The global burden of adolescent and young adult cancer in 2019 : a systematic analysis for the Global Burden of Disease Study 2019

Background In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15-39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults. Methods Using the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15-39 years to define adolescents and young adults. Findings There were 1.19 million (95% UI 1.11-1.28) incident cancer cases and 396 000 (370 000-425 000) deaths due to cancer among people aged 15-39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59.6 [54.5-65.7] per 100 000 person-years) and high-middle SDI countries (53.2 [48.8-57.9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14.2 [12.9-15.6] per 100 000 person-years) and middle SDI (13.6 [12.6-14.8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23.5 million (21.9-25.2) DALYs to the global burden of disease, of which 2.7% (1.9-3.6) came from YLDs and 97.3% (96.4-98.1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally. Interpretation Adolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe

Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Detailed, comprehensive, and timely reporting on population health by underlying causes of disability and premature death is crucial to understanding and responding to complex patterns of disease and injury burden over time and across age groups, sexes, and locations. The availability of disease burden estimates can promote evidence-based interventions that enable public health researchers, policy makers, and other professionals to implement strategies that can mitigate diseases. It can also facilitate more rigorous monitoring of progress towards national and international health targets, such as the Sustainable Development Goals. For three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has filled that need. A global network of collaborators contributed to the production of GBD 2021 by providing, reviewing, and analysing all available data. GBD estimates are updated routinely with additional data and refined analytical methods. GBD 2021 presents, for the first time, estimates of health loss due to the COVID-19 pandemic. Methods: The GBD 2021 disease and injury burden analysis estimated years lived with disability (YLDs), years of life lost (YLLs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries using 100 983 data sources. Data were extracted from vital registration systems, verbal autopsies, censuses, household surveys, disease-specific registries, health service contact data, and other sources. YLDs were calculated by multiplying cause-age-sex-location-year-specific prevalence of sequelae by their respective disability weights, for each disease and injury. YLLs were calculated by multiplying cause-age-sex-location-year-specific deaths by the standard life expectancy at the age that death occurred. DALYs were calculated by summing YLDs and YLLs. HALE estimates were produced using YLDs per capita and age-specific mortality rates by location, age, sex, year, and cause. 95% uncertainty intervals (UIs) were generated for all final estimates as the 2·5th and 97·5th percentiles values of 500 draws. Uncertainty was propagated at each step of the estimation process. Counts and age-standardised rates were calculated globally, for seven super-regions, 21 regions, 204 countries and territories (including 21 countries with subnational locations), and 811 subnational locations, from 1990 to 2021. Here we report data for 2010 to 2021 to highlight trends in disease burden over the past decade and through the first 2 years of the COVID-19 pandemic. Findings: Global DALYs increased from 2·63 billion (95% UI 2·44–2·85) in 2010 to 2·88 billion (2·64–3·15) in 2021 for all causes combined. Much of this increase in the number of DALYs was due to population growth and ageing, as indicated by a decrease in global age-standardised all-cause DALY rates of 14·2% (95% UI 10·7–17·3) between 2010 and 2019. Notably, however, this decrease in rates reversed during the first 2 years of the COVID-19 pandemic, with increases in global age-standardised all-cause DALY rates since 2019 of 4·1% (1·8–6·3) in 2020 and 7·2% (4·7–10·0) in 2021. In 2021, COVID-19 was the leading cause of DALYs globally (212·0 million [198·0–234·5] DALYs), followed by ischaemic heart disease (188·3 million [176·7–198·3]), neonatal disorders (186·3 million [162·3–214·9]), and stroke (160·4 million [148·0–171·7]). However, notable health gains were seen among other leading communicable, maternal, neonatal, and nutritional (CMNN) diseases. Globally between 2010 and 2021, the age-standardised DALY rates for HIV/AIDS decreased by 47·8% (43·3–51·7) and for diarrhoeal diseases decreased by 47·0% (39·9–52·9). Non-communicable diseases contributed 1·73 billion (95% UI 1·54–1·94) DALYs in 2021, with a decrease in age-standardised DALY rates since 2010 of 6·4% (95% UI 3·5–9·5). Between 2010 and 2021, among the 25 leading Level 3 causes, age-standardised DALY rates increased most substantially for anxiety disorders (16·7% [14·0–19·8]), depressive disorders (16·4% [11·9–21·3]), and diabetes (14·0% [10·0–17·4]). Age-standardised DALY rates due to injuries decreased globally by 24·0% (20·7–27·2) between 2010 and 2021, although improvements were not uniform across locations, ages, and sexes. Globally, HALE at birth improved slightly, from 61·3 years (58·6–63·6) in 2010 to 62·2 years (59·4–64·7) in 2021. However, despite this overall increase, HALE decreased by 2·2% (1·6–2·9) between 2019 and 2021. Interpretation: Putting the COVID-19 pandemic in the context of a mutually exclusive and collectively exhaustive list of causes of health loss is crucial to understanding its impact and ensuring that health funding and policy address needs at both local and global levels through cost-effective and evidence-based interventions. A global epidemiological transition remains underway. Our findings suggest that prioritising non-communicable disease prevention and treatment policies, as well as strengthening health systems, continues to be crucially important. The progress on reducing the burden of CMNN diseases must not stall; although global trends are improving, the burden of CMNN diseases remains unacceptably high. Evidence-based interventions will help save the lives of young children and mothers and improve the overall health and economic conditions of societies across the world. Governments and multilateral organisations should prioritise pandemic preparedness planning alongside efforts to reduce the burden of diseases and injuries that will strain resources in the coming decades. Funding: Bill & Melinda Gates Foundation

Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. Methods: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk–outcome pairs. Pairs were included on the basis of data-driven determination of a risk–outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk–outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk–outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. Findings: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7–9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4–9·2]), smoking (5·7% [4·7–6·8]), low birthweight and short gestation (5·6% [4·8–6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8–6·0]). For younger demographics (ie, those aged 0–4 years and 5–14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9–27·7]) and environmental and occupational risks (decrease of 22·0% [15·5–28·8]), coupled with a 49·4% (42·3–56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9–21·7] for high BMI and 7·9% [3·3–12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6–1·9) for high BMI and 1·3% (1·1–1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4–78·8) for child growth failure and 66·3% (60·2–72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). Interpretation: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Extraction and analysis by liquid chromatography coupled with mass spectrometry of Lawsonia inermis and the study of its anti-melanoma effect

Lawsonia inermis L. communément appelée Henné appartient à la famille des Lythraceae. Elle est connue pour son importance traditionnelle à la fois comme agent cosmétique et médicinal, en particulier dans les régions indigènes de l’Afrique du Nord, de l'Asie du Sud et des pays du Moyen-Orient. Les différentes parties de cet arbuste ; les feuilles, les tiges, les graines et les racines comportent différents constituants chimiques comme les naphtoquinones, les polyphénols, les flavonoïdes, les tanins, etc, qui ont des activités biologiques diverses.L’intérêt de cette plante méditerranéenne en plus de son utilisation cosmétique, c’est son activité biologique antimicrobienne, antiinflammatoire, anticancéreuse et plusieurs d’autres.Ce travail de recherche s’est intéressé particulièrement à l’étude de son effet anticancéreux de plus particulièrement son potentiel anti-mélanome métastatique vue son utilisation traditionnelle souvent comme traitement topique de la peau irritée.Ce travail de recherche a permis, en premier lieu, la mise au point d’un plan d’expérience pour l’optimisation du rendement global d’extraction des molécules actives à partir du Henné (Lawsonia inermis L.). En seconde étape, l’identification et la quantification des composés actifs par chromatographie liquide à haute performance couplé à la spectrométrie de masse. Une cartographie géographie des cultures du henné au sud du Maroc, utilisant l’analyse en composantes principales et basée sur la nature du climat de chaque région.Par la suite, l’effet de la plumbagin sur le mélanome métastatique a été étudié. L’étude de cette activité a été évaluée in-vitro sur des cellules murines et humaine respectivement B16F10 et SKMEL-28. La plumbagin s'est avérée inhiber de manière significative trois processus métastatiques importants : la migration, l'adhésion et l'invasion des cellules B16F10. Ces résultats ont été confirmés dans la lignée cellulaire humaine SK-MEL-28.Lawsonia inermis L. commonly called Henna belongs to the family Lythraceae. It is known for its traditional importance both as a cosmetic and medicinal agent, especially in the indigenous regions of North Africa, South Asia and Middle East countries. The different parts of this shrub; leaves, stems, seeds and roots have different chemical constituents such as naphthoquinones, polyphenols, flavonoids, tannins, etc, which have various biological activities.The interest of this Mediterranean plant, in addition to its cosmetic use, is its biological activity antimicrobial, anti-inflammatory, anticancer and many others.This research work has been particularly interested in studying its anticancerous effect and more particularly its potential anti-melanoma metastasis given its traditional use often as a topical treatment for irritated skin.This research work allowed, first of all, the development of an experimental plan for the optimization of the global yield of extraction of active molecules from Henna (Lawsonia inermis L.). In the second stage, the identification and quantification of active compounds by high performance liquid chromatography coupled with mass spectrometry. A geographical mapping of henna crops in southern Morocco, using principal component analysis and based on the nature of the climate of each region was carried out.Subsequently, the effect of plumbagin on metastatic melanoma was studied. The study of this activity was evaluated in-vitro on murine and human cells respectively B16F10 and SKMEL-28. Plumbagin was found to significantly inhibit three important metastatic processes: migration, adhesion and invasion of B16F10 cells. These results were confirmed in the human cell line SK-MEL-28

Extraction et analyse par chromatographie liquide couplée à la spectrométrie de masse de Lawsonia inermis et l’étude de son effet anti-mélanome

Lawsonia inermis L. communément appelée Henné appartient à la famille des Lythraceae. Elle est connue pour son importance traditionnelle à la fois comme agent cosmétique et médicinal, en particulier dans les régions indigènes de l’Afrique du Nord, de l'Asie du Sud et des pays du Moyen-Orient. Les différentes parties de cet arbuste ; les feuilles, les tiges, les graines et les racines comportent différents constituants chimiques comme les naphtoquinones, les polyphénols, les flavonoïdes, les tanins, etc, qui ont des activités biologiques diverses.L’intérêt de cette plante méditerranéenne en plus de son utilisation cosmétique, c’est son activité biologique antimicrobienne, antiinflammatoire, anticancéreuse et plusieurs d’autres.Ce travail de recherche s’est intéressé particulièrement à l’étude de son effet anticancéreux de plus particulièrement son potentiel anti-mélanome métastatique vue son utilisation traditionnelle souvent comme traitement topique de la peau irritée.Ce travail de recherche a permis, en premier lieu, la mise au point d’un plan d’expérience pour l’optimisation du rendement global d’extraction des molécules actives à partir du Henné (Lawsonia inermis L.). En seconde étape, l’identification et la quantification des composés actifs par chromatographie liquide à haute performance couplé à la spectrométrie de masse. Une cartographie géographie des cultures du henné au sud du Maroc, utilisant l’analyse en composantes principales et basée sur la nature du climat de chaque région.Par la suite, l’effet de la plumbagin sur le mélanome métastatique a été étudié. L’étude de cette activité a été évaluée in-vitro sur des cellules murines et humaine respectivement B16F10 et SKMEL-28. La plumbagin s'est avérée inhiber de manière significative trois processus métastatiques importants : la migration, l'adhésion et l'invasion des cellules B16F10. Ces résultats ont été confirmés dans la lignée cellulaire humaine SK-MEL-28.Lawsonia inermis L. commonly called Henna belongs to the family Lythraceae. It is known for its traditional importance both as a cosmetic and medicinal agent, especially in the indigenous regions of North Africa, South Asia and Middle East countries. The different parts of this shrub; leaves, stems, seeds and roots have different chemical constituents such as naphthoquinones, polyphenols, flavonoids, tannins, etc, which have various biological activities.The interest of this Mediterranean plant, in addition to its cosmetic use, is its biological activity antimicrobial, anti-inflammatory, anticancer and many others.This research work has been particularly interested in studying its anticancerous effect and more particularly its potential anti-melanoma metastasis given its traditional use often as a topical treatment for irritated skin.This research work allowed, first of all, the development of an experimental plan for the optimization of the global yield of extraction of active molecules from Henna (Lawsonia inermis L.). In the second stage, the identification and quantification of active compounds by high performance liquid chromatography coupled with mass spectrometry. A geographical mapping of henna crops in southern Morocco, using principal component analysis and based on the nature of the climate of each region was carried out.Subsequently, the effect of plumbagin on metastatic melanoma was studied. The study of this activity was evaluated in-vitro on murine and human cells respectively B16F10 and SKMEL-28. Plumbagin was found to significantly inhibit three important metastatic processes: migration, adhesion and invasion of B16F10 cells. These results were confirmed in the human cell line SK-MEL-28

Extraction et analyse par chromatographie liquide couplée à la spectrométrie de masse de Lawsonia inermis et l’étude de son effet anti-mélanome

Lawsonia inermis L. commonly called Henna belongs to the family Lythraceae. It is known for its traditional importance both as a cosmetic and medicinal agent, especially in the indigenous regions of North Africa, South Asia and Middle East countries. The different parts of this shrub; leaves, stems, seeds and roots have different chemical constituents such as naphthoquinones, polyphenols, flavonoids, tannins, etc, which have various biological activities.The interest of this Mediterranean plant, in addition to its cosmetic use, is its biological activity antimicrobial, anti-inflammatory, anticancer and many others.This research work has been particularly interested in studying its anticancerous effect and more particularly its potential anti-melanoma metastasis given its traditional use often as a topical treatment for irritated skin.This research work allowed, first of all, the development of an experimental plan for the optimization of the global yield of extraction of active molecules from Henna (Lawsonia inermis L.). In the second stage, the identification and quantification of active compounds by high performance liquid chromatography coupled with mass spectrometry. A geographical mapping of henna crops in southern Morocco, using principal component analysis and based on the nature of the climate of each region was carried out.Subsequently, the effect of plumbagin on metastatic melanoma was studied. The study of this activity was evaluated in-vitro on murine and human cells respectively B16F10 and SKMEL-28. Plumbagin was found to significantly inhibit three important metastatic processes: migration, adhesion and invasion of B16F10 cells. These results were confirmed in the human cell line SK-MEL-28.Lawsonia inermis L. communément appelée Henné appartient à la famille des Lythraceae. Elle est connue pour son importance traditionnelle à la fois comme agent cosmétique et médicinal, en particulier dans les régions indigènes de l’Afrique du Nord, de l'Asie du Sud et des pays du Moyen-Orient. Les différentes parties de cet arbuste ; les feuilles, les tiges, les graines et les racines comportent différents constituants chimiques comme les naphtoquinones, les polyphénols, les flavonoïdes, les tanins, etc, qui ont des activités biologiques diverses.L’intérêt de cette plante méditerranéenne en plus de son utilisation cosmétique, c’est son activité biologique antimicrobienne, antiinflammatoire, anticancéreuse et plusieurs d’autres.Ce travail de recherche s’est intéressé particulièrement à l’étude de son effet anticancéreux de plus particulièrement son potentiel anti-mélanome métastatique vue son utilisation traditionnelle souvent comme traitement topique de la peau irritée.Ce travail de recherche a permis, en premier lieu, la mise au point d’un plan d’expérience pour l’optimisation du rendement global d’extraction des molécules actives à partir du Henné (Lawsonia inermis L.). En seconde étape, l’identification et la quantification des composés actifs par chromatographie liquide à haute performance couplé à la spectrométrie de masse. Une cartographie géographie des cultures du henné au sud du Maroc, utilisant l’analyse en composantes principales et basée sur la nature du climat de chaque région.Par la suite, l’effet de la plumbagin sur le mélanome métastatique a été étudié. L’étude de cette activité a été évaluée in-vitro sur des cellules murines et humaine respectivement B16F10 et SKMEL-28. La plumbagin s'est avérée inhiber de manière significative trois processus métastatiques importants : la migration, l'adhésion et l'invasion des cellules B16F10. Ces résultats ont été confirmés dans la lignée cellulaire humaine SK-MEL-28

Focus on the GC-HRMS based analytical development for characterization of human internal exposure to pesticides, in a multiplex inter-laboratory approach

International audienceProviding a methodology for broad assessment of human internal exposure to pesticides, via suspect screening, based on urine samples.Development of an unique protocol for analysis of a single urine sample by 3 complementary analytical platforms providing extensive picture of the internal exposure to pesticides, including both parent compounds and metabolites

Widening exposome exploration by means of complementary HRMS analytical platforms: use case on pesticide exposure

International audienceHuman exposure to food and environmental contaminants (such as pesticides) is generally estimated by indirect methods. Targeted bio-monitoring is a way to assess the internal exposure on a limited number of substances, needing large sample amounts for analyses as rigorous and sensitive as possible. Thus, the human health risks associated with multi-exposure to complex mixtures currently remain under-explored.In this context, the SCREENPEST project aims at providing a unified methodology for large-scale characterisation of human internal exposure to pesticides, via a "suspect profiling" approach, using urine

Widening exposome exploration by means of complementary HRMS analytical platforms: use case on pesticide exposure

International audienceHuman exposure to food and environmental contaminants (such as pesticides) is generally estimated by indirect methods. Targeted bio-monitoring is a way to assess the internal exposure on a limited number of substances, needing large sample amounts for analyses as rigorous and sensitive as possible. Thus, the human health risks associated with multi-exposure to complex mixtures currently remain under-explored.In this context, the SCREENPEST project aims at providing a unified methodology for large-scale characterisation of human internal exposure to pesticides, via a "suspect profiling" approach, using urine