Synthesis of Novel Pyran Fragments to Incorporate into Peloruside Analogues

<p>Cancer is currently the second largest cause of death globally, leading to a high demand for new and effective chemotherapeutics. For years, natural products have been used as a source of new bioactive compounds; of particular interest in this context, as a source of new chemotherapeutics. One chemotherapeutic candidate which has attracted significant attention in synthetic and medicinal chemistry communities, is peloruside A. Peloruside A is a bioactive secondary metabolite isolated from the New Zealand marine sponge Mycale hentscheli. Since its discovery, peloruside A has shown great promise in cancer studies both in vivo and in vitro with effects observed even at nanomolar concentrations. These chemotherapeutic effects have been shown to occur by halting cell division at the G2/M checkpoint via microtubule stabilisation. Of particular interest is that this stabilisation occurs in a manner distinct from that of the already established taxane class of microtubule stabilising drugs. This means that peloruside A is able to offer both inhibition of cell division in Taxol® resistant cells and synergistic inhibition alongside the current taxane drugs. Since peloruside A is not abundantly available from its natural source, there is a strong incentive for the development of new synthetic strategies for peloruside A production. Unfortunately attempts at aquaculture and attempts at developing an industrial scale synthesis have both proven unsuccessful thus far. In an attempt to overcome some of the difficulties with the scale up of peloruside, analogues have been developed that are intended to have similar bioactivity to peloruside A but simpler, more concise, synthetic routes. These analogues will also enable further elucidation of the binding properties of peloruside A. This project focuses on the generation of a functionalised pyran fragment, starting from a simple carbohydrate, that may be incorporated into the proposed analogues.</p>

Synthesis of Novel Pyran Fragments to Incorporate into Peloruside Analogues

<p>Cancer is currently the second largest cause of death globally, leading to a high demand for new and effective chemotherapeutics. For years, natural products have been used as a source of new bioactive compounds; of particular interest in this context, as a source of new chemotherapeutics. One chemotherapeutic candidate which has attracted significant attention in synthetic and medicinal chemistry communities, is peloruside A. Peloruside A is a bioactive secondary metabolite isolated from the New Zealand marine sponge Mycale hentscheli. Since its discovery, peloruside A has shown great promise in cancer studies both in vivo and in vitro with effects observed even at nanomolar concentrations. These chemotherapeutic effects have been shown to occur by halting cell division at the G2/M checkpoint via microtubule stabilisation. Of particular interest is that this stabilisation occurs in a manner distinct from that of the already established taxane class of microtubule stabilising drugs. This means that peloruside A is able to offer both inhibition of cell division in Taxol® resistant cells and synergistic inhibition alongside the current taxane drugs. Since peloruside A is not abundantly available from its natural source, there is a strong incentive for the development of new synthetic strategies for peloruside A production. Unfortunately attempts at aquaculture and attempts at developing an industrial scale synthesis have both proven unsuccessful thus far. In an attempt to overcome some of the difficulties with the scale up of peloruside, analogues have been developed that are intended to have similar bioactivity to peloruside A but simpler, more concise, synthetic routes. These analogues will also enable further elucidation of the binding properties of peloruside A. This project focuses on the generation of a functionalised pyran fragment, starting from a simple carbohydrate, that may be incorporated into the proposed analogues.</p>

Association of Dietary Nutrient Intake with Early Age-Related Macular Degeneration in Japanese-Americans

Lifestyle factors may be associated with the development of age-related macular degeneration (AMD), in addition to demographic and genetic factors. The purpose of this cross-sectional study is to elucidate the association between nutrient intake and AMD in the Japanese-American population living in Los Angeles. We conducted a medical survey of Japanese immigrants and their descendants living in Los Angeles, including interviews on dietary habits, fundus photography, and physical examinations. Participants were classified into early AMD and control groups on the basis of fundus photographic findings. Consequently, among the 555 participants, 111 (20.0%) were diagnosed with early AMD. There were no late-stage AMD participants. Multivariate logistic regression analysis showed that the intake of animal fat and saturated fatty acids (SFA) was positively associated with early AMD (p for trend = 0.01 for animal fat, p for trend = 0.02 for SFA), and the intake of vegetable fat, total carbohydrate, simple carbohydrate, sugar, and fructose was inversely associated with early AMD (p for trend = 0.04 for vegetable fat, p for trend = 0.046 for carbohydrate, p for trend = 0.03 for simple carbohydrate, p for trend = 0.046 for sugar, p for trend = 0.02). Our findings suggest that excessive animal fat and SFA intake increases the risk for early AMD in Japanese-Americans whose lifestyles have been westernized.

A U.S. survey of pre-operative carbohydrate-containing beverage use in colorectal enhanced recovery after surgery (ERAS) programs

Background Carbohydrate-containing drinks (CCD) are administered preoperatively in most enhanced recovery after surgery (ERAS) programs. It is not known which types of CCDs are used, e.g., simple vs. complex carbohydrate, and if the choice of drink differs in patients with diabetes. Methods A national survey was performed to characterize the use of preoperative CCDs within the context of adult colorectal ERAS programs. The survey had questions regarding the use of preoperative CCDs, the types of beverages used, and the timing of beverage administration. The survey was administered electronically to members of the American Society for Enhanced Recovery (ASER) and manually to participants at the 2018 Perioperative Quality and Enhanced Recovery Conference in San Francisco, CA. Results Responses were received from 78 unique hospitals with a colorectal ERAS program of which 68 (87.2%) reported administering a preoperative drink. Of these, 98.5%, 80.9%, and 60.3% of hospitals administered a beverage to patients without diabetes, patients with diabetes not taking insulin, and patients with diabetes taking insulin, respectively. Surprisingly, one third of programs that administered a beverage to patients with diabetes used a simple carbohydrate drink. Conclusions This survey finds a high use of CHO-containing beverages in colorectal ERAS programs. More than half of all programs administer a CHO-containing beverage to patients with diabetes, and surprisingly, there is significant use of simple carbohydrate beverages in patients with diabetes receiving insulin.

High-sugar feeding and increasing cholesterol levels in infants

Hypercholesterolaemia is an important risk factor for cardiovascular disease. Both total and LDL cholesterol levels are three-fold higher at the end of the first year of life and about four-fold higher in adulthood compared with the neonatal period. In the USA, only 25% of infants are exclusively breastfed and simple carbohydrate-rich formulas are preferentially consumed. Spikes in fasting glucose and insulin have been reported in formula-fed infants and are associated with higher levels of proprotein convertase subtilisin/kexin type 9, suggesting a potential link between high simple sugar intake and consequent increase in LDL cholesterol in early childhood.

Exploring changes in the human gut microbiota and microbial-derived metabolites in response to diets enriched in simple, refined, or unrefined carbohydrate-containing foods: a post hoc analysis of a randomized clinical trial

ABSTRACT Background Dietary carbohydrate type may influence cardiometabolic risk through alterations in the gut microbiome and microbial-derived metabolites, but evidence is limited. Objectives We explored the relative effects of an isocaloric exchange of dietary simple, refined, and unrefined carbohydrate on gut microbiota composition/function, and selected microbial metabolite concentrations. Methods Participants [n = 11; age: 65 ± 8 y; BMI (in kg/m2): 29.8 ± 3.2] were provided with each of 3 diets for 4.5 wk with 2-wk washout, according to a randomized, crossover design. Diets [60% of energy (%E) carbohydrate, 15%E protein, and 25%E fat] differed in type of carbohydrate. Fecal microbial composition, metatranscriptomics, and microbial-derived SCFA and secondary bile acid (SBA) concentrations were assessed at the end of each phase and associated with cardiometabolic risk factors (CMRFs). Results Roseburia abundance was higher (11% compared with 5%) and fecal SBA concentrations were lower (lithocolic acid –50% and deoxycholic acid –64%) after consumption of the unrefined carbohydrate diet relative to the simple carbohydrate diet [false discovery rate (FDR): all P &lt; 0.05), whereas Anaerostipes abundance was higher (0.35% compared with 0.12%; FDR: P = 0.04) after the simple carbohydrate diet relative to the refined carbohydrate diet. Metatranscriptomics indicated upregulation of 2 cellular stress genes (FDR: P &lt; 0.1) after the unrefined carbohydrate diet compared with the simple carbohydrate or refined carbohydrate diets. The microbial expression of 3 cellular/oxidative stress and immune response genes was higher (FDR: P &lt; 0.1) after the simple carbohydrate diet relative to the refined carbohydrate diet. No significant diet effect was observed in fecal SCFA concentrations. Independent of diet, we observed 16 associations (all FDR: P &lt; 0.1) of taxon abundance (15 phylum and 1 genera) with serum inflammatory markers and also with fecal SCFA and SBA concentrations. Conclusions Consuming an unrefined carbohydrate–rich diet had a modest effect on the gut microbiome and SBAs, resulting in favorable associations with selected CMRFs. Simple carbohydrate– and refined carbohydrate–rich diets have distinctive effects on the gut microbiome, suggesting differential mechanisms mediate their effects on cardiometabolic health. This trial was registered at clinicaltrials.gov as NCT01610661.

Dietary patterns and fatigue in female slimmers

Purpose This paper aims to understand the association of dietary patterns with perceived fatigue and identify predictors for presence of fatigue in women who are obese and trying to lose weight. Design/methodology/approach An online survey, hosted by slimming world (SW), comprised of a questionnaire regarding weight, level of fatigue and food frequency questionnaire before joining the weight management programme (T0) and current data (T1) was conducted. In total, 543 non-pregnant women with obesity of child-bearing age (19-49 years) completed the survey (T0-T1). The principal components analysis was used to determine dietary patterns and multinomial logistic regression was used to analyse predictors for presence of fatigue. Findings The participants who have a “simple carbohydrate and high fat” dietary pattern were more likely to have fatigue at T0 (p ≤ 0.001) and those who followed a “vegetables” dietary pattern were less likely to have fatigue at T1 (p ≤ 0.05). The study findings indicate that while “simple carbohydrate and high fat” dietary pattern was associated with increased risk of fatigue, “vegetables” dietary pattern was associated with reduced risk of fatigue and a higher percentage of weight loss. Originality/value The present study appears to be the first study to examine associations between dietary patterns and fatigue. The strengths of the study included the in-depth analysis of this association in both before joining a weight management programme (SW) and currently as a member of SW with an adequate sample size.

Hubungan Pola Konsumsi Karbohidrat Sederhana dan Karbohidrat Kompleks Dengan Kadar HbA1c Pada Penderita Diabetes Mellitus Tipe 2 Di Wilayah Kerja Puskesmas Kedawung 1 Kabupaten Sragen

Background : Prevalence of Type 2 Diabetes Mellitus (DM) is epidemiologically increasing worldwide. Simple carbohidrate consumption patterns and complex carbohydrates consumption patterns are the risk factors of Type 2 DM, which can increase blood glucose levels so that it will affect DM Type 2 control through HbA1c examination. This study aimed to determine the relationship between simple carbohydrate consumption pattern and complex carbohydrates with HbA1c levels . Methods : This was an observational research using cross sectional design with 40 subject, sample was selected by total sampling which conduct in April until June 2019 at Puskesmas Kedawung 1 area. This research used FFQ questionnaire as research instrument. HbA1c levels examined using spectrophotometer. Chi square was used as statistic analysis. Results : The statistical test results suggested that there was correlation between simple carbohydrate consumption patterns and HbA1c levels (p=0,000) and also there was correlation between complex carbohydrate consumption patterns and HbA1c levels . Conclusion : There was correlation between pattern simple carbohydrate consumption and complex carbohydrate consumption with HbA1c levels. Keywords : Diabetes Mellitus, Pattern consumption , carbohydrates , HbA1c levels

Simple Carbohydrate Derivatives Diminish the Formation of Biofilm of the Pathogenic Yeast Candida albicans

The opportunistic human fungal pathogen Candida albicans relies on cell morphological transitions to develop biofilm and invade the host. In the current study, we developed new regulatory molecules, which inhibit the morphological transition of C. albicans from yeast-form cells to cells forming hyphae. These compounds, benzyl α-l-fucopyranoside and benzyl β-d-xylopyranoside, inhibit the hyphae formation and adhesion of C. albicans to a polystyrene surface, resulting in a reduced biofilm formation. The addition of cAMP to cells treated with α-l-fucopyranoside restored the yeast-hyphae switch and the biofilm level to that of the untreated control. In the β-d-xylopyranoside treated cells, the biofilm level was only partially restored by the addition of cAMP, and these cells remained mainly as yeast-form cells.