The effects of various therapies on vulvovaginal atrophy and quality of life in gynecological cancer patients: a systematic review.

PURPOSE: Tumors affecting the female genital tract and their treatments have the potential to induce adverse modifications in vaginal health and impact personal aspects of patient's lives. Vulvovaginal atrophy is one of the morphological changes observed in individuals with a history of gynecological cancer, influenced both by the biological environment of tumors and the main therapeutic modalities employed. Therefore, the purpose of this study was to identify approaches to treat vulvovaginal atrophy while assessing the impact on the emotional and sexual health of women diagnosed with gynecological cancers. METHODS: To achieve this goal, a systematic review was conducted following the methodological guidelines outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The databases used for literature research were PubMed and Web of Science. RESULTS: Initially, 886 articles were obtained. After eliminating duplicates and applying inclusion/exclusion criteria, seven articles were selected for analysis. The period of highest publication activity spanned from 2017 to 2020, with the majority conducted in Italy. Five treatment modalities were identified and categorized as vaginal suppository, oral medication, surgical procedure, CO2 laser therapy, and vaginal dilator. Twenty-four outcomes related to vaginal health and 30 outcomes related to overall, sexual, and emotional quality of life were analyzed. CONCLUSION: In general, all interventions demonstrated the ability to improve vaginal health or, at the very least, the sexual health of patients. Thus, despite limitations, all treatments have the potential to address vulvovaginal atrophy in patients with a history of gynecological cancer.

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.

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.

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.

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.

Renal expression of cytokines and chemokines in diabetic nephropathy.

BACKGROUND: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide. Inflammatory mediators have been implicated in the pathogenesis of DN, thus considered an inflammatory disease. However, further studies are required to assess the renal damage caused by the action of these molecules. Therefore, the objective of this study was to analyze the expression of cytokines and chemokines in renal biopsies from patients with DN and to correlate it with interstitial inflammation and decreased renal function. METHODS: Forty-four native renal biopsies from patients with DN and 23 control cases were selected. In situ expression of eotaxin, MIP-1α (macrophage inflammatory protein-1α), IL-8 (interleukin-8), IL-4, IL-10, TNF-α (tumor necrosis factor-α), TNFR1 (tumor necrosis factor receptor-1), IL-1ß, and IL-6 were evaluated by immunohistochemistry. RESULTS: The DN group showed a significant increase in IL-6 (p < 0.0001), IL-1ß (p < 0.0001), IL-4 (p < 0.0001) and eotaxin (p = 0.0012) expression, and a decrease in TNFR1 (p = 0.0107) and IL-8 (p = 0.0262) expression compared to the control group. However, there were no significant differences in IL-10 (p = 0.4951), TNF-α (p = 0.7534), and MIP-1α (p = 0.3816) expression among groups. Regarding interstitial inflammation, there was a significant increase in IL-6 in scores 0 and 1 compared to score 2 (p = 0.0035), in IL-10 in score 2 compared to score 0 (p = 0.0479), and in eotaxin in score 2 compared to scores 0 and 1 (p < 0.0001), whereas IL-8 (p = 0.0513) and MIP-1α (p = 0.1801) showed no significant differences. There was a tendency for negative correlation between eotaxin and estimated glomerular filtration rate (eGFR) (p = 0.0566). CONCLUSIONS: Our results indicated an increased in situ production of cytokines and chemokines in DN, including IL-6, IL-1ß, IL-4, and eotaxin. It was observed that, possibly, eotaxin may have an important role in the progression of interstitial inflammation in DN and in eGFR decrease of these patients.

T-Cell Immunophenotyping and Cytokine Production Analysis in Patients with Chagas Disease 4 Years after Benznidazole Treatment.

The major problem with Chagas disease is evolution of the chronic indeterminate form to a progressive cardiac disease. Treatment diminishes parasitemia but not clinical progression, and the immunological features involved are unclear. Here, we studied the clinical course and the immune response in patients with chronic-phase Chagas disease at 48 months after benznidazole treatment. Progression to the cardiac form of Chagas disease or its aggravation was associated with higher in vitro antigen-specific production of interferon gamma (IFN-γ) in patients with cardiac Chagas disease than in patients with the indeterminate form. Predominance of IFN-γ production over interleukin-10 (IL-10) production in antigen-specific cultures was associated with cardiac involvement. Significantly higher numbers of antigen-specific T helper 1 cells (T-Bet+ IFN-γ+) and a significantly higher IFN-γ+/IL-10+ ratio were observed in patients with cardiac Chagas disease than in patients with the indeterminate form. Cardiac damage was associated with higher numbers of T helper cells than cytotoxic T lymphocytes producing IFN-γ. Patients with cardiac Chagas disease had predominant CD25- and CD25low T regulatory (Treg) subpopulations, whereas patients with the indeterminate form manifested a higher relative mean percentage of CD25high Treg subpopulations. These findings suggest that at 48 months after benznidazole treatment, the disease can worsen or progress to the cardiac form. The progression may be related to increased IFN-γ production (mostly from CD4+ T cells) relative to IL-10 production and increased Treg percentages. Patients with the indeterminate form of Chagas disease show a more balanced ratio of proinflammatory and anti-inflammatory cytokines.

A novel single amino acid deletion impairs fibronectin function and causes familial glomerulopathy with fibronectin deposits: case report of a family.

BACKGROUND: Glomerulopathy with fibronectin deposits is an autosomal dominant disease associated with proteinuria, hematuria, hypertension and renal function decline. Forty percent of the cases are caused by mutations in FN1, the gene that encodes fibronectin. CASE PRESENTATION: This report describes two cases of Glomerulopathy with fibronectin deposits, involving a 47-year-old father and a 14-year-old son. The renal biopsies showed glomeruli with endocapillary hypercellularity and large amounts of mesangial and subendothelial eosinophilic deposits. Immunohistochemistry for fibronectin was markedly positive. Whole exome sequencing identified a novel FN1 mutation that leads to an amino-acid deletion in both patients (Ile1988del), a variant that required primary amino-acid sequence analysis for assessment of pathogenicity. Our primary sequence analyses revealed that Ile1988 is very highly conserved among relative sequences and is positioned in a C-terminal FN3 domain containing heparin- and fibulin-1-binding sites. This mutation was predicted as deleterious and molecular mechanics simulations support that it can change the tertiary structure and affect the complex folding and its molecular functionality. CONCLUSION: The current report not only documents the occurrence of two GFND cases in an affected family and deeply characterizes its anatomopathological features but also identifies a novel pathogenic mutation in FN1, analyzes its structural and functional implications, and supports its pathogenicity.

Trypanosoma cruzi Mexican Strains Differentially Modulate Surface Markers and Cytokine Production in Bone Marrow-Derived Dendritic Cells from C57BL/6 and BALB/c Mice.

Dendritic cells (DCs) are a type of antigen-presenting cells that play an important role in the immune response against Trypanosoma cruzi, the causative agent of Chagas disease. In vitro and in vivo studies have shown that the modulation of these cells by this parasite can directly affect the innate and acquired immune response of the host in order to facilitate its biological cycle and the spreading of the species. Many studies show the mechanisms by which T. cruzi modulates DCs, but the interaction of these cells with the Mexican strains of T. cruzi such as Ninoa and INC5 has not yet been properly investigated. Here, we evaluated whether Ninoa and INC5 strains evaded the immunity of their hosts by modulating the biology and function of murine DCs. The CL-Brener strain was used as the reference strain. Herein, it was demonstrated that Ninoa was more infective toward bone marrow-derived dendritic cells (BMDCs) than INC5 and CL-Brener strains in both BMDCs of BALB/c and C57BL/6 mice. Mexican strains of T. cruzi induced different cytokine patterns. In BMDCs obtained from BALB/c mice, Ninoa strain led to the reduction in IL-6 and increased IL-10 production, while in C57BL/6 mice Ninoa strain considerably increased the productions of TNF-α and IL-10. Also, Ninoa and INC5 differentially modulated BMDC expressions of MHC-II, TLR2, and TLR4 in both BALB/c and C57BL/6 mice compared to Brazilian strain CL-Brener. These results indicate that T. cruzi Mexican strains differentially infect and modulate MHC-II, toll-like receptors, and cytokine production in DCs obtained from C57BL/6 and BALB/c mice, suggesting that these strains have developed particular modulatory strategies to disrupt DCs and, consequently, the host immune responses.

Upregulation of Cardiac IL-10 and Downregulation of IFN-γ in Balb/c IL-4-/- in Acute Chagasic Myocarditis due to Colombian Strain of Trypanosoma cruzi.

Inflammatory response in Chagas disease is related to parasite and host factors. However, immune system regulation has not been fully elucidated. Thus, this study is aimed at evaluating IL-4 influence on acute phase of Trypanosoma cruzi experimental infection through dosage of cytokine levels in cardiac homogenate of infected Balb/c WT and Balb/c IL-4-/- as well as its histopathological repercussions. For such purpose, mice were divided into two groups: an infected group with 100 forms of the Colombian strain and an uninfected group. After 21 days of infection, animals were euthanized and the blood, spleen, and heart were collected. The spleen was used to culture splenic cells in 48 h. Subsequently, cytokines TNF-α, IL-12p70, IL-10, IFN-γ, and IL-17 were measured in the blood, culture supernatant, and heart apex by ELISA. The base of the heart was used for histopathological analysis. From these analysis, infected Balb/c IL-4-/- mice showed milder inflammatory infiltrate compared to Balb/c WT, but without changes in nest density and collagen deposition. IL-4 absence culminated in lower cardiac tissue IFN-γ production, although it did not affect TNF-α expression in situ. It also decreased TNF-α systemic production and increased IL-10, both systemically and in situ. In addition, IL-4 absence did not influence IL-17 expression. Splenocytes of IL-4-deficient mice produced higher amounts of IFN-γ, TNF-α, and IL-17 and lower amounts of IL-10. Thus, IL-4 absence in acute phase of experimental infection with T. cruzi Colombian strain reduces myocarditis due to lower IFN-γ production and greater IL-10 production in situ and this pattern is not influenced by splenocyte general repertoire.

Ultrastructural deposits appearing as "zebra bodies" in renal biopsy: Fabry disease?- comparative case reports.

BACKGROUND: Fabry Disease (FD) is a genetic disorder caused by alpha-galactosidase A deficiency. Certain drugs, such as hydroxychloroquine, can produce renal deposits that mimic morphological findings seen in FD, characterizing a type of drug-induced renal phospholipidosis. CASE PRESENTATION: Case 1: A 28-year-old female patient with systemic lupus erythematosus who had been using hydroxychloroquine for 14 months presented subnephrotic proteinuria. Renal biopsy showed deposits compatible with FD. Neither activity analysis of alpha-galactosidase A nor genetic analysis were available and were not performed. These deposits were not detected in a subsequent renal biopsy three years after withdrawal of the medication, characterizing a possible hydroxychloroquine-induced renal phospholipidosis. Case 2: A 29-year-old male patient presented with acroparesthesia, angiokeratomas, cornea verticillata and subnephrotic proteinuria. Deposits compatible with FD were detected upon renal biopsy. The evaluation of alpha-galactosidase A showed no activity in both blood and leukocytes. Genetic analysis identified an M284 T mutation in exon 6, and such mutation was also found in other family members. CONCLUSION: Clinical investigation is necessary in suspected cases of Fabry Disease upon renal biopsy in order to confirm diagnosis. Drug-induced renal phospholipidosis should be considered in differential diagnosis in cases with intracellular osmiophilic, lamellar inclusions in electron microscopy.

Diagnosis of congenital and infantile nephrotic syndromes in renal biopsies in Minas Gerais, Brazil: Six case reports.

Congenital or infantile nephrotic syndromes (CNS/INS) correspond to a heterogeneous group of rare diseases in which glomerular renal dysfunction and proteinuria are prominent. The aim of this study is to present six cases of possible CNS/INS with diagnoses based on clinical findings and especially histological, ultrastructural, and immunohistochemical characteristics of renal biopsies. Four cases are presented with diffuse mesangial sclerosis, one of them possibly part of Denys-Drash syndrome and two cases with CNS probably of the Finnish type in patients between 3 months old and 13 years old. The study focuses on the late evolution of Denys-Drash syndrome to end-stage renal disease in a 13-year-old patient and the diagnosis of diffuse mesangial sclerosis in an 8-year-old patient. Thus, it contributes to a better epidemiological characterization of these syndromes, demonstrating cases of CNS/INS in infrequent age groups.

Neonatal sepsis and inflammatory mediators.

Neonatal sepsis is a major cause of morbidity and mortality and its signs and symptoms are nonspecific, which makes the diagnosis difficult. The routinely used laboratory tests are not effective methods of analysis, as they are extremely nonspecific and often cause inappropriate use of antibiotics. Sepsis is the result of an infection associated with a systemic inflammatory response with production and release of a wide range of inflammatory mediators. Cytokines are potent inflammatory mediators and their serum levels are increased during infections, so changes from other inflammatory effector molecules may occur. Although proinflammatory and anti-inflammatory cytokines have been identified as probable markers of neonatal infection, in order to characterize the inflammatory response during sepsis, it is necessary to analyze a panel of cytokines and not only the measurement of individual cytokines. Measurements of inflammatory mediators bring new options for diagnosing and following up neonatal sepsis, thus enabling early treatment and, as a result, increased neonatal survival. By taking into account the magnitude of neonatal sepsis, the aim of this review is to address the role of cytokines in the pathogenesis of neonatal sepsis and its value as a diagnostic criterion.

Effects of cholinergic stimulation with pyridostigmine bromide on chronic chagasic cardiomyopathic mice.

The aim of the present study was to assess the effects of an anticholinesterase agent, pyridostigmine bromide (Pyrido), on experimental chronic Chagas heart disease in mice. To this end, male C57BL/6J mice noninfected (control:Con) or chronically infected (5 months) with Trypanosoma cruzi (chagasic:Chg) were treated or not (NT) with Pyrido for one month. At the end of this period, electrocardiogram (ECG); cardiac autonomic function; heart histopathology; serum cytokines; and the presence of blood and tissue parasites by means of immunohistochemistry and PCR were assessed. In NT-Chg mice, significant changes in the electrocardiographic, autonomic, and cardiac histopathological profiles were observed confirming a chronic inflammatory response. Treatment with Pyrido in Chagasic mice caused a significant reduction of myocardial inflammatory infiltration, fibrosis, and hypertrophy, which was accompanied by a decrease in serum levels of IFNγ with no change in IL-10 levels, suggesting a shift of immune response toward an anti-inflammatory profile. Lower nondifferent numbers of parasite DNA copies were observed in both treated and nontreated chagasic mice. In conclusion, our findings confirm the marked neuroimmunomodulatory role played by the parasympathetic autonomic nervous system in the evolution of the inflammatory-immune response to T. cruzi during experimental chronic Chagas heart disease in mice.

Effect of indomethacin on surface treatment and intracanal dressing of replanted teeth in dogs.

PURPOSE: This study evaluated the healing process of teeth replanted after root treatment and intracanal dressing with indomethacin alone or indomethacin with calcium hydroxide (Ca[OH]2). MATERIALS AND METHODS: Through a case-control study, 24 teeth of 6 adult dogs were extracted, dried, and divided into 4 groups according to the root surface treatment protocols performed before replantation and the intracanal medication used after replantation. In group 1 (negative control), root surfaces were treated by immersion in a 0.9% saline solution and then replanted. In the other groups, the roots were immersed for 10 minutes in Ca(OH)2 (group 2), indomethacin (group 3), or a solution of indomethacin and Ca(OH)2 (group 4). After 2 weeks, group 1 teeth were subjected to single-visit root canal treatment and obturation with gutta-percha and sealer consisting of zinc oxide and eugenol. The teeth in the other groups were subjected to intracanal dressing with the same material used for immersion. After an additional period of 28 weeks, the animals were euthanized and the jaws containing the replanted teeth were processed for histologic analysis. Histometric values were statistically analyzed, with significance set at a P value less than or equal to .05. RESULTS: Group 1 exhibited significantly more normal periodontium than group 4 (P = .02). Total resorption was greater in group 4 than in group 1 (P = .02). No statistically significant difference in the percentage of surface resorption or in total inactive resorption was observed between the groups. CONCLUSIONS: The findings of this study suggest that intracanal dressing and topical root treatment with Ca(OH)2 with or without indomethacin is not recommended for teeth dried for 50 minutes, but the use of indomethacin alone as root surface treatment for delayed tooth replantation deserves further study using longer drying periods. In addition, the present results suggest that a single-visit root canal, performed up to 2 weeks after replantation, might be indicated for teeth dried for up to 50 minutes.

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.

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.

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.

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.

Pulmonary innate immune response and melatonin receptors in the perinatal stress.

OBJECTIVE: To analyze the cytokines of the innate immune pulmonary response and the capacity for local response to melatonin according to the perinatal stress. METHODS: 49 cases of pediatric autopsies were evaluated, divided according to cause of death, perinatal stress, gestational age, and birth weight. The percentages of IL-6, C-reactive protein (CRP), IL-1ß, TNF-α, and melatonin receptor were evaluated by immunohistochemistry. RESULTS: The IL-6 expression was higher in the children showing chronic stress, anoxia, and infection. The IL-6 expression showed a progressive increase according to the relation between weight and GA. There was no significant difference in the expression of IL-1ß and TNF-α. The CRP expression was higher in the cases showing chronic stress and premature cases. The expression of melatonin receptors was significantly higher in the cases showing chronic stress, being more evident in the cases showing infection. CONCLUSION: The cause of death and the type of stress influence the expression in situ of melatonin and cytokines of the innate immune pulmonary response. The evaluation of IL-6 and CRP may contribute to the understanding of the evolution of neonates with chronic stress. The greater sensitivity of the lung to melatonin in these cases may indicate an attempt at controlling the immunological response, in an attempt to diminish the harmful effects of stress.