Evaluating the potential of non-immunosuppressive cyclosporin analogs for targeting Toxoplasma gondii cyclophilin: Insights from structural studies.

Toxoplasmosis persists as a prevalent disease, facing challenges from parasite resistance and treatment side effects. Consequently, identifying new drugs by exploring novel protein targets is essential for effective intervention. Cyclosporin A (CsA) possesses antiparasitic activity against Toxoplasma gondii, with cyclophilins identified as possible targets. However, CsA immunosuppressive nature hinders its use as an antitoxoplasmosis agent. Here, we evaluate the potential of three CsA derivatives devoid of immunosuppressive activity, namely, NIM811, Alisporivir, and dihydrocyclosporin A to target a previously characterized cyclophilin from Toxoplasma gondii (TgCyp23). We determined the X-ray crystal structures of TgCyp23 in complex with the three analogs and elucidated their binding and inhibitory properties. The high resolution of the structures revealed the precise positioning of ligands within the TgCyp23 binding site and the details of protein-ligand interactions. A comparison with the established ternary structure involving calcineurin indicates that substitutions at position 4 in CsA derivatives prevent calcineurin binding. This finding provides a molecular explanation for why CsA analogs can target Toxoplasma cyclophilins without compromising the human immune response.

Maternal and Perinatal Outcomes in Pregnant Women with Heart Disease: A Case-Control Study.

Objective: We analyzed the obstetric and cardiac characteristics and results of pregnant women with heart disease (HD) and compared their results with those of healthy controls. Methods: In this retrospective single-center case-control study, women with HD attended between 2010 and 2018 were matched at a 1:2 ratio (according to date of delivery, parity, and singleton or twin pregnancy) with controls without heart disease treated in the same referral center. Results: We identified 141 pregnant women with HD, of whom 132 reached 22 weeks of gestation and were paired with 264 healthy controls, for a total of 396 participants and 408 newborns. Most common HDs were congenital HD (53 women), arrhythmia (46), valvular HD (35), and cardiomyopathy (16), having women with more than one coexisting HD. During pregnancy or the puerperium, 19.9% of mothers experienced a major adverse cardiac event (MACE), with 5% requiring intensive care unit (ICU) admission. The rates of cesarean section were 37.1% in the case group and 18.2% in the control group, with an odds ratio (OR) of 2.66 (95% CI = 1.66-4.26, p < 0.001). We also found a higher use of general anesthesia, with an OR of 10.73 (95% CI = 2.32-49.75, p = 0.002); more prolonged hospitalizations, with an OR of 2.91 (95% CI 1.02-8.35, p = 0.023); and a higher incidence of low neonatal weight, with an OR of 1.96 (95% CI 1.09-3.52, p = 0.012). There were no differences between groups in terms of gestational age at delivery; however, we observed greater prematurity in women with HD, without reaching statistical significance. The rate of congenital heart disease among the newborns of mothers with HD was 13.2%. Conclusions: HD increases maternal morbidity during pregnancy and it is associated with higher rates of cesarean section and low birth weight.

A congenital periocular leiomyosarcoma in a dairy calf.

A mass was removed surgically from the right orbit of a 1-d-old Holstein calf. Grossly, the mass filled the rostral part of an enlarged orbit and compressed the globe toward the caudal pole of the orbit. The brown, 6-cm tumor had central yellow and brown areas, and a smooth, glistening cut surface. Microscopically, the neoplasm was highly cellular and composed of spindle cells arranged in irregular, broad, interlacing streams and bundles, forming a herringbone pattern and supported by a sparse collagenous matrix. Neoplastic cells infiltrated surrounding soft tissues and compressed the globe. The neoplastic cells had positive immunolabeling for α-smooth muscle actin, desmin, and vimentin, and negative immunolabeling for factor VIII, myoglobin, cytokeratin, and skeletal muscle actin. Histopathology and immunohistochemistry results confirmed a diagnosis of leiomyosarcoma. To our knowledge, congenital periocular leiomyosarcoma has not been reported in cattle previously. This rare tumor could be included as a differential diagnosis in newborn calves with periocular masses.

Sleep actigraphy results and HIV health outcomes in an urban HIV clinic sample.

Sleep disorders are prevalent and interfering conditions that affect people living with HIV (PLWH) at higher rates than the general population. Lower quality sleep has been associated with poorer health-related quality of life and immune function in PWH, though sleep is typically assessed subjectively. The current study aimed to examine the association between objective sleep/wake patterns measured via actigraphy with HIV outcomes. Participants (N = 87) were recruited from a public, urban HIV clinic located in the Southeastern United States. Participants were instructed to wear actigraphy monitors for one week (Range: 5-8 days). Log viral load and absolute CD4 were obtained via medical chart review. Linear regression analyses predicting HIV RNA Viral Load (log transformed) and CD4 Count were employed with three actigraphy sleep variables: sleep efficiency, wake after sleep onset (WASO), and sleep quantity. Backward entry regression with both significant actigraphy predictors, sleep efficiency and WASO, included as predictors resulted in sleep efficiency remaining in the model and WASO being removed. Separate models revealed that each one-unit increase in sleep efficiency was associated with a b = 0.032-point decrease in the log-transformed HIV RNA viral load (p = 0.03) and for each one-unit increase in wake after sleep onset (WASO) was associated with a b = 0.35-point increase in the log-transformed HIV RNA viral load (p = 0.04). Sleep quantity, however, was not, and none were associated with absolute CD4 count. The findings add to the evidence for an association of objectively measured poorer sleep efficiency being associated with higher HIV RNA viral load. Implications for clinical practice include assessing and addressing sleep efficiency as part of comprehensive clinical HIV care.

RAPIDASH: Tag-free enrichment of ribosome-associated proteins reveals composition dynamics in embryonic tissue, cancer cells, and macrophages.

Ribosomes are emerging as direct regulators of gene expression, with ribosome-associated proteins (RAPs) allowing ribosomes to modulate translation. Nevertheless, a lack of technologies to enrich RAPs across sample types has prevented systematic analysis of RAP identities, dynamics, and functions. We have developed a label-free methodology called RAPIDASH to enrich ribosomes and RAPs from any sample. We applied RAPIDASH to mouse embryonic tissues and identified hundreds of potential RAPs, including Dhx30 and Llph, two forebrain RAPs important for neurodevelopment. We identified a critical role of LLPH in neural development linked to the translation of genes with long coding sequences. In addition, we showed that RAPIDASH can identify ribosome changes in cancer cells. Finally, we characterized ribosome composition remodeling during immune cell activation and observed extensive changes post-stimulation. RAPIDASH has therefore enabled the discovery of RAPs in multiple cell types, tissues, and stimuli and is adaptable to characterize ribosome remodeling in several contexts.

Adherence to the EAT-Lancet index is associated with lower diet costs in the Mexican population.

BACKGROUND: Poor diet quality contributes to morbidity and mortality and affects environmental sustainability. The EAT-Lancet reference diet offers a healthy and sustainable solution. This study aimed to estimate the association between diet cost and dietary quality, measured with an EAT-Lancet Index. METHODS: An EAT-Lancet index was adapted to assess adherence to this dietary pattern from 24-h recalls data from the 2012 and 2016 Mexican National Health and Nutrition Surveys (n = 14,242). Prices were obtained from the Consumer Price Index. We dichotomized cost at the median (into low- and high-cost) and compared the EAT-Lancet index scores. We also used multivariate linear regression models to explore the association between diet cost and diet quality. RESULTS: Individuals consuming a low-cost diet had a higher EAT-Lancet score than those consuming a high-cost diet (20.3 vs. 19.4 from a possible scale of 0 to 42; p < 0.001) due to a lower intake of beef and lamb, pork, poultry, dairy, and added sugars. We found that for each one-point increase in the EAT-Lancet score, there was an average decrease of MXN$0.4 in the diet cost (p < 0.001). This association was only significant among low- and middle-SES individuals. CONCLUSIONS: Contrary to evidence from high-income countries, this study shows that in Mexico, adhering to the EAT-Lancet reference diet is associated with lower dietar costs, particularly in lower SES groups. These findings suggest the potential for broader implementation of healthier diets without increasing the financial burden.

Factors affecting rAAV titers during triple-plasmid transient transfection in HEK-293 cells.

The efficiency of triple-plasmid transfection in recombinant Adeno-Associated Virus (rAAV) production was analyzed by examining two distinct HEK-293 cells lines. These were categorized as high producer (HP) and low producer (LP) based on their differing levels of productivity under identical conditions. Analysis of RNA expression levels of viral genes revealed disparities in plasmid derived gene expression between the cell lines. Further assessment of transfection efficiency utilizing labeled plasmids revealed lower plasmid uptake and less efficient nuclear transport in LP cell line. Additionally, we observed inferior translation activity in LP, contributing to its shortcomings in overall productivity. In our attempt to optimize plasmid ratios to enhance fully packaged rAAV particle yield, we discovered cell-line-specific optimization potential. The findings highlight the transfection's complexity, urging tailored strategies for improved rAAV production based on each cell line's characteristics, enhancing understanding and guiding further efficiency optimization in rAAV production.

Topology-aware scalable resource management in multi-hop dense networks.

The current society is becoming increasingly interconnected and hyper-connected. Communication networks are advancing, as well as logistics networks, or even networks for the transportation and distribution of natural resources. One of the key benefits of the evolution of these networks is to bring consumers closer to the source of a resource or service. However, this is not a straightforward task, particularly since networks near final users are usually shaped by heterogeneous nodes, sometimes even in very dense scenarios, which may demand or offer a resource at any given moment. In this paper, we present DEN2NE, a novel algorithm designed for the automatic distribution and reallocation of resources in distributed environments. The algorithm has been implemented with six different criteria in order to adapt it to the specific use case under consideration. The results obtained from DEN2DE are promising, owing to its adaptability and its average execution time, which follows a linear distribution in relation to the topology size.

Exercise and tumor proteome: Insights from a neuroblastoma model.

BACKGROUND/AIM: The impact of exercise on pediatric tumor biology is essentially unknown. We investigated the effects of regular exercise on tumor proteome profile (as assessed with liquid chromatography with tandem mass spectrometry) in a mouse model of one of the most aggressive childhood malignancies, high-risk neuroblastoma (HR-NB). METHODS: Tumor samples of 14 male mice (aged 6-8 weeks) that were randomly allocated into an exercise (5-week combined aerobic and resistance training) or nonexercise control group (6 and 8 mice per group, respectively) were analyzed. The Search Tool for the Retrieval of Interacting Genes/Proteins database was used to generate a protein-protein interaction (PPI) network and enrichment analyses. The Systems Biology Triangle (SBT) algorithm was applied for analyses at the functional category level. RESULTS: Tumors of exercised mice showed a higher and lower abundance of 101 and 150 proteins, respectively, compared to controls [false discovery rate (FDR)<0.05], which were enriched in metabolic pathways, aminoacid metabolism, regulation of hormone levels, and peroxisome proliferator-activated receptor signaling pathway (FDR<0.05). The SBT algorithm indicated that 184 and 126 categories showed a lower and higher abundance, respectively, in the tumors of exercised mice (FDR<0.01). Categories with lower abundance were involved in energy production while those with higher abundance were related to transcription/translation, apoptosis, and tumor suppression. CONCLUSION: Regular exercise altered the abundance of hundreds of intratumoral proteins and molecular pathways, particularly those involved in energy metabolism, apoptosis, and tumor suppression. These findings provide preliminary evidence of the molecular mechanisms underlying potential effects of exercise in HR-NB.

Epigenetic profiles in blood and adipose tissue: identifying strong correlations in morbidly obese and non-obese patients.

Epigenetic alterations play a pivotal role in conditions influenced by environmental factors such as overweight and obesity. Many of these changes are tissue-specific, which entails a problem in its study since obtaining human tissue is a complex and invasive practice. While blood is widely used as a surrogate biomarker, it cannot directly extrapolate the evidence found in blood to tissue. Moreover, the intricacies of metabolic diseases add a new layer of complexity, as obesity leads to significant alterations in adipose tissue, potentially causing associated pathologies that can disrupt existing correlations seen in healthy individuals. Here, our objective was to determine which epigenetic markers exhibit correlations between blood and adipose tissue, regardless of the metabolic status. We collected paired blood and adipose tissue samples from 64 patients with morbidity obesity and non-obese and employed the MethylationEPIC 850 K array for analysis. We found that only a small fraction, specifically 4.3% (corresponding to 34,825 CpG sites), of the sites showed statistically significant correlations (R ≥ 0.6) between blood and adipose tissue. Within this subset, 5327 CpG sites exhibited a strong correlation (R ≥ 0.8) between blood and adipose tissue. Our findings suggest that the majority of epigenetic markers in peripheral blood do not reliably reflect changes occurring in visceral adipose tissues. However, it is important to note that there exists a distinct set of epigenetic markers that can indeed mirror changes in adipose tissue within blood samples. KEY MESSAGES: More than 8% of methylation sites exhibit similarity between blood and adipose tissues, regardless of BMI The correlation percentage between blood and adipose tissue is strongly influenced by gender The principal genes implicated in this correlation are related to metabolism or the immunological system.

Redox cell signalling triggered by black carbon and/or radiofrequency electromagnetic fields: Influence on cell death.

The capacity of environmental pollutants to generate oxidative stress is known to affect the development and progression of chronic diseases. This scientific review identifies previously published experimental studies using preclinical models of exposure to environmental stress agents, such as black carbon and/or RF-EMF, which produce cellular oxidative damage and can lead to different types of cell death. We summarize in vivo and in vitro studies, which are grouped according to the mechanisms and pathways of redox activation triggered by exposure to BC and/or EMF and leading to apoptosis, necrosis, necroptosis, pyroptosis, autophagy, ferroptosis and cuproptosis. The possible mechanisms are considered in relation to the organ, cell type and cellular-subcellular interaction with the oxidative toxicity caused by BC and/or EMF at the molecular level. The actions of these environmental pollutants, which affect everyday life, are considered separately and together in experimental preclinical models. However, for overall interpretation of the data, toxicological studies must first be conducted in humans, to enable possible risks to human health to be established in relation to the progression of chronic diseases. Further actions should take pollution levels into account, focusing on the most vulnerable populations and future generations.

Unraveling the ecological niche signals of Verticillium dahliae: Insights from Mediterranean landscapes.

Verticillium wilt (VW), caused by the soil-borne plant pathogenic fungus Verticillium dahliae, is a major disease impacting olive crops globally. In view of the lack of effective post-infection treatments, exclusion and avoidance strategies are essential in disease management. Assessing the risks posed by this pathogen is essential to prevent the spread and to ensure selection of suitable sites for new plantations. This study aimed to elucidate the environmental factors driving V. dahliae establishment in the Andalusia region, in southern Spain, an emblematic Mediterranean landscape for olive cultivation. To this end, we explored ecological niche signals for this fungal pathogen by analyzing 62 environmental variables across 1.6 million hectares dedicated to olive and cotton cultivation, using a 15-yr survey data on VW incidence on presence-absence from both olive and cotton fields. To ensure robust identification of ecological niche signals, we employed randomization-based, non-parametric univariate tests to compare presence records with the broader sampling universe (including absence records). Our findings identified key environmental variables that are associated significantly with V. dahliae presence, including temperature range seasonality (including mean diurnal and annual ranges), summer temperature (maximum of the warmest month, mean of the warmest quarter), and moisture and water availability (near-surface humidity, potential evapotranspiration, vapor pressure) as core niche variables for V. dahliae. Our results replicated the pathogen's known distribution, identifying the Guadalquivir Valley as a particularly high-risk area in view of its mild winters and distinct rainy seasons, providing new insights into the specific environmental conditions that facilitate the pathogen's survival and spread. Furthermore, this study introduces a novel approach to niche modeling that prioritizes variables with consistent effects and significant impact on the presence and distribution of V. dahliae and identifies potential data artifacts. This approach enhances our understanding of ecological requirements in V. dahliae and informs targeted management strategies.

Norovirus outbreaks in a nursery school in Buenos Aires, Argentina.

Norovirus (NoV) is the leading cause of outbreaks of acute gastroenteritis worldwide. These are non-enveloped viruses that are classified into 10 genogroups, of which genogroup I (GI), II (GII), IV (GIV), VIII (GVIII), and IX (GIX) are the ones that infect humans. Two outbreaks (A and B) of acute gastroenteritis that occurred in a nursery school are described. The first outbreak (A) occurred in November 2018, and the second (B) in February 2020. The detection of viral and bacterial pathogens was performed to study both outbreaks. Additionally, an epidemiological investigation of the outbreaks was conducted. In the analyzed fecal and vomit samples from both children and adults in the nursery school, NoV GII.4 [P16] Sydney 2012 and NoV GI.3 [P13] were detected in outbreaks A and B, respectively. Since the study of acute gastroenteritis outbreaks is underestimated in Argentina, it is necessary to design prevention, study, and control protocols, as well as to improve the outbreak notification system in our country.

No impact of HIV coinfection on the mortality in patients with hepatitis C virus infection after sustained virological response.

BACKGROUND: In patients with hepatitis C virus (HCV) chronic infection and advanced liver disease, the impact of human immunodeficiency virus (HIV) coinfection on the clinical outcome after sustained virological response (SVR) has not been sufficiently clarified. The aim of this study was to compare the mortality after SVR of patients bearing HCV chronic infection and advanced liver fibrosis, with and without HIV-coinfection after a prolonged follow-up. METHODS: This was a prospective multicenter cohort study including individuals with HIV/HCV-coinfection and patients with HCV-monoinfection from Spain, fulfilling: 1) Liver stiffness (LS) ≥9.5 kPa before treatment; 2) SVR with a direct-acting antiviral (DAA) based regimen; 3) LS measurement available at SVR. The main outcome was overall survival. Mortality attributable to liver disease and non-hepatic causes was also assessed. RESULTS: 1,118 patients were included, of whom 676 (60.5%) were living with HIV. The median (Q1-Q3) follow-up was 76 months (57-83). After SVR, 46 (10%) HCV-monoinfected and 74 (11%) HIV/HCV-coinfected patients died. The overall mortality rate (95% CI) was 1.9 (1.6-2.2) per 100 person-years, 1.9 (1.4-2.5) per 100 person-years in patients with HCV-monoinfection and 1.8 (1.6-2.3) per 100 person-years in people living with HIV. In the multivariable analysis, HIV-coinfection was not associated with a shorter survival [0.98 HR (95% confidence interval, CI) = (0.61-1.58), p=0.939]. CONCLUSIONS: In patients with HCV chronic infection and advanced fibrosis, HIV-coinfection does not reduce the overall survival after SVR.

Differential functional role of Orai1 variants in constitutive Ca2+ entry and calcification in luminal breast cancer cells.

Resting cytosolic Ca2+ concentration is tightly regulated to fine-tune Ca2+-dependent cellular functions. Luminal breast cancer cells exhibit constitutive Ca2+ entry mediated by Orai1 and the secretory pathway Ca2+-ATPase, SPCA2, which result in mammary microcalcifications that constitute a prognostic marker of mammary lesions. Two Orai1 isoforms have been identified, the full-length Orai1α, consisting of 301 amino acids, and the short variant, Orai1ß, lacking the 63 or 70 N-terminal amino acids comprising residues involved in channel inactivation and binding sites with Orai1 partners. We show that only the mammalian-specific Orai1α rescues SPCA2-dependent constitutive Ca2+ entry in Orai1-knockout MCF7 cells, a widely used luminal breast cancer cell line. FRET analysis and immunoprecipitation revealed that Orai1α shows a greater ability to interact with SPCA2 than Orai1ß. Deletion of the first 38 amino acids in Orai1α reduced the interaction with SPCA2 to a similar extent as Orai1ß, thus suggesting that the N-terminal 38 amino acids play a relevant role in Orai1α-SPCA2 interaction. Finally, Orai1α, but not Orai1ß, rescue the ability of Orai1-deficient cells to form in vitro microcalcifications. These findings provide compelling evidence for a functional role of Orai1α in constitutive Ca2+ entry in MCF7 cells, which might be a target to prevent the development of mammary microcalcifications in luminal breast cancer.

Timing of coronary artery bypass grafting after myocardial infarction influences late survival.

Objectives: The role of timing of coronary artery bypass grafting after acute myocardial infarction on early and late outcomes remains uncertain. Methods: We reviewed 1631 consecutive adult patients who underwent isolated coronary artery bypass grafting with information on timing of acute myocardial infarction. Early and late mortality were compared between patients receiving coronary artery bypass grafting within 24 hours after acute myocardial infarction, between 1 and 7 days after acute myocardial infarction, and more than 7 days after acute myocardial infarction. Sensitivity analyses were performed in subgroups of patients with ST-segment elevation myocardial infarction or non-ST-segment elevation myocardial infarction, and other high-risk groups. Results: A total of 124 patients (5.7%) underwent coronary artery bypass grafting within 24 hours, 972 patients (51.2%) received coronary artery bypass grafting between 1 and 7 days after acute myocardial infarction, and 535 patients (43.2%) underwent coronary artery bypass grafting more than 7 days after acute myocardial infarction. Overall operative mortality was 2.7% with comparable adjusted early mortality among 3 groups. Over a median follow-up of 13.5 years (interquartile range, 8.9-17.1), compared with patients receiving coronary artery bypass grafting between 1 and 7 days after acute myocardial infarction, those receiving coronary artery bypass grafting at 7 days had greater adjusted risk for late overall mortality (hazard ratio, 1.39, 95% CI, 1.16-1.67; P < .001), whereas those receiving coronary artery bypass grafting within 24 hours had comparable risk of late overall mortality (hazard ratio, 1.12, 95% CI, 0.86-1.47; P = .39). Timing of coronary artery bypass grafting was associated with late mortality in patients with non-ST-segment elevation myocardial infarction (patients receiving coronary artery bypass grafting at >7 days had a higher risk of late mortality [hazard ratio, 1.38, 95% CI, 1.14-1.67, P < .001] compared with those receiving coronary artery bypass grafting between 1 and 7 days), but not in patients with ST-segment elevation myocardial infarction. Conclusions: Early revascularization through coronary artery bypass grafting within 7 days during the same hospitalization appears beneficial, especially for patients presenting with non-ST-segment elevation myocardial infarction.

Pest categorisation of non-EU Scolytinae on non-coniferous hosts.

The EFSA Panel on Plant Health performed a group pest categorisation for the EU territory of non-EU Scolytinae (Coleoptera: Curculionidae) on non-coniferous hosts, which total 6495 known species. Most species attack apparently healthy, weakened or dead trees, either feeding on the phloem ('bark beetles' subgroup) or on fungi inoculated into the sapwood ('ambrosia beetles' subgroup). Smaller subgroups feed and reproduce in seeds and fruits, or in herbaceous plants. Some species are polygynous, the males initiate a gallery or a chamber on or in a new host and attract females. Others are monogamous, and the females initiate the new galleries. Many species respond to primary volatile attractants emitted by the hosts, and some produce aggregation pheromones that attract conspecifics of both sexes. The species attacking living hosts are often associated with fungi that contribute to weakening the host defences and provide nutrients to the insects. Some are inbreeding; the males in the offspring mate with their sisters and rarely leave their natal tree. The larvae of all species develop and pupate within their hosts. Based on catalogues and other published data, a database was constructed providing information on hosts, feeding and reproductive habits, geographic distribution and the Köppen-Geiger climate types in countries where species occur. The Scolytinae were screened to exclude species in the following categories: (i) 708 species attacking conifers; (ii) 127 species present in at least four EU Member States and (iii) 440 species occurring in areas with climatic conditions not occurring in the EU. Among the remaining 5220 species, 88 species known for their mobility, occupying at least two landmasses separated by geographical barriers and some of which had impact levels documented in literature, were extracted. They were grouped into four subcategories: (i) 12 species with high impact on plant health; (ii) 16 species with low or doubtful impact; (iii) 48 species with no impact; (iv) 12 species with no impact and which had never been recorded as 'introduced' in the consulted catalogues but occurring on at least two landmasses. All 88 species could enter the EU with wood or wood products, or with plants for planting, and could establish because host plants are available, and climate is suitable in parts of the EU. Control measures to inhibit introduction are available. There is considerable uncertainty regarding the potential impact of many species. Methods for the reliable identification of many species are lacking. For some species of non-EU Scolytinae on non-coniferous hosts, all criteria assessed by EFSA for consideration as potential quarantine pest are met. Nevertheless, the Panel was not able to develop a method to discriminate confidently between species that clearly meet the criteria for potential quarantine pest status and those that do not.

Traumatic bleeding and mortality in mice are intensified by iron deficiency anemia and can be rescued with tranexamic acid.

Background: Clinical evidence suggests that anemia exacerbates traumatic bleeding and worsens outcomes. Objectives: To study the influence of iron deficiency anemia on traumatic bleeding, coagulopathy, and mortality. Methods: C57BL/6J mice received an iron-deficient diet (8 weeks; ±1 mg intraperitoneal iron dextran 2 weeks before trauma). Control mice received a normal diet. Iron deficiency anemia was confirmed by hematocrit, red cell indices, and liver iron. Mice received saline or tranexamic acid (TXA; 10 mg/kg) just before liver laceration. Blood loss, coagulopathy (activated partial thromboplastin time, factor [F]II, FV, FVIII, FX, and fibrinogen), D-dimer, thrombin-antithrombin complexes, and plasmin-alpha-2-antiplasmin complexes were analyzed at 15 and 60 minutes, and a cytokine panel was performed at 60 minutes and 6 hours after trauma. Survival was monitored for 7 days. Results: Compared with nonanemic mice, anemic mice had lower hematocrit and hepatic iron content. Anemic mice experienced higher blood loss compared with nonanemic mice, which was reduced by TXA. Both groups developed traumatic coagulopathy characterized by activated partial thromboplastin time prolongation, thrombin-antithrombin complex formation, and depletion of FV, FVIII, and fibrinogen. TXA corrected the coagulopathy. However, plasmin-alpha-2-antiplasmin complex formation and D-dimers, markers of fibrinolysis, were higher in anemic mice and were not corrected by TXA. Seven-day survival was low in anemic mice, and rescued by TXA, but high in nonanemic mice without additional improvement by TXA. Among cytokines, only interleukin-6 increased, which was prevented by TXA most notably in anemic mice. Conclusion: These observations provide first and critical proof-of-principle evidence that anemia accelerates traumatic bleeding and increases mortality, which could be rescued by anemia correction (parenteral iron) or periprocedural TXA.