https://repositorio.ufu.br/handle/123456789/5496 2026-04-04T04:10:18Z 2026-04-04T04:10:18Z https://repositorio.ufu.br/handle/123456789/48506 2026-03-07T06:30:36Z 2026-02-27T00:00:00Z

Title: Avaliação dos efeitos de dendropsofina 1, um peptídeo natural antimicrobiano, e de dois peptídeos análogos sobre a inflamação crônica induzida por implante de esponja sintética em camundongos Abstract: Inflammation is a biological process aimed at restoring homeostasis after harmful stimuli. Through these events, the immune system removes injury-causing agents and promotes tissue repair. Although inflammatory events are essential for life, failure in their resolution may result in the development of chronic-degenerative diseases. Chronic inflammation is present in many disorders, such as diabetes mellitus, rheumatoid arthritis, cancer, and hard-to-heal wounds. In fact, many of the leading causes of death and major burdens on healthcare systems are diseases in which a persistent inflammatory state is present. Under these conditions, there is exacerbated activity of one or more components of chronic inflammation, namely inflammatory mediators, fibrogenesis, and/or angiogenesis. Continuous tissue damage and unsuccessful attempts at repair coexist in chronic inflammation. Thus, cytokines produced at the inflammatory site influence angiogenesis and extracellular matrix (ECM) deposition. Consequently, fibrosis may develop and local tissue function may be lost. Given this scenario, there is a clear need to search for biologically active compounds capable of keeping inflammation under control without completely silencing it; compounds that enable the return to homeostasis while minimizing functional loss. Antimicrobial peptides (AMPs) are a diverse group of bioactive proteins that constitute the first line of defense of various organisms against pathogens. Amphibian skin, for example, is an important reservoir of AMPs. In addition to exerting direct antimicrobial activity, these peptides may inhibit the expression of pro-inflammatory cytokines and chemokines, act as chemotactic molecules, activate immune cells, and modulate fibrogenic and vascular components of inflammation. The present study highlights the activity of a peptide isolated from the skin secretion of Dendropsophus columbianus, a tree frog endemic to Colombia, and two of its synthetic analogs. In 2018, the native peptide, named dendropsophin 1 (Dc1), was isolated, and subsequently the analogs Dc1.2 and Dc1.2.2 were synthesized. These peptides have documented antimicrobial activity; however, since their in vivo immunomodulatory action had not yet been elucidated, we evaluated the effects of their daily administration in a mouse model of chronic inflammation induced by polyester-polyurethane sponge implants. The sponge matrices induce a chronic foreign body-type inflammatory response and form fibrovascular tissue. Therefore, this model makes it possible to simultaneously evaluate inflammatory markers, angiogenesis, and fibrogenesis in vivo. To date, this is the first study to analyze the effects of dendropsophin 1 and its analogs in this context, and it demonstrates the therapeutic potential of this peptide for the treatment of conditions that require tissue repair and inflammatory control.

2026-02-27T00:00:00Z https://repositorio.ufu.br/handle/123456789/47332 2025-10-08T06:18:41Z 2025-04-15T00:00:00Z

Title: Evaluating Advanced Strategies in Plant Breeding using Simulation: Genomic Selection with Rapid-cycling, Speed Breeding and Gene Editing Abstract: This review summarizes findings from simulation studies on quantitative traits in plant breeding and translates these insights into practical schemes. As agricultural productivity faces growing challenges, plant breeding is central to addressing these issues. Simulations use mathematical models to replicate biological conditions, bridging theory and practice by validating hypotheses early and optimizing genetic gain and resource use. While strategies can improve trait value, they reduce genetic diversity, making a combination of approaches essential. Studies emphasize the importance of aligning strategy with trait heritability and selection timing and maintaining genetic diversity while considering genotype-environment interactions to avoid biases in early selection. Using markers accelerates breeding cycles when marker placement is precise, foreground and background selection are balanced, and QTL are effectively managed. Genomic selection increases genetic gains by shortening breeding cycles and improving parent selection, especially for low heritability traits and complex genetic architectures. Regular updates of training sets are critical, regardless of genetic architecture. Bayesian methods perform well with fewer genes and in early breeding cycles, while BLUP is more robust for traits with many QTL, and RR-BLUP proves flexible across different conditions. Larger populations lead to greater gains when clear objectives and adequate germplasm are available. Accuracy declines over generations, influenced by genetic architecture and population size. For low heritability traits, multi-trait analysis improves accuracy, especially when correlated with high heritability traits. Updates including top-performing candidates, but conserving variability enhances gains and accuracy. Low-density genotyping and imputation offer cost-effective alternatives to high-density genotyping, achieving comparable results. Targeting populations optimizes genetic relationships, further improving accuracy and breeding outcomes. Evaluating genomic selection reveals a balance between short-term gains and long-term potential and rapid-cycling genomic programs excel. Diverse approaches preserve rare alleles, achieve significant gains, and maintain diversity, highlighting the trade-offs in optimizing breeding success.

2025-04-15T00:00:00Z https://repositorio.ufu.br/handle/123456789/46736 2025-09-03T06:17:50Z 2025-03-31T00:00:00Z

Title: Análise das correlações entre variáveis antropométricas, hemodinâmicas, hematológicas e bioquímicas relacionadas à pré-eclâmpsia e os desfechos gestacionais maternos e neonatais Abstract: Preeclampsia is a multisystem syndrome with complex pathophysiology and unclear etiology, with a significant impact on global health. It is one of the leading causes of maternal and neonatal morbidity and mortality worldwide. Therefore, studies that help understand preeclampsia's pathophysiology and develop risk detection tools are essential to improve maternal and fetal prognosis. In this context, the present study aimed to investigate the correlations between parameters related to the pathophysiology of preeclampsia and maternal and neonatal outcomes. Based on these correlations, it was possible to select variables with the potential to be used in statistical risk stratification models to be developed later. For this purpose, moderation and mediation analyses were performed, contributing to a better understanding of the causal mechanisms inherent in the correlations between maternal, placental, and fetal parameters. The variables involved in moderation and mediation relationships can then serve as a starting point for constructing mathematical models that may contribute to gestational prognosis by identifying risks of adverse outcomes. Chapter 1 discusses the theoretical basis and describes the relevance of preeclampsia for global health, the pathophysiology of the syndrome, and the changes in the maternal organism most relevant to the progression of this disease. It also addresses the techniques used to obtain parameters, such as Doppler velocimetry, and the theoretical aspects of moderation and mediation analyses. Chapter 2 presents the initial population studies, with comparisons between normotensive and preeclamptic patients and correlation analyses that demonstrated associations between hemodynamic, hematological, and biochemical aspects, allowing the selection of variables to be used in the statistical models. Chapter 3 presents the moderation and mediation analyses that contributed to a better understanding of the correlations and the identification of more appropriate variables for the future construction of risk stratification models.

2025-03-31T00:00:00Z https://repositorio.ufu.br/handle/123456789/46459 2026-01-14T16:20:00Z 2024-05-28T00:00:00Z

Title: Prospecção in silico e in vitro de potenciais inibidores da enzima n-miristoiltransferase (NMT) em malaria e leishmaniose Abstract: Neglected Tropical Diseases (NTDs) are a group of infectious diseases that primarily affect populations in tropical and subtropical areas, predominantly in low-income countries. These diseases receive little attention in terms of research, drug development, and public health investment, despite causing a significant burden in terms of morbidity, mortality, and socioeconomic impact. Among the most common NTDs are dengue, leishmaniasis, Chagas disease, schistosomiasis, lymphatic filariasis, among others. These diseases are often transmitted by vectors such as mosquitoes, flies, and ticks, and frequently affect underserved communities with limited access to basic sanitation, clean water, and healthcare services.The challenges in controlling NTDs include the lack of adequate healthcare infrastructure, limited access to effective treatments, drug resistance, insufficient investment in research and development of new therapies, as well as the complexity of interactions between parasites, their hosts, and the environment. Recent efforts to combat NTDs include prevention and control programs, access to medicines and treatments, investments in research and the development of vaccines and more effective therapies, as well as initiatives to improve health infrastructure and public health education. The effective fight against NTDs requires an integrated and collaborative approach among governments, non-governmental organizations, academic institutions, and the private sector. Malaria is an infectious disease caused by parasites of the Plasmodium genus, transmitted to humans through the bite of infected Anopheles mosquitoes. Although it is not classified as a neglected disease by the World Health Organization (WHO), it remains one of the most prevalent and deadly tropical diseases worldwide, particularly in tropical and subtropical regions, with a significant impact on low-income countries. Malaria symptoms include fever, chills, headaches, nausea, and vomiting, which can progress to severe complications such as anemia, brain dysfunction, kidney failure, and even death, especially in cases caused by Plasmodium falciparum, the most lethal strain. Malaria control relies on various strategies, including the use of insecticide-treated bed nets, residual insecticide spraying, early and effective treatment of diagnosed cases, and, when possible, the development of vaccines. However, resistance to antimalarial drugs and insecticides, along with socioeconomic challenges such as limited access to healthcare and poor infrastructure, remain significant obstacles in combating the disease. Despite these challenges, significant progress has been made in reducing malaria incidence and mortality over recent decades, thanks to global control initiatives and investments in research, diagnosis, and treatment. However, the complete eradication of malaria remains a challenging goal, requiring continuous and coordinated efforts at local, national, and international levels. Another important and complex disease among NTDs is leishmaniasis, a parasitic disease caused by protozoa of the Leishmania genus. The parasite is transmitted to humans through the bite of infected sandflies of the Phlebotomus genus (in the Old World) or Lutzomyia genus (in the New World). There are different forms of leishmaniasis, including cutaneous, mucocutaneous, and visceral leishmaniasis, the latter being the most severe and potentially fatal if not properly treated. Visceral leishmaniasis, also known as kala-azar, is characterized by prolonged fever, weight loss, enlargement of the spleen and liver, anemia, and immune system impairment. Cutaneous leishmaniasis causes skin ulcers, while mucocutaneous leishmaniasis can lead to the destruction of nasal and oral mucosa. The disease is endemic in many parts of the world, particularly in tropical and subtropical regions, mainly affecting impoverished populations with limited access to healthcare and inadequate sanitation conditions. Leishmaniasis control involves preventive measures against insect bites, early diagnosis, and effective treatment with antiparasitic drugs. Despite advances in diagnosis and treatment, leishmaniasis remains a public health problem in many developing countries, with challenges such as drug resistance, the lack of an effective vaccine, and socioeconomic barriers to healthcare access. Integrated control programs, continuous research, and collaborative efforts are essential to reducing the incidence and impact of this debilitating disease. One of the approaches to tackling the problem of NTDs is the search for new therapeutics, such as the development of inhibitors targeting specific biological pathways of parasites. One of the current biological targets in malaria and trypanosomatids is the N-myristoyltransferase (NMT) enzyme. NMT is an essential enzyme in many organisms and plays a crucial role in the post-translational modification of proteins. Its main function is to add a myristic acid chain to the N-terminal end of specific proteins, which can affect their cellular localization, activity, and interactions with other molecules. Myristoylation, catalyzed by NMT, is a key process for anchoring proteins to cellular membranes, commonly occurring in proteins associated with the plasma membrane and organelles such as the endoplasmic reticulum and the Golgi complex. This modification influences protein functions in various biological processes, including cell signaling, vesicular transport, and cytoskeleton regulation. Given the significant role of this enzyme in physiological processes, NMT inhibition has been investigated as a potential therapeutic target for the development of new drugs aimed at treating various diseases, including cancer, parasitic, and viral infections. In parasites such as Plasmodium falciparum and Trypanosoma brucei, NMT is a crucial target for new drug development, as inhibiting myristoylation of essential proteins can lead to parasite death. Additionally, recent studies have explored NMT as a potential target in cancer treatment due to its role in regulating signaling pathways associated with cell proliferation and metastasis. NMT inhibitors are currently being developed and tested as a novel approach to treating certain types of cancer, offering new hope in the fight against this devastating disease. Therefore, understanding the role of NMT in the biology of these parasites is crucial for developing new therapeutic strategies for leishmaniasis and malaria, two diseases that affect millions of people worldwide, particularly in low-income regions.To identify potential NMT inhibitors, computational methods are being employed in drug development. Currently, computational approaches play a significant role in drug discovery, providing powerful tools to predict and optimize the properties of candidate molecules. These methods encompass various techniques, including molecular modeling, molecular dynamics simulations, molecular docking, virtual screening, and structure-based drug design. In molecular modeling, the three-dimensional structures of biological molecules and candidate compounds are computationally constructed and optimized, allowing predictions of physicochemical properties, molecular interactions, and biological activities. Molecular dynamics simulations enable the study of atomic-scale molecular behavior over time, providing insights into dynamics, conformational changes, and interactions with the surrounding environment. Molecular docking predicts the binding geometry and affinity between a drug candidate and its biological target, facilitating the identification of compounds with potential pharmacological activity. Virtual screening is a computational approach that rapidly identifies promising compounds from large molecular databases, selecting those most likely to interact with a specific target. Structure-based drug design uses detailed structural information about biological targets and candidate compounds to design molecules with desirable pharmacological properties, such as high selectivity, affinity, and biological activity. These computational methods are often combined with laboratory experiments (in vitro and in vivo) to accelerate drug development, reduce costs, and increase the success rate in discovering new medicines. As a result, they play a crucial role in optimizing drug candidates, identifying new therapeutic targets, and understanding the molecular mechanisms underlying diseases. This study aimed to identify potential NMT inhibitors for developing new therapeutic molecules for diseases such as malaria and leishmaniasis. The research involves screening compounds to identify molecules capable of selectively disrupting NMT activity in the parasites responsible for these diseases. The goal is to provide a foundation for the development of more effective and less toxic treatments. This thesis is divided into three chapters. Chapter 1 presents the theoretical background, beginning with an introduction to neglected tropical diseases, with an emphasis on leishmaniasis, followed by a discussion on malaria. Next, it describes the NMT enzyme as a therapeutic target, including its function and importance in disease-causing parasites. Lastly, it covers computational methods used in drug development. Chapter 2, structured as a published article, discusses the identification of potential NMT inhibitors for malaria, detailing the screening methods and identification of compounds with inhibitory potential. Chapter 3 focuses on NMT inhibitors for leishmaniasis, providing a detailed report on research findings, in silico and in vitro assays, and the relevance of these results in advancing leishmaniasis treatment.

2024-05-28T00:00:00Z