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Abstract Evasion of cell death is a hallmark of cancer, and consequently the induction of cell death is a common strategy in cancer treatment. However, the molecular mechanisms regulating different types of cell death are poorly understood. We have formerly shown that in the epidermis of hypomorphic zebrafish hai1a mutant embryos, pre-neoplastic transformations of keratinocytes caused by unrestrained activity of the type II transmembrane serine protease Matriptase-1 heal spontaneously. This healing is driven by Matriptase-dependent increased sphingosine kinase (SphK) activity and sphingosine-1-phosphate (S1P)-mediated keratinocyte loss via apical cell extrusion. In contrast, amorphic hai1a fr26 mutants with even higher Matriptase-1 and SphK activity die within a few days. Here we show that this lethality is not due to epidermal carcinogenesis, but to aberrant tp53-independent apoptosis of keratinocytes caused by increased levels of pro-apoptotic C16 ceramides, sphingolipid counterparts to S1P within the sphingolipid rheostat, which severely compromises the epidermal barrier. Mathematical modelling of sphingolipid rheostat homeostasis, combined with in vivo manipulations of components of the rheostat or the ceramide de novo synthesis pathway, indicate that this unexpected overproduction of ceramides is caused by a negative feedback loop sensing ceramide levels and controlling ceramide replenishment via de novo synthesis. Therefore, despite their initial decrease due to increased conversion to S1P, ceramides eventually reach cell death-inducing levels, making transformed pre-neoplastic keratinocytes die even before they are extruded, thereby abrogating the normally barrier-preserving mode of apical live cell extrusion. Our results offer an in vivo perspective of the dynamics of sphingolipid homeostasis and its relevance for epithelial cell survival versus cell death, linking apical cell extrusion and apoptosis. Implications for human carcinomas and their treatments are discussed.

IntroductionAs cancer survival rates increase, it has become crucial to pay attention to the long-term quality of life of survivors, including sexual functioning. The quality of sexual life and fear of cancer progression are often unmet needs, significantly impacting cancer patients’ overall quality of life. In this study, we investigate these factors in Romanian female cancer patients and highlight their relationship with mental health and demographic variables.MethodsThis study included 242 Romanian female cancer patients who completed questionnaires assessing sexual functioning (EORTC QLQ-SHQ22), fear of cancer progression (FoP-Q), depression (PHQ-9), and anxiety (GAD-7). We examined these relationships using descriptive, exploratory, and regression analyses.ResultsAround 50% of patients reported impairments in sexual satisfaction and pain during sex. Lower sexual satisfaction increased sexual dysfunction, and heightened fear of cancer progression (FCP) were associated with depression, anxiety, younger age, lower education, rural residence, and unmarried status.DiscussionThis study reveals a complex interplay between sexual health, fear of cancer progression, and psychological well-being among female cancer survivors in Romania. Addressing sexual concerns, providing psychoeducation, promoting coping with the fear of progression, and utilizing interdisciplinary interventions are essential to improving these patients’ overall quality of life. These findings underscore the need for integrated care approaches that consider both physical and psychological dimensions of cancer survivorship.

Mycotoxins are natural metabolites produced by species of filamentous fungi belonging mainly to the genera Aspergillus, Fusarium, Penicillium, and Alternaria, which can grow in various crops and foodstuffs. The South American climate is diverse, varying from tropical, temperate, and arid to cold, ideal for the growth of different types of fungi and mycotoxin production. This mini review aimed to describe the natural occurrence of mycotoxin in food in South America from 2018 to 2023, identifying research gaps and challenges in an era of climate change. We analyzed 53 studies, 21 from Brazil. Most of the mycotoxins analyzed in South America were the traditional and regulated mycotoxins, with variable occurrences depending on the region, climatic conditions, and methodology used. Emerging and modified mycotoxins have only been studied in Argentina and Brazil, where some studies have shown high occurrences. Given this, it is essential to strengthen food safety laboratories and surveillance capabilities and establish early warning systems. It is also essential to continue working to raise awareness of mycotoxins as a public health issue and to study and prevent the impact of climate change on soil microbial population, the new prevalence of fungi, and the profile of toxigenic species. An effective connection and collaboration between disciplines and sectors in different countries is needed to meet this research challenge.

Die Adressierungsanalyse wurde in den vergangenen Jahren als ein methodischer Zugang der Interaktionsforschung ausgearbeitet, der es erlauben soll, die Relationalität der Prozesse menschlichen Werdens als Subjektivierung in Praktiken der Adressierung zu untersuchen. Im Beitrag werden zwei Ziele verfolgt. Einerseits sollen die bisher in erster Linie als Methodologie ausgearbeiteten Überlegungen in zwei Hinsichten erweitert werden, nämlich bezüglich der Reichweite des Konzepts "Adressierung" und der Konkretisierung der methodischen Operationen in Abhängigkeit von den untersuchungsleitenden Fragestellungen. Andererseits prüfen wir im Beitrag, welche Potenziale der Adressierungsanalyse in der Forschung zur Lehrpersonenbildung auch in längsschnittlichen Untersuchungen zukommen, wo aber auch noch Entwicklungsbedarf und Limitationen bestehen.

IntroductionFear of cancer progression (FoP) is one of the most frequently reported unmet needs invoked by the majority of cancer patients, which may significantly impair the quality of life (QoL) of patients. The major objective of the present cross-sectional study was to investigate the specificities of the relationship between different dimensions and intensity of FoP and different aspects of patients’ QoL during the COVID-19 pandemic in Romania.MethodsA nationwide sample of 330 participants completed a survey, including measures of demographic characteristics, medical variables, QoL, and FoP. Multivariate General Linear and Hierarchical Regression Models were conducted in order to assess the relationship between variables.ResultOur results indicate that less than a quarter of the sample experienced low, between 63 and 70% moderate, and 15% high levels of FoP. Our results also indicate that anxiety/worry related to the possibility of progression of the disease, and loss of independence produced significant differences with large effect sizes in all the dimensions of QoL.DiscussionOur results indicate that besides affective reactions, the fear of cancer survivors to lose independence, not being able to attend to their own lives, seems to be a considerable threat, especially in the context of Romanian health system which has difficulties in offering qualitative psychosocial care for cancer patients. The idea that patients will have to rely on others and may not function well independently, not being able to attend to their own lives, seems to be a considerable threat, next to the experienced affective reactions per se.

Abstract Background Recurrence and resistance of Candida spp. infections is associated with the ability of these microorganisms to present several virulence patterns such as morphogenesis, adhesion, and biofilm formation. In the search for agents with antivirulence activity, essential oils could represent a strategy to act against biofilms and to potentiate antifungal drugs. Objective To evaluate the antivirulence effect of Origanum vulgare L. essential oil (O-EO) against Candida spp. and to potentiate the effect of fluconazole and nystatin. Methods The effect of O-EO was evaluated on ATCC reference strains of C. albicans and non-albicans Candida species. Minimum inhibitory concentration (MIC) was determined through broth microdilution assay. Adhesion to microplates was determined by crystal violet (CV) assay. An adapted scratch assay in 24-well was used to determine the effect of essential oil on biofilms proliferation. Viability of biofilms was evaluated by MTT reduction assay and through a checkerboard assay we determined if O-EO could act synergistically with fluconazole and nystatin. Results MIC for C. albicans ATCC-90029 and ATCC-10231 was 0.01 mg/L and 0.97 mg/L, respectively. For non-albicans Candida strains MIC values were 2.6 mg/L for C. dubliniensis ATCC-CD36 and 5.3 mg/L for C. krusei ATCC-6258. By using these concentrations, O-EO inhibited morphogenesis, adhesion, and proliferation at least by 50% for the strains assayed. In formed biofilms O-EO decreased viability in ATCC 90029 and ATCC 10231 strains (IC50 7.4 and 2.8 mg/L respectively). Finally, we show that O-EO interacted synergistically with fluconazole and nystatin. Conclusions This study demonstrate that O-EO could be considered to improve the antifungal treatment against Candida spp.

Transdisciplinary research has gained momentum in the field of environmental sustainability. Research highlights that high degrees of participation in research can help identify integrated and acceptable solutions on the ground. However, research has also shown that high degrees of participation do not automatically result in positive outcomes. This study assumes that perceptions of participation diverge in different (cultural) settings. While conceptual frameworks provide good guidance on how project managers can design participatory processes, stakeholders involved in such processes may perceive their involvement differently. This article tests this assumption in transdisciplinary research carried out at two pilot sites in Latin America where the aim was for local stakeholders and experts to co-design wastewater management solutions. Based on a comprehensive stakeholder analysis, our research focuses on how project manager's original intention of high participation is perceived by stakeholders involved across the phases of the research process from project design, via implementation, to its evaluation. Analyses are based on written project documents and a survey amongst participants on the perceived degree of participation. Results show a discrepancy between the intended participation and the perceived participation. Furthermore, we find that perceptions of transdisciplinarity vary across the phases of the research process. These results help in understanding potential differences between intended and perceived participation, supporting the effective design of transdisciplinary research in the future.

Objectives: to study the apoptotic response of auditory hair cells in the organ of Corti after exposure to neomycin within the first 6 hours. Materials and methods: auditory hair cells harvested on the postnatal day 7 from the cochleae of C57BL6 wild type mice were cultured in vitro in the presence (neomycin group, n= 59 cochleas) or absence of neomycin (control group, n= 31 cochleas). Apoptotic cells were evaluated within 6 hours of incubation for the expression of active caspases (8, 9 or 3) in the cytoplasm and counterstained using propidium iodide to highlight apoptotic nuclei. Cells were statistically quantified using average and standard deviation. The differences between the averages were tested with the help of Student T test (threshold p< 0,05). Results: The statistic comparison between the different caspase types (caspase 3, 8 and 9), the average and dispersion inside the cell groups, permitted us to detect the first step of apoptosis taking place in the cytoplasm. The comparison of the cell group where propidium iodide was accumulated in the nucleus with the cell group where both the caspase and propidium iodide appeared, permitted us to detect the initiation and development of the second step of apoptosis, the one where the nucleus has already been affected. Conclusions: Neomycin is initiating, right after 6 hours of incubation, the process of apoptosis in auditory hair cells, determining the activation of cytoplasm caspases.

A nationwide outbreak of human listeriosis in Switzerland was traced to persisting environmental contamination of a cheese dairy with Listeria monocytogenes serotype 4b, sequence type 6, cluster type 7488. Whole-genome sequencing was used to match clinical isolates to a cheese sample and to samples from numerous sites within the production environment.

Shiga toxin-producing Escherichia coli (STEC) belonging to the serogroup O91 are among the most common non-O157 STEC serogroups associated with human illness in Europe. This study aimed to analyse the virulence factors, antimicrobial resistance genes and phylogenetic relatedness among 48 clinical STEC O91 isolates collected during 2003–2019 in Switzerland. The isolates were subjected to whole genome sequencing using short-read sequencing technologies and a subset of isolates additionally to long-read sequencing. They belonged to O91:H10 (n=6), O91:H14 (n=40), and O91:H21 (n=2). Multilocus sequence typing showed that the O91:H10 isolates all belonged to sequence type (ST)641, while the O91:H14 isolates were assigned to ST33, ST9700, or were non-typeable. Both O91:H21 isolates belonged to ST442. Shiga toxin gene stx1a was the most common Shiga toxin gene subtype among the isolates, followed by stx2b, stx2d and stx2a. All isolates were LEE-negative and carried one or two copies of the IrgA adhesin gene iha. In a subset of long-read sequenced isolates, modules of the Locus of Adhesion and Autoaggregation pathogenicity island (LAA-PAI) carrying iha and other genes such as hes, lesP or agn43 were identified. A large proportion of STEC O91:H14 carried the subtilase cytotoxin gene subA, colicin genes (cba, cea, cib and cma) or microcin genes (mcmA, mchB, mchC and mchF). STEC O91:H14 were further distinguished from STEC O91:H10/H21 by one or more virulence factors found in extraintestinal pathogenic E. coli (ExPEC), including hlyF, iucC/iutA, kpsE and traT. The hlyF gene was identified on a novel mosaic plasmid that was unrelated to hlyF+ plasmids described previously in STEC. Core genome phylogenetic analysis revealed that STEC O91:H10 and STEC O91:H21 were clonally conserved, whereas STEC O91:H14 were clonally diverse. Among three STEC O91:H14 isolates, a number of resistance genes were identified, including genes that mediate resistance to aminoglycosides (aadA, aadA2, aadA9, aadA23, aph(3'')-Ib and aph(6)-Id), chloramphenicol (cmlA), sulphonamides (sul2 and sul3), and trimethoprim (drfA12). Our data contribute to understanding the genetic diversity and differing levels of virulence potential within the STEC O91 serogroup.

Background: Juglone is a naphthoquinone currently obtained by chemical synthesis with biological activities including antitumor activity. Additionally, juglone is present in the green husk of walnut, which suggests evaluating the effect of GH extracts on carcinogenic cell lines. Results: Walnut green husk ethanolic extract was obtained as 169.1 mg juglone/100 g Green Husk and antioxidant activity (ORAC) of 44,920 μmol Trolox Equivalent/100 g DW Green Husk. At 1 μM juglone in HL-60 cell culture, green husk extract showed an antiproliferative effect, but pure juglone did not; under these conditions, normal fibroblast cells were not affected. A dose-dependent effect on mitochondrial membrane potential loss was observed. Apoptosis of HL-60 was detected at 10 μM juglone. Despite high ORAC values, neither purified juglone nor the extract showed protective effects on HL-60 cells under oxidative conditions. Conclusions: Green husk extract generates an antiproliferative effect in HL-60 cells, which is related to an induction of the early stages of apoptosis and a loss of mitochondrial membrane potential. The normal cells were not affected when juglone is present at concentrations of 1 μM, while at higher concentrations, there is loss of viability of both cancerous and healthy cells. How to cite: Soto-Maldonado C, Vergara-Castro M, Jara-Quezada J, et al. Interactive 360° video to: Polyphenolic extracts of walnut (Juglans regia) green husk containing juglone inhibit the growth of HL-60 cells and induce apoptosis. Electron J Biotechnol 2022;57. https://doi.org/10.1016/j.ejbt.2022.04.002.

Background: Juglone is a naphthoquinone currently obtained by chemical synthesis with biological activities including antitumor activity. Additionally, juglone is present in the green husk of walnut, which suggests evaluating the effect of GH extracts on carcinogenic cell lines. Results: Walnut green husk ethanolic extract was obtained as 169.1 mg juglone/100 g Green Husk and antioxidant activity (ORAC) of 44,920 μmol Trolox Equivalent/100 g DW Green Husk. At 1 μM juglone in HL-60 cell culture, green husk extract showed an antiproliferative effect, but pure juglone did not; under these conditions, normal fibroblast cells were not affected. A dose-dependent effect on mitochondrial membrane potential loss was observed. Apoptosis of HL-60 was detected at 10 μM juglone. Despite high ORAC values, neither purified juglone nor the extract showed protective effects on HL-60 cells under oxidative conditions. Conclusions: Green husk extract generates an antiproliferative effect in HL-60 cells, which is related to an induction of the early stages of apoptosis and a loss of mitochondrial membrane potential. The normal cells were not affected when juglone is present at concentrations of 1 μM, while at higher concentrations, there is loss of viability of both cancerous and healthy cells.How to cite: Soto-Maldonado C, Vergara-Castro M, Jara-Quezada J, et al. Polyphenolic extracts of walnut (Juglans regia) green husk containing juglone inhibit the growth of HL-60 cells and induce apoptosis. Electron J Biotechnol 2019;39. https://doi.org/10.1016/j.ejbt.2019.02.001. Keywords: walnut husk discards, solvent extraction, antioxidant activity, mammalian cells, leukemia cells line inhibition, Polyphenolic extracts, Juglans regia, green husk, juglone, HL-60 cells, apoptosis

Currently installed wastewater treatment systems in many developing countries are unsustainable, failing in either the social, economic or ecological dimension of sustainability. Nexus research looking at resources involved in wastewater treatment could support the transition towards more sustainable systems. Nexus thinking aims to overcome bio-physical systems thinking by including transdisciplinary research methods. Approaches for integrating results from different types of analysis and disciplinary backgrounds are scarce and have not been described extensively in nexus research. Transdisciplinary research suggests creating system, target and transformation knowledge as a common framework to describe meaningful transformations. Our goal is to show how a better understanding of the level of knowledge created by different types of analysis can pave the way towards integrating results for sustainability. In this article, three types of analysis, namely sustainability assessment, stakeholder perspective analysis and wickedness analysis, were applied in two pilot case wastewater treatment systems in Latin America. Through a three-step process, generated knowledge was assessed for each type of analysis individually while also highlighting synergies between them. The results demonstrate that structuring results by generated knowledge type can help combining outcomes in a meaningful manner. The findings show that technical flaws are present and fixable, and that issues relating to behaviours or values are more challenging to address but arguably more meaningful for systemic change.

Salmonella enterica subsp. enterica serovar Bovismorbificans has caused multiple outbreaks involving the consumption of produce, hummus, and processed meat products worldwide. To elucidate the intra-serovar genomic structure of S. Bovismorbificans, a core-genome analysis with 2690 loci (based on 150 complete genomes representing Salmonella enterica serovars developed as part of this study) and a k-mer-binning based strategy were carried out on 95 whole genome sequencing (WGS) assemblies from Swiss, Canadian, and USA collections of S. Bovismorbificans strains from foodborne infections. Data mining of a digital DNA tiling array of legacy SARA and SARB strains was conducted to identify near-neighbors of S. Bovismorbificans. The core genome analysis and the k-mer-binning methods identified two polyphyletic clusters, each with emerging evolutionary properties. Four STs (2640, 142, 1499, and 377), which constituted the majority of the publicly available WGS datasets from >260 strains analyzed by k-mer-binning based strategy, contained a conserved core genome backbone with a different evolutionary lineage as compared to strains comprising the other cluster (ST150). In addition, the assortment of genotypic features contributing to pathogenesis and persistence, such as antimicrobial resistance, prophage, plasmid, and virulence factor genes, were assessed to understand the emerging characteristics of this serovar that are relevant clinically and for food safety concerns. The phylogenomic profiling of polyphyletic S. Bovismorbificans in this study corresponds to intra-serovar variations observed in S. Napoli and S. Newport serovars using similar high-resolution genomic profiling approaches and contributes to the understanding of the evolution and sequence divergence of foodborne Salmonellae. These intra-serovar differences may have to be thoroughly understood for the accurate classification of foodborne Salmonella strains needed for the uniform development of future food safety mitigation strategies.

This study analyzes different factors that affect the success of artificial insemination (AI) of cows of small farmers inserted in a program of productive and genetic improvement in one region in Chile. The success of AI was modeled as a function of different biological, environmental and social factors recorded by the program, using logistic regression. The outcome for this model was the gestational status of the inseminated cow, diagnosed by ultrasound as non-pregnant or pregnant. Predictors of interest were: smallholder's gender, province where the smallholder was located, smallholder's number of cows, inseminator's years of experience, insemination type (estrus detected or at fixed time), cow's age in years, cow's body condition, cow's ordinal number of births, cow's biotype (dairy or beef) and bull's biotype (dairy or beef). All predictors were evaluated for unconditional associations with the outcome (gestational status). When analyzing the results, the province, the number of cows the owner had, the experience of inseminators and the type of insemination were associated with the success of pregnancy. It is important to stimulate the implementation of these types of programs to help contribute to the improvement of the livelihood of small farmers who depend on low-input systems. Highlights Program of Productive and Genetic Improvement of the Cattle of the O'Higgins Region in Central Chile Artificial insemination success modeled as a function of different biological, environmental, and social factors recorded by the program using logistic regression The model output was the gestational status of the inseminated cows as diagnosed by ultrasound. All predictors were evaluated for unconditional associations with the outcome. The province, the number of cows in the herd, the experience of the inseminators, and the type of insemination were associated with the success of the pregnancy.

Cisplatin remains an indispensable drug for the systemic treatment of many solid tumors. However, a major dose-limiting side-effect is ototoxicity. In some scenarios, such as treatment of germ cell tumors or adjuvant therapy of non-small cell lung cancer, cisplatin cannot be replaced without undue loss of efficacy. Inhibition of polyadenosine diphosphate-ribose polymerase-1 (PARP1), is presently being evaluated as a novel anti-neoplastic principle. Of note, cisplatin-induced PARP1 activation has been related to inner ear cell death. Thus, PARP1 inhibition may exert a protective effect on the inner ear without compromising the antitumor activity of cisplatin. Here, we evaluated PARP1 deficiency and PARP1 pharmacological inhibition as a means to protect the auditory hair cells from cisplatin-mediated ototoxicity. We demonstrate that cisplatin-induced loss of sensory hair cells in the organ of Corti is attenuated in PARP1-deficient cochleae. The PARP inhibitor pirenzepine and its metabolite LS-75 mimicked the protective effect observed in PARP1-deficient cochleae. Moreover, the cytotoxic potential of cisplatin was unchanged by PARP inhibition in two different cancer cell lines. Taken together, the results from our study suggest that the negative side-effects of cisplatin anti-cancer treatment could be alleviated by a PARP inhibition adjunctive therapy.

The exposome encompasses an individual's exposure to exogenous chemicals, as well as endogenous chemicals that are produced or altered in response to external stressors. While the exposome concept has been established for human health, its principles can be extended to include broader ecological issues. The assessment of exposure is tightly interlinked with hazard assessment. Here, we explore if mechanistic understanding of the causal links between exposure and adverse effects on human health and the environment can be improved by integrating the exposome approach with the adverse outcome pathway (AOP) concept that structures and organizes the sequence of biological events from an initial molecular interaction of a chemical with a biological target to an adverse outcome. Complementing exposome research with the AOP concept may facilitate a mechanistic understanding of stress-induced adverse effects, examine the relative contributions from various components of the exposome, determine the primary risk drivers in complex mixtures, and promote an integrative assessment of chemical risks for both human and environmental health. Keywords: Exposome, AOP, Systems toxicology, Systems biology, Systems chemistry, Risk assessment

In the biopharmaceutical sector, Chinese hamster ovary (CHO) cells have become the host of choice to produce recombinant proteins (r-proteins) due to their capacity for correct protein folding, assembly, and posttranslational modification. However, the production of therapeutic r-proteins in CHO cells is expensive and presents insufficient production yields for certain proteins. Effective culture strategies to increase productivity (qp) include a high glucose concentration in the medium and mild hypothermia (28-34 °C), but these changes lead to a reduced specific growth rate. To study the individual and combined impacts of glucose concentration, specific growth rate and mild hypothermia on culture performance and cell metabolism, we analyzed chemostat cultures of recombinant human tissue plasminogen activator (rh-tPA)-producing CHO cell lines fed with three glucose concentrations in feeding media (20, 30 and 40 mM), at two dilution rates (0.01 and 0.018 1/h) and two temperatures (33 and 37 °C). The results indicated significant changes in cell growth, cell cycle distribution, metabolism, and rh-tPA productivity in response to the varying environmental culture conditions. High glucose feed led to constrained cell growth, increased specific rh-tPA productivity and a higher number of cells in the G2/M phase. Low specific growth rate and temperature (33 °C) reduced glucose consumption and lactate production rates. Our findings indicated that a reduced specific growth rate coupled with high feed glucose significantly improves r-protein productivity in CHO cells. We also observed that low temperature significantly reduced qp, but not cell growth when dilution rate was manipulated, regardless of the glucose concentration or dilution rate. In contrast, we determined that feed glucose concentration and consumption rate were the dominant aspects of the growth and productivity in CHO cells by using multivariate analysis.

This case report discusses continuous epidural administration of ropivacaine 0.56 mg kg−1 h −1 for 8 days in a 7-year-old trauma patient to prevent pain, after performing a lower right and upper left leg guillotine amputation. Venous sampling after 8 days revealed bound and unbound ropivacaine concentrations of 1.1 mg/l and 0.06 mg/l in plasma, respectively. Arterial sampling for bound and unbound ropivacaine was 1.2 mg/l and 0.05 mg/l in plasma, respectively. In this case report, long-term high dose epidural infiltration of ropivacaine did not result in severe side effects or complications. Further studies are needed to explore safety of these concentrations in larger populations of children.

This study investigates the Water Footprint (WF) resulting from the agricultural imports of the European Union (EU-28). Import trade statistics were compiled and linked with crop- and country-specific water consumption data and water scarcity factors. Within the study, the virtual water imports of 104 agricultural commodities for the baseline year 2015 were assessed and product and country hotspots were evaluated. It was shown that (a) Europe imported 100 million tons of agricultural goods and 11 km3 of associated virtual irrigation water; (b) the highest impacts of water consumption do not necessarily result from high import amounts, but from water-intensive goods produced in water scarce countries; (c) the largest external EU-28 water footprint occurred due to the product categories cotton, nuts and rice; and (d) the highest share of the EU external water footprint took place in the United States (US), Pakistan, Turkey, Egypt and India.

The complex tissue remodeling process of menstruation is experienced by humans and some primates, whereas most placental mammals, including mice, go through an estrous cycle. How menstruation and the underlying mechanisms evolved is still unknown. Here we demonstrate that the process of menstruation is not just species-specific but also depends on factors which can be induced experimentally. In intact female mice endogenous progesterone levels were raised by the induction of pseudopregnancy. Following an intrauterine oil injection, the decidualization of the endometrium was reliably induced as a prerequisite for menstruation. The natural drop of endogenous progesterone led to spontaneous breakdown of endometrial tissue within an average of 3 days post induction of decidualization. Interestingly, morphological changes such as breakdown and repair of the endometrial layer occurred in parallel in the same uterine horn. Most importantly, endometrial breakdown was accompanied by vaginally visible (overt) bleeding and flushing out of shed tissue comparable to human menstruation. Real-time PCR data clearly showed temporal changes in the expression of multiple factors participating in inflammation, angiogenesis, tissue modulation, proliferation, and apoptosis, as has been described for human menstruating endometrium. In conclusion, human menstruation can be mimicked in terms of extravaginally visible bleeding, tissue remodeling, and gene regulation in naturally non-menstruating species such as intact female mice without the need for an exogenous hormone supply.