Toxicity and Sublethal Effects of Piper hispidinervum Essential Oil on Behavioral and Physiological Responses of Sitophilus zeamais Populations.

This study aimed to evaluate the toxicity of Piper hispidinervum essential oil (PHEO) against 11 Brazilian populations of Sitophilus zeamais (Coleoptera: Curculionidae). The effects of sublethal doses of PHEO on the behavior (walking and flying), respiration, and population growth (ri) of the insect populations were investigated. PHEO toxicity was determined through concentration-mortality bioassays, with mortality curves established using increasing PHEO concentrations ranging from 140.00 to 1000.00 µL kg-1. Behavior was evaluated based on walking distance, walking time, walking speed, walking time proportion, flight height, and flight takeoff success. Respiration was measured via the respiratory rate, while population growth (ri) was assessed through the instantaneous growth rate. All 11 populations of S. zeamais were susceptible to PHEO, showing no signs of resistance. The populations exhibited varying behavioral and physiological responses to sublethal exposure to PHEO, indicating different mitigation strategies. The results confirm that PHEO possesses insecticidal potential for controlling S. zeamais populations. However, the observed behavioral and physiological responses should be considered when establishing control measures in pest management programs for stored products.

Mortality due to cervical and breast cancer in health regions of Brazil: impact of public policies on cancer care.

OBJECTIVE: This analysis assessed the association between regional income, screening coverage for cervical and breast cancer, and temporal trends in mortality from these cancers in different Brazilian health regions. STUDY DESIGN: Spatiotemporal ecological study across 450 health regions of Brazil. METHODS: Data from 2010 Demographic Census were used to assess income. Variations in income distribution within health regions were measured using the Gini index. Data on screening coverage were obtained from the Ambulatory Information System (SIA/SUS). Mortality was assessed from the Global Burden of Disease Study 2019 data. The average annual percentage change (AAPC) in cervical and breast cancer mortality rates, 2010-2018, was calculated by health regions. Results were presented in regional maps. The associations between income, screening coverage and mortality changes were estimated by bivariate spatial correlation. RESULTS: Health regions located in the South and Southeast regions of Brazil had the greatest percentages of screening coverage and highest per capita incomes with the lowest Gini index values. From 2010 to 2018, mortality rates for cervical cancer were highest in the North and Northeast health regions. Breast cancer mortality rates were highest in the South and Southeast health regions. The AAPC in breast and cervical cancer mortality had a negative association with per capita income and screening coverage, and a positive association with the Gini index. CONCLUSIONS: There are large regional variations in income, screening coverage, and mortality rates for women with breast and cervical cancer. These inequities could be mitigated by policies to address income disparities and improved access to screening.

In Silico Screening of Therapeutic Targets as a Tool to Optimize the Development of Drugs and Nutraceuticals in the Treatment of Diabetes mellitus: A Systematic Review.

The Target-Based Virtual Screening approach is widely employed in drug development, with docking or molecular dynamics techniques commonly utilized for this purpose. This systematic review (SR) aimed to identify in silico therapeutic targets for treating Diabetes mellitus (DM) and answer the question: What therapeutic targets have been used in in silico analyses for the treatment of DM? The SR was developed following the guidelines of the Preferred Reporting Items Checklist for Systematic Review and Meta-Analysis, in accordance with the protocol registered in PROSPERO (CRD42022353808). Studies that met the PECo strategy (Problem, Exposure, Context) were included using the following databases: Medline (PubMed), Web of Science, Scopus, Embase, ScienceDirect, and Virtual Health Library. A total of 20 articles were included, which not only identified therapeutic targets in silico but also conducted in vivo analyses to validate the obtained results. The therapeutic targets most frequently indicated in in silico studies were GLUT4, DPP-IV, and PPARγ. In conclusion, a diversity of targets for the treatment of DM was verified through both in silico and in vivo reassessment. This contributes to the discovery of potential new allies for the treatment of DM.

Comparison of the recovery profile of sufentanil and remifentanil in total intravenous anesthesia: a systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Remifentanil is a short-acting opioid and can be administered during surgery without the risk of delayed postoperative recovery but concerns about hyperalgesia and the shortages of remifentanil lead anesthetists to consider long-acting opioids for Total Intravenous Anesthesia (TIVA). Sufentanil is a more potent opioid with a longer context-sensitive half-life but can promote good postoperative analgesia due to its residual effect. This meta-analysis aimed to compare the recovery profile of remifentanil and sufentanil for TIVA. METHODS: The search strategy was performed in PubMed, CENTRAL, and Web of Science for RCTs comparing sufentanil and remifentanil as part of TIVA in adults undergoing noncardiac surgery. Risk of bias and the quality of evidence were performed using RoB2 and GRADEpro, respectively. The primary outcome was time to tracheal extubation. Secondary analyses included postoperative analgesia, respiratory depression, and Postoperative Nausea and Vomiting (PONV). RESULTS: Sufentanil increases the time to extubate, MD = 4.29 min; 95% CI: 2.33 to 6.26; p = 0.001. It also reduces the need for postoperative rescue analgesia, logOR = -1.07; 95% CI: -1.62 to -0.52; p = 0.005. There were no significant differences between both opioids for PONV, logOR = 0.50; 95% CI: -0.10 to 1.10; p = 0.10 and respiratory depression, logOR = 1.21; 95% CI: -0.42 to 2.84; p = 0.15. CONCLUSION: Sufentanil delays the time to tracheal extubation compared with remifentanil but is associated with a reduced need for postoperative rescue analgesia. No significant differences were observed between the two opioids in terms of postoperative respiratory depression or PONV.

Feeding Behavior, Water Intake, and Physiological Parameters of Feedlot Lambs Fed with Diets Containing Babassu Oil Associated with Sunflower Oil Blend.

This study aimed to investigate the impact of dietary inclusion of babassu oil (BO) associated with sunflower oil (SO) on feeding behavior, water intake, and physiological parameters of feedlot lambs. Thirty-five castrated male lambs (16.6 kg ± 3.9 kg) were distributed in a randomized block design with 5 treatments (diets) and 7 replications. The tested diets were oil-free diet (OF), 45 g/kg BO (BO), 30 g/kg BO with an additional 15 g/kg SO (1.5 SO), 22.5 g/kg BO with an additional 22.5 g/kg SO (2.25 SO), and 30 g/kg SO with an additional 15 g/kg BO (3.0 SO) on dry matter (DM) basis. The experimental period lasted 60 days. Animals that received BO diet and the combination of BO with SO had lower intakes of DM and neutral detergent fiber (NDF) compared to the control diet (P < 0.05). Differences on the respiratory rate (RR) was observed between animals in the control diet and those in the diets containing SO (P=0.001), with a linear increase in RR as the levels of SO in the diets increased (P=0.004). All physiological parameters showed a time effect (P < 0.05). Animals fed with the control diet had higher water intake via drinking fountain (P=0.030) and total water intake (P=0.029) compared to animals fed with diets containing SO. In relation to SO levels, water intake via drinking fountain (P=0.002), total water intake (P=0.002), and total water intake per kg of DM ingested (P=0.001) linearly increased with the levels increase in the composition of the diets. The tested diets did not alter the feeding behavior of the feedlot lambs. However, the combination of BO with different levels of SO reduced DM and water intake via drinking fountain and RR.

Sulfur fractionation using high-resolution continuum source molecular absorption spectrometry with calcium and hydrophobic palladium nanoparticles as chemical modifiers.

The unprecedented use of high-resolution continuum source molecular absorption spectrometry (HR-CS MAS) for the fractionation of organic and inorganic sulfur (S) species through monitoring the CS molecule is presented here. Two separate methods for determining organic (CSorg) and inorganic (CSino) sulfur were developed to work sequentially. The optimized temperature program for both methodologies has two pyrolysis steps and one vaporization step (1st Tpyr: 1800 and 2ndTpyr: 800 °C, and Tvap: 2500 °C). The fractionation was achieved by implementing hydrophobic Pd NPs and Ca as chemical modifiers for the CSorg and CSino methods. Method development was performed by applying different statistical models, allowing the definition of optimal conditions for the chemical modifier mass, and minimizing the S species interconversion, i.e., Doehlert design, and central composite design. The limits of detection (LoD) for CSorg and CSino were 2.4 and 2.1 mg L-1, respectively. Recovery tests evaluated the method's specificity and accuracy; over 92 % recovery was found for both CSorg and CSino. Thus, the proposed methods offer a reliable alternative for fractionating organic and inorganic S by using HR-CS MAS.

Analysis of agreement between specialists for the evaluation of radiological findings of necrotizing enterocolitis.

OBJECTIVE: The analysis of abdominal radiography is essential for the diagnosis and management of necrotizing enterocolitis (NEC) in newborns (NB). Studies, however, show a lack of agreement among physicians in the interpretation of images. This study aims to evaluate the agreement in the radiological interpretation of the NEC between examiners from different specialties (interexaminer analysis) and between the same examiner at different times (intraexaminer analysis). METHODS: Cross-sectional study for concordance analysis using plain radiographs of the abdomen of NB with suspected or confirmed NEC. The study included two neonatologists (Neo), two surgeons (SU), and two radiologists (RD). The participants filled out a form with questions about the radiographic findings; regarding the presence of intestinal loop distension, the specialists answered subjectively (yes or no) and objectively (calculation of the ratio between loop diameter and lumbar vertebrae measurements). Kappa coefficients were calculated for agreement analysis. RESULTS: A total of 90 radiological images were analyzed. For the interexaminer evaluation, the agreement was low (kappa<0.4) in 30 % of the answers (Neo versus SU), 38 % (Neo versus RD), and 46 % (SU versus RD). In the intraexaminer evaluation, the neonatologist and the surgeon presented substantial or almost perfect agreement in 92 % of the answers, and the radiologist in 77 %. In the evaluation of intestinal loop distention, the greatest agreement between the specialties occurred when done objectively. CONCLUSION: The results confirmed the low intra- and interexaminer agreement in the radiological analysis of the NEC, reinforcing the importance of standardizing the methods of radiological interpretation of the disease.

Formulating plant-based hexosomes for the sustained delivery of food proteins.

Hexosomes (HEXs) are nanoparticles formed by dispersing a lipid reverse hexagonal phase in water. Although they have attracted a great interest in the development of delivery systems, few lipids have been employed in their production. Galactolipids, especially monogalactosyldiacylglycerol (MGDG), are the main lipid constituents of plants and can be obtained from vegetal biomass, making them good candidates for the obtention of HEXs. In this work, the aqueous phase behavior of MGDG from sweet potato leaves was investigated and the resulting hexagonal phase was downsized into HEXs with the aid of stabilizer decaglycerol monooleate (DGMO), a food-grade emulsifier from vegetable oils. The nanoparticles presented enhanced long-term colloidal stability in different storage conditions and their inner liquid crystalline structure could be tuned by the amount of DGMO employed. Moreover, by adding sodium oleate (NaO) HEXs displayed enhanced loading efficiency of lysozyme, an edible protein with biological properties. Finally, the sustained release of incorporated protein could be finely tuned by changing HEXs composition. Collectively, the results demonstrate, for the first time, the viability of producing biobased, renewable sourced galactolipid hexosomes with potential applications in the development of functional foods, also contributing to a sustainable management of biomass waste.

From Traditionally Extensive to Sustainably Intensive: A Review on the Path to a Sustainable and Inclusive Beef Farming in Brazil.

Brazil is the second largest beef producer and a leading exporter, contributing to some 3000 t CWE in global markets (27.7% of market share). The sector has experienced substantial development, but yields remain far below potential, and there are growing concerns regarding land use change and greenhouse gas emissions. The need for sustainable technologies, such as sound pasture management and integrated farming systems, is evident, but adoption may be low amongst farmers unable to keep up with technological advances. This article describes the historical developments of Brazilian beef farming towards sustainability and discusses possible socioenvironmental outcomes. We combined an extensive literature review, public data, and our own insights as senior researchers to achieve that. The trajectory shown here evidenced the technological intensification of Brazilian beef farming, with strong support of public policies for decarbonizing agriculture. Nonetheless, the pace of this transition may affect small to medium farmers with limited access to information, technologies, and credit. Our recommendations involve a broad program of technical assistance and training on sustainable technologies, including financial and digital literacy. A novel approach to financing farmers is suggested to support a sustainable and inclusive transition in beef farming in Brazil.

In Vivo Effects of Biosilica and Spongin-Like Collagen Scaffolds on the Healing Process in Osteoporotic Rats.

Due to bioactive properties, introducing spongin-like collagen (SPG) into the biosilica (BS) extracted from marine sponges would present an enhanced biological material for improving osteoporotic fracture healing by increasing bone formation rate. Our aim was to characterize the morphology of the BS/SPG scaffolds by scanning electron microscopy (SEM), the chemical bonds of the material by Fourier transform infrared spectroscopy (FTIR), and evaluating the orthotopic in vivo response of BS/SPG scaffolds in tibial defects of osteoporotic fractures in rats (histology, histomorphometry, and immunohistochemistry) in two experimental periods (15 and 30 days). SEM showed that scaffolds were porous, showing the spicules of BS and fibrous aspect of SPG. FTIR showed characteristic peaks of BS and SPG. For the in vivo studies, after 30 days, BS and BS/SPG showed a higher amount of newly formed bone compared to the first experimental period, observed both in the periphery and in the central region of the bone defect. For histomorphometry, BS/SPG presented higher %BV/TV compared to the other experimental groups. After 15 days, BS presented higher volumes of collagen type I. After 30 days, all groups demonstrated higher volumes of collagen type III compared to volumes at 15 days. After 30 days, BS/SPG presented higher immunostaining of osteoprotegerin compared to the other experimental groups at the same experimental period. The results showed that BS and BS/SPG scaffolds were able to improve bone healing. Future research should focus on the effects of BS/SPG on longer periods in vivo studies.

The Big Five Personality Traits in Dyslexic Adults: An Exploratory Study.

BACKGROUND: Dyslexia is a neurodevelopmental disorder that causes a pattern of learning difficulties that can be characterized by deficits in word reading accuracy, speed or fluency, and reading comprehension. Due to all this damage, emotional difficulties have been described in the literature mainly for childhood and adolescence. Within this emotional component, personality can be included. In Brazil, at the time of carrying out this research, no research had been found that investigated the personality of dyslexic adults. Thus, the present study aimed to investigate the personality of Brazilian adults with dyslexia. METHODS: A semi-structured interview was administered and the Factorial Personality Battery, based on the Big Five personality traits. The sample was composed of two groups: one with dyslexia and another control. The first was formed by nine participants, aged between 18 and 47 (M = 31.7; standard deviation (SD) = 11.8), six of whom were women. The control group was formed by 60 participants, aged between 18 and 45 years (M = 26.4; SD = 8.8), 38 of whom were women. RESULTS: The data did not show significant differences between the groups in most of the analyzed factors and subfactors. Increased rates of "passivity/lack of energy" and lowered rates of "openness to new ideas" were identified in the group with dyslexia. CONCLUSION: These results could be useful for describing personality profiles in dyslexic adults, with these descriptions possibly providing clinical support for diagnoses and intervention procedures.

Inflammatory Profile of Chronic Rhinosinusitis With Nasal Polyp Patients in Brazil: Multicenter Study.

OBJECTIVES: To determine the inflammatory profile of CRSwNP in Brazil and characterize the subgroups of CRSwNP patients in this population through cluster analysis. STUDY DESIGN: Multicenter cross-sectional study involving 15 centers representing different regions of Brazil. SUBJECTS AND METHODS: Clinical data of 166 patients and 80 controls, aged 18 to 70 years old, number of surgeries for CRS, history of asthma and aspirin sensitivity, and Lund-Mackay scores on CT scans. During nasal endoscopy, we obtained the Lund-Kennedy scores and collected 2 samples of nasal polyps: one for eosinophil and neutrophil tissue counts and one to quantify different cytokines. RESULTS: 79.6% of our patients had 10 or more eosinophils/HPF. CRSwNP groups exhibited significantly lower concentrations of TNF-alpha and significantly higher concentrations of IFN-gamma, CCL11/Eotaxin, CCL24/Eotaxin-2/MPIF-2, and CCL26/Eotaxin-3 versus the control group (Kruskal-Wallis test). Comparison between CRSwNP groups (≥10 vs <10 eosinophils/HPF) showed no difference in cytokine concentration (Mann-Whitney test). Hierarchical clustering and PCA according to cytokine concentrations revealed 2 main Clusters, with a significantly higher concentration of all cytokines in Cluster 1 (n = 35) than in Cluster 2 (n = 121), except IL-6 and IL-33 (Mann-Whitney test). According to ROC curve analysis the best cut-off to differentiate the 2 clusters was 43 eosinophils/HPF. The group with ≥43 presented a higher prevalence of men and a higher Lund-Mackay score (Mann-Whitney test). CONCLUSIONS: CRSwNP patients in Brazil present mixed inflammation, with 2 distinct groups (high and low inflammatory pattern) that can be distinguished by tissue eosinophilia of ≥43 eosinophils/HPF cut-off in nasal polyps.

Batch and Continuous Flow Total Synthesis of Cannabidiol.

Herein, we present a comprehensive total synthesis of cannabidiol integrating both batch and continuous flow conditions. Our approach is planned to streamline the synthesis of olivetolic acid derivatives and utilize an enantiomerically pure monoterpene moiety obtained from naturally occurring (R)-(+)-limonene by photocatalysis. Key reactions, including the synthesis of olivetolic ester and a Friedel-Crafts alkylation, are successfully adapted to continuous flow, resulting in improved yields and selectivities. This study not only offers a scalable and efficient route for cannabidiol synthesis but also contributes to the synthetic approaches to access cannabinoids (diversity synthesis), with potential applications in medicinal and industrial contexts.

Combined Brilliant and Trypan Blue As Vital Dyes for Chromovitrectomy.

Brilliant blue 0.05% and trypan blue 0.1% were mixed in a proportion of 1:1 in a 1-mL syringe. This combination produced a waterfall effect with the fast sinking of the dye to the posterior pole and little diffusion through the vitreous cavity. Therefore, it can effectively stain the internal limiting membrane and the epiretinal membrane with a good contrast during surgeries for a macular hole, myopic foveoschisis, and macular pucker.

A prospective study of the proteome of equine pre-implantation embryo.

The present study was conducted to investigate the global proteome of 8-day-old equine blastocysts. Follicular dynamics of eight adult mares were monitored by ultrasonography and inseminated 24 h after the detection of a preovulatory follicle. Four expanded blastocysts were recovered, pooled, and subjected to protein extraction and mass spectrometry. Protein identification was conducted based on four database searches (PEAKS, Proteome Discoverer software, SearchGUI software, and PepExplorer). Enrichment analysis was performed using g:Profiler, Panther, and String platforms. After the elimination of identification redundancies among search tools (at three levels, based on identifiers, peptides, and cross-database mapping), 1977 proteins were reliably identified in the samples of equine embryos. Proteomic analysis unveiled robust metabolic activity in the 8-day equine embryo, highlighted by an abundance of proteins engaged in key metabolic pathways like the TCA cycle, ATP biosynthesis, and glycolysis. The prevalence of chaperones among highly abundant proteins suggests that regulation of protein folding, and degradation is a key process during embryo development. These findings pave the way for developing new strategies to improve equine embryo media and optimize in vitro fertilization techniques.

Association between food insecurity and long COVID in adults from southern Brazil: findings of the PAMPA cohort.

BACKGROUND: Social and economic factors, such as food insecurity, contribute to long coronavirus disease (COVID). During the pandemic, a significant rise in food insecurity was observed, both in Brazil and worldwide. We aimed to investigate the association between food insecurity and long COVID in Brazilian adults. METHODS: Cross-sectional study nested within the Prospective study About Mental and Physical Health in Adults (PAMPA) Cohort. Participants completed an online questionnaire in June 2022. We assessed food insecurity using the Brazilian Scale of Food Insecurity. Long COVID was defined as any post-coronavirus disease 2019 symptoms that persisted for at least 3 months after infection. RESULTS: A total of 956 participants were included (74.0% female, median age 36 (Interquartile Range [IQR] (29-45.7). The prevalence of food insecurity was 29.4%, and 77.8% had long COVID. Food insecurity was associated with an increased probability of long COVID (prevalence ratio [PR]: 1.15, 95% confidence interval [CI]: 1.08-1.22). Participants in food insecurity situations had a higher likelihood of experiencing neurological (PR: 1.19, 95% CI: 1.10-1.28), pulmonary (PR: 1.33, 95% CI: 1.17-1.52) and gastrointestinal (PR: 1.57, 95% CI: 1.31-1.88) symptoms after infection. CONCLUSIONS: Food insecurity was associated with long COVID. Governments must plan public policies to mitigate the effects of long COVID and food insecurity.

Targeting Myeloperoxidase Ameliorates Gouty Arthritis: A Virtual Screening Success Story.

This study presents a new approach for identifying myeloperoxidase (MPO) inhibitors with strong in vivo efficacy. By combining inhibitor-like rules and structure-based virtual screening, the pipeline achieved a 70% success rate in discovering diverse, nanomolar-potency reversible inhibitors and hypochlorous acid (HOCl) scavengers. Mechanistic analysis identified RL6 as a genuine MPO inhibitor and RL7 as a potent HOCl scavenger. Both compounds effectively suppressed HOCl production in cells and neutrophils, with RL6 showing a superior inhibition of neutrophil extracellular trap release (NETosis). In a gout arthritis mouse model, intraperitoneal RL6 administration reduced edema, peroxidase activity, and IL-1ß levels. RL6 also exhibited oral bioavailability, significantly reducing paw edema when administered orally. This study highlights the efficacy of integrating diverse screening methods to enhance virtual screening success, validating the anti-inflammatory potential of potent inhibitors, and advancing the MPO inhibitor research.

Vitamin D levels in couples undergoing in vitro fertilization treatment: lack of association with embryo quality or pregnancy rates.

OBJECTIVE: To investigate the potential impact of vitamin D (VD) serum levels on couples going through in vitro fertilization treatment in terms of embryo quality and pregnancy rates. DESIGN: A retrospective cohort study. SETTING: A private human reproduction center. PATIENT(S): A total of 267 couples underwent intracytoplasmic sperm injections between January 2017 and March 2019. INTERVENTION(S): The couples were categorized into four groups on the basis of 25-hydroxy VD (25OHD) levels measured at the beginning of the stimulation protocol: group 1 with 25OHD levels ≥30 ng/mL for both women and men; group 2 with 25OHD levels <30 ng/mL for both; group 3 women with 25OHD levels <30 ng/mL and men with 25OHD levels ≥30 ng/mL; and group 4 with women with 25OHD level ≥30 ng/mL and men with 25OHD level <30 ng/mL. MAIN OUTCOME MEASURE(S): We consider the quantity and quality of embryos during the cleavage as well as blastocyst stages as primary outcomes. Correspondingly, the clinical pregnancy rate (CPR) was regarded as a secondary outcome. RESULT(S): Our findings revealed no significant correlations between the studied VD groups and the evaluated outcomes. This includes the quantity and quality of embryos during the cleavage and blastocyst stages, as well as the CPR. Primary analysis revealed a small but statistically significant difference in the duration of controlled ovarian stimulation between group 1 and group 2 (95% confidence interval, 0.07-3.04) and between group 1 and group 3 (95% confidence interval, 0.05-3.23). CONCLUSION(S): The present study found no correlation between the studied VD levels and the quantity as well as quality of cleavage or blastocyst stage embryos, nor did it show any impact on CPRs. Further well-designed, prospective studies are warranted to determine whether and how vitamin D affects reproductive outcomes.

Pharmaceutical innovativeness index: methodological approach for assessing the value of medicines - a case study of oncology drugs.

BACKGROUND: We propose a framework to assess the value of pharmaceutical innovations, with explicit clinical and methodological parameters, based on the therapeutic value and health needs. RESEARCH DESIGN AND METHODS: The study was based on the adaptation of health technology assessment methods documented in the literature, which was applied to a sample of oncological drugs. Difficulties and issues during the application of those tools were identified and addressed to develop a new framework with new and revised domains and clear classification criterion for each domain. Scores were assigned to each level and domain according to their relevance to generate the final score of innovativeness. RESULTS: The Pharmaceutical Innovation Index (PII) includes four domains, two related to clinical and social dimensions - Therapeutic Need and Added Therapeutic Value - and other two about methodological features - Study Design and Quality (risk of bias). The scores combined after assigned to each domain results Index of the Innovativeness of the medicines represents the degree of pharmaceutical innovation. CONCLUSION: This work proposes a transparent methodology with well-defined criteria and script; the algorithm developed with authors' weightings and criteria may be switched to best adjust to other applications, perspective or clinical indications, while keeping the transparency and objectiveness.

Loss of c-Kit in Endothelial Cells Protects against Hindlimb Ischemia.

BACKGROUND: Critical limb ischemia (CLI) is the end stage of peripheral artery disease (PAD), and around 30% of CLI patients are ineligible for current treatments. The angiogenic benefits of c-Kit have been reported in the ischemia scenario; however, the present study demonstrates the effects of specific endothelial c-Kit signaling in arteriogenesis during hindlimb ischemia. METHODS: We created conditional knockout mouse models that decrease c-Kit (c-Kit VE-Cadherin CreERT2-c-Kit) or its ligand (SCF VE-Cadherin CreERT2-SCF) specifically in endothelial cells (ECs) after tamoxifen treatment. These mice and a control group (wild-type VE-Cadherin CreERT2-WT) were subjected to hindlimb ischemia or aortic crush to evaluate perfusion/arteriogenesis and endothelial barrier permeability, respectively. RESULTS: Our data confirmed the lower gene expression of c-Kit and SCF in the ECs of c-Kit and SCF mice, respectively. In addition, we confirmed the lower percentage of ECs positive for c-Kit in c-Kit mice. Further, we found that c-Kit and SCF mice had better limb perfusion and arteriogenesis compared to WT mice. We also demonstrated that c-Kit and SCF mice had a preserved endothelial barrier after aortic crush compared to WT. CONCLUSIONS: Our data demonstrate the deleterious effects of endothelial SCF/c-Kit signaling on arteriogenesis and endothelial barrier integrity.