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Monday, May 29, 2017

Health benefits of bananas supported by scientific findings


Guest post by Leo Tat.

Bananas are among the most commonly consumed fruits in the world.
In the United States, people eat more fresh bananas than any other fruit, including apples and oranges, in the course of a year (1).
The reason for their popularity boils down to their great taste, convenience as a snack and overall health benefits.
Below are the top 15 benefits of bananas that are proven by scientific evidence.



Sunday, May 28, 2017

What are the effects of ketogenic diet on cardiovascular health?


Abstract (as presented by the authors of the scientific work):

"The treatment of obesity and cardiovascular diseases is one of the most difficult and important challenges nowadays. Weight loss is frequently offered as a therapy and is aimed at improving some of the components of the metabolic syndrome. Among various diets, ketogenic diets, which are very low in carbohydrates and usually high in fats and/or proteins, have gained in popularity. Results regarding the impact of such diets on cardiovascular risk factors are controversial, both in animals and humans, but some improvements notably in obesity and type 2 diabetes have been described. Unfortunately, these effects seem to be limited in time. Moreover, these diets are not totally safe and can be associated with some adverse events. Notably, in rodents, development of nonalcoholic fatty liver disease (NAFLD) and insulin resistance have been described. The aim of this review is to discuss the role of ketogenic diets on different cardiovascular risk factors in both animals and humans based on available evidence."


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Thursday, May 25, 2017

Gut microbiota and autism: what is the connection?


Abstract (as presented by the authors of the scientific work):

"Gastrointestinal (GI) symptoms are a common comorbidity in patients with autism spectrum disorder (ASD), but the underlying mechanisms are unknown. Many studies have shown alterations in the composition of the fecal flora and metabolic products of the gut microbiome in patients with ASD. The gut microbiota influences brain development and behaviors through the neuroendocrine, neuroimmune and autonomic nervous systems. In addition, an abnormal gut microbiota is associated with several diseases, such as inflammatory bowel disease (IBD), ASD and mood disorders. Here, we review the bidirectional interactions between the central nervous system and the gastrointestinal tract (brain-gut axis) and the role of the gut microbiota in the central nervous system (CNS) and ASD. Microbiome-mediated therapies might be a safe and effective treatment for ASD."


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Tuesday, May 23, 2017

Are ancient grains nutritionally better?


Guest post by Sudhir Ahluwalia.

The four major grains in use in the world—wheat, rice, corn and sorghum—come from a common ancestor that grew 65 million years ago. Wild cereal grains were discovered from Ohalo II site in Israel. These dated as far back as 23,500 years ago. (Nature. 2004 Aug 5;430(7000):670-3). Agriculture likely began in the dying years of the Ice Age about 11,700 years ago. Evidence of use of sickles to harvest wild barley has been unearthed from the Levant region, according to the Encyclopedia Britannica.

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Monday, May 22, 2017

Complementary and integrative medicine for headache: a review


Abstract (as presented by the authors of the scientific work):

"Headaches, including primary headaches such as migraine and tension-type headache, are a common clinical problem. Complementary and integrative medicine (CIM), formerly known as complementary and alternative medicine (CAM), uses evidence informed modalities to assist in the health and healing of patients. CIM commonly includes the use of nutrition, movement practices, manual therapy, traditional Chinese medicine, and mind-body strategies. This review summarizes the literature on the use of CIM for primary headache and is based on five meta-analyses, seven systematic reviews, and 34 randomized controlled trials (RCTs). The overall quality of the evidence for CIM in headache management is generally low and occasionally moderate. Available evidence suggests that traditional Chinese medicine including acupuncture, massage, yoga, biofeedback, and meditation have a positive effect on migraine and tension headaches. Spinal manipulation, chiropractic care, some supplements and botanicals, diet alteration, and hydrotherapy may also be beneficial in migraine headache. CIM has not been studied or it is not effective for cluster headache. Further research is needed to determine the most effective role for CIM in patients with headache."


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Sunday, May 21, 2017

Precision nutrition in obesity and weight loss: the significance of gene-diet interactions


Abstract (as presented by the authors of the scientific work):

"The rapid rise of obesity during the past decades has coincided with a profound shift of our living environment, including unhealthy dietary patterns, a sedentary lifestyle, and physical inactivity. Genetic predisposition to obesity may have interacted with such an obesogenic environment in determining the obesity epidemic. Growing studies have found that changes in adiposity and metabolic response to low-calorie weight loss diets might be modified by genetic variants related to obesity, metabolic status and preference to nutrients. This review summarized data from recent studies of gene-diet interactions, and discussed integration of research of metabolomics and gut microbiome, as well as potential application of the findings in precision nutrition."


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Thursday, May 18, 2017

3D-printed artificial ovaries display restoration of fertility in a new study


Abstract (as presented by the authors of the scientific work):

"Emerging additive manufacturing techniques enable investigation of the effects of pore geometry on cell behavior and function. Here, we 3D print microporous hydrogel scaffolds to test how varying pore geometry, accomplished by manipulating the advancing angle between printed layers, affects the survival of ovarian follicles. 30° and 60° scaffolds provide corners that surround follicles on multiple sides while 90° scaffolds have an open porosity that limits follicle-scaffold interaction. As the amount of scaffold interaction increases, follicle spreading is limited and survival increases. Follicle-seeded scaffolds become highly vascularized and ovarian function is fully restored when implanted in surgically sterilized mice. Moreover, pups are born through natural mating and thrive through maternal lactation. These findings present an in vivo functional ovarian implant designed with 3D printing, and indicate that scaffold pore architecture is a critical variable in additively manufactured scaffold design for functional tissue engineering."


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Sunday, May 14, 2017

Probiotics to combat diabetes in pregnancy


Abstract (as presented by the authors of the scientific work):

"The metabolic effects of probiotic administration in women with gestational diabetes mellitus (GDM) is unknown. The objective of this review was to investigate the effect of probiotics on fasting plasma glucose (FPG), insulin resistance (HOMA-IR) and LDL-cholesterol levels in pregnant women diagnosed with GDM. Seven electronic databases were searched for RCTs published in English between 2001 and 2017 investigating the metabolic effects of a 6-8 week dietary probiotic intervention in pregnant women following diagnosis with GDM. Eligible studies were assessed for risk of bias and subjected to qualitative and quantitative synthesis using a random effects model meta-analyses. Four high quality RCTs involving 288 participants were included in the review. Probiotic supplementation was not effective in decreasing FBG (Mean Difference = -0.13; 95% CI -0.32, 0.06, p = 0.18) or LDL-cholesterol (-0.16; 95% CI -0.45, 0.13, p = 0.67) in women with GDM. However, a significant reduction in HOMA-IR was observed following probiotic supplementation (-0.69; 95% CI -1.24, -0.14, p = 0.01). There were no significant differences in gestational weight gain, delivery method or neonatal outcomes between experimental and control groups, and no adverse effects of the probiotics were reported. Probiotic supplementation for 6-8 weeks resulted in a significant reduction in insulin resistance in pregnant women diagnosed with GDM. The use of probiotic supplementation is promising as a potential therapy to assist in the metabolic management of GDM. Further high quality studies of longer duration are required to determine the safety, optimal dose and ideal bacterial composition of probiotics before their routine use can be recommended in this patient group."


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Sunday, May 7, 2017

Ketogenic diet: highly cited open access scientific publications


I have aimed to compile a list of open access scientific works examining ketogenic diet, which have provoked most interest in the scientific community up to know (quantified by the number of received citations in Scopus). The identified works are listed below.



Wednesday, May 3, 2017

Ketogenic diet and its effects in mental disorders


Abstract (as presented by the authors of the scientific work):

"BACKGROUND:
The ketogenic diet (KD) has been used in treatment-resistant epilepsy since the 1920s. It has been researched in a variety of neurological conditions in both animal models and human trials. The aim of this review is to clarify the potential role of KD in psychiatry.
METHODS:
Narrative review of electronic databases PubMED, PsychINFO, and Scopus.
RESULTS:
The search yielded 15 studies that related the use of KD in mental disorders including anxiety, depression, bipolar disorder, schizophrenia, autism spectrum disorder (ASD), and attention deficit hyperactivity disorder (ADHD). These studies comprised nine animal models, four case studies, and two open-label studies in humans. In anxiety, exogenous ketone supplementation reduced anxiety-related behaviors in a rat model. In depression, KD significantly reduced depression-like behaviors in rat and mice models in two controlled studies. In bipolar disorder, one case study reported a reduction in symptomatology, while a second case study reported no improvement. In schizophrenia, an open-label study in female patients (n = 10) reported reduced symptoms after 2 weeks of KD, a single case study reported no improvement. In a brief report, 3 weeks of KD in a mouse model normalized pathological behaviors. In ASD, an open-label study in children (n = 30) reported no significant improvement; one case study reported a pronounced and sustained response to KD. In ASD, in four controlled animal studies, KD significantly reduced ASD-related behaviors in mice and rats. In ADHD, in one controlled trial of KD in dogs with comorbid epilepsy, both conditions significantly improved.
CONCLUSION:
Despite its long history in neurology, the role of KD in mental disorders is unclear. Half of the published studies are based on animal models of mental disorders with limited generalizability to the analog conditions in humans. The review lists some major limitations including the lack of measuring ketone levels in four studies and the issue of compliance to the rigid diet in humans. Currently, there is insufficient evidence for the use of KD in mental disorders, and it is not a recommended treatment option. Future research should include long-term, prospective, randomized, placebo-controlled crossover dietary trials to examine the effect of KD in various mental disorders."


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Sunday, April 16, 2017

Health implications of the influence of diet on the gut microbiome


Abstract (as presented by the authors of the scientific work):

"Recent studies have suggested that the intestinal microbiome plays an important role in modulating risk of several chronic diseases, including inflammatory bowel disease, obesity, type 2 diabetes, cardiovascular disease, and cancer. At the same time, it is now understood that diet plays a significant role in shaping the microbiome, with experiments showing that dietary alterations can induce large, temporary microbial shifts within 24 h. Given this association, there may be significant therapeutic utility in altering microbial composition through diet. This review systematically evaluates current data regarding the effects of several common dietary components on intestinal microbiota. We show that consumption of particular types of food produces predictable shifts in existing host bacterial genera. Furthermore, the identity of these bacteria affects host immune and metabolic parameters, with broad implications for human health. Familiarity with these associations will be of tremendous use to the practitioner as well as the patient."


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Monday, April 10, 2017

Inflammation regulation by short chain fatty acids


Abstract (as presented by the authors of the scientific work):

"The short chain fatty acids (SCFAs) acetate (C(2)), propionate (C(3)) and butyrate (C(4)) are the main metabolic products of anaerobic bacteria fermentation in the intestine. In addition to their important role as fuel for intestinal epithelial cells, SCFAs modulate different processes in the gastrointestinal (GI) tract such as electrolyte and water absorption. These fatty acids have been recognized as potential mediators involved in the effects of gut microbiota on intestinal immune function. SCFAs act on leukocytes and endothelial cells through at least two mechanisms: activation of GPCRs (GPR41 and GPR43) and inhibiton of histone deacetylase (HDAC). SCFAs regulate several leukocyte functions including production of cytokines (TNF-α, IL-2, IL-6 and IL-10), eicosanoids and chemokines (e.g., MCP-1 and CINC-2). The ability of leukocytes to migrate to the foci of inflammation and to destroy microbial pathogens also seems to be affected by the SCFAs. In this review, the latest research that describes how SCFAs regulate the inflammatory process is presented. The effects of these fatty acids on isolated cells (leukocytes, endothelial and intestinal epithelial cells) and, particularly, on the recruitment and activation of leukocytes are discussed. Therapeutic application of these fatty acids for the treatment of inflammatory pathologies is also highlighted."


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Saturday, April 8, 2017

Dietary constituents with “exercise mimetic'' action


Abstract (as presented by the authors of the scientific work):

"Endurance exercise, when performed regularly as part of a training program, leads to increases in whole-body and skeletal muscle-specific oxidative capacity. At the cellular level, this adaptive response is manifested by an increased number of oxidative fibers (Type I and IIA myosin heavy chain), an increase in capillarity and an increase in mitochondrial biogenesis. The increase in mitochondrial biogenesis (increased volume and functional capacity) is fundamentally important as it leads to greater rates of oxidative phosphorylation and an improved capacity to utilize fatty acids during sub-maximal exercise. Given the importance of mitochondrial biogenesis for skeletal muscle performance, considerable attention has been given to understanding the molecular cues stimulated by endurance exercise that culminate in this adaptive response. In turn, this research has led to the identification of pharmaceutical compounds and small nutritional bioactive ingredients that appear able to amplify exercise-responsive signaling pathways in skeletal muscle. The aim of this review is to discuss these purported exercise mimetics and bioactive ingredients in the context of mitochondrial biogenesis in skeletal muscle. We will examine proposed modes of action, discuss evidence of application in skeletal muscle in vivo and finally comment on the feasibility of such approaches to support endurance-training applications in humans."


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Thursday, April 6, 2017

Chronic diseases and aging: potential applications of circadian clock-enhancing small molecules


Abstract (as presented by the authors of the scientific work):

"Normal physiological functions require a robust biological timer called the circadian clock. When clocks are dysregulated, misaligned, or dampened, pathological consequences ensue, leading to chronic diseases and accelerated aging. An emerging research area is the development of clock-targeting compounds that may serve as drug candidates to correct dysregulated rhythms and hence mitigate disease symptoms and age-related decline. In this review, we first present a concise view of the circadian oscillator, physiological networks, and regulatory mechanisms of circadian amplitude. Given a close association of circadian amplitude dampening and disease progression, clock-enhancing small molecules (CEMs) are of particular interest as candidate chronotherapeutics. A recent proof-of-principle study illustrated that the natural polymethoxylated flavonoid nobiletin directly targets the circadian oscillator and elicits robust metabolic improvements in mice. We describe mood disorders and aging as potential therapeutic targets of CEMs. Future studies of CEMs will shed important insight into the regulation and disease relevance of circadian clocks."


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Tuesday, April 4, 2017

Avocado: scientific review of possible health benefits


Abstract (as presented by the authors of the scientific work):

"Hass avocados, the most common commercial avocado cultivars in the world, contain a variety of essential nutrients and important phytochemicals. Although the official avocado serving is one-fifth of a fruit (30 g), according to NHANES analysis the average consumption is one-half an avocado (68 g), which provides a nutrient and phytochemical dense food consisting of the following: dietary fiber (4.6 g), total sugar (0.2 g), potassium (345 mg), sodium (5.5 mg), magnesium (19.5 mg), vitamin A (43 μg), vitamin C (6.0 mg), vitamin E (1.3 mg), vitamin K1 (14 μg), folate (60 mg), vitamin B-6 (0.2 mg), niacin (1.3 mg), pantothenic acid (1.0 mg), riboflavin (0.1 mg), choline (10 mg), lutein/zeaxanthin (185 μg), phytosterols (57 mg), and high-monounsaturated fatty acids (6.7 g) and 114 kcals or 1.7 kcal/g. The avocado oil consists of 71% monounsaturated fatty acids (MUFA), 13% polyunsaturated fatty acids (PUFA), and 16% saturated fatty acids (SFA), which helps to promote healthy blood lipid profiles and enhance the bioavailability of fat soluble vitamins and phytochemicals from the avocado or other fruits and vegetables, naturally low in fat, which are consumed with avocados. There are eight preliminary clinical studies showing that avocado consumption helps support cardiovascular health. Exploratory studies suggest that avocados may support weight management and healthy aging."


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Sunday, April 2, 2017

Recent advances in Parkinson's disease therapy


Abstract (as presented by the author of the scientific work):

"This article summarizes (1) the recent achievements to further improve symptomatic therapy of motor Parkinson's disease (PD) symptoms, (2) the still-few attempts to systematically search for symptomatic therapy of non-motor symptoms in PD, and (3) the advances in the development and clinical testing of compounds which promise to offer disease modification in already-manifest PD. However, prevention (that is, slowing or stopping PD in a prodromal stage) is still a dream and one reason for this is that we have no consensus on primary endpoints for clinical trials which reflect the progression in prodromal stages of PD, such as in rapid eye movement sleep behavior disorder (RBD) -a methodological challenge to be met in the future."


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Friday, March 31, 2017

What are the effects of essential oils from plants on pathogenic bacteria?


Abstract (as presented by the authors of the scientific work):

"The increasing resistance of microorganisms to conventional chemicals and drugs is a serious and evident worldwide problem that has prompted research into the identification of new biocides with broad activity. Plants and their derivatives, such as essential oils, are often used in folk medicine. In nature, essential oils play an important role in the protection of plants. Essential oils contain a wide variety of secondary metabolites that are capable of inhibiting or slowing the growth of bacteria, yeasts and moulds. Essential oils and their components have activity against a variety of targets, particularly the membrane and cytoplasm, and in some cases, they completely change the morphology of the cells. This brief review describes the activity of essential oils against pathogenic bacteria."


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Tuesday, March 28, 2017

New study points that two-thirds of cancers might be due to unavoidable errors associated with DNA replication, not inheritance or lifestyle


Abstract (as presented by the authors of the scientific work):

"Cancers are caused by mutations that may be inherited, induced by environmental factors, or result from DNA replication errors (R). We studied the relationship between the number of normal stem cell divisions and the risk of 17 cancer types in 69 countries throughout the world. The data revealed a strong correlation (median = 0.80) between cancer incidence and normal stem cell divisions in all countries, regardless of their environment. The major role of R mutations in cancer etiology was supported by an independent approach, based solely on cancer genome sequencing and epidemiological data, which suggested that R mutations are responsible for two-thirds of the mutations in human cancers. All of these results are consistent with epidemiological estimates of the fraction of cancers that can be prevented by changes in the environment. Moreover, they accentuate the importance of early detection and intervention to reduce deaths from the many cancers arising from unavoidable R mutations."


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Saturday, March 25, 2017

Cancer acidity and its potential as therapeutic target


Abstract (as presented by the authors of the scientific work):

"The link between cancer metabolism and immunosuppression, inflammation and immune escape has generated major interest in investigating the effects of low pH on tumor immunity. Indeed, microenvironmental acidity may differentially impact on diverse components of tumor immune surveillance, eventually contributing to immune escape and cancer progression. Although the molecular pathways underlying acidity-related immune dysfunctions are just emerging, initial evidence indicates that antitumor effectors such as T and NK cells tend to lose their function and undergo a state of mostly reversible anergy followed by apoptosis, when exposed to low pH environment. At opposite, immunosuppressive components such as myeloid cells and regulatory T cells are engaged by tumor acidity to sustain tumor growth while blocking antitumor immune responses. Local acidity could also profoundly influence bioactivity and distribution of antibodies, thus potentially interfering with the clinical efficacy of therapeutic antibodies including immune checkpoint inhibitors. Hence tumor acidity is a central regulator of cancer immunity that orchestrates both local and systemic immunosuppression and that may offer a broad panel of therapeutic targets. This review outlines the fundamental pathways of acidity-driven immune dysfunctions and sheds light on the potential strategies that could be envisaged to potentiate immune-mediated tumor control in cancer patients."


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Thursday, March 23, 2017

The health-promoting and microbiota-modulating properties of the fermented beverage kefir


Abstract (as presented by the authors of the scientific work):

"Kefir is a complex fermented dairy product created through the symbiotic fermentation of milk by lactic acid bacteria and yeasts contained within an exopolysaccharide and protein complex called a kefir grain. As with other fermented dairy products, kefir has been associated with a range of health benefits such as cholesterol metabolism and angiotensin-converting enzyme (ACE) inhibition, antimicrobial activity, tumor suppression, increased speed of wound healing, and modulation of the immune system including the alleviation of allergy and asthma. These reports have led to increased interest in kefir as a focus of research and as a potential probiotic-containing product. Here, we review those studies with a particular emphasis on the microbial composition and the health benefits of the product, as well as discussing the further development of kefir as an important probiotic product."


Covered topics (the letter size corresponds to the frequency of mentioning in the text):



Traditional use of medicinal plants to combat disease: special journal issue


Submission is open for an ethnopharmacology-focused special issue of the journal Frontiers in Pharmacology (IF=4.4, Q1), guest edited by Atanas G. Atanasov, Judith Maria Rollinger, Judit Hohmann, and Anna Karolina Kiss.

With an emphasis on traditional European medicine, the special issue encourages submissions related to phytochemistry, clinical studies with herbal preparations, bioactivities and mechanism of action studies with natural products, pharmacokinetics and biotransformation of phytochemicals, field and observational studies on the use of local and traditional medicinal plants etc.



Sunday, March 19, 2017

The novel dietary supplement methylsulfonylmethane (MSM): applications and safety


Abstract (as presented by the authors of the scientific work):

"Methylsulfonylmethane (MSM) has become a popular dietary supplement used for a variety of purposes, including its most common use as an anti-inflammatory agent. It has been well-investigated in animal models, as well as in human clinical trials and experiments. A variety of health-specific outcome measures are improved with MSM supplementation, including inflammation, joint/muscle pain, oxidative stress, and antioxidant capacity. Initial evidence is available regarding the dose of MSM needed to provide benefit, although additional work is underway to determine the precise dose and time course of treatment needed to provide optimal benefits. As a Generally Recognized As Safe (GRAS) approved substance, MSM is well-tolerated by most individuals at dosages of up to four grams daily, with few known and mild side effects. This review provides an overview of MSM, with details regarding its common uses and applications as a dietary supplement, as well as its safety for consumption."


Covered topics (the letter size corresponds to the frequency of mentioning in the text):



Thursday, March 16, 2017

Stress-induced despair behavior and intestinal microbiota: can eating yogurt combat depression?


Abstract (as presented by the authors of the scientific work):

"Depressive disorders often run in families, which, in addition to the genetic component, may point to the microbiome as a causative agent. Here, we employed a combination of behavioral, molecular and computational techniques to test the role of the microbiota in mediating despair behavior. In chronically stressed mice displaying despair behavior, we found that the microbiota composition and the metabolic signature dramatically change. Specifically, we observed reduced Lactobacillus and increased circulating kynurenine levels as the most prominent changes in stressed mice. Restoring intestinal Lactobacillus levels was sufficient to improve the metabolic alterations and behavioral abnormalities. Mechanistically, we identified that Lactobacillus-derived reactive oxygen species may suppress host kynurenine metabolism, by inhibiting the expression of the metabolizing enzyme, IDO1, in the intestine. Moreover, maintaining elevated kynurenine levels during Lactobacillus supplementation diminished the treatment benefits. Collectively, our data provide a mechanistic scenario for how a microbiota player (Lactobacillus) may contribute to regulating metabolism and resilience during stress."


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Monday, March 13, 2017

The stomach in health and disease


Abstract (as presented by the authors of the scientific work):

"The stomach is traditionally regarded as a hollow muscular sac that initiates the second phase of digestion. Yet this simple view ignores the fact that it is the most sophisticated endocrine organ with unique physiology, biochemistry, immunology and microbiology. All ingested materials, including our nutrition, have to negotiate this organ first, and as such, the stomach is arguably the most important segment within the GI tract. The unique biological function of gastric acid secretion not only initiates the digestive process but also acts as a first line of defence against food-borne microbes. Normal gastric physiology and morphology may be disrupted by Helicobacter pylori infection, the most common chronic bacterial infection in the world and the aetiological agent for most peptic ulcers and gastric cancer. In this state-of-the-art review, the most relevant new aspects of the stomach in health and disease are addressed. Topics include gastric physiology and the role of gastric dysmotility in dyspepsia and gastroparesis; the stomach in appetite control and obesity; there is an update on the immunology of the stomach and the emerging field of the gastric microbiome. H. pylori-induced gastritis and its associated diseases including peptic ulcers and gastric cancer are addressed together with advances in diagnosis. The conclusions provide a future approach to gastric diseases underpinned by the concept that a healthy stomach is the gateway to a healthy and balanced host. This philosophy should reinforce any public health efforts designed to eradicate major gastric diseases, including stomach cancer."


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Sunday, March 12, 2017

How beneficial is Silymarin/Silybin use in chronic liver disease?


Abstract (as presented by the authors of the scientific work):

"
Silymarin is the extract of Silybum marianum, or milk thistle, and its major active compound is silybin, which has a remarkable biological effect. It is used in different liver disorders, particularly chronic liver diseases, cirrhosis and hepatocellular carcinoma, because of its antioxidant, anti-inflammatory and antifibrotic power. Indeed, the anti-oxidant and anti-inflammatory effect of silymarin is oriented towards the reduction of virus-related liver damages through inflammatory cascade softening and immune system modulation. It also has a direct antiviral effect associated with its intravenous administration in hepatitis C virus infection. With respect to alcohol abuse, silymarin is able to increase cellular vitality and to reduce both lipid peroxidation and cellular necrosis. Furthermore, silymarin/silybin use has important biological effects in non-alcoholic fatty liver disease. These substances antagonize the progression of non-alcoholic fatty liver disease, by intervening in various therapeutic targets: oxidative stress, insulin resistance, liver fat accumulation and mitochondrial dysfunction. Silymarin is also used in liver cirrhosis and hepatocellular carcinoma that represent common end stages of different hepatopathies by modulating different molecular patterns. Therefore, the aim of this review is to examine scientific studies concerning the effects derived from silymarin/silybin use in chronic liver diseases, cirrhosis and hepatocellular carcinoma."


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Thursday, March 9, 2017

Role of intestinal microbiota and metabolites in human diseases


Abstract (as presented by the authors of the scientific work):

"
BACKGROUND:
A vast diversity of microbes colonizes in the human gastrointestinal tract, referred to intestinal microbiota. Microbiota and products thereof are indispensable for shaping the development and function of host innate immune system, thereby exerting multifaceted impacts in gut health.
METHODS:
This paper reviews the effects on immunity of gut microbe-derived nucleic acids, and gut microbial metabolites, as well as the involvement of commensals in the gut homeostasis. We focus on the recent findings with an intention to illuminate the mechanisms by which the microbiota and products thereof are interacting with host immunity, as well as to scrutinize imbalanced gut microbiota (dysbiosis) which lead to autoimmune disorders including inflammatory bowel disease (IBD), Type 1 diabetes (T1D) and systemic immune syndromes such as rheumatoid arthritis (RA).
RESULTS:
In addition to their well-recognized benefits in the gut such as occupation of ecological niches and competition with pathogens, commensal bacteria have been shown to strengthen the gut barrier and to exert immunomodulatory actions within the gut and beyond. It has been realized that impaired intestinal microbiota not only contribute to gut diseases but also are inextricably linked to metabolic disorders and even brain dysfunction.
CONCLUSIONS:
A better understanding of the mutual interactions of the microbiota and host immune system, would shed light on our endeavors of disease prevention and broaden the path to our discovery of immune intervention targets for disease treatment."


Covered topics (the letter size corresponds to the frequency of mentioning in the text):


Tuesday, March 7, 2017

Potential benefits and harms of fasting


Abstract (as presented by the authors of the scientific work):

"Intermittent energy restriction (IER) has become popular as a means of weight control amongst people who are overweight and obese, and is also undertaken by normal weight people hoping spells of marked energy restriction will optimise their health. This review summarises randomised comparisons of intermittent and isoenergetic continuous energy restriction for weight loss to manage overweight and obesity. It also summarises the potential beneficial or adverse effects of IER on body composition, adipose stores and metabolic effects from human studies, including studies amongst normal weight subjects and relevant animal experimentation. Six small short term (<6 month) studies amongst overweight or obese individuals indicate that intermittent energy restriction is equal to continuous restriction for weight loss, with one study reporting greater reductions in body fat, and two studies reporting greater reductions in HOMA insulin resistance in response to IER, with no obvious evidence of harm. Studies amongst normal weight subjects and different animal models highlight the potential beneficial and adverse effects of intermittent compared to continuous energy restriction on ectopic and visceral fat stores, adipocyte size, insulin resistance, and metabolic flexibility. The longer term benefits or harms of IER amongst people who are overweight or obese, and particularly amongst normal weight subjects, is not known and is a priority for further investigation."


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Monday, March 6, 2017

Functional components and medicinal properties of food: a scientific review



Abstract (as presented by the authors of the scientific work):

"Research has proved a relationship between functional components of food, health and well-being. Thus, functional components of food can be effectively applied in the treatment and prevention of diseases. They act simultaneously at different or identical target sites with the potential to impart physiological benefits and promotion of wellbeing including reducing the risk of cancer, cardiovascular disease, osteoporosis, inflammation, type II diabetes, and other chronic degenerative diseases, lowering of blood cholesterol, neutralization of reactive oxygen species and charged radicals, anticarcinogenic effect, low-glycaemic response, etc. Previously, it was thought that functional ingredients such as non-starchy carbohydrates including soluble and insoluble dietary fibres, fucoidan; antioxidants including polyphenols, carotenoids, tocopherols, tocotrienols, phytosterols, isoflavones, organosulphur compounds; plant sterols and soy phytoestrogens occur only in plant foods (whole grains, fruits, and vegetables) as phytochemicals. However, probiotics, prebiotics, conjugated linolenic acid, long-chain omega-3, -6 and -9-polyunsaturated fatty acids, and bioactive peptides have proved that functional components are equally available in animal products such as milk, fermented milk products and cold-water fish. The way a food is processed affects its functional components. Many processing techniques have been found to lower the concentration of functional components in food. Conversely, other techniques were found to increase them. Hence, in a time when the role of a healthy diet in preventing non-communicable diseases is well accepted, the borderline between food and medicine is becoming very thin."


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Sunday, March 5, 2017

The health-promoting potential of Dendrobium species (Orchidaceae)



Abstract (as presented by the authors of the scientific work):

"Dendrobium species, commonly known as "Shihu" or "Huangcao," represents the second largest genus of Orchidaceae, which are used commonly as tonic herbs and healthy food in many Asian countries. The aim of this paper is to review the history, chemistry, and pharmacology of different Dendrobium species on the basis of the latest academic literatures found in Google Scholar, PubMed, Sciencedirect, Scopus, and SID."


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Saturday, March 4, 2017

Mushrooms for improvement of health and life quality


 
Abstract (as presented by the authors of the scientific work):

"Mushrooms have been consumed since earliest history; ancient Greeks believed that mushrooms provided strength for warriors in battle, and the Romans perceived them as the "Food of the Gods." For centuries, the Chinese culture has treasured mushrooms as a health food, an "elixir of life." They have been part of the human culture for thousands of years and have considerable interest in the most important civilizations in history because of their sensory characteristics; they have been recognized for their attractive culinary attributes. Nowadays, mushrooms are popular valuable foods because they are low in calories, carbohydrates, fat, and sodium: also, they are cholesterol-free. Besides, mushrooms provide important nutrients, including selenium, potassium, riboflavin, niacin, vitamin D, proteins, and fiber. All together with a long history as food source, mushrooms are important for their healing capacities and properties in traditional medicine. It has reported beneficial effects for health and treatment of some diseases. Many nutraceutical properties are described in mushrooms, such as prevention or treatment of Parkinson, Alzheimer, hypertension, and high risk of stroke. They are also utilized to reduce the likelihood of cancer invasion and metastasis due to antitumoral attributes. Mushrooms act as antibacterial, immune system enhancer and cholesterol lowering agents; additionally, they are important sources of bioactive compounds. As a result of these properties, some mushroom extracts are used to promote human health and are found as dietary supplements."


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Thursday, March 2, 2017

What is inside the smoke of hallucinogen Salvia divinorum?



Abstract (as presented by the authors of the scientific work):

"Salvia divinorum is a hallucinogen sold over the internet in several forms. Perhaps the most common method of use is smoking the dried leaf material. The sole presumed active constituent, salvinorin A, is a selective kappa-opioid receptor agonist. Upon smoking of the dried leaf material, some of the salvinorin A is destroyed or converted to other materials, leaving in question the actual amount of salvinorin A delivered that leads to the psychotomimetic effect. On average, 133 μg of salvinorin A was delivered in the smoke from an 830 mg per cigarette, which contained ∼2.7 mg of salvinorin A. Hence, only ∼5% of the salvinorin A available in the dried plant material was delivered in the smoke. Upon smoking, hydrolysis of salvinorin A to salvinorin B, an inactive and minor component of the leaf material, also occurs as evidenced by a higher delivered amount of salvinorin B vs salvinorin A (217 vs 133 μg per cigarette). Since smoking is an effective means of achieving the hallucinogenic effect and salvinorin A is the presumed sole active ingredient in the plant, the estimated effective dose of salvinorin A by inhalation is <133 μg per person. Considering the reported rapid metabolism of salvinorin A in vivo, the dose reaching the brain would be substantially less."



Covered topics (the letter size corresponds to the frequency of mentioning in the text):



Results and discussion (as presented by the authors of the scientific work):

"The average values of chemical analytes found in the smoke of a tobacco and an S. divinorum cigarette are listed in Table I. Excluding the psychoactive constituents of the respective plants, most of the analytes were found in similar amounts in the two plants. The S. divinorum plant material used in this study demonstrated some variation even within the small sampling of the leaf material used for the smoking studies. The three samples analyzed for 2.20 ± 0.30, 3.82 ± 0.65 and 3.69 ± 0.04 mg salvinorin A per gram of plant material (n = 4 for each determination). The grand average of these determinations is 3.24 mg salvinorin A per gram of plant material or 0.324% of the dried plant material, which is near the average 0.245% salvinorin A content reported by Siebert (3). An 830 mg cigarette would then have ∼2.7 mg salvinorin A present. In the smoke, 133 μg of salvinorin A was delivered (∼5% yield) indicating significant conversion of salvinorin A to other components during combustion. Some evidence for this was seen by the presence of 217 μg of salvinorin B, which is a non-psychoactive hydrolysis product of salvinorin A. Additionally, the presence of small amounts (18 μg) of related salvinorin D or E was detected as indicated by their MW. Since salvinorins D and E can interconvert, the observed material is likely a mixture of D & E (9). Additionally, salvinorins D and E are partial hydrolysis products of salvinorin C, which is present in the plant (3); therefore, the salvinorin D or E observed here are likely combinations of amounts present in the plant and products of the combustion process in a manner comparable to the conversion of salvinorin B from salvinorin A.Considering that smoking S. divinorum as a cigarette is an effective method of achieving a psychoactive effect and salvinorin A is considered to be the sole active ingredient in the plant accounting for the effects (1), then the 133 μg of salvinorin A represents a high estimate of the minimal dosage needed to obtain a psychoactive effect from the drug. The actual amount of salvinorin A that needs to reach the brain would be significantly less due to the rapid metabolism of salvinorin A in vivo (10).

These results are in good agreement to the findings of the vaporization studies of Johnson et al. (4), where they determined that 210–420 μg using a vaporizer as the minimally effective dose in a 70 kg. It should be noted that this was the dose applied to the vaporizer and that the amount actually delivered to the subject was not determined. The vaporization method used (heating of salvinorin A in a glass vessel) might be expected to lead to less degradation of the salvinorin A than pyrolysis in a cigarette. Hence, our finding of 133 μg delivered the S. divinorum cigarette smoke compares well. Caveats to these studies are that first a single sample of S. divinorum was used and that amounts of salvinorin A can vary significantly in the plant (3) and second, the mode of simulated inhalation in the smoking apparatus may not fully replicate the inhalation pattern utilized by individuals smoking the plant material to achieve an effect. Therefore, while the numbers reported cannot be said to precisely define the average dose of salvinorin A delivered by the smoking route, it does present a value that should be within the range of delivered doses by this route."


The referenced scientific work at PubMed:

Krstenansky JL, Muzzio M. Analysis of the smoke of cigarettes containing Salvia divinorum. J Anal Toxicol. 2014 Sep;38(7):451-5. doi: 10.1093/jat/bku054. PubMed PMID: 24908261.


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Plant Alkaloids for the Treatment of Depression



Abstract (as presented by the authors of the scientific work):

"Depression is a heterogeneous mood disorder that has been classified and treated in a variety of ways. Although, a number of synthetic drugs are being used as standard treatment for clinically depressed patients, but they have adverse effects that can compromise the therapeutic treatments and patient's compliance. Unlike, synthetic medications, herbal medicines are widely used across the globe due to their wide applicability and therapeutic efficacy associated with least side effects, which in turn has initiated the scientific research regarding the antidepressant activity. This review is mostly based on the literature of the last decade, aimed at exploring the preclinical profile of plant-based alkaloids (the abundant secondary metabolite) as an emerging therapy for depression."


Covered topics (the letter size corresponds to the frequency of mentioning in the text):



Conclusion (as presented by the authors of the scientific work):

"Our review on the basis of available literature suggested that alkaloids could play a potential role as natural antidepressants. Keeping in mind their abundance in nature, the alkaloids could be an economical source of healing the depressive disorder. The available therapeutic agents fail to produced effect in all patients; approximately 30–40% failure has been reported to first-line antidepressant drugs accompanied by the very slow onset of action. Several alkaloids are in clinical practice and producing outstanding results in different therapeutic classes. These reported alkaloids though evoked antidepressant effects in various animal studies, but still deficient in clinical evidence. In conclusion, enough scientific evidence gathered in our review supported that the plant-based alkaloids can serve as leads for antidepressant drug discovery. It is key to subject these alkaloids to further clinical studies for efficacy, potency, and safety to ensure their clinical status."


The referenced scientific work at PubMed:

Perviz S, Khan H, Pervaiz A. Plant Alkaloids as an Emerging Therapeutic Alternative for the Treatment of Depression. Front Pharmacol. 2016 Feb 15;7:28. doi: 10.3389/fphar.2016.00028. Review. PubMed PMID: 26913004; PubMed Central PMCID: PMC4753303.


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Monday, February 27, 2017

Natural products for cancer prevention and therapy by targeting the arachidonic acid pathway



Abstract (as presented by the authors of the scientific work):

"Arachidonic acid (AA) pathway, a metabolic process, plays a key role in carcinogenesis. Hence, AA pathway metabolic enzymes phospholipase A2s (PLA2s), cyclooxygenases (COXs) and lipoxygenases (LOXs) and their metabolic products, such as prostaglandins and leukotrienes, have been considered novel preventive and therapeutic targets in cancer. Bioactive natural products are a good source for development of novel cancer preventive and therapeutic drugs, which have been widely used in clinical practice due to their safety profiles. AA pathway inhibitory natural products have been developed as chemopreventive and therapeutic agents against several cancers. Curcumin, resveratrol, apigenin, anthocyans, berberine, ellagic acid, eugenol, fisetin, ursolic acid, [6]-gingerol, guggulsteone, lycopene and genistein are well known cancer chemopreventive agents which act by targeting multiple pathways, including COX-2. Nordihydroguaiaretic acid and baicalein can be chemopreventive molecules against various cancers by inhibiting LOXs. Several PLA2s inhibitory natural products have been identified with chemopreventive and therapeutic potentials against various cancers. In this review, we critically discuss the possible utility of natural products as preventive and therapeutic agents against various oncologic diseases, including prostate, pancreatic, lung, skin, gastric, oral, blood, head and neck, colorectal, liver, cervical and breast cancers, by targeting AA pathway. Further, the current status of clinical studies evaluating AA pathway inhibitory natural products in cancer is reviewed. In addition, various emerging issues, including bioavailability, toxicity and explorability of combination therapy, for the development of AA pathway inhibitory natural products as chemopreventive and therapeutic agents against human malignancy are also discussed."



Covered topics (the letter size corresponds to the frequency of mentioning in the text):



Conclusions and future directions (as presented by the authors of the scientific work):

"AA cascade, a metabolic pathway, has been found to have involvement in cancer initiation, promotion and progression. Roles of AA metabolizing enzymes and their products have been well characterized in cancer progression and development. Several chemical carcinogens, UV-radiation, tobacco, and proinflammatory cytokines are involved in carcinogenesis by activating multiple pathways, including AA cascade. PLA2s are a group of enzymes which initiate AA cascade by acting on membrane-bound phospholipids to form LPLs and AA. Further, the released AA is oxygenated by variety of oxygenases, including COXs, LOXs and CYP dependent monoxygenases to form bioactive signaling oxylipids like PGs, LTs and epoxy/hydroxy- eicosatrienoic acids respectively.

sPLA2s are first identified PLA2 isoforms and their roles in cancer have not been well characterized. Accumulated literature suggests that GIIA, GV and GX sPLA2s have key roles in inflammation, but several studies have demonstrated the anti-tumor activities of several sPLA2s isoforms. The role of sPLA2s in cancer is thus controversial and further investigations are required. Among GIV(A-F) cPLA2 isoforms, GIVA cPLA2 plays an important role in initiation and progression of inflammation and cancer and it can be a novel chemopreventive and therapeutic target. Several research findings suggested that iPLA2 is also involved in carcinogenesis, but it has been characterized as housekeeping enzyme. LPLA2 is also necessary for normal physiological functions. Lp-PLA2 does not have significant involvement in cancer. Surprisingly, AdPLA exhibits tumor-suppressive activity.

COX has two important isoforms COX-1 and COX-2. COX-1 is a constitutive enzyme but COX-2 expression is observed in several cancers. As the conventional NSAIDs inhibit both COX-1 and COX-2, they were found to have many side effects as a result of inhibition of cytoprotective COX-1. In this scenario, COX-2 selective inhibitors (COXIBs) have been believed to be safe drugs. However, their clinical utility has been hampered due to their side effects. Several synthetic COX-2 inhibitors were withdrawn from the market due to their severe adverse effects. Although most of the pro-tumorigenic activity of COX-2 is attributed to the generation of PGE2, it is important to highlight that the other COX-2-derived products can also affect tumor development. Accumulating evidences suggest that EP(1-3) have pro-tumorigenic roles in several cancers and their antagonists/genes suppressors can be potential chemopreventive agents. Recent findings suggest that COX-2 and PGs have key role in the development of drug resistance in cancer patients undergoing chemotherapy. In this scenario, inhibition of COX-2 pathway could be a potential strategy to overcome the drug resistance problem. 5-LOX and its major metabolic product, LTB4, have been characterized as novel chemopreventive targets for cancers among other LOX isoforms. Moreover, BLT1&2, receptors for LTB4 have been characterized as protumorigenic mediators. In this context, antagonists for BLT1&2 can be developed as novel chemopreventive agents.

Recent findings suggest that pathway diversion is a major problem in targeting the AA pathway. For instance, COX-2 pathway inhibition caused shunting AA metabolism towards the LOX or CYP pathways. In the same way, 5-LOX inhibition caused shunting AA metabolism towards the COX-2 or CYP pathways. In addition, recently identified HK pathway linked with both 5-LOX and COX-2. Hence, blocking two major pathways involved in carcinogenesis, namely the 5-LOX and COX-2 pathways, can be a plausible approach to better inhibit cancer progression. At the same time, PLA2 initiates the AA cascade and inhibition of PLA2 prevents the liberation of AA and LPLs. Hence, researchers have been considering PLA2s to be a better therapeutic target than the downstream enzymes, namely COX-2 and 5-LOX. However, a fundamental problem in drug development is diversity and redundancy in PLA2 isoforms. Moreover, complete physiological roles of PLA2 isoforms are not clearly known. However, several recent findings suggest that inhibition of AA specific-GIVA cPLA2 is advantageous as it is upstream to COX-2 and 5-LOX and prevents liberation of AA and LPLs. Overall, multi-targeting of AA pathway is highly advantageous for effective prevention and/or treatment of several cancers.

Realizing the role of AA pathway in several cancers, considerable efforts are being made to the discovery and development of inhibitors of AA pathway as cancer preventive and therapeutic agents. NSAIDs have been explored as chemopreventive agents for several cancers. However, several side effects associated with usage of NSAIDs hampered their clinical applications. Natural products have a much better safety profile than synthetic molecules. In this context, research on AA pathway inhibitory natural products has gained momentum to develop them as novel chemopreventive and therapeutic agents. Apigenin (1), anthocyans (2), baicalein (3), berberine (4), curcumin (5), diallyl sulfides (6), ellagic acid (7), epigallocatechin gallate (8), eugenol (9), fisetin (10), garcinol (11), genistein (12), [6]-gingerol (13), guggulsterone (14), indole-3-carbinol (15), lycopene (16), nordihydroguaiaretic acid (17), C-phycocyanin (18), piperine (19), quercetin (20), resveratrol (21), silibinin (22), sulforaphane (23), thymoquinone (24), triptolide (25), ursolic acid (26) and wogonin (27) are some of the important AA pathway targeting natural products which have been identified from natural sources and these are under development as cancer chemopreventive and therapeutic agents at various stages, including their clinical development.

Curcumin, berberine and garcinol blocked multiple COX-2, LOXs and cPLA2 pathways, thereby exhibiting chemopreventive and therapeutic potentials against several cancers. Resveratrol exerted chemopreventive activity by blocking COX-2, LOX and CYP pathways. Thymoquinone, garcinol, lycopene and piperine exhibited dual 5-LOX and COX-2 inhibitory activities. Baicalein showed chemopreventive and anti-cancer activities against several cancers by inhibiting 12-LOX. NDGA exhibited anti-cancer activities by inhibiting the activities of 5-LOX, and other LOXs. Apigenin, cyanidin-3-glucoside, delphinidin, curcumin, diallyl sulfide, fisetin, [6]-gingerol, resveratrol, silibinin, and wogonin prevented UVB radiation-induced skin carcinogenesis by inhibiting COX-2 pathway. Curcumin, guggulsterone and indole-3-carbinol blocked tobacco and its constitutents-induced inflammation and carcinogenesis by down-regulating COX-2. Apigenin, curcumin, genistein, [6]-gingerol, gugglosterone, piperine, resveratrol, silibinin, sulforaphane and ursolic acid prevented chemically-induced tumorigenesis by targeting COX-2 pathway. Berbeine and ellagic acid suppressed cPLA2 expression while garcinol prevented activation of cPLA2 by inhibiting its phosphorylation. Curcum suppressed cPLA2 expression and prevented cPLA2 activation by inhibitiong MAPK-mediated phosphorylation. Rosmarinic acid reported to possess sPLA2 and COX-2 inhibitory activities. Several PLA2-inhibitory natural products have been identified, but their anti-cancer efficacy has not been examined systematically. Metabolic pathway diversion is a major problem in development of AA pathway inhibitors. Seveal studies suggest that either COX-2 or LOX inhibitor are ineffective in countering inflammation and thus inflammation-induced carcinogenesis. Recently we have isolated COX and 5-LOX dual inhibitory compounds dammarane triterpeniod 1 and chebulagic acid from seed coat of B. flabellifer and fruits of T. chebula respectively, and found their anticancer and pro-apoptotic potentials in cancer cells. Also COX-2 and 5-LOX dual inhibitors have been developed by several other groups which are at different stages of clinical development. Futher in vivo anticancer, toxicity and pharmacokinetic studies are required for their clinical developemnt.

Natural products, in genral, are known to exhibit better safety profile in toxicity studies and are non-mutagenic and non-genotoxic in nature. Curcumin is characterized as non-toxic and “Generally Recognized As Safe” (GRAS) by the US FDA. However, recently a committee of the FDA voted to prohibit its use intravenously due to inadequate evidence of safety or efficacy. This decision is not yet law in the US, and is currently being challenged. Recent reports on genotoxic effects of [6]-gingerol are controversial and need futher investigations. Anthocyans are less toxic with anti-oxidant and anti-genotoxic potentials. The available data is not sufficient to conclude that anthocyans are less/non toxic. Further, a detailed and long-term toxicity studies on anthocyans are required. NDGA was once classified as “Generally Recognized As Safe” by US FDA but later this classification was withdrawn due to its toxicity concerns. NDGA was not overtly toxic at low doses. However, high doses of NDGA have been associated with several adverse effects. Further detailed studies are necessary to get clarity on toxic effect of NDGA which is a major problem in clinical use of NDGA. Eugenol, a cancer chemopreventive agent, exhibits genotoxic and carcinogenuc properties. Aspirin eugenol ester, a hybrid molecule, shows comparable anti-inflammatory activity with aspirin and eugenol, but it is no or less toxic. Resveratrol, curcumin, ellagic acid, silibinin and thymoquinone exhibit protective effects against xenobiotic-induced toxicity in addition to their safety profile in toxicity studies. C-Phycocyanin containing water extract of Spirulina, generally recognized as safe by US FDA, is a promising agent as potent anti-oxidant, anti-inflammatory, chemopreventive and chemotherapeutic agent for variety of cancers. However, its high molecular weight and delivery problems limit its further development as a clinical agent. Hence there is need for identifying a fragment of this biliprotein without loosing its therapeutic properties.

Bioavailability of the natural products is a major problem for their clinical development. Several nano-particle based drug delivery methods have been explored for improvement of bioavailability of natural products. Also several analogs of the natural products have been synthesized with enhancement of their bioavailability as well as improving therapeutic potentials. Aspirin, acetyl ester of salicylic acid, is the most successful anti-inflammatory drug developed as a natural product analog targeting COXs. Several analogs of the natural products have been synthesized with enhancement of their bioavailability. Internal metabolization is one of the reasons for low bioavailability of curcumin, resveratrol and other natural products. Piperine enhances the bioavailability of curcumin as well as resveratrol by inhibiting internal metabolization of these phytochemicals.

Combinatorial therapy using AA pathway-inhibitory natural products may also be advantageous not only for improving the chemopreventive efficacy, but also useful in overcoming the several problems, including bioavailability and drug resistance. Combinations of piperine with curcumin or resveratrol caused enhancement of bioavailability of both compounds and exhibit better chempeventive efficacy. Combinations of indole-3-carbinol and silibinin effectively prevented carcinogen-induced lung tumorigenesis in mouse by suppressing pro-inflammatory and pro-carcinogenic mediators, including COX-2, than alone. Ursolic acid in combination with resveratrol effectively prevented TPA-induced skin tumor promotion by suppressing inflammatory mediators, including COX-2. Several studies proved that eugenol and combination with sulforaphane or gemcitabine can be useful for chemoprevention of cervical cancer. Lycopene and fish oil acted synergistically as chemopreventive agents against colon carcinogenesis by blocking COX-2 pathway. Therefore, various combination/formulation of AA pathway-inhibitory natural products may be useful to improve its efficacy towards cancer prevention and therapy.

Drug resistance is a major problem in current chemotherapy for cancers. We and others have suggested that COX-2 and PGs have key roles in drug resistance in cancer and their inhibitors can be useful to reverse the drug resistance and sensitize the chemoptherpeutic drugs. C-phycocyanin, a COX-2 selective inhibitor, inhibited MDR1-mediated drug resistance in HepG2 cells. Drug resistance-inhibitory potency of C-phycocyanin was due to its COX-2 inhibition activity and by inhibiting ROS generation. Similarly it was shown by several investigators have shown that celecoxib and guggulsterone overcome imatinib resistance and induces apoptosis in imatinib-resistant leukemic cells by inhibiting COX-2 and P-glycoprotein. Hence, researchers may explore COX-2 inhibitory natural products as sensitizers of drugs and/or inhibitors of drug resistance.

Overall, research on development of AA pathway inhibitory natural products in cancer prevention and therapy is in good progress. Safety profile of AA pathway inhibitory natural products in toxicity studies represents an advantage for their clinical development. However, poor bioavailability of the AA pathway inhibitory natural products is a major problem for their clinical development as cancer chemopreventive and therapeutic agents. At the same time, several alternative strategies have been developed by several investigators to enhance the bioavailability of some of the natural products. In this context, discovery of new inhibitors of AA pathway from natural sources as well as a detailed investigations including clinical evaluation on existing AA pathway inhibitory natural products are needed for their development as effective and safe drugs for cancer prevention and therapy."


The referenced scientific work at PubMed:

Yarla NS, Bishayee A, Sethi G, Reddanna P, Kalle AM,
Dhananjaya BL, Dowluru KS, Chintala R, Duddukuri GR.
Targeting arachidonic acid pathway by natural products for
cancer prevention and therapy. Semin Cancer Biol.
2016 Oct;40-41:48-81. doi: 10.1016/j.semcancer.2016.02.001.
https://www.ncbi.nlm.nih.gov/pubmed/26853158


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https://www.researchgate.net/publication/292610650_Targeting_arachidonic_acid_pathway_by_natural_products_for_cancer_prevention_and_therapy

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Thursday, February 23, 2017

Ageing, neurodegeneration, and brain rejuvenation (NATURE INSIGHT REVIEW)



Abstract (as presented by the author of the scientific work):

"Although systemic diseases take the biggest toll on human health and well-being, increasingly, a failing brain is the arbiter of a death preceded by a gradual loss of the essence of being. Ageing, which is fundamental to neurodegeneration and dementia, affects every organ in the body and seems to be encoded partly in a blood-based signature. Indeed, factors in the circulation have been shown to modulate ageing and to rejuvenate numerous organs, including the brain. The discovery of such factors, the identification of their origins and a deeper understanding of their functions is ushering in a new era in ageing and dementia research."


Covered topics (the letter size corresponds to the frequency of mentioning in the text):



Outlook (as presented by the author of the scientific work):

"In humans, the old brain shows the classic hallmarks of ageing and is particularly susceptible to abnormal protein accumulation and impairments in the phagolysosomal system, which leads to fluid boundaries between ageing and neurodegenerative diseases. Consequently, many old people have pathological abnormalities of the brain that do not necessarily correlate with their cognitive abilities. This has important implications for the treatment of those with clinical symptoms as well as for designing clinical trials to target protein abnormalities in a specific manner. Given the crucial functions that immune responses and inflammation have in brain ageing and neurodegeneration, it will be essential to discern beneficial attempts to maintain or repair damage from maladaptive ones. Clearly, the term neuroinflammation fails to capture the age- or disease-related changes in this sophisticated interplay between the surveillance, identification, targeting and execution functions of immunity and should probably be avoided. When studying age-related neurodegenerative diseases in animal models, it is important to consider ageing; those that have been genetically engineered to develop disease during adolescence and before midlife are unlikely to be influenced sufficiently by ageing and are therefore not very informative about age-related factors in sporadic neurodegeneration.

The increasing number of studies that show systemic effects on the brain, including those of young plasma or heterochronic parabiosis, as well as the effects of the microbiome, should remind neuroscientists that neurons do not function in isolation; instead, they are part of a sophisticated network that includes glial cells, vascular cells and peripheral cells.

So far, there is no published evidence that young blood or plasma has beneficial effects on an ageing human body, and the observation that young plasma can modulate brain ageing in mice presents more questions and opportunities than answers. Only a handful of proteins, which might represent factors involved in ageing or rejuvenation, have been shown to mimic the effects of plasma. However, many more proteins or other types of molecules are likely to exist, some of which might have direct therapeutic applications. Basic research will address the exciting questions that surround the origins of these factors, how they signal to the brain and why they change with age. Ultimately, it is hoped that by using such knowledge to alter basic processes involved in ageing, it will become feasible to counter the cellular abnormalities that lead to neurodegeneration."


The referenced scientific work at PubMed:

Wyss-Coray T. Ageing, neurodegeneration and brain rejuvenation. Nature. 2016
Nov 10;539(7628):180-186. doi: 10.1038/nature20411. Review. PubMed PMID:
27830812; PubMed Central PMCID: PMC5172605.


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