Kaspar Hauser, the Child of Europe: Are smallpox vaccination scars the clue to a 2-century-old mystery?

We have explored the 19th century mystery of the identity of Kaspar Hauser, the so-called Child of Europe, from the perspective of the smallpox vaccination. We have highlighted the improbability that he was secretly inoculated based on the vaccination policies and methodologies applied at the time. This consideration allows for a reflection on the whole case and the importance of vaccination scars in ascertaining immunization against one of humanity's deadliest killers, especially given the recent monkeypox outbreak

Airborne pathogens diffusion: A comparison between tracer gas and pigmented aerosols for indoor environment analysis

The evaluation of airborne pathogens diffusion is a crucial practice in preventing airborne diseases like COVID-19, especially in indoor environments. Through this transmission route, pathogens can be carried by droplets, droplet nuclei and aerosols and be conveyed over long distances. Therefore, understanding their diffusion is vital for prevention and curbing disease transmission. There are different techniques used for this purpose, and one of the most common is the utilization of tracer gas, however, it has limitations such as the difference in size between the gas molecules and the respiratory droplets, as well as its incapability to take into account evaporation. For this reason, a new method for evaluating the diffusion of respiratory droplets has been developed. This approach involves the use of an ultrasonic emitter to release and disperse pigmented aerosols, and a colorimeter for the following quantitative evaluation. A comparison with the tracer gas technique has been carried out, showing for the pigmented aerosols methodology a response that is dependent on different relative humidity conditions, while there is no clear difference in the dispersion of tracer gas at high or low humidity

Mitochondrial DNA and exercise: Implications for health and injuries in sports

Recently, several studies have highlighted the tight connection between mitochondria and physical activity. Mitochondrial functions are important in high-demanding metabolic activities, such as endurance sports. Moreover, regular training positively affects metabolic health by increasing mitochondrial oxidative capacity and regulating glucose metabolism. Exercise could have multiple effects, also on the mitochondrial DNA (mtDNA) and vice versa; some studies have investigated how mtDNA polymorphisms can affect the performance of general athletes and mtDNA haplogroups seem to be related to the performance of elite endurance athletes. Along with several stimuli, including pathogens, stress, trauma, and reactive oxygen species, acute and intense exercise also seem to be responsible for mtDNA release into the cytoplasm and extracellular space, leading to the activation of the innate immune response. In addition, several sports are characterized by a higher frequency of injuries, including cranial trauma, associated with neurological consequences. However, with regular exercise, circulating cell-free mtDNA levels are kept low, perhaps promoting cf-mtDNA removal, acting as a protective factor against inflammation

Synthesis and anticancer activity of CDDO and CDDO-me, two derivatives of natural triterpenoids

Triterpenoids are natural compounds synthesized by plants through cyclization of squalene, known for their weak anti-inflammatory activity. 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO), and its C28 modified derivative, methyl-ester (CDDO-Me, also known as bardoxolone methyl), are two synthetic derivatives of oleanolic acid, synthesized more than 20 years ago, in an attempt to enhance the anti-inflammatory behavior of the natural compound. These molecules have been extensively investigated for their strong ability to exert antiproliferative, antiangiogenic, and antimetastatic activities, and to induce apoptosis and differentiation in cancer cells. Here, we discuss the chemical properties of natural triterpenoids, the pathways of synthesis and the biological effects of CDDO and its derivative CDDO-Me. At nanomolar doses, CDDO and CDDO-Me have been shown to protect cells and tissues from oxidative stress by increasing the transcriptional activity of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2). At doses higher than 100 nM, CDDO and CDDO-Me are able to modulate the differentiation of a variety of cell types, both tumor cell lines or primary culture cell, while at micromolar doses these compounds exert an anticancer effect in multiple manners; by inducing extrinsic or intrinsic apoptotic pathways, or autophagic cell death, by inhibiting telomerase activity, by disrupting mitochondrial functions through Lon protease inhibition, and by blocking the deubiquitylating enzyme USP7. CDDO-Me demonstrated its efficacy as anticancer drugs in different mouse models, and versus several types of cancer. Several clinical trials have been started in humans for evaluating CDDO-Me efficacy as anticancer and anti-inflammatory drug; despite promising results, significant increase in heart failure events represented an obstacle for the clinical use of CDDO-Me

Sporadic and hereditary hemangioblastoma: The role of endothelial cells

Hemangioblastomas HBs are benign, highly vascularized tumors of the central nervous system. Approximately 75 of HBs are sporadic, while 25 are associated with von Hippel Lindau disease. HBs consist of two main components: A rich capillary network composed of vascular endothelia and pericytes, within large vacuolated stromal cells, which harbor the genetic defect

DNA Topoisomerase I differentially modulates R-loops across the human genome

Background: Co-transcriptional R-loops are abundant non-B DNA structures in mammalian genomes. DNA Topoisomerase I (Top1) is often thought to regulate R-loop formation owing to its ability to resolve both positive and negative supercoils. How Top1 regulates R-loop structures at a global level is unknown. Results: Here, we perform high-resolution strand-specific R-loop mapping in human cells depleted for Top1 and find that Top1 depletion results in both R-loop gains and losses at thousands of transcribed loci, delineating two distinct gene classes. R-loop gains are characteristic for long, highly transcribed, genes located in gene-poor regions anchored to Lamin B1 domains and in proximity to H3K9me3-marked heterochromatic patches. R-loop losses, by contrast, occur in gene-rich regions overlapping H3K27me3-marked active replication initiation regions. Interestingly, Top1 depletion coincides with a block of the cell cycle in G0/G1 phase and a trend towards replication delay. Conclusions: Our findings reveal new properties of Top1 in regulating R-loop homeostasis in a context-dependent manner and suggest a potential role for Top1 in modulating the replication process via R-loop formation

Circulating and Tumor-Associated Neutrophils in the Era of Immune Checkpoint Inhibitors: Dynamics, Phenotypes, Metabolism, and Functions.

Neutrophils are the most abundant myeloid cells in the blood and are a considerable immunological component of the tumor microenvironment. However, their functional importance has often been ignored, as they have always been considered a mono-dimensional population of terminally differentiated, short-living cells. During the last decade, the use of cutting-edge, single-cell technologies has revolutionized the classical view of these cells, unmasking their phenotypic and functional heterogeneity. In this review, we summarize the emerging concepts in the field of neutrophils in cancer, by reviewing the recent literature on the heterogeneity of both circulating neutrophils and tumor-associated neutrophils, as well as their possible significance in tumor prognosis and resistance to immune checkpoint inhibitors

Circulating and Tumor-Associated Neutrophils in the Era of Immune Checkpoint Inhibitors: Dynamics, Phenotypes, Metabolism, and Functions

Simple Summary Neutrophils are the most abundant leukocytes in the circulation, represent the first line of defense in the immune system and mediate inflammation. Increasing evidence suggests that neutrophils constitute a large population of cells with phenotypic and functional heterogeneity. In this review, we summarize and discuss new findings delineating that both circulating neutrophils and tumor-associated neutrophils have a role in tumor prognosis and resistance to immune checkpoint inhibitors. Neutrophils are the most abundant myeloid cells in the blood and are a considerable immunological component of the tumor microenvironment. However, their functional importance has often been ignored, as they have always been considered a mono-dimensional population of terminally differentiated, short-living cells. During the last decade, the use of cutting-edge, single-cell technologies has revolutionized the classical view of these cells, unmasking their phenotypic and functional heterogeneity. In this review, we summarize the emerging concepts in the field of neutrophils in cancer, by reviewing the recent literature on the heterogeneity of both circulating neutrophils and tumor-associated neutrophils, as well as their possible significance in tumor prognosis and resistance to immune checkpoint inhibitors