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"David, Bruno"
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pharmaceutical industry and natural products: historical status and new trends
Owing to the high diversity of terrestrial and marine organisms, natural products (secondary metabolites) are some of the most successful source of drug leads for the treatment of many diseases and illnesses. In the 1990s, advancements in automation [high-throughput screening (HTS)] and isolation technologies resulted in the surge in research towards natural products both in the fields of human health and agriculture. These strategies and techniques generated a substantial shift towards this ‘green Eldorado’, a real ‘Green Rush’ between 1990 and 2000. However, in the early 2000s most of the big Pharmas terminated their HTS and bioprospecting endeavours but to date, the low productivity of combichem and rational drug design is silently positioning pharmacognosy back on the rails and natural product discovery is remerging as a reputable source of current drugs on the market. Meanwhile, the World Health Organization has come to the realisation of the importance of biodiversity which would be able to offer affordable, therapeutic solutions to the majority of the world population. The preservation of the world’s biodiversity and its access is a critical issue which could hamper a serene utilisation of natural products in the developing world with herbal-based phytopharmaceuticals representing a significant share of the total world pharmaceutical market. This review presents an industrial perspective discussing natural product drug discovery, lead research, botanicals, pro-drugs, synergy effects, drugs interactions with botanicals, traditional medicines, reverse pharmacognosy and presents the difficulties in accessing biodiversity.
Journal Article
Injustice 2
\"The war is over. But a new battle is about to begin. After years of conflict and carnage, Batman and his rebel allies have finally triumphed over their tyrannical foe, Superman. Now the Man of Steel is behind bars, and the Dark Knight holds the future of the world in his hands. But that future is about to slip from his grasp. Superman still has many friends who will work tirelessly to free their leader from captivity. And a new force is about to emerge from the shadows. A winged warrior is assembling a Suicide Squad of the world's most dangerous villains to pursue plans of his own, by any means necessary. And this man in black is out to claim the mantle of the Batman himself. As old foes and new enemies collide, can Bruce Wayne preserve the fragile peace for which so many heroes have sacrificed? or is a new era of injustice about to dawn?\" -- Back cover of volume 1.
Book
New regulations for accessing plant biodiversity samples, what is ABS?
In Rio de Janeiro, in order to preserve biodiversity a virtuous circle was set up in 1992: The sustainable use of biodiversity (genetic resources) will generate benefits which will then be used to preserve biodiversity. The Nagoya Protocol elaborated in 2010 was designed to bring clarification and allow the practical implementation of this virtuous circle of access and benefit sharing. The scope was clarified: research on genetic and biochemical content of plants, animals, fungi and microorganisms. Since many countries have now implemented access rules, it is important for academic and industrial users of biological resources to be fully aware of the regulations and to respect them.
Journal Article
Botanical ingredient identification and quality assessment: strengths and limitations of analytical techniques
Interest in botanical medicines is increasing worldwide with current global market values estimated to be greater than US $72 billion. To ensure ingredients used in botanical preparations are appropriately identified and will deliver the intended benefit while minimizing potential for risk, good manufacturing practices (GMPs) are required. GMPs require that scientifically valid analytical techniques be used. This review discusses a variety of techniques of quality assessment taking into account the different challenges between academicians and manufacturers with the basic premise that all techniques are scientifically valid if used appropriately, and conversely, are limited if not used in a scientifically valid manner. The strengths and limitations, applications and inapplicability, of some of these techniques will be discussed, as will differences between traditional and more modern analytical techniques. A strong emphasis is placed on classical botanical and traditional macromorphological assessment techniques that represent the basis of identification and quality assessment upstream of other techniques such as analytical chemistry and genetics. It will be shown that it is the suite of botanical and chemical techniques that provides the greatest confidence for ensuring the identity and quality of botanical medicines.
Journal Article
The landscape of natural product diversity and their pharmacological relevance from a focus on the Dictionary of Natural Products
Nature is considered a prolific source of diverse biologically active chemotypes. While most reviews have focused on the characteristics of the chemical backbones of natural products (NPs), few have tried to provide an overview of their origins (the living organisms in which they are produced), chemical classes, and biological activities. This review discusses the current knowledge on NP diversity by focusing on the
Dictionary of Natural Products
®
(DNP). We datamined the 300,000 NPs covered by the DNP to reveal relevant, albeit dormant, knowledge about NP diversity. This holistic picture of NPs allows us to discuss the most abundant biological sources of NPs investigated in relation to their chemical features and biological activities. In a nutshell, a large part of NPs originated from plants (67%), especially from the Compositae and Leguminosae families. Among all kingdoms, NPs isolated from
Streptomyces
spp. were largely represented, while terpenoids and alkaloids were the two most represented chemical classes. Out of all NPs documented, only 3882 were reported to be bioactive (1163 from plants and 1006 from bacteria), with antibacterial, antibiotics, and antineoplastic agents being the most frequent therapeutic classes. In this paper, we also address the advantages and limitations of NP research from a pharmaceutical industry perspective. This work will provide useful insights and guidance to researchers involved in drug discovery from NPs.
Journal Article
Comparison of the Phytochemical Composition of Serenoa repens Extracts by a Multiplexed Metabolomic Approach
Phytochemical extracts are highly complex chemical mixtures. In the context of an increasing demand for phytopharmaceuticals, assessment of the phytochemical equivalence of extraction procedures is of utmost importance. Compared to routine analytical methods, comprehensive metabolite profiling has pushed forward the concept of phytochemical equivalence. In this study, an untargeted metabolomic approach was used to cross-compare four marketed extracts from Serenoa repens obtained with three different extraction processes: ethanolic, hexanic and sCO2 (supercritical carbon dioxide). Our approach involved a biphasic extraction of native compounds followed by liquid chromatography coupled to a high-resolution mass spectrometry based metabolomic workflow. Our results showed significant differences in the contents of major and minor compounds according to the extraction solvent used. The analyses showed that ethanolic extracts were supplemented in phosphoglycerides and polyphenols, hexanic extracts had higher amounts of free fatty acids and minor compounds, and sCO2 samples contained more glycerides. The discriminant model in this study could predict the extraction solvent used in commercial samples and highlighted the specific biomarkers of each process. This metabolomic survey allowed the authors to assess the phytochemical content of extracts and finished products of S. repens and unequivocally established that sCO2, hexanic and ethanolic extracts are not chemically equivalent and are therefore unlikely to be pharmacologically equivalent.
Journal Article
Genetic structure and demographic inference of the regular sea urchin Sterechinus neumayeri (Meissner, 1900) in the Southern Ocean: The role of the last glaciation
One of the most relevant characteristics of the extant Southern Ocean fauna is its resiliency to survive glacial processes of the Quaternary. These climatic events produced catastrophic habitat reductions and forced some marine benthic species to move, adapt or go extinct. The marine benthic species inhabiting the Antarctic upper continental shelf faced the Quaternary glaciations with different strategies that drastically modified population sizes and thus affected the amount and distribution of intraspecific genetic variation. Here we present new genetic information for the most conspicuous regular sea urchin of the Antarctic continental shelf, Sterechinus neumayeri. We studied the patterns of genetic diversity and structure in this broadcast-spawner across three Antarctic regions: Antarctic Peninsula, the Weddell Sea and Adélie Land in East Antarctica. Genetic analyses based on mitochondrial and nuclear markers suggested that S. neumayeri is a single genetic unit around the Antarctic continent. The species is characterized by low levels of genetic diversity and exhibits a typical star-like haplotype genealogy that supports the hypothesis of a single in situ refugium. Based on two mutation rates standardized for this genus, the Bayesian Skyline plot analyses detected a rapid demographic expansion after the Last Glacial Maximum. We propose a scenario of rapid postglacial expansion and recolonization of Antarctic shallow areas from a less ice-impacted refugium where the species survived the LGM. Considering the patterns of genetic diversity and structure recorded in the species, this refugium was probably located in East Antarctica.
Journal Article
TICI: a taxon-independent community index for eDNA-based ecological health assessment
Global biodiversity is declining at an ever-increasing rate. Yet effective policies to mitigate or reverse these declines require ecosystem condition data that are rarely available. Morphology-based bioassessment methods are difficult to scale, limited in scope, suffer prohibitive costs, require skilled taxonomists, and can be applied inconsistently between practitioners. Environmental DNA (eDNA) metabarcoding offers a powerful, reproducible and scalable solution that can survey across the tree-of-life with relatively low cost and minimal expertise for sample collection. However, there remains a need to condense the complex, multidimensional community information into simple, interpretable metrics of ecological health for environmental management purposes. We developed a riverine taxon-independent community index (TICI) that objectively assigns indicator values to amplicon sequence variants (ASVs), and significantly improves the statistical power and utility of eDNA-based bioassessments. The TICI model training step uses the Chessman iterative learning algorithm to assign health indicator scores to a large number of ASVs that are commonly encountered across a wide geographic range. New sites can then be evaluated for ecological health by averaging the indicator value of the ASVs present at the site. We trained a TICI model on an eDNA dataset from 53 well-studied riverine monitoring sites across New Zealand, each sampled with a high level of biological replication ( n = 16). Eight short-amplicon metabarcoding assays were used to generate data from a broad taxonomic range, including bacteria, microeukaryotes, fungi, plants, and animals. Site-specific TICI scores were strongly correlated with historical stream condition scores from macroinvertebrate assessments (macroinvertebrate community index or MCI; R 2 = 0.82), and TICI variation between sample replicates was minimal (CV = 0.013). Taken together, this demonstrates the potential for taxon-independent eDNA analysis to provide a reliable, robust and low-cost assessment of ecological health that is accessible to environmental managers, decision makers, and the wider community.
Journal Article
Use of HCV-Positive Livers in HCV-Negative Recipients
There are only limited data on the survival outcomes after transplanting HCV RNA-positive liver into HCV RNA-negative recipients. The objective of our study was to determine whether there were graft and patient survival differences when HCV-negative patients received HCV RNA (nucleic acid amplification testing [NAT] positive)-positive liver grafts.
We queried the United Network for Organ Sharing data sets from January 2014 to December 2018, and recipients (N = 24,724) were stratified into 6 groups based on the status of HCV antibody and RNA of recipients and donors. The Cox proportional hazard regression was used to estimate the relationship between groups and 1-year post-LT graft or patient survival.
During the study period, 1,358 recipients received NAT-positive liver grafts. Two hundred ten of the recipients were HCV negative. During the same period, 707 HCV antibody-positive but NAT-negative grafts were transplanted into 516 HCV-positive and 191 HCV-negative recipients. There were no differences in survival in HCV-positive recipients whether they received NAT-positive grafts (n = 1,148) or HCV antibody-negative/NAT-negative grafts (n = 6,321). Recipients of grafts from HCV antibody-positive/NAT-negative donors had similar survival whether recipients were HCV-negative patients (n = 191) or HCV-positive patients (n = 516), and their survival probabilities were similar to those of HCV-negative recipients (n = 6,321) receiving grafts from HCV antibody-negative/NAT-negative donors. Patient survival was lower (P = 0.049) when HCV-negative recipients (n = 210) received NAT-positive grafts compared with HCV-positive patients (n = 1,148) receiving NAT-positive grafts; however, when adjusted for recipient and donor characteristics, the difference was not significant.
HCV-negative recipients receiving HCV-positive liver grafts (NAT positive) have excellent 1-year survival outcomes.
Journal Article