Real-time in vivo ROS monitoring with luminescent nanoparticles reveals skin inflammation dynamics

Reactive oxygen species (ROS) are key regulators in numerous pathological contexts, including cancer or inflammation. Their role is complex, which justifies the need for methods enabling their quantitative and time-resolved monitoring in vivo, in the perspective to profile tissues of individual patients. However, current ROS detection methods do not provide these features. Here, we propose a new method based on the imaging of lanthanide-ion nanoparticles (GdVO 4 :Eu), whose photoluminescence is modulated by the surrounding ROS concentration. We monitored their luminescence after intradermic injection in a mouse ear submitted to an inflammation-inducing topical stimulus. Based on this approach, we quantified the ROS concentration after inflammation induction and identified a two-step kinetics of ROS production, which may be attributed to the response of resident immune cells and their further recruitment at the inflammation locus

In vivo echographic evidence of tumoral vascularization and microenvironment interactions in metastatic orthotopic human neuroblastoma xenografts

Human neuroblastoma (NB) is the second most frequent solid tumor of childhood and represents a highly heterogeneous disease at clinical and biologic levels. Little progress has been made to improve the poor prognosis of patients with high-stage NB. Tumor progression and metastatic dissemination still represent major obstacles to the successful treatment of advanced stage disease. In order to develop and evaluate new, targeted, therapeutic strategies, fully defined and biologically relevant in vivo models of NB are strongly needed. We have developed an orthotopic model of metastatic human NB in the nude mouse, using 2 well-characterized NB cell lines. Tumor growth, vascular properties and metastatic patterns were investigated using a sensitive and newly developed in vivo echographic technology in addition to immunohistochemistry and PCR analyses. Results show that implantation of low numbers of NB cells directly into the adrenal gland of nude mice resulted in rapid and homogeneous tumor growth without tumor morbidity. Nude mice were shown to rapidly develop highly vascularized adrenal tumors that selectively metastasized to the liver and bone marrow. In addition, the newly formed mouse vessels in orthotopic but not in heterotopic tumors, were found to express the highly angiogenic alphavbeta3 integrin marker, indicating the development of a truly malignant neovasculature in orthotopic conditions only. This observation confirms the impact of the regional microenvironment on tumor biology and suggests the existence of cross-talk with the tumor cells. In conclusion, such model faithfully reproduces the growth, vascular and metastatic patterns as observed in patients. It therefore represents a powerful and biologically relevant tool to improve our understanding of the biology of NB and to develop and assess new antiangiogenic and metastasis-targeted therapies

Changes in Cannabis Consumption During the Global COVID-19 Lockdown: The International COVISTRESS Study

Introduction: COVID-19 lockdown measures have been sources of both potential stress and possible psychological and addiction complications. A lack of activity and isolation during lockdown are among the factors thought to be behind the growth in the use of psychoactive substances and worsening addictive behaviors. Previous studies on the pandemic have attested to an increase in alcohol consumption during lockdowns. Likewise, data suggest there has also been a rise in the use of cannabis, although it is unclear how this is affected by external factors. Our study used quantitative data collected from an international population to evaluate changes in cannabis consumption during the lockdown period between March and October, 2020. We also compared users and non-users of the drug in relation to: (1) socio-demographic differences, (2) emotional experiences, and (3) the information available and the degree of approval of lockdown measures. Methods: An online self-report questionnaire concerning the lockdown was widely disseminated around the globe. Data was collected on sociodemographics and how the rules imposed had influenced the use of cannabis and concerns about health, the economic impact of the measures and the approach taken by government(s). Results: One hundred eighty two respondents consumed cannabis before the lockdown vs. 199 thereafter. The mean cannabis consumption fell from 13 joints per week pre-lockdown to 9.75 after it (p < 0.001). Forty-nine respondents stopped using cannabis at all and 66 admitted to starting to do so. The cannabis users were: less satisfied with government measures; less worried about their health; more concerned about the impact of COVID-19 on the economy and their career; and more frightened of becoming infected in public areas. The risk factors for cannabis use were: age (OR = 0.96); concern for physical health (OR = 0.98); tobacco (OR = 1.1) and alcohol consumption during lockdown (OR = 1.1); the pre-lockdown anger level (OR = 1.01); and feelings of boredom during the restrictions (OR = 1.1). Conclusion: In a specific sub-population, the COVID-19 lockdown brought about either an end to the consumption of cannabis or new use of the drug. The main risk factors for cannabis use were: a lower age, co-addictions and high levels of emotions