebo (PLA), twice per day for seven consecutive days. A simulated, high-intensity, stochastic road cycling trial, lasting 109 min, was completed on days 5, 6 and 7. Oxidative stress and inflammation were measured from blood samples collected at baseline and immediately pre- and post-trial on days 5, 6 and 7. Analyses for lipid hydroperoxides (LOOH), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin-8 (IL-8), interleukin-1-beta (IL-1-β), high-sensitivity C-reactive protein (hsCRP) and creatine kinase (CK) were conducted. LOOH (p < 0.01), IL-6 (p < 0.05) and hsCRP (p < 0.05) responses to trials were lower in the MC group versus PLA. No group or interaction effects were found for the other markers. The attenuated oxidative and inflammatory responses suggest MC may be efficacious in combating post-exercise oxidative and inflammatory cascades that can contribute to cellular disruption. Additionally, we demonstrate direct application for MC in repeated days cycling and conceivably other sporting scenario’s where back-to-back performances are required.

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Flavonoid-Enriched Apple Fraction AF4 Induces Cell Cycle Arrest, DNA Topoisomerase II Inhibition, and Apoptosis in Human Liver Cancer HepG2 Cells.

Apples are a major source of dietary phytochemicals such as flavonoids in the Western diet. Here we report anticancer properties and possible mechanism of action of apple flavonoid-enriched fraction (AF4) isolated from the peels of Northern Spy apples in human hepatocellular carcinoma cells, HepG2. Treatment with AF4 induced cell growth inhibition in HepG2 cells in time- and dose-dependent manner. Concentration of 50 μg/ml (50 μg total monomeric polyphenols/ml) AF4 was sufficient to induce a significant reduction in cell viability within 6 h of treatment (92%, P < 0.05) but had very low toxicity (minimum 4% to maximum 16%) on primary liver and lung cells, which was significantly lower than currently prescribed chemotherapy drug Sorafenib (minimum 29% to maximum 49%, P < 0.05). AF4 induced apoptosis in HepG2 cells within 6 h of treatment via activation of caspase-3. Cell cycle analysis via flow-cytometer showed that AF4 induced G2/M phase arrest. Further, results showed that AF4 acts as a strong DNA topoisomerase II catalytic inhibitor, which may be a plausible reason to drive the cells to apoptosis. Overall, our data suggests that AF4 possesses a significantly stronger antiproliferative and specific action than Sorafenib in vitro and is a potential natural chemotherapy agent for treatment of liver cancer.

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Misconduct, not error, accounts for at least 67% of scientific paper retractions

Misconduct, not error, accounts for at least 67% of scientific paper retractions | A Tale of Two Medicines | Scoop.it

 In sharp contrast to previous studies suggesting that errors account for the majority of retracted scientific papers, a new analysis—the most comprehensive of its kind—has found that misconduct is responsible for two-thirds of all retractions. In the paper, misconduct included fraud or suspected fraud, duplicate publication and plagiarism. The paper’s findings show as a percentage of all scientific articles published, retractions for fraud or suspected fraud have increased 10-fold since 1975. The study, from a collaboration between three scientists including one at Albert Einstein College of Medicine of Yeshiva University, published online today in the Proceedings of the National Academy of Sciences (PNAS).

 

“Biomedical research has become a winner-take-all game—one with perverse incentives that entice scientists to cut corners and, in some instances, falsify data or commit other acts of misconduct,” said senior author Arturo Casadevall, M.D., Ph.D. , the Leo and Julia Forchheimer Chair and professor of microbiology & immunology and professor of medicine at Einstein. Dr. Casadevall is also editor-in-chief of the journal mBio.

 

The study reviewed 2,047 papers retracted from the biomedical literature through May 2012. To determine the reasons for the retractions, the researchers consulted several secondary sources, such as the National Institutes of Health (NIH) Office of Research Integrity and Retractionwatch.com, which investigate scientific misconduct.

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Is Cancer Growth Nocturnal?

Is Cancer Growth Nocturnal? | A Tale of Two Medicines | Scoop.it

They emerge at night, while we sleep unaware, growing and spreading out as quickly as they can - and they are deadly. No, I am not talking about werewolves or zombies. According to a new study, it turns out that tumors may grow faster at night, suggesting that cancer growth might be a nocturnal mechanism.

 

Scientists hope that their findings provide evidence that administering certain treatments in time with the body's day-night cycle could boost their efficiency.

 

"It seems to be an issue of timing," Professor Yosef Yarden of the Weizmann Institute of Science, one of the study's researchers, said in a statement.


Via Graham Player Ph.D.
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Graham Player Ph.D.'s curator insight, October 7, 11:36 AM

This study reveals there may be an advantage in considering the time of day when administering certain cancer treatments.

Professor Yosef Yarden of the Weizmann Institute of Science, one of the study's researchers, points out that "cancer treatments are often administered in the daytime, just when the patient's body is suppressing the spread of the cancer on its own."

You can read the full report published in the journal Nature Communications here - http://www.nature.com/ncomms/2014/141003/ncomms6073/full/ncomms6073.html

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Honeysuckle-encoded atypical microRNA2911 directly targets influenza A viruses

Honeysuckle-encoded atypical microRNA2911 directly targets influenza A viruses | A Tale of Two Medicines | Scoop.it

Influenza A viruses (IAVs), particularly H1N1, H5N1 and H7N9, pose a substantial threat to public health worldwide. Here, we report that MIR2911, a honeysuckle (HS)-encoded atypical microRNA, directly targets IAVs with a broad spectrum. MIR2911 is highly stable in HS decoction, and continuous drinking or gavage feeding of HS decoction leads to a significant elevation of the MIR2911 level in mouse peripheral blood and lung. Bioinformatics prediction and a luciferase reporter assay showed that MIR2911 could target various IAVs, including H1N1, H5N1 and H7N9. Synthetic MIR2911 significantly inhibited H1N1-encoded PB2 and NS1 protein expression, but did not affect mutants in which the MIR2911-binding nucleotide sequences were altered. Synthetic MIR2911, extracted RNA from HS decoction and HS decoction all significantly inhibited H1N1 viral replication and rescued viral infection-induced mouse weight loss, but did not affect infection with a mutant virus in which the MIR2911-binding nucleotide sequences of PB2 and NS1 were altered. Importantly, the inhibitory effect of HS decoction on viral replication was abolished by an anti-MIR2911 antagomir, indicating that the physiological concentration of MIR2911 in HS decoction could directly and sufficiently suppress H1N1 viral replication. MIR2911 also inhibited H5N1 and H7N9 viral replication in vitro and in vivo. Strikingly, administration of MIR2911 or HS decoction dramatically reduced mouse mortality caused by H5N1 infection. Our results demonstrate that MIR2911 is the first active component identified in Traditional Chinese Medicine to directly target various IAVs and may represent a novel type of natural product that effectively suppresses viral infection.

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Ellagic acid derivatives, ellagitannins, proanthocyanidins and other phenolics, vitamin C and antioxidant capacity of two powder products from camu-camu fruit (Myrciaria dubia).

The aims of this study were the evaluation of polyphenols and vitamin C content, and antioxidant capacity of dehydrated pulp powder and the dried flour obtained from the skin and seeds residue remaining after pulp preparation from camu-camu (Myrciaria dudia). Fifty-three different phenolics were characterised by HPLC-DAD-ESI-MS-MS and UPLC-HR-QTOF-MS-MS. The phenolic content of camu-camu flour was higher than that of the pulp powder (4007.95 mg/100 g vs. 48.54 mg/100 g). In both products the flavonol myricetin and conjugates, ellagic acid and conjugates and ellagitannins were detected. Cyanidin 3-glucoside, and quercetin and its glycosides were only found in the pulp powder, while proanthocyanidins were only present in the flour (3.5 g/100 g, mean degree of polymerisation 3). The vitamin C content was lower in pulp powder (3.5%) than in the flour (9.1%). The radical-scavenging capacity of both powders was determined by the DPPH, ABTS and ORAC assays, and was higher for camu-camu flour as could be expected for its higher phenolics and vitamin C content. Comparative analyses with fresh camu-camu berries indicate that some transformations occur during processing. Analysis of fresh berries showed that ellagic acid derivatives and ellagitannins were mainly present in the seeds, while proanthocyanidins were present both in the seeds and skin.

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Systemic inflammatory load in humans is suppressed by consumption of two formulations of dried, encapsulated juice concentrate.

Chronic inflammation contributes to an increased risk for developing chronic conditions such as cardiovascular disease, diabetes, and cancer. A high "inflammatory load" is defined as elevated inflammation markers in blood or other tissues. We evaluated several markers of systemic inflammation from healthy adults and tested the hypothesis that two formulations of encapsulated fruit and vegetable juice powder concentrate with added berry powders (FVB) or without (FV) could impact markers of inflammatory load. Using a double-blind, placebo-controlled approach, 117 subjects were randomly assigned to receive placebo, FV, or FVB capsules. Blood was drawn at baseline and after 60 d of capsule consumption. We measured inflammatory markers (high sensitivity C-Reactive Protein, Monocyte Chemotactic Protein-1, Macrophage Inflammatory Protein 1-β, and Regulated upon Activation, Normal T cell Expressed and Secreted), superoxide dismutase, and micronutrients (β-carotene, vitamin C, and vitamin E). Results showed Monocyte Chemotactic Protein-1, Macrophage Inflammatory Protein 1-β, and RANTES levels were significantly reduced and superoxide dismutase and micronutrient levels were significantly increased in subjects consuming both FV and FVB, relative to placebo. Data suggest a potential health benefit by consuming either formulation of the encapsulated juice concentrates through their anti-inflammatory properties.

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A Case of Metastatic Bladder Cancer in Both Lungs Treated with Korean Medicine Therapy Alone

A Case of Metastatic Bladder Cancer in Both Lungs Treated with Korean Medicine Therapy Alone | A Tale of Two Medicines | Scoop.it

This case report is aimed to investigate the effects of Korean medicine therapy (KMT) including oral herbal medicine and herb nebulizer therapy in treating metastatic bladder cancer in the lungs. A 74-year-old man was diagnosed with metastatic bladder cancer in both lungs in August 2013. He refused any chemotherapy and was admitted to our hospital in a much progressed state on January 11, 2014. Since then, he was treated with KMT until May 17, 2014. The main oral herbal medicines were Hyunamdan made of heat-processed ginseng, Hangamdan S made of Cordyceps militaris, Panax ginseng radix, Commiphora myrrha, calculus bovis, margarita, Boswellia carteri, Panax notoginseng radix and Cremastra appendiculata tuber, and nebulizer therapy with Soram nebulizer solution made of wild ginseng and Cordyceps sinensis distillate. Their effect was evaluated considering the change of the main symptoms and using serial chest X-ray. The size and number of multiple metastatic nodules in both lungs were markedly decreased and the symptoms had disappeared. These results suggest that KMT can be an effective method to treat metastatic bladder cancer in the lungs.

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