Analysis of glomerular deposition of IgM and C3 in patients with podocytopathies.

Minimal Change Disease (MCD) and Focal Segmental Glomerulosclerosis (FSGS) are the main causes of nephrotic syndrome in the world. The complement system appears to play an important role in the pathogenesis of these diseases. To evaluate the deposition of immunoglobulins and particles of the complement system in renal biopsies of patients with FSGS and MCD and relate to laboratory data, we selected 59 renal biopsies from patients with podocytopathies, 31 from patients with FSGS and 28 with MCD. Epidemiological, clinical, laboratory information and the prognosis of these patients were evaluated. Analysis of the deposition of IgM, IgG, C3, C1q and C4d in renal biopsies was performed. We related IgM and C3 deposition with laboratory parameters. Statistical analysis was performed using GraphPad Prism version 7.0. Glomerular deposition of IgM was significantly higher in the FSGS group, as was codeposition of IgM and C3. The clinical course of patients and laboratory data were also worse in cases of FSGS, with a higher percentage progressing to chronic kidney disease and death. Patients with C3 deposition had significantly higher mean serum creatinine and significantly lower eGFR, regardless of disease. Patients with FSGS had more IgM and C3 deposition in renal biopsies, worse laboratory data and prognosis than patients with MCD. C3 deposition, both in FSGS and MCD, appears to be related to worsening renal function.

Toxicity Assessment of New Ag-ZnO/AgO Nanocomposites: An In Vitro and In Vivo Approach.

Zinc oxide nanoparticles (ZnO NPs) are metal oxide nanomaterials, which are important for several applications: antibacterial, anthelmintic, antiprotozoal and antitumoral, among others. These applications are mainly related to the ability to spontaneously produce and induce the production of reactive oxygen species that are important components for the destruction of pathogens and tumor cells. While trying to potentiate ZnO NPs, studies have associated these NPs with silver oxide (AgO) or silver (Ag) NPs. It has already been reported that this combination (Ag-ZnO/AgO NPs) is able to enhance the microbicidal potential. Although possessing much potential for several purposes, it is important to evaluate whether this association also poses the risk of toxicity to cells and experimental models. Therefore, this work aimed to evaluate the toxicity of various Ag-ZnO/AgO NP nanocomposites, in vitro and in vivo. Accordingly, ZnO nanocrystals and nanocomposites with various concentrations of AgO (ZnO:5Ag, ZnO:9Ag or ZnO:11Ag) were used in different cytotoxicity models: Galleria mellonella (G. mellonella), cell lines (VERO and RAW 264.7) and C57BL/6 mice. In the G. mellonella model, four concentrations were used in a single dose, with subsequent evaluation of mortality. In the case of cells, serial concentrations starting at 125 µg/mL were used, with subsequent cytotoxicity assessment. Based on the safe doses obtained in G. mellonella and cell models, the best doses were used in mice, with subsequent evaluations of weight, biochemistry as also renal and liver histopathology. It was observed that the toxicity, although low, of the nanocomposites was dependent upon the concentration of AgO used in association with ZnO NPs, both in vitro and in vivo.

Metallic nanoparticles and treatment of cutaneous leishmaniasis: A systematic review.

BACKGROUND: Cutaneous leishmaniasis (LC) is an infectious vector-borne disease caused by parasites belonging to the genus Leishmania. Metallic nanoparticles (MNPs) have been investigated as alternatives for the treatment of LC owing to their small size and high surface area. Here, we aimed to evaluate the effect of MNPs in the treatment of LC through experimental, in vitro and in vivo investigations. METHODS: The databases used were MEDLINE/ PubMed, Scopus, Web of Science, Embase, and Science Direct. Manual searches of the reference lists of the included studies and grey literature were also performed. English language and experimental in vitro and in vivo studies using different Leishmania species, both related to MNP treatment, were included. This study was registered in PROSPERO (CRD42021248245). RESULTS: A total of 93 articles were included. Silver nanoparticles are the most studied MNPs, and L. tropica is the most studied species. Among the mechanisms of action of MNPs in vitro, we highlight the production of reactive oxygen species, direct contact of MNPs with the biomolecules of the parasite, and release of metal ions. CONCLUSION: MNPs may be considered a promising alternative for the treatment of LC, but further studies are needed to define their efficacy and safety.

The Influence of IL-11 on Cardiac Fibrosis in Experimental Models: A Systematic Review.

Fibrosis is one of the main factors that impair the function of many organs. In the heart, fibrosis leads to contractile dysfunction and arrhythmias, which are important in the development of heart failure. Interleukin (IL)-11 is regulated in various heart diseases and has recently been reported to be an important cytokine in fibrosis in this organ. However, this topic has been little explored, and many questions persist. Thus, this systematic review aimed to report on possible IL-11 therapies evaluated in rodent model-induced cardiac fibrosis. Inclusion criteria were experimental in vivo studies that used different rodent models for cardiac fibrosis associated with IL-11 interventions, without year and language restrictions. The search in PubMed, Web of Science, and Embase databases was performed in October 2022. The risk of bias assessment of the studies was based on the guidelines of the SYRCLE tool, and data from the selected articles were also presented in a table as a narrative description. This review was based on eight studies in which five different interventions were used: recombinant human IL-11 (rhIL-11), anti-IL11 (X203), recombinant mouse IL-11 (rmIL-11), lentivirus (LV)-IL-11 + lutein, and anti-IL11RA (X209). Based on the included studies, the results were variable, with IL-11 overexpression inducing cardiac fibrosis, while inhibition protected against this process, preserving the function of this organ. Therefore, IL-11 stands out as a promising therapeutic target for cardiac fibrosis. However, further studies are needed to understand the mechanisms triggered by each treatment, as well as its safety and immunogenicity.

Melatonin: A look at protozoal and helminths.

Melatonin is a pleiotropic neurohormone found in different animal, plant, and microorganism species. It is a product resulting from tryptophan metabolism in the pineal gland and is widely known for its ability to synchronize the circadian rhythm to antitumor functions in different types of cancers. The molecular mechanisms responsible for its immunomodulatory, antioxidant and cytoprotective effects involve binding to high-affinity G protein-coupled receptors and interactions with intracellular targets that modulate signal transduction pathways. In vitro and in vivo studies have reported the therapeutic potential of melatonin in different infectious and parasitic diseases. In this review, the protective and pathophysiological roles of melatonin in fighting protozoan and helminth infections and the possible mechanisms involved against these stressors will be discussed.

RNA vaccines in infectious diseases: A systematic review.

Infectious diseases are a major health concern worldwide, especially as they are one of the main causes of mortality in underdeveloped and developing countries. Those that are considered emerging and re-emerging are characterized by unpredictability, high morbidity and mortality, exponential spread, and substantial social impact. These characteristics highlight the need to create an "on demand" control method, with rapid development, large-scale production, and wide distribution. In view of this, RNA vaccines have been investigated as an effective alternative for the treatment and prevention of infectious diseases since they can meet those needs and are considered safe, affordable, and totally synthetic. Therefore, this systematic review aimed to evaluate the use of RNA vaccines for infectious diseases from experimental, in vivo, and in vitro studies. PubMed, Web of Science, and Embase were searched for suitable studies. Additionally, further investigations, such as grey literature checks, were performed. A total of 723 articles were found, of which only 41 met the inclusion criteria. These studies demonstrated the potential of using RNA vaccines to control 19 different infectious diseases, of which COVID-19 was the most studied. Similarly, viruses comprised the largest number of reported vaccine targets, followed by protozoa and bacteria. The mRNA vaccines were the most widely used, and the intramuscular route of administration was the most reported. Regarding preclinical experimental models, mice were the most used to evaluate the impact and safety of the RNA vaccines developed. Thus, although further studies and evaluation of the subject are necessary, it is evident that RNA vaccines can be considered a promising alternative in the treatment and prophylaxis of infectious diseases.

In situ assessment of Mindin as a biomarker of podocyte lesions in diabetic nephropathy.

Diabetic nephropathy (DN) is the leading cause of chronic kidney disease and end-stage renal failure worldwide. Several mechanisms are involved in the pathogenesis of this disease, which culminate in morphological changes such as podocyte injury. Despite the complex diagnosis and pathogenesis, limited attempts have been made to establish new biomarkers for DN. The higher concentration of Mindin protein in the urine of patients with type 2 diabetes mellitus suggests that it plays a role in DN. Therefore, this study investigated whether in situ protein expression of Mindin can be considered a potential DN biomarker. Fifty renal biopsies from patients diagnosed with DN, 57 with nondiabetic glomerular diseases, including 17 with focal segmental glomerulosclerosis (FSGS), 14 with minimal lesion disease (MLD) and 27 with immunoglobulin A nephropathy (IgAN), and 23 adult kidney samples from autopsies (control group) were evaluated for Mindin expression by immunohistochemistry. Podocyte density was inferred by Wilms' tumor 1 (WT1) immunostaining, while foot process effacement was assessed by transmission electron microscopy. Receiver operative characteristic (ROC) analysis was performed to determine the biomarker sensitivity/specificity. Low podocyte density and increased Mindin expression were observed in all cases of DN, regardless of their class. In the DN group, Mindin expression was significantly higher than that in the FSGS, MCD, IgAN and control groups. Higher Mindin expression was significantly positively correlated with foot process effacement only in class III DN cases. Furthermore, Mindin protein presented high specificity in the biopsies of patients with DN (p < 0.0001). Our data suggest that Mindin may play a role in DN pathogenesis and is a promising biomarker of podocyte lesions.

Revisiting the hallmarks of cancer: A new look at long noncoding RNAs in breast cancer.

Breast cancer is one of the leading causes of death in women worldwide. The increasing understanding of the molecular mechanisms underlying its heterogeneity favors a better understanding of tumor biology and consequently the development of better diagnostic and treatment techniques. The advent of tumor genome sequencing techniques has highlighted more participants in the process, in addition to protein-coding genes. Thus, it is now known that long noncoding RNAs, previously described as transcriptional noise with no biological function, are intimately associated with tumor development. In breast cancer, they are abnormally expressed and closely associated with tumor progression, which makes them attractive diagnostic biomarkers and prognostic and specific therapeutic targets. Therefore, a thorough understanding of the regulatory mechanisms of long noncoding RNAs in breast cancer is essential for the search for new treatment strategies. In this review, we summarize the major long noncoding RNAs and their association with the cancer characteristics of the ability to sustain proliferative signaling, evasion of growth suppressors, replicative immortality, activation of invasion and metastasis, induction of angiogenesis, resistance to cell death, reprogramming of energy metabolism, genomic instability and sustained mutations, promotion of tumor inflammation, and evasion of the immune system. In addition, we report and suggest how they can be used as prognostic biomarkers and possible therapeutic targets.

Cannabis sativa: A look at protozoa, helminths, insect vectors, and pests.

Active principles extracted from plants, such as essential oils, have been commonly described in the literature as therapeutic targets for numerous pathological conditions. Cannabis sativa, which has an ancient and peculiar history, has been used for various purposes, from recreational to compounds of pharmacotherapeutic and industrial importance, such as pesticides based on this plant. It is a plant that contains approximately 500 described cannabinoid compounds and is the target of in vitro and in vivo studies at different locations. This review clarifies the role of cannabinoid compounds in parasitic infections caused by helminths and protozoa. In addition, this study briefly presented the use of C. sativa constituents in the formulation of pesticides for vector control, as the latter topic is justified by the economic burden faced by several regions where vector-borne diseases are a troubling reality. Studies involving cannabis compounds with pesticidal potential should be encouraged, especially those that evaluate their effectiveness against the different life cycles of insects, seeking to interrupt vector proliferation after egg laying. Actions aimed at the management and cultivation of plant species with ecologically correct pharmacotherapeutic and pesticide potentials are becoming urgent.

Cancer and Trypanosoma cruzi: Tumor induction or protection?

Trypanosoma cruzi causes Chagas disease, a neglected disease that can be divided, overall, into acute and chronic phases. Understanding the mechanisms underlying its progression is based on the parasite-host interactions occurring during the infection. Although the pathophysiology of the main symptomatic forms of Chagas disease has been the subject of several studies, little is known about their relationship with the development of different types of cancer. Therefore, knowledge regarding the molecular aspects of infection in the host, as well as the influence of the immune response in the parasite and the host, can help to understand the association between Chagas disease and tumor development. This review aims to summarize the main molecular mechanisms related to T. cruzi-dependent carcinogenic development and the mechanisms associated with tumor protection mediated by different parasite components.

Antitumor effect of melatonin on breast cancer in experimental models: A systematic review.

Breast cancer is the most frequent malignant neoplasm in females. While conventional treatments such as chemotherapy and radiotherapy are available, they are highly invasive and toxic to oncological patients. Melatonin is a promising molecule for the treatment of breast cancer with antitumor effects on tumorigenesis and tumor progression. The aim of this systematic review was to synthesize knowledge about the antitumor effect of melatonin on breast cancer in experimental models and propose the main mechanisms of action already described in relation to the processes regulated by melatonin. PubMed, Web of Science, and Embase databases were used. The inclusion criteria were in vitro and in vivo experimental studies that used different formulations of melatonin as a treatment for breast cancer, without year or language restrictions. Risk of bias for studies was assessed using the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) tool. Data from selected articles were presented as narrative descriptions and tables. Seventy-five articles on different breast cancer cell lines and experimental models treated with melatonin alone, or in combination with other compounds were included. Melatonin showed antitumor effects on proliferative pathways related to the cell cycle and tumorigenesis, tumor death, angiogenesis, and tumor metastasis, as well as on oxidative stress and immune regulatory pathways. These effects were either dependent or independent of melatonin receptors. Herein, we clarify the antitumor action of melatonin on different tumorigenic processes in breast cancer in experimental models. Systematic review registration: PROSPERO database (CRD42022309822/https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022309822).

A Revision of Polymeric Nanoparticles as a Strategy to Improve the Biological Activity of Melatonin.

Drug delivery systems based on nanotechnology exhibit a number of advantages over traditional pharmacological formulations. Polymeric nanoparticles are commonly used as delivery systems and consist of synthetic or natural polymers that protect drugs from degradation in physiological environments. In this context, indolamine melatonin has been associated with several biological functions, including antioxidant, antitumor, immunoregulatory, neuroprotective, and cardioprotective effects. However, its availability, half-life, and absorption depend upon the route of administration, and this can limit its therapeutic potential. An alternative is the use of polymeric nanoparticle formulations associated with melatonin to increase its bioavailability and therapeutic dose at sites of interest. Thus, the objective of this review is to provide a general and concise approach to the therapeutic association between melatonin and polymeric nanoparticles applied to different biological disorders and to also highlight its advantages and potential applications compared to those of the typical drug formulations that are available.

Development of Ag-ZnO/AgO Nanocomposites Effectives for Leishmania braziliensis Treatment.

Tegumentary leishmaniasis (TL) is caused by parasites of the genus Leishmania. Leishmania braziliensis (L.b) is one of the most clinically relevant pathogens that affects the skin and mucosa, causing single or multiple disfiguring and life-threatening injuries. Even so, the few treatment options for patients have significant toxicity, high dropout rates, high cost, and the emergence of resistant strains, which implies the need for studies to promote new and better treatments to combat the disease. Zinc oxide nanocrystals are microbicidal and immunomodulatory agents. Here, we develop new Ag-ZnO/xAgO nanocomposites (NCPs) with three different percentages of silver oxide (AgO) nanocrystals (x = 49%, 65%, and 68%) that could act as an option for tegumentary leishmaniasis treatment. Our findings showed that 65% and 68% of AgO inhibit the extra and intracellular replication of L.b. and present a high selectivity index. Ag-ZnO/65%AgO NCPs modulate activation, expression of surface receptors, and cytokine production by human peripheral blood mononuclear cells toward a proinflammatory phenotype. These results point to new Ag-ZnO/AgO nanocomposites as a promising option for L. braziliensis treatment.

Immunophenotypic Analysis of T Lymphocytes and Cytokine Production in Elderly Practicing Physical Activities and Its Relationship with Quality of Life and Depression.

Aging is a complex process often associated with a chronic inflammatory profile that alters several biological functions, including the immune system and cognitive and physical capacity. The practice of physical activity is increasingly gaining popularity as a method of preventing infections, depression, and other disorders that affect the quality of life of the elderly. Thus, this work analyzes the profile of cytokines and molecular markers expressed in immune cells of elderly people who practice physical activities or not, evaluating their impacts on the immune system and quality of life. For this, 48 individuals were recruited, and peripheral blood samples were collected for hemogram analysis, cytokine determination, and immunophenotyping. Elderly people were separated into two groups: practitioners with low-intensity physical activity and non-practitioners. Quality of life was assessed using the Whoqol-Old instrument, and depression was assessed using the Beck II Depression Inventory. When comparing the scores of the Whoqol-Old and Beck questionnaires, we observed a significant negative correlation between these two factors. The perception of a higher quality of life was present in the elderly who exercised and was related to greater autonomy and sensory abilities, whereas the presence of depression was lower. In the hemogram, we observed higher basophil and segmented counts in the sedentary elderly, whereas lymphocytes and monocytes had lower counts. Elderly practitioners of physical activities had higher levels of IFN-γ, IL-4, and IL-10; increased expression of CD69, PD1, and TIM-3 in CD4+ T lymphocytes and increased CD14+CD80+ and CD14+CD86+ monocytes. Elderly people with an increased perception of quality of life had higher levels of IFN-γ, higher expression of CD14+CD80+CD86+, and decreased levels of TRAIL. An increase in TRAIL was observed in individuals with depression, in addition to an increased expression of CD14+CD86+. These results show a clear correlation between the quality of life, level of depression, physical activity, and immune system function. Although some cytokines with a typical proinflammatory profile (IFN-γ) were observed, the results point to a protective state with benefits reflected in the general well-being of the elderly who exercise.

Neuroprotective Treatments for Digestive Forms of Chagas Disease in Experimental Models: A Systematic Review.

Chagas disease is an anthropozoonosis caused by the protozoan Trypanosoma cruzi and is characterized as a neglected disease. It is currently endemic in 21 countries on the Latin American continent, including Bolivia, Argentina, and Paraguay. Unfortunately, there are no optimally effective treatments that can reduce the damage caused in the digestive form of the disease, such as the neuronal destruction of the myenteric plexus of both the esophagus and the colon. Therefore, the objective of this systematic review was to report the possible pharmacological neuroprotective agents that were tested in murine models of the digestive form of Chagas disease. Inclusion criteria are in vivo experimental studies that used different murine models for digestive forms of Chagas disease related to pharmacological interventions with neuroprotective potential, without year and language restriction. On the other hand, the exclusion criteria were studies that did not approach murine models with the digestive form of the disease or did not use neuroprotective treatments, among others. The search in the PubMed, Web of Science, Embase, and LILACS databases was performed on September 4, 2021. In addition, a manual search was performed using the references of the included articles. The risk of bias assessment of the studies was performed based on the SYRCLE tool guidelines, and the data from the selected articles are presented in this review as a narrative description and in tables. Eight articles were included, 4 of which addressed treatment with acetylsalicylic acid, 3 with cyclophosphamide, and 1 with Lycopodium clavatum 13c. In view of the results of the studies, most of them show neuroprotective activity of the treatments, with the potential to reduce the number of damaged neurons, as well as positive changes in the structure of these cells. However, more studies are needed to understand the mechanisms triggered by each drug, as well as their safety and immunogenicity. Systematic review registration is as follows: PROSPERO database (CRD42022289746).

Clinical and epidemiological characterization of newborns with necrotizing enterocolitis / Caracterização clínica e epidemiológica de recém-nascidos com enterocolite necrosante

INTRODUCTION: Necrotizing enterocolitis (NEC) is a severe inflammatory disorder that can affect the whole gastrointestinal system, particularly the ileum, and is a major cause of morbidity in premature infants. OBJECTIVE: To describe the clinical and epidemiological profile of newborns with NEC, seeking to identify the causes, evolution and severity of the disease. METHODS: The study selected 94 patients who developed NEC (cases) and 60 patients who did not develop the disease during hospitalization (controls) and presented similar clinical signs of the case group. The variables analyzed divided into maternal and neonatal. The frequency tests were applied using the Statistical Package for the Social Sciences (SPSS) version 21.0 and comparative analysis using the GraphPad Prism® 5.0 software. RESULTS: There was a higher number of prenatal consultations in cases with NEC. Newborns with NEC had shorter hospital stay, longer parenteral nutrition and antibiotics use and a predominant use of infant formula. The Bell criteria modified by Walsh and Kleigman was negatively correlated to maternal age and positively correlated to gestational age, birth weight and time of parenteral nutrition. CONCLUSION: Although being a disease of the newborn, the present study indicated that maternal characteristics may be related to its onset of NEC. Therefore, the greater number of prenatal consultations and neonatal factors such as length of stay, prolonged use of parenteral nutrition and antibiotic therapy, and formula use may influence the development of the disease.

INTRODUÇÃO: A Enterocolite Necrosante (ECN) é um grave distúrbio inflamatório que pode afetar todo o sistema gastrointestinal, em particular o íleo, é uma causa de morbiletalidade em prematuros. OBJETIVO: Delinear o perfil clínico-epidemiológico de recém-nascidos com ECN, buscando identificar as causas, modo de evolução e gravidade da doença. MÉTODOS: Foram selecionados 94 pacientes que desenvolveram ECN (casos) e 60 pacientes que não desenvolveram a doença no período de internação (controles) e apresentavam sinais clínicos semelhantes do grupo caso. As variáveis analisadas foram classificadas em maternas e neonatais. Foram realizados testes de frequência usando o programa Statistical Package for the Social Sciences (SPSS) versão 21.0 e análise comparativa usando o teste programa GraphPad Prism® 5.0. RESULTADOS: Nos casos com ECN houve maior número de consultas pré-natal. Os recém-nascidos com ECN apresentaram menor tempo de internação, maior tempo de nutrição parenteral e uso de antibióticos tiveram predomínio no uso de fórmula infantil. A classificação modificada de Bell por Walsh and Kleigman apresentou correlação negativa com idade materna e positiva com idade gestacional, peso ao nascer e o tempo de nutrição parenteral. CONCLUSÃO: Apesar de ser uma doença do recém-nascido, esse estudo sugere que características maternas podem ter relação com o aparecimento da ECN. O número maior de consultas pré-natal e os fatores neonatais como o tempo de internação, uso prolongado de nutrição parenteral, antibioticoterapia e uso de fórmulas pode influenciar o desenvolvimento da doença.

The Colombian Strain of Trypanosoma cruzi Induces a Proinflammatory Profile, Neuronal Death, and Collagen Deposition in the Intestine of C57BL/6 Mice Both during the Acute and Early Chronic Phase.

The objective of this study was to evaluate the histopathological changes caused by infection with the Colombian strain of Trypanosoma cruzi (T. cruzi) in the acute and chronic experimental phases. C57Bl/6 mice were infected with 1000 trypomastigote forms of the Colombian strain of T. cruzi. After 30 days (acute phase) and 90 days (early chronic phase) of infection, the animals were euthanized, and the colon was collected and divided into two parts: proximal and distal. The distal portion was used for histopathological analysis, whereas the proximal portion was used for quantification of pro- and anti-inflammatory cytokines. In addition, the weight of the animals and parasitemia were assessed. The infection induced gradual weight loss in the animals. In addition, the infection induced an increase in interferon gamma (IFNγ) and tumor necrosis factor-alpha (TNF-α) in the intestine in the acute phase, in which this increase continued until the early chronic phase. The same was observed in relation to the presence of intestinal inflammatory infiltrates. In relation to interleukin (IL)-10, there was an increase only in the early chronic phase. The Colombian strain infection was also able to induce neuronal loss in the myenteric plexus and deposition of the collagen fibers during the acute phase. The Colombian strain of T. cruzi is capable of causing histopathological changes in the intestine of infected mice, especially in inducing neuronal destructions. Thus, this strain can also be used to study the intestinal form of Chagas disease in experimental models.

Antiprotozoal and Anthelmintic Activity of Zinc Oxide Nanoparticles.

Nanomaterials represent a wide alternative for the treatment of several diseases that affect both human and animal health. The use of these materials consists, mainly, in trying to solve the problem of resistance that pathogenic organisms acquire to conventional drugs. A well-studied example that represents a potential component for biomedical applications is the use of zinc oxide (ZnO) nanoparticles (NPs). Its antimicrobial function is related, especially to the ability to generate/induce ROS that affects the homeostasis of the pathogen in question. Protozoa and helminths that harm human health and the economic performance of animals have already been exposed to this type of nanoparticle. Thus, through this review, our goal is to discuss the state-of-the-art effect of ZnONPs on these parasites.

Congenital transmission of Mexican strains of Trypanosoma cruzi TcIa: interaction between parasite and human placental explants.

Congenital transmission of Chagas disease plays an important role in endemic countries because it is not a diagnosis that is encountered frequently in prenatal care. Due to limited information regarding congenital transmission of Trypanosoma cruzi in Mexico, the present study aimed to investigate protozoan infectivity and modulation of immune responses in human placental explants infected with T. cruzi Ia Mexican strains. The Inc-5 strain showed increased infectivity and modulated IL-1ß, IL-10 and TLR-4, decreasing their expression after 24 h of infection. Both strains (Inc-5 and Ninoa) stimulated the production of TNF-α and decreased IL-6 levels 96 h after infection. An important detachment of the syncytiotrophoblast caused by infection with T. cruzi was observed after 24 h of infection. In this study, ex vivo infection of human placental villi was performed to better understand interactions involving parasitic T. cruzi and human placental tissue. It was concluded that the strains of TcIa present parasitism in placental tissue, modulation of the innate immune system of the placenta, and cause intense detachment of the syncytiotrophoblast, a fact that may be more associated with abortion and premature birth events than the congenital transmission itself, justifying the low rate of this transmission mechanism by this genotype.

Novel Therapeutic Options for Chagas Disease Based on Bioactive Compounds from Algae, Bacteria and Fungi Species.

Chagas Disease, also known as American trypanosomiasis, is a Neglected Tropical Disease that affects around seven million people, especially in Latin America. Noteworthy, there has been an increase in the numbers of case reports in non-endemic areas, such as North America, Europe, Japan, and Australia. The disease is a vector-borne disease caused by the pathogen Trypanosoma cruzi being transmitted by infected bugs. It is known that about forty percent of infected patients develop cardiac, digestive, or neurological alterations. There are only two drugs currently used for treatment, benznidazole and nifurtimox. However, both therapeutic regimens present several limitations, such as toxicity, mutagenicity and low efficiency during the chronic phase. Some reports in the literature point to the occurrence of parasite resistance. To overcome these limitations, the bioprospection of novel molecules as alternatives is one of the major goals to improve therapeutic success in this chronic disease. Bioprospecting active metabolites from natural resources might bring new hopes for disease control and parasite elimination. Here we summarize the most recent advances to identify and test Algae, Bacteria and Fungi-derived bioactive compounds with trypanocidal activity using experimental models, in vitro testing and in silico approaches.