An overview of anti-diabetic plants used in Gabon: Pharmacology and Toxicology

© 2017 Elsevier B.V. All rights reserved.Ethnopharmacological relevance: The management of diabetes mellitus management in African communities, especially in Gabon, is not well established as more than 60% of population rely on traditional treatments as primary healthcare. The aim of this review was to collect and present the scientific evidence for the use of medicinal plants that are in currect by Gabonese traditional healers to manage diabetes or hyperglycaemia based here on the pharmacological and toxicological profiles of plants with anti-diabetic activity. There are presented in order to promote their therapeutic value, ensure a safer use by population and provide some bases for further study on high potential plants reviewed. Materials and methods: Ethnobotanical studies were sourced using databases such as Online Wiley library, Pubmed, Google Scholar, PROTA, books and unpublished data including Ph.D. and Master thesis, African and Asian journals. Keywords including ‘Diabetes’ ‘Gabon’ ‘Toxicity’ ‘Constituents’ ‘hyperglycaemia’ were used. Results: A total of 69 plants currently used in Gabon with potential anti-diabetic activity have been identified in the literature, all of which have been used in in vivo or in vitro studies. Most of the plants have been studied in human or animal models for their ability to reduce blood glucose, stimulate insulin secretion or inhibit carbohydrates enzymes. Active substances have been identified in 12 out of 69 plants outlined in this review, these include Allium cepa and Tabernanthe iboga. Only eight plants have their active substances tested for anti-diabetic activity and are suitables for further investigation. Toxicological data is scarce and is dose-related to the functional parameters of major organs such as kidney and liver. Conclusion: An in-depth understanding on the pharmacology and toxicology of Gabonese anti-diabetic plants is lacking yet there is a great scope for new treatments. With further research, the use of Gabonese anti-diabetic plants is important to ensure the safety of the diabetic patients in Gabon.Peer reviewedFinal Accepted Versio

A per-cent-level determination of the nucleon axial coupling from quantum chromodynamics

The axial coupling of the nucleon, gA, is the strength of its coupling to the weak axial current of the standard model of particle physics, in much the same way as the electric charge is the strength of the coupling to the electromagnetic current. This axial coupling dictates the rate at which neutrons decay to protons, the strength of the attractive long-range force between nucleons and other features of nuclear physics. Precision tests of the standard model in nuclear environments require a quantitative understanding of nuclear physics that is rooted in quantum chromodynamics, a pillar of the standard model. The importance of gA makes it a benchmark quantity to determine theoretically—a difficult task because quantum chromodynamics is non-perturbative, precluding known analytical methods. Lattice quantum chromodynamics provides a rigorous, non-perturbative definition of quantum chromodynamics that can be implemented numerically. It has been estimated that a precision of two per cent would be possible by 2020 if two challenges are overcome [1,2]: contamination of gA from excited states must be controlled in the calculations and statistical precision must be improved markedly [2,3,4,5,6,7,8,9,10]. Here we use an unconventional method11 inspired by the Feynman–Hellmann theorem that overcomes these challenges. We calculate a gA value of 1.271 ± 0.013, which has a precision of about one per cent

Enhancing chemosensitivity to gemcitabine via RNA interference targeting the catalytic subunits of protein kinase CK2 in human pancreatic cancer cells

<p>Abstract</p> <p>Background</p> <p>Pancreatic cancer is a complex genetic disorder that is characterized by rapid progression, invasiveness, resistance to treatment and high molecular heterogeneity. Various agents have been used in clinical trials showing only modest improvements with respect to gemcitabine-based chemotherapy, which continues to be the standard first-line treatment for this disease. However, owing to the overwhelming molecular alterations that have been reported in pancreatic cancer, there is increasing focus on targeting molecular pathways and networks, rather than individual genes or gene-products with a combination of novel chemotherapeutic agents.</p> <p>Methods</p> <p>Cells were transfected with small interfering RNAs (siRNAs) targeting the individual CK2 subunits. The CK2 protein expression levels were determined and the effect of its down-regulation on chemosensitization of pancreatic cancer cells was investigated.</p> <p>Results</p> <p>The present study examined the impact on cell death following depletion of the individual protein kinase CK2 catalytic subunits alone or in combination with gemcitabine and the molecular mechanisms by which this effect is achieved. Depletion of the CK2α or -α' subunits in combination with gemcitabine resulted in marked apoptotic and necrotic cell death in PANC-1 cells. We show that the mechanism of cell death is associated with deregulation of distinct survival signaling pathways. Cellular depletion of CK2α leads to phosphorylation and activation of MKK4/JNK while down-regulation of CK2α' exerts major effects on the PI3K/AKT pathway.</p> <p>Conclusions</p> <p>Results reported here show that the two catalytic subunits of CK2 contribute differently to enhance gemcitabine-induced cell death, the reduced level of CK2α' being the most effective and that simultaneous reduction in the expression of CK2 and other survival factors might be an effective therapeutic strategy for enhancing the sensitivity of human pancreatic cancer towards chemotherapeutic agents.</p

The significance of the complement system for the pathogenesis of age-related macular degeneration — current evidence and translation into clinical application

BACKGROUND: Dysregulation of the complement system has been shown to play a major role in the pathogenesis of age-related macular degeneration (AMD). METHODS: The current evidence from human studies derives from immunohistochemical and proteomic studies in donor eyes, genetic association studies, and studies of blood complement protein levels. These lines of evidence are corroborated by in vitro and animal studies. RESULTS: In AMD donor eyes, detection of complement proteins in drusen suggested local inflammatory processes involving the complement system. Moreover, higher levels of complement proteins in the Bruch's membrane/choroid complex could be detected in AMD donor eyes compared to controls. A large number of independent genetic studies have consistently confirmed the association of AMD with risk or protective variants in genes coding for complement proteins, including complement factor H (CFH), CFH-related proteins 1 and 3, factor B/C2, C3 and factor I. Another set of independent studies detected increased levels of complement activation products in plasma of AMD patients, suggesting that AMD may be a systemic disease and the macula a vulnerable anatomic site of minimal resistance to complement activation. Genotype-phenotype correlations, including the impact of genetic variants on disease progression, gene-environment and pharmacogenetic interactions, have been investigated. There is evidence that complement gene variants may be associated with the progression from early to late forms of AMD, whereas they do not appear to play a significant role when late atrophic AMD has already developed. There are indications for an interaction between genetic variants and supplementation and dietary factors. Also, there is some evidence that variants in the CFH gene influence treatment effects in patients with neovascular AMD. CONCLUSIONS: Such data suggest that the complement system may have a significant role for developing new prophylactic and therapeutic interventions in AMD. In fact, several compounds acting on the complement pathway are currently in clinical trials. Therapeutics that modulate the complement system need to balance inhibition with preservation of sufficient functional activity in order to maintain adequate immune responses and tissue homeostasis. Specifically, targeting the dysfunction appears more adequate than a global suppression of complement activation in chronic diseases such as AMD

The molecular phylogeny of eph receptors and ephrin ligands

<p>Abstract</p> <p>Background</p> <p>The tissue distributions and functions of Eph receptors and their ephrin ligands have been well studied, however less is known about their evolutionary history. We have undertaken a phylogenetic analysis of Eph receptors and ephrins from a number of invertebrate and vertebrate species.</p> <p>Results</p> <p>Our findings indicate that Eph receptors form three major clades: one comprised of non-chordate and cephalochordate Eph receptors, a second comprised of urochordate Eph receptors, and a third comprised of vertebrate Eph receptors. Ephrins, on the other hand, fall into either a clade made up of the non-chordate and cephalochordate ephrins plus the urochordate and vertebrate ephrin-Bs or a clade made up of the urochordate and vertebrate ephrin-As.</p> <p>Conclusion</p> <p>We have concluded that Eph receptors and ephrins diverged into A and B-types at different points in their evolutionary history, such that primitive chordates likely possessed an ancestral ephrin-A and an ancestral ephrin-B, but only a single Eph receptor. Furthermore, ephrin-As appear to have arisen in the common ancestor of urochordates and vertebrates, whereas ephrin-Bs have a more ancient bilaterian origin. Ancestral ephrin-B-like ligands had transmembrane domains; as GPI anchors appear to have arisen or been lost at least 3 times.</p

Diagnostic thinking and information used in clinical decision-making: a qualitative study of expert and student dental clinicians

<p>Abstract</p> <p>Background</p> <p>It is uncertain whether the range and frequency of Diagnostic Thinking Processes (DTP) and pieces of information (concepts) involved in dental restorative treatment planning are different between students and expert clinicians.</p> <p>Methods</p> <p>We video-recorded dental visits with one standardized patient. Clinicians were subsequently interviewed and their cognitive strategies explored using guide questions; interviews were also recorded. Both visit and interview were content-analyzed, following the Gale and Marsden model for clinical decision-making. Limited tests used to contrast data were t, χ², and Fisher's. Scott's π was used to determine inter-coder reliability.</p> <p>Results</p> <p>Fifteen dentists and 17 senior dental students participated in visits lasting 32.0 minutes (± 12.9) among experts, and 29.9 ± 7.1 among students; contact time with patient was 26.4 ± 13.9 minutes (experts), and 22.2 ± 7.5 (students). The time elapsed between the first and the last instances of the clinician looking in the mouth was similar between experts and students. Ninety eight types of pieces of information were used in combinations with 12 DTPs. The main differences found in DTP utilization had dentists conducting diagnostic interpretations of findings with sufficient certainty to be considered definitive twice as often as students. Students resorted more often to more general or clarifying enquiry in their search for information than dentists.</p> <p>Conclusions</p> <p>Differences in diagnostic strategies and concepts existed within clearly delimited types of cognitive processes; such processes were largely compatible with the analytic and (in particular) non-analytic approaches to clinical decision-making identified in the medical field. Because we were focused on a clinical presentation primarily made up of non-emergency treatment needs, use of other DTPs and concepts might occur when clinicians evaluate emergency treatment needs, complex rehabilitative cases, and/or medically compromised patients.</p

Integrating chromosomal aberrations and gene expression profiles to dissect rectal tumorigenesis

<p>Abstract</p> <p>Background</p> <p>Accurate staging of rectal tumors is essential for making the correct treatment choice. In a previous study, we found that loss of 17p, 18q and gain of 8q, 13q and 20q could distinguish adenoma from carcinoma tissue and that gain of 1q was related to lymph node metastasis. In order to find markers for tumor staging, we searched for candidate genes on these specific chromosomes.</p> <p>Methods</p> <p>We performed gene expression microarray analysis on 79 rectal tumors and integrated these data with genomic data from the same sample series. We performed supervised analysis to find candidate genes on affected chromosomes and validated the results with qRT-PCR and immunohistochemistry.</p> <p>Results</p> <p>Integration of gene expression and chromosomal instability data revealed similarity between these two data types. Supervised analysis identified up-regulation of <it>EFNA1 </it>in cases with 1q gain, and <it>EFNA1 </it>expression was correlated with the expression of a target gene (<it>VEGF</it>). The <it>BOP1 </it>gene, involved in ribosome biogenesis and related to chromosomal instability, was over-expressed in cases with 8q gain. <it>SMAD2 </it>was the most down-regulated gene on 18q, and on 20q, <it>STMN3 </it>and <it>TGIF2 </it>were highly up-regulated. Immunohistochemistry for SMAD4 correlated with <it>SMAD2 </it>gene expression and 18q loss.</p> <p>Conclusion</p> <p>On basis of integrative analysis this study identified one well known CRC gene (<it>SMAD2</it>) and several other genes (<it>EFNA1, BOP1, TGIF2 </it>and <it>STMN3</it>) that possibly could be used for rectal cancer characterization.</p