Multiplex PCR for the detection of toxigenic cyanobacteria in dietary supplements produced for human consumption

The production of food supplements containing cyanobacteria is a growing worldwide industry. While there have been several reports of health benefits that can be gained from the consumption of these supplements, there have also been a growing number of studies showing the presence of toxins some of which (for example microcystins) are known to affect human health. In this paper, we report a multiplex polymerase chain reaction (PCR) technique that can be used to identify microcystin contamination in dietary supplements produced for human consumption. This method involves a PCR reaction containing three primer pairs, the first of which is used to amplify a 220-bp fragment of 16s rDNA specific to Microcystis, the most common microcystin-producing cyanobacterium. The second primer pair is used to amplify a 300-bp fragment of the mcyA gene, linked to microcystin biosynthesis in Anabaena, Microcystis, and Planktothrix. A third primer pair, used as a positive control, results in the amplification of a 650-bp fragment from the phycocyanin operon common to all cyanobacteria. This technique was found to be useful for detecting the presence of toxigenic Microcystis in all dietary supplements produced from the nontoxic cyanobacterium Aphanizomenon flos-aquae.     

Isoflavones and bone: animal and human evidence of efficacy

Previous reports of soy extracts and isoflavone-enriched preparations studied in animals and humans have found that these molecules, when given at appropriate doses, have positive effects on the skeleton, including improvements in bone mineral content (BMC) and bone mineral density (BMD). A reduction in fracture risk of human subjects has not yet been shown in a prospective trial. Isoflavones, which exist in significant amounts only in soybeans, exert estrogen-like effects in human bone cells because of their unique organic structures that are similar to that of estradiol. The discovery of the b isoform of the estrogen receptor (ER) suggests that the molecular regulation of bone remodeling by estrogens, or estrogen-like molecules, including isoflavones, is more complex than previously thought. Depending on the type of ER present in a particular tissue, isoflavones may act as weak estrogen agonists or as weak estrogen antagonists. For example, isoflavones act as weak estrogen agonists in osteoblasts, but in reproductive cells, such as in the breast and uterus, they behave as weak estrogen antagonists. Weak agonistic effects of the isoflavones include stimulation of osteoblast proliferation and differentiation and increasing the production of cytokines that may inhibit osteclastic activity. The selective beneficial effects of estrogen-like molecules in bone tissues, compared to the anti-estrogenic effects in cells of reproductive tissues, make isoflavones attractive for the promotion of bone health. Relatively greater values of BMC and BMD of Asian populations with high consumption of soy isoflavones throughout life, compared to those with lower intakes, indirectly support the skeletal benefits of this pattern of intake of these estrogen-like molecules.     

Selecting anesthetic agents for human safety and animal recovery surgery

This review provides information to scientists performing animal surgery with recommendations for choosing an appropriate anesthetic agent. The human health risks from exposure to various anesthetic agents as well as methods to minimize exposure are discussed. In brief, methoxyflurane, used with precautions, is recommended for rodent bench-top surgery. When a precision vaporizer is available, isoflurane is usually the agent of choice. Other agents, including injectables, are considered.     

Neuropeptide Y (NPY) and depression: from animal studies to the human condition

Neuropeptide Y (NPY) is widely distributed throughout the central nervous system (CNS) and is one of the most conserved peptides in evolution, suggesting an important role in the regulation of basic physiological functions. In addition, both pre-clinical and clinical evidence have suggested that NPY, together with its receptors, may have a direct implication in several psychiatric disorders, including depression and related illnesses. NPY-like immunoreactivity and NPY receptors are expressed throughout the brain, with varying concentrations being found throughout the limbic system. Such brain structures have been repeatedly implicated in the modulation of emotional processing, as well as in the pathogenesis of depressive disorders. This review will concentrate on the distribution of NPY, its receptors, and the putative role played by this peptide in depressive illness based on both pre-clinical and clinical evidence.     

Disruption of mitochondrial homeostasis in organic acidurias: insights from human and animal studies

Organic acidurias or organic acidemias constitute a group of inherited disorders caused by deficient activity of specific enzymes of amino acids, carbohydrates or lipids catabolism, leading to large accumulation and excretion of one or more carboxylic (organic) acids. Affected patients usually present neurologic symptoms and abnormalities, sometimes accompanied by cardiac and skeletal muscle alterations, whose pathogenesis is poorly known. However, in recent years growing evidence has emerged indicating that mitochondrial dysfunction is directly or indirectly involved in the pathology of various organic acidemias. Mitochondrial impairment in some of these diseases are generally due to mutations in nuclear genes of the tricarboxylic acid cycle or oxidative phosphorylation, while in others it seems to result from toxic influences of the endogenous organic acids to the mitochondrion. In this minireview, we will briefly summarize the present knowledge obtained from human and animal studies showing that disruption of mitochondrial homeostasis may represent a relevant pathomechanism of tissue damage in selective organic acidemias. The discussion will focus on mitochondrial alterations found in patients affected by organic acidemias and by the deleterious effects of the accumulating organic acids on mitochondrial pathways that are crucial for ATP formation and transfer. The elucidation of the mechanisms of toxicity of these acidic compounds offers new perspectives for potential novel adjuvant therapeutic strategies in selected disorders of this group.     

Cancer prevention by bovine lactoferrin: from animal studies to human trial

Colorectal cancer (CRC) is one of the most frequently diagnosed cancers and, despite improved colonoscopic screening, CRC is a leading cause of death from cancer. Administration of bovine lactoferrin (bLF) suppresses carcinogenesis in the colon and other organs of test animals, and recently it was shown that ingestion of bLF inhibits the growth of adenomatous polyps in human patients. Here we review work which established bLF as an anti-carcinogenic agent in laboratory animals and the results of a clinical trial which demonstrated that bLF can reduce the risk of colon carcinogenesis in humans.     

Efficacy and safety of new medicines: a human focus

The introduction of safe and effective new medicines is proving ever more difficult, a problem arguably due at least in part to over-reliance on experimental animal-based test systems. In light of the increasing awareness of the lack of predictiveness of such non-human approaches, the necessity to focus on human-based test methods is clear. There has been considerable progress in human in vivo (microdosing) and in silico approaches, primarily to identify ADMET issues, however, in vitro functional studies using human tissues are receiving inadequate attention. The potential scope of human tissue-based research is considerable, but much methodological development is required, which necessitates an increased willingness on the part of the Pharma industry to support it. This approach also requires considerably improved access to the cells and tissues themselves. While current acquisition is almost exclusively from surgery and post mortem, the range of tissue types, the quantity, quality and frequency of supply will remain inadequate to support human tissue as a key component of pre-clinical efficacy and safety testing. Additional routine access to non-transplantable tissues from organ donors for research purposes would be of inestimable value, but in order to realise this, true collaboration will be required between NHS, the Pharma and biotech industries, and the general public.     

Efficacy and safety of apatinib for the treatment of AFP-producing gastric cancer

BackgroundAlpha-fetoprotein-producing gastric cancer (AFPGC) poses a therapeutic challenge worldwide because of its poor prognosis. This study aimed to evaluate the efficacy and safety of antiangiogenic drug apatinib in advanced AFPGC in a real-world setting.MethodsFrom September 2015 to December 2017, twenty-one patients identified with AFPGC from the clinical trial AHEAD-G202, an open-label, prospective, multicenter, non-interventional study of apatinib for advanced metastatic gastric cancer, were enrolled to perform this analysis. Patients received oral apatinib as monotherapy or combination therapy. A treatment cycle was defined as 28 days. The primary outcome was progression-free survival (PFS) and overall survival (OS), and the secondary outcomes included safety, objective response rate (ORR), and disease control rate (DCR).ResultsTwenty patients were evaluated for the apatinib efficacy analysis. The ORR of apatinib was 10%, whereas the DCR was 70%. The median PFS was 3.5 months [95%confidence interval (CI): 2.34–4.66]. The median OS was 4.5 months (95%CI: 3.49–5.51). Median OS of AFPGC patients without carcinoembryonic antigen (CEA) elevation achieved 30.8 months. CEA elevation was considered to be a potential independent predictive factor for OS (P = 0.030) and PFS (P = 0.047) by the analysis of multivariate analysis. The most common grade 3 to 4 adverse events (AEs) were hypertension (4.8%), hand-foot syndrome (4.8%), anorexia (4.8%), and vomiting and nausea (4.8%).ConclusionApatinib showed promising efficacy and an acceptable safety profile in patients with advanced AFPGC. Antiangiogenic therapy may be a good strategy for the treatment of AFPGC as a rare sub-type of gastric cancer.Trial registrationAHEAD-G202 ({"type":"clinical-trial","attrs":{"text":"NCT02668380","term_id":"NCT02668380"}}NCT02668380).     

Productivity,obesity, and human capital: Panel data evidence

The consequences of obesity for adults and children are well documented in the extant literature. We use panel data of 105 countries from 1990 to 2019 to estimate the effect of obesity on economic performance. We predict obesity using lagged values of child obesity as instruments. Predicted obesity has a negative and significant effect on productivity. This effect is independent of the effect of human capital and other macroeconomic determinants of economic performance. There is only weak evidence that this effect operates through the deterioration of human capital formation caused by childhood obesity.     

Methylselenocysteine treatment leads to diselenide formation in human cancer cells: evidence from X-ray absorption spectroscopy studies

The selenoamino acids methylselenocysteine (MeSeCys) and selenomethionine (SeMet) have disparate efficacies as anticancer agents. Herein, we use X-ray absorption spectroscopy to determine the chemical form of selenium in human neuroblastoma cells. Cells treated with MeSeCys contain a significant diselenide component, which is absent from SeMet-treated cells and suggests that metabolites of MeSeCys are capable of altering the redox status of the cells. The differences in the speciation of Se in the selenoamino acid-treated cells may provide insight into the differing anticancer activities of MeSeCys and SeMet.     

Antiarrhythmic effects of n-3 fatty acids: evidence from human studies

PURPOSE OF REVIEW: N-3 fatty acids from fish reduce cardiovascular mortality including sudden cardiac death. In this paper, the authors discuss the results of human studies with regard to the hypothesis that n-3 fatty acids reduce the risk of fatal coronary heart disease through antiarrhythmic effects. RECENT FINDINGS: Results from two recent clinical trials do not support a protective effect of n-3 fatty acids. In light of the earlier published bulk of evidence that n-3 fatty acids reduce cardiovascular mortality and sudden cardiac death, it is hard to explain these findings. Two recent observational studies confirmed that intake of n-3 fatty acids from fish is associated with less cardiovascular disease in the general population. They indicated that the protective effect of a fish meal may depend on the n-3 fatty acid content or preparation method and suggested a protective effect on arrhythmia rather than on atherosclerosis. Intervention studies on electrophysiological predictors of arrhythmia do not clearly confirm a beneficial effect of n-3 fatty acids. However, most of these studies were small or performed in healthy populations. SUMMARY: The available evidence still suggests that n-3 fatty acids may prevent fatal cardiac arrhythmia, but more conclusive studies are urgently needed.     

Neuroprotective action of omega-3 polyunsaturated fatty acids against neurodegenerative diseases: evidence from animal studies

Studies in animals clearly show that oral intake of docosahexaenoic acid (DHA) can alter brain DHA concentrations and thereby modify brain functions. This provides us with an opportunity to use DHA as a nutraceutical or pharmaceutical tool in brain disorders such as Alzheimer disease (AD) and Parkinson disease (PD). Most of the published epidemiological studies are consistent with a positive association between high reported DHA consumption or high DHA blood levels and a lower risk of developing AD later in life. Such observations have prompted the investigation of DHA in three different transgenic models of AD. These analyses show that animal models of AD are more vulnerable to DHA depletion than controls and that DHA exerts a beneficial effect against pathological signs of AD, including A beta accumulation, cognitive impairment, synaptic marker loss, and hyperphosphorylation of tau. Multiple mechanisms of action can be associated with the neuroprotective effects of DHA and include antioxidant properties and activation of distinct cell signaling pathways. Although the first randomized clinical assays have yet failed to demonstrate convincing beneficial effects of DHA for AD patients, the knowledge gathered in recent years holds out a hope for prevention and suggests that the elderly and people bearing a genetic risk for AD should at least avoid DHA deficiency.     

A metabolite fingerprinting for the characterization of commercial botanical dietary supplements

Phytopharmaceuticals, phytomedicines and botanical dietary supplements are products of wide interest considering the increase of their use. The development of fast and effective analytical methods able to give a fingerprinting of the product, on the basis of the plant extracts declared to be contained in it, is surely of high interest. In a previous investigation electrospray mass spectrometry was proved to be effective for the characterization of plant extracts. The direct infusion of the samples and the analyses in both positive and negative ion mode lead to a clear differentiation of the different samples. To verify if the same approach can be effective also for mixtures of plant extracts, five different commercial dietary supplements [Sedivitax gocce (1), Finocarbo Plus opercoli (2), Sollievo Bio tavolette (3), MiniMas opercoli (4) and Ruscoven gocce (5), all products from Aboca S.p.A., Sansepolcro, Italy] were analyzed by ESI. In order to evaluate possible changes in the metabolic profile with respect to different years of production, ten different batches of the commercial dietary supplements were considered. The mass spectral data were evaluated by multivariate analysis and the obtained results suggest that the method allows a satisfactory and rapid characterization of complex mixtures of commercial dietary supplements.     

Dental microwear evidence for a dietary shift between two nonmaize-reliant prehistoric human populations from Indiana

Several recent studies have demonstrated the efficacy of dental microwear analysis (DMA) for dietary reconstruction among nonhuman primates, early hominids, and prehistoric humans. The current study seeks microwear evidence for a paleobotanically suggested change in the types of foods that were consumed by two temporally distinct populations of the North American eastern woodlands. This particular dietary shift between the Late Archaic and the Early/Middle Woodland periods did not include the introduction of maize or any other tropical cultigen. In contrast, most dietary reconstructions from this area have compared later populations that consumed tropical cultigens (such as maize) with those that did not. High-resolution casts of adult mandibular second molar protoconid phase II wear facets were viewed via a scanning electron microscope at 500x. Photomicrographs of the microwear features were analyzed with specialized software, Microware 2.2 (Ungar [1995] Scanning 17:57-59). Analysis of variance statistical tests were performed, with one variable requiring rank-transformation. A dietary transition is evidenced by a statistically significant increase in the mean number of pits and concomitant decreases in scratch width and scratch length from the Late Archaic to the Early/Middle Woodland. Overall, the diet became harder and less abrasive. The implication here is that dental microwear analysis is able to discern relatively subtle dietary transitions in human populations that may not be as readily accessible by other means of dietary reconstruction.     

Effects of some dietary phytoestrogens in animal studies: review of a confusing landscape

A variety of effects have been attributed to phytoestrogens, which are present in variable concentrations in soy-based laboratory animal diets. The authors review the inherent complexities in evaluating the effects of soy and dietary phytoestrogens on various in vitro and in vivo systems.