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  1. Fulltext Khat (Catha edulis) and Obesity: A Scoping Review of Animal and Human Studies
    Alshagga MA, Alshawsh MA, Seyedan A, Alsalahi A, Pan Y, Mohankumar SK, et al.
    Ann Nutr Metab, 2016;69(3-4):200-211.
    PMID: 27871070 DOI: 10.1159/000452895
    BACKGROUND: Khat (Catha edulis) is a plant that is deeply rooted in the cultural life of East African and Southwestern Arabian populations. Prevalent traditional beliefs about khat are that the plant has an effect on appetite and body weight.

    SUMMARY: This review assesses the accumulated evidences on the mutual influence of monoamines, hormones and neuropeptides that are linked to obesity. A few anti-obesity drugs that exert their mechanisms of action through monoamines are briefly discussed to support the notion of monoamines being a critical target of drug discovery for new anti-obesity drugs. Subsequently, the review provides a comprehensive overview of central dopamine and serotonin changes that are associated with the use of khat or its alkaloids. Then, all the studies on khat that describe physical, biochemical and hormonal changes are summarised and discussed in depth.

    CONCLUSION: The reviewed studies provide relatively acceptable evidence that different khat extracts or cathinone produces changes in terms of weight, fat mass, appetite, lipid biochemistry and hormonal levels. These changes are more pronounced at higher doses and long durations of intervention. The most suggested mechanism of these changes is the central action that produces changes in the physiology of dopamine and serotonin. Nonetheless, there are a number of variations in the study design, including species, doses and durations of intervention, which makes it difficult to arrive at a final conclusion about khat regarding obesity, and further studies are necessary in the future to overcome these limitations.

  2. Effect of 95% Ethanol Khat Extract and Cathinone on in vitro Human Recombinant Cytochrome P450 (CYP) 2C9, CYP2D6, and CYP3A4 Activity
    Lim SYM, Binti Azidin AR, Ung YT, Al-Shagga M, Alshawsh MA, Mohamed Z, et al.
    Eur J Drug Metab Pharmacokinet, 2019 Jun;44(3):423-431.
    PMID: 30306496 DOI: 10.1007/s13318-018-0518-2
    BACKGROUND AND OBJECTIVE: A significant number of people worldwide consume khat on daily basis. Long term of khat chewing has shown negative impact on several organ systems. It is likely that these people are co-administered khat preparations and conventional medication, which may lead to khat-drug interactions. This study aimed to reveal the inhibitory potencies of khat ethanol extract (KEE) and its major active ingredient (cathinone) on human cytochrome P450 (CYP) 2C9, CYP2D6, and CYP3A4 enzymes activities, which are collectively responsible for metabolizing 70-80% clinically used drugs.

    METHODS: In vitro fluorescence-based enzyme assays were developed and the CYP enzyme activities were quantified in the presence and absence of KEE and cathinone employing Vivid® CYP450 Screening Kits.

    RESULTS: KEE inhibited human CYP2C9, CYP2D6, and CYP3A4 enzyme activities with IC50 of 42, 62, and 18 μg/ml. On the other hand, cathinone showed negligible inhibitory effect on these CYPs. Further experiments with KEE revealed that KEE inhibited CYP2C9 via non-competitive or mixed mode with Ki of 14.7 μg/ml, CYP2D6 through competitive or mixed mode with Ki of 17.6 μg/ml, CYP3A4 by mixed inhibition mode with Ki of 12.1 μg/ml.

    CONCLUSION: Khat-drug interactions are possible due to administration of clinical drugs metabolized by CYP2C9/CYP2D6/CYP3A4 together with khat chewing. Further in vivo studies are required to confirm our findings and identify the causative constituents of these inhibitory effects.

  3. An update of aurones: food resource, health benefit, biosynthesis and application
    Yang J, Gao Z, Yu Z, Hou Y, Tang D, Yan H, et al.
    Crit Rev Food Sci Nutr, 2023 Aug 21.
    PMID: 37599623 DOI: 10.1080/10408398.2023.2248244
    Aurones are a subclass of active flavonoids characterized with a scaffold of 2-benzylidene-3(2H)-benzofuranone. This type of chemicals are widely distributed in fruit, vegetable and flower, and contribute to human health. In this review, we summarize the natural aurones isolated from dietary plants. Their positive effects on immunomodulation, antioxidation, cancer prevention as well as maintaining the health status of cardiovascular, nervous system and liver organs are highlighted. The biosynthesis strategies of plant-derived aurones are elaborated to provide solutions for their limited natural abundance. The potential application of natural aurones in food coloration are also discussed. This paper combines the up-to-date information and gives a full image of dietary aurones.
  4. Intracellular and exosomal microRNAome profiling of human vascular smooth muscle cells during replicative senescence
    Nguyen DDN, Zain SM, Kamarulzaman MH, Low TY, Chilian WM, Pan Y, et al.
    Am J Physiol Heart Circ Physiol, 2021 10 01;321(4):H770-H783.
    PMID: 34506226 DOI: 10.1152/ajpheart.00058.2021
    Vascular aging is highly associated with cardiovascular morbidity and mortality. Although the senescence of vascular smooth muscle cells (VSMCs) has been well established as a major contributor to vascular aging, intracellular and exosomal microRNA (miRNA) signaling pathways in senescent VSMCs have not been fully elucidated. This study aimed to identify the differential expression of intracellular and exosomal miRNA in human VSMCs (hVSMCs) during replicative senescence. To achieve this aim, intracellular and exosomal miRNAs were isolated from hVSMCs and subsequently subjected to whole genome small RNA next-generation sequencing, bioinformatics analyses, and qPCR validation. Three significant findings were obtained. First, senescent hVSMC-derived exosomes tended to cluster together during replicative senescence and the molecular weight of the exosomal protein tumor susceptibility gene 101 (TSG-101) increased relative to the intracellular TSG-101, suggesting potential posttranslational modifications of exosomal TSG-101. Second, there was a significant decrease in both intracellular and exosomal hsa-miR-155-5p expression [n = 3, false discovery rate (FDR) < 0.05], potentially being a cell type-specific biomarker of hVSMCs during replicative senescence. Importantly, hsa-miR-155-5p was found to associate with cell-cycle arrest and elevated oxidative stress. Lastly, miRNAs from the intracellular pool, that is, hsa-miR-664a-3p, hsa-miR-664a-5p, hsa-miR-664b-3p, hsa-miR-4485-3p, hsa-miR-10527-5p, and hsa-miR-12136, and that from the exosomal pool, that is, hsa-miR-7704, were upregulated in hVSMCs during replicative senescence (n = 3, FDR < 0.05). Interestingly, these novel upregulated miRNAs were not functionally well annotated in hVSMCs to date. In conclusion, hVSMC-specific miRNA expression profiles during replicative senescence potentially provide valuable insights into the signaling pathways leading to vascular aging.NEW & NOTEWORTHY This is the first study on intracellular and exosomal miRNA profiling on human vascular smooth muscle cells during replicative senescence. Specific dysregulated sets of miRNAs were identified from human vascular smooth muscle cells. Hsa-miR-155-5p was significantly downregulated in both intracellular and exosomal hVSMCs, suggesting its crucial role in cellular senescence. Hsa-miR-155-5p might be the mediator in linking cellular senescence to vascular aging and atherosclerosis.
  5. Fulltext Genetic Connections and Convergent Evolution of Tropical Indigenous Peoples in Asia
    Deng L, Pan Y, Wang Y, Chen H, Yuan K, Chen S, et al.
    Mol Biol Evol, 2022 Feb 03;39(2).
    PMID: 34940850 DOI: 10.1093/molbev/msab361
    Tropical indigenous peoples in Asia (TIA) attract much attention for their unique appearance, whereas their genetic history and adaptive evolution remain mysteries. We conducted a comprehensive study to characterize the genetic distinction and connection of broad geographical TIAs. Despite the diverse genetic makeup and large interarea genetic differentiation between the TIA groups, we identified a basal Asian ancestry (bASN) specifically shared by these populations. The bASN ancestry was relatively enriched in ancient Asian human genomes dated as early as ∼50,000 years before the present and diminished in more recent history. Notably, the bASN ancestry is unlikely to be derived from archaic hominins. Instead, we suggest it may be better modeled as a survived lineage of the initial peopling of Asia. Shared adaptations inherited from the ancient Asian ancestry were detected among the TIA groups (e.g., LIMS1 for hair morphology, and COL24A1 for bone formation), and they are enriched in neurological functions either at an identical locus (e.g., NKAIN3), or different loci in an identical gene (e.g., TENM4). The bASN ancestry could also have formed the substrate of the genetic architecture of the dark pigmentation observed in the TIA peoples. We hypothesize that phenotypic convergence of the dark pigmentation in TIAs could have resulted from parallel (e.g., DDB1/DAK) or genetic convergence driven by admixture (e.g., MTHFD1 and RAD18), new mutations (e.g., STK11), or notably purifying selection (e.g., MC1R). Our results provide new insights into the initial peopling of Asia and an advanced understanding of the phenotypic convergence of the TIA peoples.
  6. Study on sentinel hosts for surveillance of future COVID-19-like outbreaks
    Li Y, Hu J, Hou J, Lu S, Xiong J, Wang Y, et al.
    Sci Rep, 2024 Oct 19;14(1):24595.
    PMID: 39427096 DOI: 10.1038/s41598-024-76506-7
    The spread of SARS-CoV-2 to animals has the potential to evolve independently. In this study, we distinguished several sentinel animal species and genera for monitoring the re-emergence of COVID-19 or the new outbreak of COVID-19-like disease. We analyzed SARS-CoV-2 genomic data from human and nonhuman mammals in the taxonomic hierarchies of species, genus, family and order of their host. We find that SARS-CoV-2 carried by domestic dog (Canis lupus familiaris), domestic cat (Felis catus), mink (Neovison vison), and white-tailed deer (Odocoileus virginianus) cluster closely to human-origin viruses and show no differences in the majority of amino acids, but have the most positively selected sites and should be monitored to prevent the re-emergence of COVID-19 caused by novel variants of SARS-CoV-2. Viruses from the genera Panthera (especially lion (Panthera leo)), Manis and Rhinolophus differ significantly from human-origin viruses, and long-term surveillance should be undertaken to prevent the future COVID-19-like outbreaks. Investigation of the variation dynamics of sites 142, 501, 655, 681 and 950 within the S protein may be necessary to predict the novel animal SARS-CoV-2 variants.
  7. Fulltext REST and Neural Gene Network Dysregulation in iPSC Models of Alzheimer's Disease
    Meyer K, Feldman HM, Lu T, Drake D, Lim ET, Ling KH, et al.
    Cell Rep, 2019 01 29;26(5):1112-1127.e9.
    PMID: 30699343 DOI: 10.1016/j.celrep.2019.01.023
    The molecular basis of the earliest neuronal changes that lead to Alzheimer's disease (AD) is unclear. Here, we analyze neural cells derived from sporadic AD (SAD), APOE4 gene-edited and control induced pluripotent stem cells (iPSCs). We observe major differences in iPSC-derived neural progenitor (NP) cells and neurons in gene networks related to neuronal differentiation, neurogenesis, and synaptic transmission. The iPSC-derived neural cells from SAD patients exhibit accelerated neural differentiation and reduced progenitor cell renewal. Moreover, a similar phenotype appears in NP cells and cerebral organoids derived from APOE4 iPSCs. Impaired function of the transcriptional repressor REST is strongly implicated in the altered transcriptome and differentiation state. SAD and APOE4 expression result in reduced REST nuclear translocation and chromatin binding, and disruption of the nuclear lamina. Thus, dysregulation of neural gene networks may set in motion the pathologic cascade that leads to AD.
  8. Fulltext PGG.SNV: understanding the evolutionary and medical implications of human single nucleotide variations in diverse populations
    Zhang C, Gao Y, Ning Z, Lu Y, Zhang X, Liu J, et al.
    Genome Biol, 2019 10 22;20(1):215.
    PMID: 31640808 DOI: 10.1186/s13059-019-1838-5
    Despite the tremendous growth of the DNA sequencing data in the last decade, our understanding of the human genome is still in its infancy. To understand the implications of genetic variants in the light of population genetics and molecular evolution, we developed a database, PGG.SNV ( https://www.pggsnv.org ), which gives much higher weight to previously under-investigated indigenous populations in Asia. PGG.SNV archives 265 million SNVs across 220,147 present-day genomes and 1018 ancient genomes, including 1009 newly sequenced genomes, representing 977 global populations. Moreover, estimation of population genetic diversity and evolutionary parameters is available in PGG.SNV, a unique feature compared with other databases.
  9. Ancient DNA reveals genetic admixture in China during tiger evolution
    Sun X, Liu YC, Tiunov MP, Gimranov DO, Zhuang Y, Han Y, et al.
    Nat Ecol Evol, 2023 Nov;7(11):1914-1929.
    PMID: 37652999 DOI: 10.1038/s41559-023-02185-8
    The tiger (Panthera tigris) is a charismatic megafauna species that originated and diversified in Asia and probably experienced population contraction and expansion during the Pleistocene, resulting in low genetic diversity of modern tigers. However, little is known about patterns of genomic diversity in ancient populations. Here we generated whole-genome sequences from ancient or historical (100-10,000 yr old) specimens collected across mainland Asia, including a 10,600-yr-old Russian Far East specimen (RUSA21, 8× coverage) plus six ancient mitogenomes, 14 South China tigers (0.1-12×) and three Caspian tigers (4-8×). Admixture analysis showed that RUSA21 clustered within modern Northeast Asian phylogroups and partially derived from an extinct Late Pleistocene lineage. While some of the 8,000-10,000-yr-old Russian Far East mitogenomes are basal to all tigers, one 2,000-yr-old specimen resembles present Amur tigers. Phylogenomic analyses suggested that the Caspian tiger probably dispersed from an ancestral Northeast Asian population and experienced gene flow from southern Bengal tigers. Lastly, genome-wide monophyly supported the South China tiger as a distinct subspecies, albeit with mitochondrial paraphyly, hence resolving its longstanding taxonomic controversy. The distribution of mitochondrial haplogroups corroborated by biogeographical modelling suggested that Southwest China was a Late Pleistocene refugium for a relic basal lineage. As suitable habitat returned, admixture between divergent lineages of South China tigers took place in Eastern China, promoting the evolution of other northern subspecies. Altogether, our analysis of ancient genomes sheds light on the evolutionary history of tigers and supports the existence of nine modern subspecies.
  10. Fulltext Native diversity buffers against severity of non-native tree invasions
    Delavaux CS, Crowther TW, Zohner CM, Robmann NM, Lauber T, van den Hoogen J, et al.
    Nature, 2023 Sep;621(7980):773-781.
    PMID: 37612513 DOI: 10.1038/s41586-023-06440-7
    Determining the drivers of non-native plant invasions is critical for managing native ecosystems and limiting the spread of invasive species1,2. Tree invasions in particular have been relatively overlooked, even though they have the potential to transform ecosystems and economies3,4. Here, leveraging global tree databases5-7, we explore how the phylogenetic and functional diversity of native tree communities, human pressure and the environment influence the establishment of non-native tree species and the subsequent invasion severity. We find that anthropogenic factors are key to predicting whether a location is invaded, but that invasion severity is underpinned by native diversity, with higher diversity predicting lower invasion severity. Temperature and precipitation emerge as strong predictors of invasion strategy, with non-native species invading successfully when they are similar to the native community in cold or dry extremes. Yet, despite the influence of these ecological forces in determining invasion strategy, we find evidence that these patterns can be obscured by human activity, with lower ecological signal in areas with higher proximity to shipping ports. Our global perspective of non-native tree invasion highlights that human drivers influence non-native tree presence, and that native phylogenetic and functional diversity have a critical role in the establishment and spread of subsequent invasions.
  11. Fulltext Author Correction: Native diversity buffers against severity of non-native tree invasions
    Delavaux CS, Crowther TW, Zohner CM, Robmann NM, Lauber T, van den Hoogen J, et al.
    Nature, 2023 Oct;622(7982):E2.
    PMID: 37752352 DOI: 10.1038/s41586-023-06654-9
  12. Fulltext Integrated global assessment of the natural forest carbon potential
    Mo L, Zohner CM, Reich PB, Liang J, de Miguel S, Nabuurs GJ, et al.
    Nature, 2023 Dec;624(7990):92-101.
    PMID: 37957399 DOI: 10.1038/s41586-023-06723-z
    Forests are a substantial terrestrial carbon sink, but anthropogenic changes in land use and climate have considerably reduced the scale of this system1. Remote-sensing estimates to quantify carbon losses from global forests2-5 are characterized by considerable uncertainty and we lack a comprehensive ground-sourced evaluation to benchmark these estimates. Here we combine several ground-sourced6 and satellite-derived approaches2,7,8 to evaluate the scale of the global forest carbon potential outside agricultural and urban lands. Despite regional variation, the predictions demonstrated remarkable consistency at a global scale, with only a 12% difference between the ground-sourced and satellite-derived estimates. At present, global forest carbon storage is markedly under the natural potential, with a total deficit of 226 Gt (model range = 151-363 Gt) in areas with low human footprint. Most (61%, 139 Gt C) of this potential is in areas with existing forests, in which ecosystem protection can allow forests to recover to maturity. The remaining 39% (87 Gt C) of potential lies in regions in which forests have been removed or fragmented. Although forests cannot be a substitute for emissions reductions, our results support the idea2,3,9 that the conservation, restoration and sustainable management of diverse forests offer valuable contributions to meeting global climate and biodiversity targets.
  13. Fulltext The global biogeography of tree leaf form and habit
    Ma H, Crowther TW, Mo L, Maynard DS, Renner SS, van den Hoogen J, et al.
    Nat Plants, 2023 Nov;9(11):1795-1809.
    PMID: 37872262 DOI: 10.1038/s41477-023-01543-5
    Understanding what controls global leaf type variation in trees is crucial for comprehending their role in terrestrial ecosystems, including carbon, water and nutrient dynamics. Yet our understanding of the factors influencing forest leaf types remains incomplete, leaving us uncertain about the global proportions of needle-leaved, broadleaved, evergreen and deciduous trees. To address these gaps, we conducted a global, ground-sourced assessment of forest leaf-type variation by integrating forest inventory data with comprehensive leaf form (broadleaf vs needle-leaf) and habit (evergreen vs deciduous) records. We found that global variation in leaf habit is primarily driven by isothermality and soil characteristics, while leaf form is predominantly driven by temperature. Given these relationships, we estimate that 38% of global tree individuals are needle-leaved evergreen, 29% are broadleaved evergreen, 27% are broadleaved deciduous and 5% are needle-leaved deciduous. The aboveground biomass distribution among these tree types is approximately 21% (126.4 Gt), 54% (335.7 Gt), 22% (136.2 Gt) and 3% (18.7 Gt), respectively. We further project that, depending on future emissions pathways, 17-34% of forested areas will experience climate conditions by the end of the century that currently support a different forest type, highlighting the intensification of climatic stress on existing forests. By quantifying the distribution of tree leaf types and their corresponding biomass, and identifying regions where climate change will exert greatest pressure on current leaf types, our results can help improve predictions of future terrestrial ecosystem functioning and carbon cycling.
  14. Fulltext Predicting attitudinal and behavioral responses to COVID-19 pandemic using machine learning
    Pavlović T, Azevedo F, De K, Riaño-Moreno JC, Maglić M, Gkinopoulos T, et al.
    PNAS Nexus, 2022 Jul;1(3):pgac093.
    PMID: 35990802 DOI: 10.1093/pnasnexus/pgac093
    At the beginning of 2020, COVID-19 became a global problem. Despite all the efforts to emphasize the relevance of preventive measures, not everyone adhered to them. Thus, learning more about the characteristics determining attitudinal and behavioral responses to the pandemic is crucial to improving future interventions. In this study, we applied machine learning on the multinational data collected by the International Collaboration on the Social and Moral Psychology of COVID-19 (N = 51,404) to test the predictive efficacy of constructs from social, moral, cognitive, and personality psychology, as well as socio-demographic factors, in the attitudinal and behavioral responses to the pandemic. The results point to several valuable insights. Internalized moral identity provided the most consistent predictive contribution-individuals perceiving moral traits as central to their self-concept reported higher adherence to preventive measures. Similar results were found for morality as cooperation, symbolized moral identity, self-control, open-mindedness, and collective narcissism, while the inverse relationship was evident for the endorsement of conspiracy theories. However, we also found a non-neglible variability in the explained variance and predictive contributions with respect to macro-level factors such as the pandemic stage or cultural region. Overall, the results underscore the importance of morality-related and contextual factors in understanding adherence to public health recommendations during the pandemic.
  15. Fulltext The PREDICTS database: a global database of how local terrestrial biodiversity responds to human impacts
    Hudson LN, Newbold T, Contu S, Hill SL, Lysenko I, De Palma A, et al.
    Ecol Evol, 2014 Dec;4(24):4701-35.
    PMID: 25558364 DOI: 10.1002/ece3.1303
    Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species' threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project - and avert - future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups - including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems - http://www.predicts.org.uk). We make site-level summary data available alongside this article. The full database will be publicly available in 2015.
  16. Fulltext The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
    Hudson LN, Newbold T, Contu S, Hill SL, Lysenko I, De Palma A, et al.
    Ecol Evol, 2017 Jan;7(1):145-188.
    PMID: 28070282 DOI: 10.1002/ece3.2579
    The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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