Purification and Characterization of a Novel Galloyltransferase Involved in Catechin Galloylation in the Tea Plant

Abstract

Catechins (flavan-3-ols), the most important secondary metabolites in the tea plant, have positive effects on human health and are crucial in defense against pathogens of the tea plant. The aim of this study was to elucidate the biosynthetic pathway of galloylated catechins in the tea plant. The results suggested that galloylated catechins were biosynthesized via 1-O-glucose ester-dependent two-step reactions by acyltransferases, which involved two enzymes, UDP-glucose:galloyl-1-O-β-d-glucosyltransferase (UGGT) and a newly discovered enzyme, epicatechin:1-O-galloyl-β-d-glucose O-galloyltransferase (ECGT). In the first reaction, the galloylated acyl donor β-glucogallin was biosynthesized by UGGT from gallic acid and uridine diphosphate glucose. In the second reaction, galloylated catechins were produced by ECGT catalysis from β-glucogallin and 2,3-cis-flavan-3-ol. 2,3-cis-Flavan-3-ol and 1-O-galloyl-β-d-glucose were appropriate substrates of ECGT rather than 2,3-trans-flavan-3-ol and 1,2,3,4,6-pentagalloylglucose. Purification by more than 1641-fold to apparent homogeneity yielded ECGT with an estimated molecular mass of 241 to 121 kDa by gel filtration. Enzyme activity and SDS-PAGE analysis indicated that the native ECGT might be a dimer, trimer, or tetramer of 60- and/or 58-kDa monomers, and these monomers represent a heterodimer consisting of pairs of 36- or 34- of and 28-kDa subunits. MALDI-TOF-TOF MS showed that the protein SCPL1199 was identified. Epigallocatechin and epicatechin exhibited higher substrate affinities than β-glucogallin. ECGT had an optimum temperature of 30 °C and maximal reaction rates between pH 4.0 and 6.0. The enzyme reaction was inhibited dramatically by phenylmethylsulfonyl fluoride, HgCl2, and sodium deoxycholate.

Introduction

Flavonoids, a major class of secondary metabolites in plants, have a number of important physiological roles as endogenous auxin transport regulators, root development , seed germination, allelopathy , plant-bacterium interaction , UV-B protection , and plant defense against pathogens and environmental stress.

Flavonoids can be grouped into several subgroups including chalcone, flavone, flavonol, flavandiol, anthocyanin, proanthocyanidin (oligomer or polymer of flavan-3-ols and flavan-3,4-diol units) and other specialized forms. Flavan-3-ols (catechins), which comprise ∼70–80% of tea polyphenols, are rich in young leaves and shoots of the tea plant (Camellia sinensis (L.) O. Kuntze). Catechins, with a basic 2-phenylchromone structure, are characterized by the di- or tri-hydroxyl group substitution of the B ring, the 2,3-position isomer of the C ring, and presence of a galloyl group at the 3-postion of the C ring . On the basis of the classical definition proposed of galloyl group structural features, catechins are divided into galloylated and nongalloylated compounds. Galloylated catechins, including (−)-epigallocatechin gallate (EGCG)3 and (−)-epicatechin gallate (ECG), esterified often with gallic acid (GA) in the 3-hydroxyl group of the flavan-3-ol units are major catechin compounds that account for up to 76% of catechins in the tea plant .

Resource: http://www.ncbi.nlm.nih.gov
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Benefits of Green Tea

Abstract

The health benefits of green tea for a wide variety of ailments, including different types of cancer, heart disease, and liver disease, were reported. Many of these beneficial effects of green tea are related to its catechin, particularly (-)-epigallocatechin-3-gallate, content. There is evidence from in vitro and animal studies on the underlying mechanisms of green tea catechins and their biological actions. There are also human studies on using green tea catechins to treat metabolic syndrome, such as obesity, type II diabetes, and cardiovascular risk factors.

Long-term consumption of tea catechins could be beneficial against high-fat diet-induced obesity and type II diabetes and could reduce the risk of coronary disease. Further research that conforms to international standards should be performed to monitor the pharmacological and clinical effects of green tea and to elucidate its mechanisms of action.

Background

In recent years, the health benefits of consuming green tea, including the prevention of cancer and cardiovascular diseases, the anti-inflammatory, antiarthritic, antibacterial, antiangiogenic, antioxidative , antiviral, neuroprotective, and cholesterol-lowering effects of green tea and isolated green tea constituents are under investigation. However, adding green tea to the diet may cause other serious health concerns.

The health-promoting effects of green tea are mainly attributed to its polyphenol content, particularly flavanols and flavonols, which represent 30% of fresh leaf dry weight. Recently, many of the aforementioned beneficial effects of green tea were attributed to its most abundant catechin, (-)-epigallocatechin-3-gallate (EGCG). Green Tea Extract are more stable than pure epigallocatechin gallate, one of the major constituents of green tea, because of the presence of other antioxidant constituents in the extract. In general, herbal medicines are complex mixtures of different compounds that often act in a synergistic fashion to exert their full beneficial effect . However, relatively few herbal medicines have been well characterized and their efficacy demonstrated in systematic clinical trials as compared to Western drugs. This review article highlights the recent research on the efficacy, action mechanisms, and side effects of green tea and its catechins in in vitro, in vivo, and ex vivo systems .

The review on green tea and its catechins focused on language literature in English. The literature search was conducted in the following databases: Pubmed (1980-2009), EMBASE (1980-2009), Allied and complementary Medicine Database (AMED, 1985-2009) and China Journals Full Text Database (1975-2009). The keywords used were selected from the following terms: green tea, catechins, anticancer, diabetes, polyphenols, in vivo studies, general pharmacology and toxicology. The health benefits and adverse effects of green tea and its catechins were reviewed.

The authors read full articles and reached consensus after discussion. Articles included in the study covered the following effects of green tea:  the health benefits in humans and animals, absorption of metal ions and drug-metabolizing enzymes,  antioxidation and inhibition of oxidative stress,  carbohydrate metabolism and diabetes mellitus, and adverse effects. A total of 105 peer-reviewed papers in English were selected for this review.

Resource: http://www.ncbi.nlm.nih.gov
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Weight Loss Information in a Popular Diet Book: Is It Fact, Fiction, or Something in Between?

Abstract

BACKGROUND/OBJECTIVE

Diet books dominate the New York Times Advice Best Seller list and consumers cite such books as an important source of nutrition information. However, the scientific support for nutrition claims presented as fact (nutrition facts) in diet books is not known.

DESIGN/MEASUREMENTS

We assessed the quality of nutrition facts in the best-selling South Beach Diet using support in peer-reviewed literature as a measure of quality. We performed structured literature searches on nutrition facts located in the books' text, and then assigned each fact to 1 of 4 categories (1) fact supported, (2) fact not supported, (3) fact both supported and not supported, and (4) no related papers. A panel of expert reviewers adjudicated the findings.

RESULTS

Forty-two nutrition facts were included. Fourteen (33%) facts were supported, 7 (17%) were not supported, 18 (43%) were both supported and not supported, and 3 (7%) had no related papers, including the fact that the diet had been “scientifically studied and proven effective.”

CONCLUSIONS

Consumers obtain nutrition information from diet books. We found that over 67% of nutrition facts in a best-seller diet book may not be supported in the peer-reviewed literature. These findings have important implications for educating consumers about nutrition information sources.

Resource: http://www.ncbi.nlm.nih.gov/
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Effects of Hydrotherapy Treatment on Various Systems of the Body

Abstract

The use of water for various treatments (hydrotherapy) is probably as old as mankind. Hydrotherapy is one of the basic methods of treatment widely used in the system of natural medicine, which is also called as water therapy, aquatic therapy, pool therapy, and balneotherapy. Use of water in various forms and in various temperatures can produce different effects on different system of the body. Many studies/reviews reported the effects of hydrotherapy only on very few systems and there is lack of studies/reviews in reporting the evidence-based effects of hydrotherapy on various systems. We performed PubMed and PubMed central search to review relevant articles in English literature based on “effects of hydrotherapy/balneotherapy” on various systems of the body. Based on the available literature this review suggests that the hydrotherapy has a scientific evidence-based effect on various systems of the body.

Introduction

Hydrotherapy is the external or internal use of water in any of its forms (water, ice, steam) for health promotion or treatment of various diseases with various temperatures, pressure, duration, and site. It is one of the naturopathic treatment modality used widely in ancient cultures including India, Egypt, China, etc. Though many countries used water to produce different physiological/therapeutic effects on different part of the system for maintaining health, preventing, and treating the diseases, the scientific evidence-based effects are not well documented. There are many studies/reviews that reported either physiological or therapeutic or combination of both the effects of hydrotherapy on particular system but did not report in all the major systems of the body, which made us to do this review with the aim and objective to report scientific evidenced-based effects of hydrotherapy on various systems of the body. In order to provide a general overview, we performed PubMed and PubMed central search to review relevant articles in English literature based on “effects of hydrotherapy/balneotherapy” on various systems of the body. Articles published from 1986 to 2012 were included in this review.

Resource: http://www.ncbi.nlm.nih.gov
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In 18350- 1900 Healthy Skin Definition

Abstract

The concept of a healthy skin penetrated the lives of many people in late-nineteenth-century Britain. Popular writings on skin and soap advertisements are significant for pointing to the notions of the skin as a symbolic surface: a visual moral ideal. Popular health publications reveal how much contemporary understanding of skin defined and connected ideas of cleanliness and the visual ideals of the healthy body in Victorian Britain. Characterised as a ‘sanitary commissioner’ of the body, skin represented the organ of drainage for body and society. The importance of keeping the skin clean and purging it of waste materials such as sweat and dirt resonated in a Britain that embraced city sanitation developments, female beauty practices, racial identities and moral reform. By focusing on the popular work by British surgeon and dermatologist Erasmus Wilson (1809–84), this article offers a history of skin through the lens of the sanitary movement and developments in the struggle for control over healthy skin still in place today.

Resource: http://www.ncbi.nlm.nih.gov/
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Botanicals Uses in Skin Care

Abstract

Cosmeceuticals are the fastest growing sector of the cosmetic industry, and the future of antiaging cosmeceuticals in particular is very promising. Botanical extracts that support the health, texture, and integrity of the skin, hair, and nails are widely used in cosmetic formulations. They form the largest category of cosmeceutical additives found in the marketplace today due to the rising consumer interest and demand for natural products. Various plant extracts that formed the basis of medical treatments in ancient civilizations and many traditional cultures are still used today in cleansers, moisturizers, astringents, and many other skin care products. New botanical skin care treatments are emerging, presenting dermatologists and their patients the challenge of understanding the science behind these cosmeceuticals. Thus, dermatologists must have a working knowledge of these botanicals and keep up with how they evolve to provide optimal medical care and answer patient questions. The most popular botanicals commonly incorporated into skin care protocols are discussed.

The cosmeceutical market is one of constant fluctuation depending upon consumer demand. Skin care companies are continuously pressured to release new, innovative products that promise to transform the appearance of aging skin overnight. Over the past decade, there has been fervent interest in products found in nature because of their perceived safety. Skin care products are often developed from plants. Many believe that if a product can be safely ingested, it will also be safe for topical application. In general, plant-derived, botanical, cosmeceutical products tend to be antioxidant in action since these organisms must thrive in constant direct ultraviolet (UV) light, the Earth's most prolific manufacturer of free radicals. In this article, the authors review the most popular ingredients in this class and comment on their possible usefulness in skin care protocols.

Soy

Soy extract has positive research support for its antioxidant, antiproliferative, and anticarcinogenic activities. Topical application of soy has been used to reduce hyperpigmentation, enhance skin elasticity, control oil production, moisturize the skin, and delay hair regrowth. Soy also has the potential to decrease photoaging of the skin and prevent skin cancers through the estrogen-type and antioxidant effects of its metabolites.

The major components of soy are phospholipids, such as phosphatidylcholine and essential fatty acids. The minor components of soy include the most active compounds, such as isoflavones, saponins, essential amino acids, phytosterols, calcium, potassium, iron, and proteases soybean trypsin inhibitor (STI) and Bowman-Birk inhibitor (BBI). The various components of soy have a variety of beneficial effects making them useful additions to skin care products. The most potent isoflavones are the phytoestrogens known as genistein and daidzein. Genistein is a potent antioxidant that inhibits lipid peroxidation and chemical and ultraviolet light B (UVB)-induced carcinogenesis. Genistein was shown to significantly inhibit chemical, carcinogen-induced, reactive oxygen species; oxidative DNA damage; and proto-oncogene expression, as well as the initiation and promotion of skin carcinogenesis in mouse skin. Topical estrogens have been shown to promote collagen synthesis and increase skin thickness, which may be beneficial for postmenopausal women who develop a thinner dermis and decreased collagen. The small proteases STI and BBI appear to promote skin lightening and reduce unwanted facial and body hair in human clinical trials. Beyond the depigmenting activity, STI, BBI, and soy milk were also found to prevent UV-induced pigmentation both in vitro and in vivo. In addition, soy lipids, lecithins, and phytosterols are believed to restore barrier function and replenish moisture.

Beyond its moisturizing ability, soy appears to be a safe and effective treatment for postmenopausal women and for hyperpigmentation disorders (other than melasma, which is somewhat estrogen mediated). Although further research is necessary, the antioxidant and anticarcinogenic activities of soy and its isoflavones show a promising role for this botanical in the cosmeceutical industry. Soy has therefore become a popular addition to a wide variety of skin care products.

Resource: http://www.ncbi.nlm.nih.gov
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Atypical Occurrence of Two Biotin Protein Ligases in Francisella novicida

ABSTRACT

The physiological function of biotin requires biotin protein ligase activity in order to attach the coenzyme to its cognate proteins, which are enzymes involved in central metabolism. The model intracellular pathogen Francisella novicida is unusual in that it encodes two putative biotin protein ligases rather than the usual single enzyme. F. novicida BirA has a ligase domain as well as an N-terminal DNA-binding regulatory domain, similar to the prototypical BirA protein in E. coli. However, the second ligase, which we name BplA, lacks the N-terminal DNA binding motif. It has been unclear why a bacterium would encode these two disparate biotin protein ligases, since F. novicida contains only a single biotinylated protein. In vivo complementation and enzyme assays demonstrated that BirA and BplA are both functional biotin protein ligases, but BplA is a much more efficient enzyme. BirA, but not BplA, regulated transcription of the biotin synthetic operon. Expression of bplA (but not birA) increased significantly during F. novicida infection of macrophages. BplA (but not BirA) was required for bacterial replication within macrophages as well as in mice. These data demonstrate that F. novicida has evolved two distinct enzymes with specific roles; BplA possesses the major ligase activity, whereas BirA acts to regulate and thereby likely prevent wasteful synthesis of biotin. During infection BplA seems primarily employed to maximize the efficiency of biotin utilization without limiting the expression of biotin biosynthetic genes, representing a novel adaptation strategy that may also be used by other intracellular pathogens.

IMPORTANCE

Our findings show that Francisella novicida has evolved two functional biotin protein ligases, BplA and BirA. BplA is a much more efficient enzyme than BirA, and its expression is significantly induced upon infection of macrophages. Only BplA is required for F. novicida pathogenicity, whereas BirA prevents wasteful biotin synthesis. These data demonstrate that the atypical occurrence of two biotin protein ligases in F. novicida is linked to distinct roles in virulence and biotin metabolism.

Resource: http://www.ncbi.nlm.nih.gov
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Assessing the Ability of an Oral Supplement to Increase Hair Growth in Women with Thinning Hair.

Abstract

Objective: To assess the ability of an oral supplement to increase hair growth in women with thinning hair. Design: A randomized, placebo-controlled, double-blind study. Setting: One United States clinical site. Participants: Healthy women aged 21 to 75 years with Fitzpatrick I to IV photo skin types with self-perceived thinning hair. Measurements: Subjects were randomized to treatment with the study medication (N=10) or placebo (N=5) twice daily for 180 days. A 4cm2 area of scalp was selected for hair counts performed after 90±7 and 180±7 days of treatment. The primary efficacy measure was the change in terminal and vellus hairs in each target area. The secondary measure was changes in a self-assessment questionnaire. Results: The mean (SD) number of terminal vellus hairs among placebo-treated subjects at baseline was 256.0 (24.1), remaining at 245.0 (22.4) and 242.2 (26.9) after 90 and 180 days, respectively. The mean baseline number of terminal hairs in control-treated subjects was 271.0 (24.2) increasing to 571 (65.7) and 609.6 (66.6) after 90 and 180 days, respectively (for each, p<0.001 vs. placebo). The mean number of vellus hairs among placebo-and control-treated subjects did not significantly change. Significantly more control-treated subjects perceived improvements in overall hair volume, scalp coverage, and thickness of hair body after 90 days. Additional improvement after 180 days included hair shine, skin moisture retention, and skin smoothness. No adverse events were reported. Conclusion: The oral supplement assessed in this study safely and effectively promotes significant hair growth in women with temporary hair thinning.

Androgenic alopecia or male-pattern baldness is the most common form of hair loss in men and less commonly a cause of hair loss in women. More common causes of hair loss in women include medical conditions, such as hypothyroidism; medications including oral contraceptives; nutritional deficiencies; and physiological and emotional stresses. The causes of hair loss in elderly women may be multifactorial.Among 100 adult women with diffuse hair loss in one study, probable causes were determined to be psychological stress (30%), fever (33%), abortion and delivery (21%), trauma or surgical operations (13%), and hypothyroidism (10%).4 More than 50 percent of women had more than one likely cause of hair loss while a cause could not be determined in six percent.

The effects of hair loss on self-image and self-esteem have been well documented. In one study, significantly diminished quality of life among adult men and women with various forms of hair loss was significantly correlated with symptoms of clinical depression, and the psychological impact of hair loss among women appears to be more severe than for men. Consequently, a drug therapy that will safely and effectively increase hair growth in women is highly desirable.

An oral compound consisting of proteins and glycosaminoglycans of marine origin was found to have beneficial effects on women with sun-damaged skin. The results of two studies demonstrated improvements in the appearance of sun-damaged skin and increased skin thickness and elasticity. Brittle hair and nails returned to normal after 90 days of treatment. Subsequent studies assessed the use of a similar marine extract with the addition of other natural compounds (Viviscal® Hair Nourishment System; Lifes good, Inc., Chicago, Illinois) for the treatment of androgenetic alopecia. Several six-month, randomized, controlled studies have demonstrated the efficacy of Viviscal (the product used in these studies was originally marketed under the brand name Hairgain® [Parexel Medstat AS, Lillestrøm, Norway]) for the treatment of androgenetic alopecia. Similar results were achieved in 8- and 12-month, open-label studie Since these studies enrolled men, less is known about the use of Viviscal in women with thinning hair.

The objective of this randomized, double-blind, placebo-controlled study was to test the hypothesis that the administration of this new oral supplement over a six-month period will increase hair growth in adult women with self-perceived thinning hair associated with poor diet, stress, hormonal influences, or abnormal menstrual cycles. Preliminary results of this study have been presented elsewhere.

Resource: http://www.ncbi.nlm.nih.gov
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Association of Green Tea with Risk of Coronary Heart Disease (CHD)

Abstract

Prospective studies on the association of green tea with risk of coronary heart disease (CHD) incidence were scarce. This study examined whether green tea can reduce CHD incidence and have a beneficial effect on CHD-related risk markers in middle-aged and older Chinese population. We included 19 471 participants who were free of CHD, stroke or cancer at baseline from September 2008 to June 2010, and were followed until October 2013. Cox proportional hazard models were used to examine the hazard ratios (HR) of CHD incidence in relation to green tea consumption. Linear regression models were used to evaluate the effect of green tea on 5-year changes of CHD-related biomarkers. Compared with non-green tea consumers, the multivariable-adjusted HR for CHD was 0.89 (95% CI, 0.81-0.98) in green tea consumers. Particularly, the reduced risk of CHD incidence with green tea consumption was more evident among participants who were male, more than 60 years old, overweight, or with diabetes mellitus. In addition, green tea consumption improved multiple CHD-related risk markers including total cholesterol, HDL-cholesterol, triglycerides, mean platelet volume, and uric acid. In conclusion, green tea consumption was associated with a reduced risk of CHD incidence in the middle-aged and older Chinese populations, and the association might be partly due to altered CHD-related biomarkers.

Cardiovascular disease (CVD) has become the leading cause of death and continues to exert a heavy burden in China. The number of patients with CVD increased to 290 million in 2014 with one out five Chinese adults suffering from the disease1. Coronary heart disease (CHD) accounts for the greatest proportion of CVD, and the prevalence of Chinese people with CHD is increasing substantially due to ageing, imbalanced diets, unhealthy behaviors and the raising standard of living. Thus, early prevention and control of CHD has become an extremely important public health concern.

Tea, a beverage made from leaves of Camellia sinensis, is the second most consumed beverage worldwide, only close to plain water. Tea was generally categorized into black, green and oolong tea according to the manufacturing process. Black tea, which covers about 78% of the total tea production, is usually consumed in the West; whereas green tea, which covers 20%, is consumed primarily in Japan, China and other East Asian countries5. A recent meta-analysis of prospective studies based mainly on evidence from black tea or unspecified tea showed that tea consumption was associated with a reduced risk of CHD, and found that the associations between tea consumption and cardiovascular outcomes differ according to sex, ethnicity, and the type of tea consumed. On the contrary, data on the association between green tea and CHD was limited and inconclusive. Several cohort studies have suggested an inverse association between green tea and CVD mortality. Although dose-response relationship between green tea and risk of CHD was reported in case-control and cross-sectional studies only two cohort studies have examined the impact of green tea consumption on risk of CHD incidence and no significant association was observed. On the other hand, favorable changes in CHD-related biomarkers, such as blood pressure, LDL cholesterol and glucose levels, were reported with green tea in randomized controlled trials which suggested a possible protective effect of green tea against CHD. However, most existing studies have only focused on one aspect: either green tea versus CHD, or green tea versus biomarkers; seldom studies have so far examined both of them on a same population.

Because of the high consumption of green tea in China and relatively high rate of CHD incidence and mortality, exploring the health effects of green tea on CHD might provide clues to resolve an important public health issue. Therefore, we aimed to 1) verify the relationship between green tea and CHD incidence in the Dongfeng-Tongji cohort; 2) examine whether the association between green tea and CHD was modified by differences in population characteristics and disease status; and 3) evaluate the effect of green tea on changes of multiple CHD-related biomarkers.

Resource: http://www.ncbi.nlm.nih.gov/
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Assessing the Efficacy of Green Coffee Extract (GCE) as a Weight Loss Supplement

Abstract

The purpose of this paper is to assess the efficacy of green coffee extract (GCE) as a weight loss supplement, using data from human clinical trials. Electronic and nonelectronic searches were conducted to identify relevant articles, with no restrictions in time or language. Two independent reviewers extracted the data and assessed the methodological quality of included studies. Five eligible trials were identified, and three of these were included. All studies were associated with a high risk of bias. The meta-analytic result reveals a significant difference in body weight in GCE compared with placebo (mean difference: −2.47 kg; 95%CI: −4.23, −0.72). The magnitude of the effect is moderate, and there is significant heterogeneity amongst the studies. It is concluded that the results from these trials are promising, but the studies are all of poor methodological quality. More rigorous trials are needed to assess the usefulness of GCE as a weight loss tool.

Introduction

Overweight and obesity have become a serious health concern. Different weight management strategies are presently utilised, and a variety of weight loss supplements sold as “slimming aids” are readily available. However, the efficacy of some of these food supplements remains uncertain. One such supplement is the green coffee extract (GCE).

GCE is present in green or raw coffee. It is also present in roasted coffee, but much of the GCE is destroyed during the roasting process. Some GCE constituents, such as chlorogenic acid (CGA) can also be found in a variety of fruits and vegetables. The daily intake of CGA in persons drinking coffee varies from 0.5 to 1 g. The traditional method of extraction of GCE from green coffee bean, Coffea canephora robusta, involves the use of alcohol as a solvent. Extracted GCE is marketed as a weight loss supplement under a variety of brand names as a weight loss supplement such as “Coffee Slender”, and “Svetol”.

Evidence is accumulating from animal studies regarding the use of GCE as a weight loss supplement. In human subjects, coffee intake has been reported to be inversely associated with weight gain. Consumption of coffee has also been shown to produce changes in several glycaemic markers in older adults. Similarly, other research has indicated that the consumption of caffeinated coffee can lead to some reductions in long-term weight gain, an effect which is likely to be due to the known thermogenic effects of caffeine intake as well as effects of GCE and other pharmacologically active substances present in coffee. GCE has also been postulated to modify hormone secretion and glucose tolerance in humans. This effect is accomplished by facilitating the absorption of glucose from the distal, rather than the proximal part of the gastrointestinal tract.

The objective of this paper is to analyse the results of human clinical trials assessing the efficacy of GCE as a weight-reducing agent.

Resource: http://www.ncbi.nlm.nih.gov
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Effect of Omega 3 and Omega 6 Fatty Acids on Prostate Cancer

Abstract

Although a causal role of genetic alterations in human cancer is well established, it is still unclear whether dietary fat can modulate cancer risk in a predisposed population. Epidemiological studies suggest that diets rich in omega-3 polyunsaturated fatty acids reduce cancer incidence. To determine the influence of fatty acids on prostate cancer risk in animals with a defined genetic lesion, we used prostate-specific Pten-knockout mice, an immune-competent, orthotopic prostate cancer model, and diets with defined polyunsaturated fatty acid levels. We found that omega-3 fatty acids reduced prostate tumor growth, slowed histopathological progression, and increased survival, whereas omega-6 fatty acids had opposite effects. Introducing an omega-3 desaturase, which converts omega-6 to omega-3 fatty acids, into the Pten-knockout mice reduced tumor growth similarly to the omega-3 diet. Tumors from mice on the omega-3 diet had lower proportions of phosphorylated Bad and higher apoptotic indexes compared with those from mice on omega-6 diet. Knockdown of Bad eliminated omega-3–induced cell death, and introduction of exogenous Bad restored the sensitivity to omega-3 fatty acids. Our data suggest that modulation of prostate cancer development by polyunsaturated fatty acids is mediated in part through Bad-dependent apoptosis. This study highlights the importance of gene-diet interactions in prostate cancer.

Introduction

A causal role of genetic alterations in human cancer is well established; however, environmental influence on cancer risk is not clearly understood. Over 2 decades, epidemiologic studies have been reported on the effect of dietary fat on prostate cancer risk. However, the mechanistic role of dietary fat in prostate cancer remains ill defined. Prostate cancer is the most frequently diagnosed cancer and a leading cause of cancer death in men in the US. There is a wide variation in international prostate cancer mortality rates; these are particularly high in Northern Europe and North America and much lower in Japan and other Asian countries. Yet small, latent carcinomas of the prostate diagnosed at autopsy are as common in Asian countries as in Western countrie. Immigrants from Poland and Japan exhibit a significant increase in the risk of developing clinical prostate cancer when resident in the US. These findings implicate environmental variables, and possibly diet, as significant contributing factors.

Omega-3 and omega-6 polyunsaturated FAs (PUFAs) are essential FAs: mammals can neither synthesize them de novo nor interconvert them; therefore, they have to be taken in from diet. Many vegetable oils contain high levels of omega-6 PUFAs, whereas fish oil is a rich source of omega-3 PUFAs, mainly eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3). Diets with an omega-6/omega-3 PUFA ratio of 1 are recommended for human consumption by a panel of nutritionists, and diets with a similar ratio are consumed by some populations such as the Inuit . Current Western diets have omega-6/omega-3 ratios of approximately 30 , although they can be as high as 50. Some evidence suggests that cyclooxygenase inhibitors, which block the metabolism of omega-6 PUFAs, are beneficial in prevention of colon and prostate cancer. However, the cardiovascular toxicity of cyclooxygenase-2 inhibitors has jeopardized the clinical utility of these drugs. Reducing the intake of omega-6 PUFAs and increasing the proportion of dietary omega-3 is an attractive approach.

Inaccuracy in reporting dietary intake and difficulties in conducting mechanistic studies on human populations have hampered investigations on the role of dietary fat in prostate cancer development. Most experiments using animals have been performed in xenograft models and are limited by the fact that tumors grow at an ectopic site in an immune-deficient host environment. Moreover, dietary composition in animal diets is often poorly defined, and dietary intake is inadequately monitored. In an effort to overcome these limitations, we used prostate-specific Pten-knockout mice, an immune-competent, orthotopic prostate cancer model, and designed diets to investigate the influence of dietary PUFAs on prostate cancer risk in animals with this defined genetic lesion.

Resource: http://www.ncbi.nlm.nih.gov/
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Association of Omega-3 Fatty Acid Blood Levels with Telomere Length in Coronary Heart Disease Patient.

Abstract

Context

Increased dietary intake of marine omega-3 fatty acids is associated with prolonged survival in patients with coronary heart disease. However, the mechanisms underlying this protective effect are poorly understood.

Objective

To investigate the association of omega-3 fatty acid blood levels with temporal changes in telomere length, an emerging marker of biological age.

Design, Setting, and Participants

Prospective cohort study of 608 ambulatory outpatients in California with stable coronary artery disease recruited from the Heart and Soul Study between September 2000 and December 2002 and followed up to January 2009 (median, 6.0 years; range, 5.0-8.1 years).

Main Outcome Measures

We measured leukocyte telomere length at baseline and again after 5 years of follow-up. Multivariable linear and logistic regression models were used to investigate the association of baseline levels of omega-3 fatty acids (docosahexaenoic acid [DHA] and eicosapentaenoic acid [EPA]) with subsequent change in telomere length.

Results

Individuals in the lowest quartile of DHA3EPA experienced the fastest rate of telomere shortening (0.13 telomere-to-single-copy gene ratio [T/S] units over 5 years; 95% confidence interval [CI], 0.09-0.17), whereas those in the highest quartile experienced the slowest rate of telomere shortening (0.05 T/S units over 5 years; 95% CI, 0.02-0.08; P<.001 for linear trend across quartiles). Levels of DHA+EPA were associated with less telomere shortening before (unadjusted β coefficient × 10−3=0.06; 95% CI, 0.02-0.10) and after (adjusted β coefficient × 10−3=0.05; 95% CI, 0.01-0.08) sequential adjustment for established risk factors and potential confounders. Each 1-SD increase in DHA+EPA levels was associated with a 32% reduction in the odds of telomere shortening (adjusted odds ratio, 0.68; 95% CI, 0.47-0.98).

Conclusion

Among this cohort of patients with coronary artery disease, there was an inverse relationship between baseline blood levels of marine omega-3 fatty acids and the rate of telomere shortening over 5 years.

Resource: http://www.ncbi.nlm.nih.gov/
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Therapies on Omega - 3 Fatty Acids - Overview

Abstract

The triglyceride (TG)-lowering benefits of the very-long-chain omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are well documented. Available as prescription formulations and dietary supplements, EPA and DHA are recommended by the American Heart Association for patients with coronary heart disease and hypertriglyceridemia. Dietary supplements are not subject to the same government regulatory standards for safety, efficacy, and purity as prescription drugs are; moreover, supplements may contain variable concentrations of EPA and DHA and possibly other contaminants. Reducing low-density lipoprotein-cholesterol (LDL-C) levels remains the primary treatment goal in the management of dyslipidemia. Dietary supplements and prescription formulations that contain both EPA and DHA may lower TG levels, but they may also increase LDL-C levels.

Two prescription formulations of long-chain omega-3 fatty acids are available in the U.S. Although prescription omega-3 acid ethyl esters (OM-3-A EEs, Lovaza) contain high-purity EPA and DHA, prescription icosapent ethyl (IPE, Vascepa) is a high-purity EPA agent. In clinical trials of statin-treated and non–statin-treated patients with hypertriglyceridemia, both OM-3-A EE and IPE lowered TG levels and other atherogenic markers; however, IPE did not increase LDL-C levels.

Results of recent outcomes trials of long-chain omega-3 fatty acids, fibrates, and niacin have been disappointing, failing to show additional reductions in adverse cardiovascular events when combined with statins. Therefore, the REDUCE–IT study is being conducted to evaluate the effect of the combination of IPE and statins on cardiovascular outcomes in high-risk patients. The results of this trial are eagerly anticipated.

INTRODUCTION

It is now established that omega-3 and omega-6 fatty acids play important roles in human health and disease. Both are considered essential fatty acids, because they are not endogenously synthesized and must be obtained from the diet. Long-chain omega-6 fatty acids include linoleic, gamma-linolenic, and arachidonic acids. Omega 3 Fish Oil 1000mg acids include the long-chain alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA).

EPA and DHA are often called very-long-chain omega-3 fatty acids. The typical Western diet is rich in omega-6 fatty acids because of the abundance of linoleic acid present in corn, sunflower, and safflower oils.Conversely, omega-3 fatty acids account for only a small percentage of the daily dietary fat intake and are obtained from two main dietary sources—plants and fish. Plant oils from walnuts, flaxseed, and canola contain the omega-3 fatty acid ALA, which is a metabolic precursor of the very-long-chain omega-3 fatty acids EPA and DHA; however, the conversion from ALA to EPA and DHA in the body is inefficient. The most concentrated food source of EPA and DHA is fatty fish such as albacore tuna, salmon, mackerel, sardines, and herring.

Following consumption, polyunsaturated fatty acids, such as the omega-3 and omega-6 fatty acids, are incorporated into cell membranes, where they modulate membrane protein function, cellular signaling, and gene expression. Dietary omega-3 fatty acids compete with omega-6 fatty acids for incorporation into cell membranes. When omega-6 fatty acids predominate in cell membranes, proinflammatory mediators such as thromboxanes, prostaglandins, and leukotrienes are produced via the cyclooxygenase and 5-lipoxygenase pathways. Conversely, the presence of omega-3 fatty acids promotes secretion of anti-inflammatory prostaglandins and less potent leukotrienes, resulting in a shift to a milieu of less inflammatory mediators.These proinflammatory and anti-inflammatory effects represent the primary pharmacological difference between omega-3 and omega-6 fatty acids.

In addition to their anti-inflammatory activity, very-long-chain omega-3 fatty acids have well-described effects on various risk factors for cardiovascular disease. Epidemiological and clinical studies support the cardiovascular benefits of EPA and DHA; however, there is less evidence to support the benefits of ALA. Potential mechanisms for the cardioprotective effects of omega-3 fatty acids include.

•     reduction of triglyceride (TG) levels.
•     attenuation of atherosclerotic plaques.
•     exertion of antidysrhythmic, antithrombotic, and anti-inflammatory effects.
•     lowering of systolic and diastolic blood pressures.
•     improvement in endothelial function.

Resource: http://www.ncbi.nlm.nih.gov
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Experiment of Transplantation of Entire Bones with their Joint Surfaces

Abstract

Arthur Bruce Gill was born in Western Pennsylvania and obtained his undergraduate degree at Muskingum College in New Concord, Ohio. He then obtained his medical degree at the University of Pennsylvania in 1905, interned there, and remained on the staff for 47 years. He became the third chairman of that department in 1920. He was active in a large number of organizations well into the 1950s.

One writer noted he “...was not a prolific writer, but whatever he wrote was extremely clear and well prepared. There are sixty-nine publications listed under his name in the Index Medicus and Quarterly Cumulative Index...” A substantial number of those publications related to problems of childhood and at least six related to new procedures. Yet, Dr. Gill was wary of new operations. In his Presidential lecture at the AAOS in 1938, he wisely commented, “Let us beware of adopting new methods too hastily.” He added, “Are too many operations performed in the practice of orthopaedic surgery?...many of our young men believe that they can attain distinction only by the invention of a new operation,” and recognized the need to refrain from “fads and fancies”.

We republish an abridged version of experiments he performed in 1914 in which he transplanted whole bones with their joint surfaces within one animal. Portions excluded include his description of the six operations and their results, and a scholarly discussion of the knowledge of transplantation and regeneration at the time. (Interested readers in such material would be well advised to also review an extensive discussion of the knowledge of bone biology in Sir Arthur Keith’s classic monograph, “Menders of the Maimed”.) Dr. Gill concluded fresh bone with cartilage surfaces was readily transplantable as long as “periosteum, medulla, and bony tissue” were all included in the graft. Immunology as a field was not well developed at the time, nor the known problems with transplantation between individuals and species. Nonetheless, his experiments formed a basis for the principles of whole bone transplantation.

The following experiments in bone transplantation were undertaken to determine whether or not it is possible to secure the healing in of entire bones with their articular surfaces, and whether or not such bones, if they do become healed in, will remain alive and unabsorbed, and, finally, to observe any other conditions that may have a bearing upon the subject of bone transplantation in general.

Full-grown dogs were operated upon under complete surgical anaesthesia by ether. The second long metatarsal bone was excised in the front paws and each one was implanted in the opposite paw. The ends of the bone were held in the position by chromic catgut sutures. Tendons and fascia were sutured over it with interrupted sutures of silk floss. Asepsis was attempted by shaving the paws and painting the skin with tincture of iodine and by clamping the margin of the incision to sterile towels. After the incision was closed it was painted with tincture of iodine. No dressings were applied and the dogs were permitted to walk about. This they usually did on the day following operation without any evidence of pain.

Resource: http://www.ncbi.nlm.nih.gov/
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Influence of Forensic Medicine on Therapeutic Medicine

Abstract

This paper analyzes the influence of forensic medicine on therapeutic medicine through a case study of Qian Xiuchang and Hu Tingguang, two Chinese doctors who specialized in treating traumatic injuries. During the early nineteenth century, both men compiled medical treatises that sought to improve on a scholarly model of “rectifying bones” articulated in 1742 by the Imperially-Compiled Golden Mirror of the Medical Lineage. Both texts also incorporated information from forensic medicine, including official inquest diagrams and checklists promulgated by the Qing government. I show that they drew on these forensic materials to help address two interlinked medical issues: understanding the effects of injury on different parts of the body, and clarifying the location and form of the body’s bones. Overall, I suggest that the exchange of ideas between the realm of therapeutic medicine and forensic medicine was an important epistemological strategy that doctors and officials alike employed to improve their knowledge of the material body.

Introduction

How do you assess an injury when you cannot directly see the affected body part? This was a concern for the doctor Qian Xiuchang, an expert in treating injuries. In his 1808 text Supplemented Essentials of Medicine for Injuries, Qian pointed out that “when someone has a dislocated or fractured bone, the bone and joint are wrapped in flesh. Looking at it from the exterior, it is hard to get a clear understanding, and there is the danger of making an error.” In China, as elsewhere in the world, there were historically many healers like Qian who treated wounds and traumatic injuries: bashed skulls and snapped legs, contused and lacerated flesh, torn ears and protruding intestines. Such injuries required the doctor to restore the body’s structural integrity as well as its healthy functioning. In assessing injuries obscured by skin and flesh, furthermore, Qian and his global counterparts in the pre-X-ray age relied on their expert reading of externally discoverable signs, collated with their knowledge about the forms and functions of the body’s normal structure. But where did this bodily knowledge came from?

In the history of Western European medicine, an important source of information came from dissecting dead bodies and extrapolating these findings to the bodies of the living. Prior to the mid-nineteenth century, much of this knowledge had little direct impact on improving general therapeutics; despite some advances in surgery, the limited ability to control pain and infection circumscribed what the surgeon could do. However, many other cultural forces also motivated anatomical study in Europe, and people used knowledge derived from dissection to serve a wide range of artistic, religious, philosophical, scientific, or political ends. In the medical realm, furthermore, access to anatomical training constituted a form of professional capital that different groups of physicians and surgeons used to claim superiority over their competitors.

Resource: http://www.ncbi.nlm.nih.gov
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Osteoporosis management with use of calcium & vitamin D supplements

Abstract

Osteoporosis poses a significant public health issue, causing significant morbidity and mortality. Calcium and vitamin D utilization in the optimization of bone health is often overlooked by patients and health care providers. In addition, the optimal standard of care for osteoporosis should encompass adequate calcium and vitamin D intake. Dietary intake or supplementation with calcium and vitamin D will be reviewed, including recent recommendations for increased vitamin D intake. Compliance to calcium and vitamin D therapy is paramount for effective prevention of osteoporotic fractures. A recently released algorithm (FRAX) estimating absolute fracture risk allows the health care provider to decide when pharmacologic therapy is warranted in addition to calcium and vitamin D. When pharmacologic therapy is advised, continued use of calcium and vitamin D is recommended for optimal fracture risk reduction. A ‘bricks and mortar’ analogy is often helpful when counseling patients and this analogy will be explained. This manuscript reviews relevant data related to calcium and vitamin D use for patients at risk for fracture due to bone loss.

Osteoporosis overview

The skeletal disease of bone thinning and compromised bone strength, osteoporosis, continues to be a major public health issue as the population ages. This disease is characterized by bone fragility and an increased susceptibility to fractures, especially of the spine and hip, although any bone can be affected. It is estimated that over 10 million Americans over the age of 50 have osteoporosis. Risk for osteoporosis has been reported in people of all ethnic backgrounds. An additional 34 million have reduced bone mass, called osteopenia, which puts them at higher risk for fractures later in life. The risk of fracture from osteoporosis increases with age. There are approximately 1.5 million osteoporotic fractures per year reported in women and men in the US, including over 300,000 hip fractures. As the population ages, this number will probably increase. The US Surgeon General estimates that one out of every two women over the age of 50 will have an osteoporosis-related fracture in their lifetime. In addition, 20% of those affected by osteoporosis are men with 6% of white males over the age of 50 suffering a hip fracture. It is estimated that the national direct care costs for osteoporotic fractures is US$12.2 to 17.9 billion per year in 2002 dollars, with costs rising. This cost is comparable to the Medicare expense for coronary heart disease.

Since bone loss occurs without symptoms, osteoporosis is often considered a ‘silent disease’. As deterioration of bone tissue mounts and disruption of bone architecture occurs, the bone becomes so weak that a relatively minor bump or fall causes a fracture or vertebrae to collapse. The resulting fracture may lead to loss of mobility and independence, with 25% requiring long term care. Fractures caused by either osteoporosis or low bone mass can lead to chronic pain, disability, as well as psychological symptoms, including depression. A woman’s risk of hip fracture is equal to her combined risk of breast, uterine and ovarian cancer). Unfortunately, approximately 24% of patients with hip fractures over the age of 50 will die in the year following the fracture.

Fortunately, the importance of this debilitating bone disease is being recognized. President Bush has declared 2002–2011 as the Decade of the Bone and Joint. Important advances have been made to understand the disease process and help create therapies to treat the condition. Bone health is optimized by creating an environment to achieve peak bone mass during adolescence, maintenance of healthy bone throughout life and prevention of bone loss with aging. Health care providers are vital to identify patients at risk for bone loss and diagnose bone thinning so that prevention and treatment strategies are effective.

The US Surgeon General has outlined a ‘pyramid approach’ to treating bone diseases. Prevention of falls with maintenance of bone health through adequate calcium, vitamin D, and physical activity represent the base of the pyramid for all individuals, including those with bone disease. The second tier of this pyramid relates to identifying and treating secondary causes of osteoporosis. Lastly, the third tier revolves around pharmacotherapy.

Calcium and vitamin D have long been recognized as important and required nutrients for bone health and maintenance. The continuation of calcium and vitamin D in a patient with bone loss is critical for optimal care. Unfortunately, 90% of women may not be getting enough calcium and over 50% of women treated for bone loss have inadequate vitamin D levels. Currently, there are a number of pharmacologic treatments for osteoporosis which provide improvements in bone mass and reduction in fracture risk. These treatments have been studied where adequate calcium and vitamin D supplementation had been achieved. Therefore, their use is predicated on proper calcium and vitamin D therapy. The goal of this manuscript is to review data related to calcium and vitamin D in the management of osteoporosis.

Resource: http://www.ncbi.nlm.nih.gov
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The organization of the human cerebral cortex estimated by intrinsic functional connectivity

Abstract

Information processing in the cerebral cortex involves interactions among distributed areas. Anatomical connectivity suggests that certain areas form local hierarchical relations such as within the visual system. Other connectivity patterns, particularly among association areas, suggest the presence of large-scale circuits without clear hierarchical relations. In this study the organization of networks in the human cerebrum was explored using resting-state functional connectivity MRI. Data from 1,000 subjects were registered using surface-based alignment. A clustering approach was employed to identify and replicate networks of functionally coupled regions across the cerebral cortex. The results revealed local networks confined to sensory and motor cortices as well as distributed networks of association regions. Within the sensory and motor cortices, functional connectivity followed topographic representations across adjacent areas. In association cortex, the connectivity patterns often showed abrupt transitions between network boundaries. Focused analyses were performed to better understand properties of network connectivity. A canonical sensory-motor pathway involving primary visual area, putative middle temporal area complex (MT+), lateral intraparietal area, and frontal eye field was analyzed to explore how interactions might arise within and between networks. Results showed that adjacent regions of the MT+ complex demonstrate differential connectivity consistent with a hierarchical pathway that spans networks. The functional connectivity of parietal and prefrontal association cortices was next explored. Distinct connectivity profiles of neighboring regions suggest they participate in distributed networks that, while showing evidence for interactions, are embedded within largely parallel, interdigitated circuits. We conclude by discussing the organization of these large-scale cerebral networks in relation to monkey anatomy and their potential evolutionary expansion in humans to support cognition.

complex behaviors are subserved by distributed systems of brain areas . The organization of these systems can be studied in nonhuman animals by using invasive techniques including histology, anatomical tract tracing, electrophysiology, and lesion methods. The organization of brain systems in the human has been inferred by comparing cytoarchitectonically defined homologies between species and by noting similarities in neuropsychological deficits following accidental brain injury to deficits present in animal ablation studies. General agreement has emerged from these comparisons that the basic organization of brain systems is similar across mammalian species. However, there is also evidence that the human cerebral cortex, particularly association cortex, is not simply a scaled version of other species.

The German anatomist Korbinian  first emphasized that areas comprising the human inferior parietal lobule do not have clear homologs in the monkey, an observation that continues to motivate contemporary debates. Gross differences are also observed in the human brain when it is compared to those of our evolutionarily closest relatives. For example, the human brain is triple the size of modern great ape brains, but motor and visual cortices are about the same absolute size. This observation suggests that expansion of the human cerebrum disproportionately involves areas beyond those subserving basic sensory and motor functions. In a recent analysis of cortical expansion based on 23 homologous areas between the macaque and human, Van Essen and colleagues noted that the greatest growth occurs in regions distributed across frontal, parietal, and temporal association cortices. came to a similar conclusion in a detailed review of comparative anatomy. Thus, in addition to expecting the human brain to show broadly similar organizational properties with other well-studied species, expansion and perhaps elaboration of association networks is also expected.

In this article we report results of a comprehensive analysis of networks within the human cerebral cortex using intrinsic functional connectivity MRI (fcMRI). The analysis was based on 1,000 young adults who contributed uniformly collected MRI data. The data were brought into a common surface coordinate system to help preserve the surface topology of the cortical mantle. Analyses were motivated by two goals. First, we sought to provide reference maps that are a current best estimate of the organization of the human cerebral cortex as measured by functional connectivity. Second, we wanted to better understand how patterns of functional connectivity might give rise to the organizational properties that underlie distributed brain systems. Particular focus was placed on parietal and frontal association cortices. The foundations for the present work come from traditional anatomical studies of cortical organization.

Resource: http://www.ncbi.nlm.nih.gov
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Efficacy of an Anti-Wrinkle and Dark Circle eye pad in a convenient, healthy, and cosmeceutical base.

Abstract

Background:

People strive to maintain the best look and have a youthful appearance. The skin around the eye is an area without many oil glands and collagen in comparison to the body rest, so it is more prone to fine lines and dehydration, which makes it look dull. The aim of this research is to develop and evaluate in vivo efficacy of an anti-wrinkle and dark circle eye pad consisting of 3% w/w caffeine and 1% vitamin K in a convenient, healthy, and cosmeceutical base.

Materials and Methods:

Pre-emulsions containing selected ingredients in a specified effective concentration were prepared. The selected formulation, based upon pharmaceutical parameters, was coated on a nonwoven fabric in an eye counter shape, and stored in a jar. Then in vivo trial was carried out for investigation of its anti-wrinkling efficacy on 11 healthy women. In a single blind trial, the sample pad was applied under the right eye and the placebo pad, consisting of water, was placed under the left eye simultaneously. The efficacy and safety of the formulation was evaluated visually and with a multi skin test MC 900 instrument.

Result:

After four weeks, the skin around the right eye of all the subjects experienced a reduction in the depth of wrinkles and dark circles, and from a subjective point of view, the appearance and elasticity of the skin were improved.

Conclusions:

The caffeine pad containing vitamin K in an Emu oil base shows an improvement in eye counter appearance with anti-dark circle capacity and as an emollient.

Resource: http://www.ncbi.nlm.nih.gov/
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Application of metabonomic analytical techniques in modernization of Chinese medicine.

Abstract

In the recent years, a wide range of metabonomic analytical techniques are widely used in the modern research of traditional Chinese medicine (TCM). At the same time, the international community has attached increasing importance to TCM toxicity problems. Thus, many studies have been implemented to investigate the toxicity mechanisms of TCM. Among these studies, many metabonomic-based methods have been implemented to facilitate TCM toxicity investigation. At present, the most prevailing methods for TCM toxicity research are mainly single analysis techniques using only one analytical means. These techniques include nuclear magnetic resonance (NMR), gas chromatography-mass spectrometry (GC-MS), and liquid chromatography-mass spectrometry (LC-MS), etc.; with these techniques, some favourable outcomes have been gained in the toxic reaction studies of TCM, such as the action target organs assay, the establishment of action pattern, the elucidation of action mechanism and the exploration of action material foundation. However, every analytical technique has its advantages and drawbacks, no existing analytical technique can be versatile. Multi-analysed techniques can partially overcome the shortcomings of single-analysed techniques. Combination of GC-MS and LC-MS metabolic profiling approaches has unravelled the pathological outcomes of aristolochic acid-induced nephrotoxicity, which can not be achieved by single-analysed techniques. It is believed that with the further development of metabonomic analytical techniques, especially multi-analysed techniques, metabonomics will greatly promote TCM toxicity research and be beneficial to the modernization of TCM in terms of extending the application of modern means in the TCM safety assessment, assisting the formulation of TCM safety norms and establishing the international standards indicators.

Introduction

Metabonomics is an emerging subject of the post-genome era, which, together with genomics, transcriptomics and proteomics, jointly constitutes the ‘Systems Biology’. Metabonomics is the branch of science concerned with the quantitative understandings of the metabolite component of integrated living systems and its dynamic responses to the changes of both endogenous factors (such as physiology and development) and exogenous factors (such as environmental factors and xenobiotics). Recently, as a novel systemic approach to study metabolic profile and accelerate the course of drug development, metabonomics has achieved great growth, which is attracting more and more concerns from the academic community. The main subjects of metabonomics are a variety of predominantly low molecular weight metabolites that serve as the substrates and products of metabolic pathways, and its main biological samples are urine, plasma and serum. Integrity of metabonomic processes includes sample collection and pretreatment, data collection and analysis, and metabolic variation interpretation. Generally, the main technologies metabonomics relied are the nuclear magnetic resonance (NMR)-based method, chromatography-based method and mass spectrometry (MS)-based method. Depending on a series analysis of different sample spectra and combination with chemical pattern recognition methods, metabonomics can be used to identify organisms in pathophysiological state, gene function, drug toxicity and efficacy, and associated biomarkers.

Resource: http://www.ncbi.nlm.nih.gov
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Pure Garcinia Cambogia Extract usage as a Weight Loss Supplement

Abstract

The aim of this systematic review is to examine the efficacy of Garcinia extract, hydroxycitric acid (HCA) as a weight reduction agent, using data from randomised clinical trials (RCTs). Electronic and nonelectronic searches were conducted to identify relevant articles, with no restrictions in language or time. Two independent reviewers extracted the data and assessed the methodological quality of included studies. Twenty-three eligible trials were identified and twelve were included. Nine trials provided data suitable for statistical pooling. The meta-analysis revealed a small, statistically significant difference in weight loss favouring HCA over placebo (MD: −0.88 kg; 95% CI: −1.75, −0.00). Gastrointestinal adverse events were twice as common in the HCA group compared with placebo in one included study. It is concluded that the RCTs suggest that Garcinia extracts/HCA can cause short-term weight loss. The magnitude of the effect is small, and the clinical relevance is uncertain. Future trials should be more rigorous and better reported.

Introduction

The prevalence of overweight and obesity has increased over the last decade, and current measures have not been able to stem the tide. A wide variety of weight management strategies are presently available, and some involve the use of dietary supplements marketed as slimming aids. One such slimming aid is Garcinia extract, (-)-hydroxycitric acid (HCA).

HCA is a derivative of citric acid and can be found in plant species native to South Asia such as Garcinia cambogia, Garcinia indica, and Garcinia atroviridis. HCA is usually marketed as a weight loss supplement either alone or in combination with other supplements. Some authors have suggested that HCA causes weight loss by competitively inhibiting the enzyme adenosine triphosphatase-citrate-lyase. HCA has also been reported to increase the release or availability of serotonin in the brain, thereby leading to appetite suppression. Other postulated weight loss mechanisms include inhibition of pancreatic alpha amylase and intestinal alpha glucosidase, thereby leading to a reduction in carbohydrate metabolism.

Animal studies have suggested that HCA causes weight loss, and human trials involving the use of HCA as a weight loss supplement have been carried out.

The primary objective of this systematic review was to examine the efficacy of HCA in reducing body weight in humans, using data from randomised clinical trials.

Methods

Electronic searches of the literature were conducted in the following databases: Medline, Embase, The Cochrane Library, Amed, and Cinahl. The search terms used included dietary supplements, antiobesity agents, body weight, hydroxycitrate, garcinia, and derivatives of these. Each database was searched from inception until March, 2010. We also searched the Internet for relevant conference proceedings and hand searched relevant medical journals, and our own files. The bibliographies of all located articles were also searched.

Only randomised, double-blind, placebo-controlled studies were included in this paper. To be considered for inclusion, studies had to test the efficacy of oral HCA or any of its salts for weight reduction in obese or overweight humans. Included studies also had to report body weight as an outcome. No age, time, or language restrictions were imposed for inclusion of studies. Studies which involved the use of HCA as part of a combination treatment (dietary interventions containing other supplements in addition to HCA), or not involving obese or overweight subjects based on body mass index (BMI) values, were excluded from this paper.

Two independent reviewers assessed the eligibility of studies to be included in the paper. Data were extracted systematically by two independent reviewers according to the patient characteristics, interventions, and results. The methodological quality of all included studies was assessed by the use of a quality assessment checklist adapted from the Consolidated Standard of Reporting Trials (CONSORT) guidelines. In addition, the Jadad score was also used to assess the quality of included studies. Disagreements were resolved through discussion with the other authors.

Data are presented as means with standard deviations. Mean changes in body weight were used as common endpoints to assess the differences between HCA and placebo groups. Using the standard meta-analysis software , we calculated mean differences (MDs) and 95% confidence intervals (CIs). Studies included in the meta-analysis were weighted by SD (a proxy for study size). If a trial had 3 arms, only the HCA and placebo arms were included in the meta-analysis. The I2 statistic was used to assess for statistical heterogeneity amongst studies. A funnel plot was used to test for publication bias.

Resource: http://www.ncbi.nlm.nih.gov
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"Lamaze Method of Colonscopy" - Unsedation Colonscopy Can not be that Painful.

Abstract

AIM: To evaluate the pain relieving effect of intervention with “Lamaze method of colonoscopy” in the process of colonoscopy.

METHODS: Five hundred and eighty-five patients underwent colonoscopy were randomly divided into three groups, Lamaze group, anesthetic group and control group. Two hundred and twenty-four patients of Lamaze group, the “Lamaze method of colonoscopy” were practiced in the process of colonoscopy. The Lamaze method of colonoscopy is modified from the Lamaze method of childbirth, which helped patients to relieve pain through effective breathing control. One hundred and seventy-eight patients in anesthetic group accepted sedation colonoscopy. For 183 patients in control group, colonoscopy was performed without any intervention. The satisfactory of colon cleaning, intestinal lesions, intubation time, success ratio, pain grading and complications were recorded. All data were statistically analyzed.

RESULTS: There were no significant differences at base line of the three groups (P > 0.05). Anesthetic group shows advantage in intubation time than the other two groups (P < 0.05). Lamaze group shows no advantage in intubation time than that in control group (P > 0.05). The anesthetic group showed an apparent advantage in relieving pain (P < 0.01). Therefore, the “Lamaze method of colonoscopy” performed in colonoscopy could relieve pain effectively comparing with control group (P < 0.05). The patients in anesthetic group had the highest incidence of complications (P < 0.05).

CONCLUSION: The performance of the “Lamaze method of colonoscopy” in the process of colonoscopy could relieve patients’ pain, minimize the incidence of complications, and is worthy promotion in clinical practice.

Resource: http://www.ncbi.nlm.nih.gov/
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Urine Drug Test with Subversion after Use of Detoxifying Kit - A Case of Psychosis.

Abstract

Context: The practice of drug testing in the workplace has been adopted for US federal government employees, and many state and local governments as well as private businesses have followed suit. However, a parallel industry dedicated to subverting the results of urine drug testing has emerged with little or no regulation.

Evidence Acquisition: First, the case of a 19-year-old man who developed psychosis after the use of a detoxification kit is presented. Second, a review of the existing literature on the techniques, risks, and regulations associated with the use of drug tampering kits is provided. PubMed, Cochrane Database, and Google Scholar were searched using the keywords UDS, urine toxicology, pass the drug test, and clean UA, with no restrictions on publication date. Case reports, letters to the editor, and original research and review articles in multiple languages were reviewed, as were federal regulations and acts on the topic. The search yielded 4,082 results, of which 49 articles were selected for relevance. Some articles were later omitted as they had cited the original article and had nothing new to offer.

Results: Three commonly used tampering techniques are in vivo adulteration, urine substitution, and in vitro adulteration. Review of the literature regarding the risks involved with use of tampering kits yielded no results. In 1986, an executive order was issued requiring all federal employees to refrain from illicit drug use, and the 1988 Drug-Free Workplace Act precipitated the Substance Abuse and Mental Health Services Administration guidelines and their subsequent revisions. Recently, many states have made regulatory efforts to bring drug test defrauding under the ambit of law.

Conclusions: Clinicians need to be aware of the tampering techniques and the possibility of false-negative urine drug tests. Cognizance of inherent risks involved with using these techniques including psychiatric and/or medical complications is also warranted. The manufacture, sale, and use of these products have little or no regulation by state or federal authorities, making them potentially dangerous and imposing new challenges in testing for abused drugs. The extent of use of these products and techniques is not known at this time and is an area that warrants further research.

Resource: http://www.ncbi.nlm.nih.gov/
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Treatment of Flatulence From a Traditional Persian Medicine (TPM) Viewpoint

Abstract

 
Context

The feeling of abdominal fullness, bloating, and movement of gas in the abdomen is a very uncomfortable sensation termed flatulence. Since flatulence is one of the most common gastrointestinal symptoms that is bothersome to patients, it is important to identify effective methods to resolve this issue. In modern medicine, management of flatulence is often not satisfactory. On the other hand, traditional systems of medicine can be considered good potential sources to find new approaches for preventing and treating flatulence. The aim of this study is to review flatulence treatments from a traditional Persian medicine (TPM) viewpoint.

Evidence Acquisition

In this study, the reasons for flatulence and methods for its prevention and treatment are reviewed in traditional Persian medicine (TPM) texts and then related with evidence from modern medicine by searching in databases, including PubMed, Scopus, Google Scholar, and IranMedex.

Results

From a traditional Persian scholar viewpoint, one of the most important causes of flatulence is an incorrect manner of eating; valuable advice to correct bad eating habits will be illustrated. In addition, traditional practitioners describe some herbs and vegetables as well as herbal compounds that are effective food additives to relieve flatulence. The anti-flatulent effect of most of these herbs has been experimentally verified using modern medicine.

Conclusions

Attention to TPM can lead to the identification of new preventive and curative approaches to avoid and treat flatulence. In addition, Persian viewpoints from the medieval era regarding flatulence are historically important.

Resource: http://www.ncbi.nlm.nih.gov
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Antioxidant Activities of Extract from the the Mangrove Plant Kandelia candel

Abstract

The antioxidant activities of 70% acetone extract (70% AE) from the hypocotyls of the mangrove plant Kandelia candel and its fractions of petroleum ether (PF), ethyl acetate (EF), water (WF), and the LF (WF fraction further purified through a Sephadex LH-20 column), were investigated by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging and ferric reducing/antioxidant power (FRAP) assays. The results showed that all the extract and fractions possessed potent antioxidant activity. There was a significant linear correlation between the total phenolics concentration and the ferric reducing power or free radical scavenging activity of the extract and fractions. Among the extract and fractions, the LF fraction exhibits the best antioxidant performance. The MALDT-TOF MS and HPLC analyses revealed that the phenolic compounds associated with the antioxidant activity of the LF fraction contains a large number of procyanidins and a small amount of prodelphinidins, and the epicatechin is the main extension unit.

Introduction

Reactive oxygen species (ROS), including superoxide radicals, hydroxyl radicals, singlet oxygen and hydrogen peroxide, are often generated as by-products of biological reactions or from exogenous factors. Increasing evidence has suggested that many human diseases, such as cancer, cardiovascular disease, and neurodegenerative disorders, are the results of the oxidative damage by reactive oxygen species. The antioxidants are molecules that mainly decelerate or prevent the oxidation reaction in vitro and in vivo by terminating the oxidation chain reaction. The application of antioxidants in pharmacology is valuable to improve current treatments for diseases.

In recent years, there has been a great interest in finding natural antioxidants from plant materials to replace synthetic antioxidants, which are being restricted due to their carcinogenicity. Numerous crude extracts and pure natural compounds from plants were reported to have antioxidant and radical scavenging activities. Within the antioxidant compounds, flavonoids and phenolics, with a large distribution in nature, have been studied more comprehensively.

Mangroves are a diverse group of trees that grow in intertidal tropical forests. In mangrove species, phenolics are abundant components, which prevent damage from herbivores, but they also exhibit a diversity of other biological activities of historic and potential importance to humans. Mangrove extracts have been used for diverse medicinal purposes and have a variety of antibacterial, antiherpetic and antihelminthic activities. The extracts of some mangrove species indicate significant antioxidant activity. Kandelia candel (Rhizophoraceae) is mostly widely distributed in the tropical and subtropical coastlines of China. According to a previous study, phenolics are important components in the leaf extract of K. candel and show excellent antioxidant activities. The hypocotyls of K. candel also have high phenolics levels. Therefore, the K. candel hypocotyls may be a good candidate for further development as an antioxidant remedy. In this study, we investigated the antioxidant activities of the 70% acetone extract and its fractions of K. candel hypocotyls for the first time, and identified the active compounds by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and reversed phase high performance liquid chromatography (HPLC) analyses.

Resource: http://www.ncbi.nlm.nih.gov/
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Powerful health effects of Pomegranate

Abstract

Accumulating data clearly claimed that Punica granatum L. (pomegranate) has several health benefits. Pomegranates can help prevent or treat various disease risk factors including high blood pressure, high cholesterol, oxidative stress, hyperglycemia, and inflammatory activities. It is demonstrated that certain components of pomegranate such as polyphenols have potential antioxidant, anti-inflammatory, and anticarcinogenic effects. The antioxidant potential of pomegranate juice is more than that of red wine and green tea, which is induced through ellagitannins and hydrosable tannins. Pomegranate juice can reduce macrophage oxidative stress, free radicals, and lipid peroxidation. Moreover, pomegranate fruit extract prevents cell growth and induces apoptosis, which can lead to its anticarcinogenic effects. In addition, promoter inhibition of some inflammatory markers and their production are blocked via ellagitannins. In this article, we highlight different studies on the therapeutic effects of pomegranate and their suggested mechanisms of actions.

INTRODUCTION

Punica granatum L. (Pomegranate) is a long-lived and drought-tolerant plant. Arid and semiarid zones are popular for growing pomegranate trees. They are widely cultivated in Iran, India, and the Mediterranean countries such as Turkey, Egypt, Tunisia, Spain, and Morocco. However, pomegranate is categorized as a berry but it belongs to its own botanical family, Punicaceae. The only genus is Punica, with one predominant species called P. granatum.

The trees can grow up to 30 feet in height. The leaves are opposite, narrow, oblong with 3-7 cm long and 2 cm broad. It has bright red, orange, or pink flowers, which are 3 cm in diameter with four to five petals. Edible fruit has a rounded hexagonal shape, with 5-12 cm in diameter and weighing 200 g. The thick skin surrounds around 600 arils, which encapsulates the seeds.

Resource: http://www.ncbi.nlm.nih.gov/
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Approaches for Malignant Gliomas Treatment

Abstract

Malignant gliomas, which include glioblastomas and anaplastic astrocytomas, are the most common primary tumors of the brain. Over the past 30 years, the standard treatment for these tumors has evolved to include maximal safe surgical resection, radiation therapy and temozolomide chemotherapy. While the median survival of patients with glioblastomas has improved from 6 months to 14.6 months, these tumors continue to be lethal for the vast majority of patients. There has, however, been recent substantial progress in our mechanistic understanding of tumor development and growth. The translation of these genetic, epigenetic and biochemical findings into therapies that have been tested in clinical trials is the subject of this review.

Introduction

Gliomas are the most common primary tumors of the brain and are classified on the basis of two histological criteria, the resemblance of tumor cells to normal glial cells and the relative degree of malignancy. Astrocytomas, for example, are comprised of tumor cells that resemble astrocytes while oligodendroglial tumors contain neoplastic cells that resemble oligodendrocytes. Malignancy is graded using a progressive 4 tier scale in which grades I and II are assigned to low grade or benign tumors and grades III and IV are assigned to high grade or malignant tumors.

Grade I astrocytomas are generally benign and frequently curable with complete surgical removal. Grade II astrocytomas also demonstrate slow growth and a high degree of cellular differentiation, but frequently infiltrate surrounding brain tissues. The median overall survival (OS) time after surgical diagnosis ranges from 6–8 years and is reflective of the time required for tumors to transform into higher grade lesions. Grade III astrocytomas, also known as anaplastic astrocytomas (AA), are diffusely infiltrating lesions with focal or dispersed regions of anaplasia and marked proliferative potential. The median OS time ranges from 2–3 years and is also generally determined by the amount of time required for the progression of tumors to grade IV. Grade IV astrocytomas, also known as glioblastoma multiforme or glioblastomas (GBM), are the most common and malignant glioma subtype. GBMs typically contain cellular polymorphism, nuclear atypia, brisk mitotic activity, neovascular proliferation, and areas of frank necrosis. Additionally, the aggressive invasion and diffuse infiltration of tumor cells into the surrounding brain tissue negate any possibility for a complete surgical tumor removal.

Over the past 30 years, significant changes in the standard treatment of malignant gliomas have been limited. Prior to the 1980’s, the median OS of patients with malignant gliomas was 6 months. In 1980, a prospective randomized trial was reported in which 467 patients with malignant gliomas were randomized to one of four treatment groups: semustine (MeCCNU), radiotherapy (XRT), carmustine (BCNU) plus XRT, or semustine plus XRT. Toxicities included acceptable skin reactions secondary to XRT and thrombocytopenia due to chemotherapy. Patients who received XRT alone or in combination with a nitrosourea (carmustine or semustine) had significantly improved OS compared to patients treated with semustine alone. The median OS of the carmustine plus XRT group (51 weeks) was greater than that of the semustine plus XRT (42 weeks) and XRT alone (36 weeks) groups, but the differences were not statistically significant.

Resource: http://www.ncbi.nlm.nih.gov/
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Biotin Utilization in the Zoonotic Pathogen Streptococcus Suis

Abstract

Biotin protein ligase is universal in three domains of life. The paradigm version of BPL is the Escherichia coli BirA that is also a repressor for the biotin biosynthesis pathway. Streptococcus suis, a leading bacterial agent for swine diseases, seems to be an increasingly-important opportunistic human pathogen. Unlike the scenario in E. coli, S. suis lacks the de novo biotin biosynthesis pathway. In contrast, it retains a bioY, a biotin transporter-encoding gene, indicating an alternative survival strategy for S. suis to scavenge biotin from its inhabiting niche. Here we report functional definition of S. suis birA homologue. The in vivo functions of the birA paralogue with only 23.6% identity to the counterpart of E. coli, was judged by its ability to complement the conditional lethal mutants of E. coli birA. The recombinant BirA protein of S. suis was overexpressed in E. coli, purified to homogeneity and verified with MS. Both cellulose TLC and MALDI-TOFF-MS assays demonstrated that the S. suis BirA protein catalyzed the biotinylation reaction of its acceptor biotin carboxyl carrier protein. EMSA assays confirmed binding of the bioY gene to the S. suis BirA. The data defined the first example of the bifunctional BirA ligase/repressor in Streptococcus.

Biotin (vitamin H) is one of two known sulfur-containing fatty acid derivatives (biotinand lipoic acid), and acts as an enzyme cofactor universal in three domains of the life. Although the biotin-requiring enzymes are rare proteins (in that mammals have only four such proteins whereas Escherichia coli has only a single biotinylated protein), they play critical roles in certain important reactions (like carboxylation, decarboxylation and trans-carboxylation) implicated into fatty acid synthesis, gluconeogenesis and amino acid degradation in both prokaryotes and eukaryotes. Right now, it is aware that most microorganisms (bacteria and fungi) and plants possess the ability to synthesize biotin, whereas mammals and birds cannot4. The earlier steps of biotin synthesis are involved in a modified type II fatty acid synthesis pathway in E. coli whereas the latter of biotin synthesis route refers to a highly-conserved four-step reactions catalyzed by BioF, BioA, BioD and BioB, respectively. In light that biotin is an energetically-expansive molecule in that generally ATP equivalents are estimated to be consumed via its paths of de novo synthesis for each biotin4, it seems reasonable that bacteria have developed diversified mechanisms to tightly monitor the level of biotin production in vivo. In addition to the paradigm E. coli BirA regulatory system that also retains the activity of biotin-protein ligase, at least two more regulatory machineries have been reported. Among them, one is the two-protein system of BirA coupled with BioR, the GntR-family transcription factor1, and the other denotes the two-protein system of the BirA linked to BioQ, a TetR family of transcription factor.

In fact, bacteria have evolved two different mechanisms to obtain the biotin cofactor for the metabolic requirement, one of which is de novo synthesis route, the other is a system of BioY transporter-mediated uptake. Unlike the human pathogen Brucella, a member of α-proteobacteria that encodes the above two systems for the availability of biotin11, it seems likely that the species of Streptococcus/Lactococcus family only have the BioY-based scavenging route and compensates the lack of the de novo biotin synthesis pathway. Among microorganisms, the paradigm enzyme with the biotin requirement refers to biotin carboxyl carrier protein (abbreviated as BCCP, i.e., the AccB subunit of acetyl-CoA carboxylase (ACC)) that catalyzes the first committed reaction for type II fatty acid synthesis pathway. Biotin protein ligase (BPL) is widespread in three domains of the life in that it transfers/attaches the biotin cofactor to the specific domain of the relevant subunits of key enzymes from the certain central metabolisms. Most of bacteria including E. colil and Bacillus only encode a single BPL to account for such kind of physiological requirement, while the pathogen Fracisella novicida developed an additional BPL to gain the competitive advantage in the infected host environment. In general, the BPL members are categorized into the following two groups (Group I and Group II) that can be easily distinguished by the presence of N-terminal DNA-binding domain that allow the BirA protein to bind the cognate genes (e.g., bio operon), and thereafter inhibit expression of biotin metabolism. Unlike the paradigm Group II BPL proteins, the E. coli birA gene product retaining the DNA-binding activity, the Group I BPL that lacks the N-terminal helix-turn-helix domain solely function as an enzyme responsible for protein biotinylation. In particular, the regulatory role of the Group II BPL depends on the participation of the physiological ligand/effector (biotinoyl-5′-AMP), the product of the first ligase half reaction for biotin utilization/protein biotinylation.

Resource: http://www.ncbi.nlm.nih.gov/
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Profile Classes of Proteins on the Basis of Changes in their Activity

Abstract

With the postgenome era rapidly approaching, new strategies for the functional analysis of proteins are needed. To date, proteomics efforts have primarily been confined to recording variations in protein level rather than activity. The ability to profile classes of proteins on the basis of changes in their activity would greatly accelerate both the assignment of protein function and the identification of potential pharmaceutical targets. Here, we describe the chemical synthesis and utility of an active-site directed probe for visualizing dynamics in the expression and function of an entire enzyme family, the serine hydrolases. By reacting this probe, a biotinylated fluorophosphonate referred to as FP-biotin, with crude tissue extracts, we quickly and with high sensitivity detect numerous serine hydrolases, many of which display tissue-restricted patterns of expression. Additionally, we show that FP-biotin labels these proteins in an activity-dependent manner that can be followed kinetically, offering a powerful means to monitor dynamics simultaneously in both protein function and expression.

Serine hydrolases play important roles in numerous developmental and tissue-specific events in vivo, including blood coagulation, inflammation, angiogenesis, neural plasticity, peptide hormone processing, and T-lymphocyte-mediated cytotoxicity. Additionally, several human diseases are associated with dysfunctions in serine proteases and/or their endogenous inhibitory proteins, including hemorrhagic disorders, emphysema, and cancer. The large number of mammalian serine hydrolases identified to date is both impressive and perplexing, with the endogenous functions of many members of this enzyme family remaining unknown. As ORFs encoding putative serine hydrolases continue to accumulate in public databases , the need for alternative experimental methods to study these enzymes is evident. One attractive approach for the analysis of serine hydrolase function would be to characterize these enzymes collectively, rather than individually. In particular, the majority of serine hydrolases are potently and irreversibly inhibited by fluorophosphonate/fluorophosphate (FP) derivatives like diisopropyl fluorophosphate , whereas cysteine, aspartyl, and metallohydrolases are for the most part inert to such agents. Moreover, the reactivity of FPs with serine hydrolases requires that the enzymes be in a catalytically active state. Accordingly, we hypothesized that an FP linked to a small molecule reporter group might serve as a potent and selective probe for monitoring simultaneously the activities of multiple serine hydrolases. In this manner, serine hydrolases could be visualized on a systems level of analysis, greatly accelerating the assignment of potential functions and malfunctions to members of this enzyme family. Here, we report the synthesis and characterization of a biotinylated long-chain fluorophosphonate, referred to as FP-biotin and highlight its utility as an agent for profiling dynamics in serine hydrolase expression and function.

Resource: http://www.ncbi.nlm.nih.gov
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Effect of tea polyphenol on oxidative injury

Abstract

The purpose of this study was to evaluate the antioxidant nature of tea polyphenol on S180 cells induced liver cancer in mice. In the present study, hepatocellular carcinoma was induced by tumor transplantation of liver in situ. The antitumor activity of tea polyphenol has been determined in vivo in hepatocellular carcinoma mice after treatment of drug (50, 100, 150 mg/kg body weight) by gavage for 20 days. Results showed that a significant increase in serum aspartate transaminase (AST), alkaline phosphatase (ALP), alanine aminotransfere (ALT), malondialdehyde (MDA) level, decrease in serum white blood cells (WBC), serum total protein (TP), albumin (ALB), A/G, tumor necrosis factor-α (TNF-α) and interferon-gamma (IFN-γ), liver reduced glutathione (GSH) levels were observed. In addition, the levels of enzymic and non-enzymic antioxidants were decreased when subjected to S180 cells induction. These altered enzyme levels were ameliorated significantly by administration of tea polyphenol at the concentration of 50, 100, 150 mg/kg body weight in drug-treated animals. These results indicate that the protective effect of tea polyphenol was associated with inhibition of MDA induced by S180 cells and to maintain the antioxidant enzyme levels.

Introduction

Hepatocellular carcinoma (HCC), a leading cause of death in China and many Asian countries, is difficult to treat because of early progression and metastasis. It is well known that angiogenesis is essential for the survival, growth, and metastasis of tumor cells. Hepatitis B (HBV) and Hepatitis C virus (HCV) are the risk factors attributed to 80% of HCC cases globally [6]. Cirrhosis, radiation, free radicals, genetic changes, metabolic disorder and exposure to certain chemical carcinogens such as aflatoxin, ethionine, diethylnitrosamine (DEN) and 2-acetylaminofluorene (AAF) have also been implicated in the pathogenesis of hepatocarcinoma.

Several human chronic disease states including cancer have been associated with oxidative stress produced through either an increased free radical generation and/or a decreased antioxidant level in the target cells and tissues. A role for reactive oxygen radicals in the etiology of cancer is supported by epidemiologic studies. Specifically these epidemiologic studies illustrated the protective role for antioxidants against cancer development. Continuous production of oxygen radicals leads to the formation of covalent bond adduct with DNA nucleic acid, which will subsequently result in mutagenicity. Endogenous antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) have been reported to reduce the free radical formation and prevent oxidative damage.

Herbal medicines derived from plant extracts are being increasingly utilized to treat a wide variety of clinical disease. More attention has been paid to the protective effects of natural antioxidants against drug-induced toxicities especially whenever free radical generation is involved. Green tea and its constituent catechins are best known for their antioxidant properties, which has led to their evaluation in a number of diseases associated with reactive oxygen species (ROS), such as cancer, cardiovascular and neurodegenerative diseases. Several epidemiological studies as well as studies in animal models have shown that green tea can afford protection against various cancers such as those of the skin, breast, prostate and lung. In addition to the cancer chemopreventive properties, green tea and EGCG have been shown to be anti-angiogenic (prevention of tumor blood vessel growth) and anti-mutagenic. Other health benefits attributed to green tea include antibacterial, anti-HIV, anti-aging and anti-inflammatory activity.

Resource: http://www.ncbi.nlm.nih.gov
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