Studies of Malaysian Plants in Prevention and Treatment of Colorectal Cancer

Incidence rates vary 10-fold globally for colorectal cancer (CRC). Asia has lower rates than Western countries, but as the Western life-style becomes more prevalent in economically developing Asian countries, rates are increasing. Clinical therapy has improved over the last few decades, and national screening programmes are a proven and effective means of reducing mortality; chemoprevention through diet and life-style choices may provide additional value. Diet has strong associations with the aetiology of CRC, considerable epidemiological evidence exist that fruits and vegetables are associated with reduced risk of CRC. There is also extensive experimental evidence that phytochemicals from fruit and vegetables can modulate pathways of carcinogenesis. In this chapter, we consider Malaysia specifically, with its rich ethnopharmacological heritage and megabiodiversity; Malaysian natural compounds may be a source of potentially chemo-protective with relevance to CRC

Impact of a (poly)phenol-rich extract from the brown algae Ascophyllum nodosum on DNA damage and antioxidant activity in an overweight or obese population: a randomized controlled trial

Background Epidemiologic evidence suggests that a diet rich in (poly)phenols has beneficial effects on many chronic diseases. Brown seaweed is a rich source of (poly)phenols. Objective The aim of this study was to investigate the bioavailability and effect of a brown seaweed (Ascophyllum nodosum) (poly)phenol extract on DNA damage, oxidative stress, and inflammation in vivo. Design A randomized, double-blind, placebo-controlled crossover trial was conducted in 80 participants aged 30–65 y with a body mass index (in kg/m2) ≥25. The participants consumed either a 400-mg capsule containing 100 mg seaweed (poly)phenol and 300 mg maltodextrin or a 400-mg maltodextrin placebo control capsule daily for an 8-wk period. Bioactivity was assessed with a panel of blood-based markers including lymphocyte DNA damage, plasma oxidant capacity, C-reactive protein (CRP), and inflammatory cytokines. To explore the bioavailability of seaweed phenolics, an untargeted metabolomics analysis of urine and plasma samples after seaweed consumption was determined by ultra-high-performance liquid chromatography–high-resolution mass spectrometry. Results Consumption of the seaweed (poly)phenols resulted in a modest decrease in DNA damage but only in a subset of the total population who were obese. There were no significant changes in CRP, antioxidant status, or inflammatory cytokines. We identified phlorotannin metabolites that are considered potential biomarkers of seaweed consumption including pyrogallol/phloroglucinol-sulfate, hydroxytrifurahol A-glucuronide, dioxinodehydroeckol-glucuronide, diphlorethol sulfates, C-O-C dimer of phloroglucinol sulfate, and C-O-C dimer of phloroglucinol. Conclusions To the best of our knowledge, this work represents the first comprehensive study investigating the bioactivity and bioavailability of seaweed (poly)phenolics in human participants. We identified several potential biomarkers of seaweed consumption. Intriguingly, the modest improvements in DNA damage were observed only in the obese subset of the total population. The subgroup analysis should be considered exploratory because it was not preplanned; therefore, it was not powered adequately. Elucidation of the biology underpinning this observation will require participant stratification according to weight in future studies. This trial was registered at clinicaltrials.gov as NCT02295878

Long-term supplementation with anthocyanin-rich or -poor Rubus idaeus berries does not influence microvascular architecture nor cognitive outcome in the APP/PS-1 mouse model of Alzheimer's disease

Disruption of microvascular architecture is a common pathogenic mechanism in the progression of Alzheimer's disease (AD). Given the anti-angiogenic activity of berry (poly)phenols, we investigated whether long-term feeding of Rubus idaeus (raspberries) could ameliorate cerebral microvascular pathology and improve cognition in the APP/PS-1 mouse model of AD. Male C57Bl/6J mice (50 wild type, 50 APP/PS-1) aged 4-months were fed for 24-weeks, with a normal diet enriched with either 100 mg/day glucose (control diet) or supplemented with glucose and freeze-dried anthocyanin-rich (red) or -poor (yellow) raspberries (100 mg/day) and assessed/sampled post intervention. Cerebral microvascular architecture of wild-type mice was characterised by regularly spaced capillaries with uniform diameters, unlike APP/PS-1 transgenic mice which showed dysregulated microvascular architecture. Long-term feeding of raspberries demonstrated limited modulation of microbiota and no substantive effect on microvascular architecture or cognition in either mice model although changes were evident in endogenous cerebral and plasmatic metabolite

Sensitization in transplantation: Assessment of risk (STAR) 2019 Working Group Meeting Report.

The purpose of the STAR 2019 Working Group was to build on findings from the initial STAR report to further clarify the expectations, limitations, perceptions, and utility of alloimmune assays that are currently in use or in development for risk assessment in the setting of organ transplantation. The goal was to determine the precision and clinical feasibility/utility of such assays in evaluating both memory and primary alloimmune risks. The process included a critical review of biologically driven, state-of-the-art, clinical diagnostics literature by experts in the field and an open public forum in a face-to-face meeting to promote broader engagement of the American Society of Transplantation and American Society of Histocompatibility and Immunogenetics membership. This report summarizes the literature review and the workshop discussions. Specifically, it highlights (1) available assays to evaluate the attributes of HLA antibodies and their utility both as clinical diagnostics and as research tools to evaluate the effector mechanisms driving rejection; (2) potential assays to assess the presence of alloimmune T and B cell memory; and (3) progress in the development of HLA molecular mismatch computational scores as a potential prognostic biomarker for primary alloimmunity and its application in research trial design

Discovery of a morphologically and genetically distinct population of Black-tailed Godwits in the East Asian-Australasian Flyway

Occurring across Eurasia, the Black-tailed GodwitLimosa limosahas three recognized subspecies,melanuroides,limosaandislandicafrom east to west, respectively. With the smallest body size,melanuroideshas been considered the only subspecies in the East Asian-Australasian Flyway. Yet, observations along the Chinese coast indicated the presence of distinctively large individuals. Here we compared the morphometrics of these larger birds captured in northern Bohai Bay, China, with those of the three known subspecies and explore the genetic population structuring of Black-tailed Godwits based on the control region of the mitochondrial genome (mtDNA). We found that the Bohai Godwits were indeed significantly larger thanmelanuroides, resemblinglimosamore thanislandica, but with relatively longer bills thanislandica. The level of genetic differentiation between Bohai Godwits and the three recognized subspecies was of similar magnitude to the differentiation among previously recognized subspecies. Based on these segregating morphological and genetic characteristics, we propose that these birds belong to a distinct population, which may be treated and described as a new subspecies

Persistence of anticancer activity in berry extracts after simulated gastrointestinal digestion and colonic fermentation

Fruit and vegetable consumption is associated at the population level with a protective effect against colorectal cancer. Phenolic compounds, especially abundant in berries, are of interest due to their putative anticancer activity. After consumption, however, phenolic compounds are subject to digestive conditions within the gastrointestinal tract that alter their structures and potentially their function. However, the majority of phenolic compounds are not efficiently absorbed in the small intestine and a substantial portion pass into the colon. We characterized berry extracts (raspberries, strawberries, blackcurrants) produced by in vitro-simulated upper intestinal tract digestion and subsequent fecal fermentation. These extracts and selected individual colonic metabolites were then evaluated for their putative anticancer activities using in vitro models of colorectal cancer, representing the key stages of initiation, promotion and invasion. Over a physiologically-relevant dose range (0–50 µg/ml gallic acid equivalents), the digested and fermented extracts demonstrated significant anti-genotoxic, anti-mutagenic and anti-invasive activity on colonocytes. This work indicates that phenolic compounds from berries undergo considerable structural modifications during their passage through the gastrointestinal tract but their breakdown products and metabolites retain biological activity and can modulate cellular processes associated with colon cancer

The effect of a brief social intervention on the examination results of UK medical students: a cluster randomised controlled trial

Background: Ethnic minority (EM) medical students and doctors underperform academically, but little evidence exists on how to ameliorate the problem. Psychologists Cohen et al. recently demonstrated that a written self-affirmation intervention substantially improved EM adolescents' school grades several months later. Cohen et al.'s methods were replicated in the different setting of UK undergraduate medical education.Methods: All 348 Year 3 white (W) and EM students at one UK medical school were randomly allocated to an intervention condition (writing about one's own values) or a control condition (writing about another's values), via their tutor group. Students and assessors were blind to the existence of the study. Group comparisons on post-intervention written and OSCE (clinical) assessment scores adjusted for baseline written assessment scores were made using two-way analysis of covariance. All assessment scores were transformed to z-scores (mean = 0 standard deviation = 1) for ease of comparison. Comparisons between types of words used in essays were calculated using t-tests. The study was covered by University Ethics Committee guidelines.Results: Groups were statistically identical at baseline on demographic and psychological factors, and analysis was by intention to treat [intervention group EM n = 95, W n = 79; control group EM n = 77; W n = 84]. As predicted, there was a significant ethnicity by intervention interaction [F(4,334) = 5.74; p = 0.017] on the written assessment. Unexpectedly, this was due to decreased scores in the W intervention group [mean difference = 0.283; (95% CI = 0.093 to 0.474] not improved EM intervention group scores [mean difference = -0.060 (95% CI = -0.268 to 0.148)]. On the OSCE, both W and EM intervention groups outperformed controls [mean difference = 0.261; (95% CI = -0.047 to -0.476; p = 0.013)]. The intervention group used more optimistic words (p < 0.001) and more "I" and "self" pronouns in their essays (p < 0.001), whereas the control group used more "other" pronouns (p < 0.001) and more negations (p < 0.001).Discussion: Cohen et al.'s finding that a brief self-affirmation task narrowed the ethnic academic achievement gap was replicated on the written assessment but against expectations, this was due to reduced performance in the W group. On the OSCE, the intervention improved performance in both W and EM groups. In the intervention condition, participants tended to write about themselves and used more optimistic words than in the control group, indicating the task was completed as requested. The study shows that minimal interventions can have substantial educational outcomes several months later, which has implications for the multitude of seemingly trivial changes in teaching that are made on an everyday basis, whose consequences are never formally assessed

Association Between Androgen Deprivation Therapy and Mortality Among Patients With Prostate Cancer and COVID-19

Importance: Androgen deprivation therapy (ADT) has been theorized to decrease the severity of SARS-CoV-2 infection in patients with prostate cancer owing to a potential decrease in the tissue-based expression of the SARS-CoV-2 coreceptor transmembrane protease, serine 2 (TMPRSS2). Objective: To examine whether ADT is associated with a decreased rate of 30-day mortality from SARS-CoV-2 infection among patients with prostate cancer. Design, Setting, and Participants: This cohort study analyzed patient data recorded in the COVID-19 and Cancer Consortium registry between March 17, 2020, and February 11, 2021. The consortium maintains a centralized multi-institution registry of patients with a current or past diagnosis of cancer who developed COVID-19. Data were collected and managed using REDCap software hosted at Vanderbilt University Medical Center in Nashville, Tennessee. Initially, 1228 patients aged 18 years or older with prostate cancer listed as their primary malignant neoplasm were included; 122 patients with a second malignant neoplasm, insufficient follow-up, or low-quality data were excluded. Propensity matching was performed using the nearest-neighbor method with a 1:3 ratio of treated units to control units, adjusted for age, body mass index, race and ethnicity, Eastern Cooperative Oncology Group performance status score, smoking status, comorbidities (cardiovascular, pulmonary, kidney disease, and diabetes), cancer status, baseline steroid use, COVID-19 treatment, and presence of metastatic disease. Exposures: Androgen deprivation therapy use was defined as prior bilateral orchiectomy or pharmacologic ADT administered within the prior 3 months of presentation with COVID-19. Main Outcomes and Measures: The primary outcome was the rate of all-cause 30-day mortality after COVID-19 diagnosis for patients receiving ADT compared with patients not receiving ADT after propensity matching. Results: After exclusions, 1106 patients with prostate cancer (before propensity score matching: median age, 73 years [IQR, 65-79 years]; 561 (51%) self-identified as non-Hispanic White) were included for analysis. Of these patients, 477 were included for propensity score matching (169 who received ADT and 308 who did not receive ADT). After propensity matching, there was no significant difference in the primary end point of the rate of all-cause 30-day mortality (OR, 0.77; 95% CI, 0.42-1.42). Conclusions and Relevance: Findings from this cohort study suggest that ADT use was not associated with decreased mortality from SARS-CoV-2 infection. However, large ongoing clinical trials will provide further evidence on the role of ADT or other androgen-targeted therapies in reducing COVID-19 infection severity

Motor control or graded activity exercises for chronic low back pain? A randomised controlled trial

Background: Chronic low back pain remains a major health problem in Australia and around the world. Unfortunately the majority of treatments for this condition produce small effects because not all patients respond to each treatment. It appears that only 25-50% of patients respond to exercise. The two most popular types of exercise for low back pain are graded activity and motor control exercises. At present however, there are no guidelines to help clinicians select the best treatment for a patient. As a result, time and money are wasted on treatments which ultimately fail to help the patient