Polarization of Melatonin-Modulated Colostrum Macrophages in the Presence of Breast Tumor Cell Lines.

Human colostrum and milk contain diverse cells and soluble components that have the potential to act against tumors. In breast cancer, macrophages play a significant role in immune infiltration and contribute to the progression and spread of tumors. However, studies suggest that these cells can be reprogrammed to act as an antitumor immune response. This study aimed to evaluate the levels of melatonin and its receptors, MT1 (melatonin receptor 1) and MT2 (melatonin receptor 2), in colostrum and assess the differentiation and polarization of the colostrum macrophages modulated by melatonin in the presence of breast tumor cells. Colostrum samples were collected from 116 mothers and tested for their melatonin and receptor levels. The colostrum cells were treated with or without melatonin and then cultured for 24 h in the presence or absence of breast tumor cells. The results showed that melatonin treatment increased the expression of MT1 and MT2 in the colostrum cells. Furthermore, melatonin treatment increased the percentage of M1 macrophages and decreased the percentage of M2 macrophages. When the colostrum macrophages were cocultured with breast tumor cells, melatonin reduced the percentage of both macrophage phenotypes and the cytokines tumor necrosis factor-alpha (TNF-α) and interleukin 8 (IL-8). These data suggest that melatonin can regulate the inflammatory process via M1 macrophages in the tumor microenvironment and, simultaneously, the progression of M2 macrophages that favor tumorigenesis.

Leptin, Adiponectin, and Melatonin Modulate Colostrum Lymphocytes in Mothers with Obesity.

Pregnancy complicated by obesity is associated with adverse triggered gestational and neonatal outcomes, with reductions in the subtypes of CD4+ T-lymphocytes representing the modulators of inflammation. It needs to be better established how maternal nutritional statuses impact the neuroendocrine-immune system's action and affect the immunological mechanisms of the maternal-infant relationship via breastfeeding. This study examined the effects of maternal obesity on human colostrum lymphocytes and the intracellular mechanisms of lymphocyte modulation in the presence of leptin, adiponectin, and melatonin via cell proliferation; the release of intracellular calcium; and apoptosis induction. This cross-sectional study analyzed colostrum samples from 52 puerperal splits and divided them into overweight and eutrophic groups. Colostrum lymphocytes underwent immunophenotyping and cell proliferation by flow cytometry and intracellular calcium release and apoptosis assays by immunofluorescence in the presence or absence of hormones. Significant differences were considered when p < 0.05 by the chi-square or t-test. Maternal obesity reduced the population of T-lymphocytes and TCD4+ in human colostrum and proliferative activities (p < 0.05). These hormones restore lymphocyte proliferation to a level similar to the eutrophic group (p < 0.05). Leptin, adiponectin, melatonin hormones, and biological actions consolidated in the scientific literature also represent maternal and infant protection mechanisms via colostrum and the modulation of human colostrum lymphocytes.

Melatonin and Cytokines Modulate Daily Instrumental Activities of Elderly People with SARS-CoV-2 Infection.

The Comprehensive Geriatric Assessment analyzes the health and quality of life of the elderly. Basic and instrumental daily activities may be compromised due to neuroimmunoendocrine changes, and studies suggest that possible immunological changes occur during infections in the elderly. Thus, this study aimed to analyze cytokine and melatonin levels in serum and correlate the Comprehensive Geriatric Assessment in elderly patients with SARS-CoV-2 infection. The sample consisted of 73 elderly individuals, 43 of whom were without infection and 30 of whom had positive diagnoses of COVID-19. Blood samples were collected to quantify cytokines by flow cytometry and melatonin by ELISA. In addition, structured and validated questionnaires were applied to assess basic (Katz) and instrumental (Lawton and Brody) activities. There was an increase in IL-6, IL-17, and melatonin in the group of elderly individuals with infection. In addition, a positive correlation was observed between melatonin and IL-6 and IL-17 in elderly patients with SARS-CoV-2 infection. Furthermore, there was a reduction in the score of the Lawton and Brody Scale in the infected elderly. These data suggest that the melatonin hormone and inflammatory cytokines are altered in the serum of the elderly with SARS-CoV-2 infection. In addition, there is a degree of dependence, mainly regarding the performance of daily instrumental activities, in the elderly. The considerable impact on the elderly person's ability to perform everyday tasks necessary for independent living is an extremely important result, and changes in cytokines and melatonin probably are associated with alterations in these daily activities of the elderly.

Serotonin and Interleukin 10 Can Influence the Blood and Urine Viscosity in Gestational Diabetes Mellitus and Pregnancy-Specific Urinary Incontinence.

Serotonin and interleukin 10 (IL-10) may play a role in gestational diabetes mellitus. Hyperglycemic environment, the detrusor musculature of the bladder and pelvic floor muscles may become damaged, leading to urination problems and urine viscosity in pregnant women with gestational diabetes mellitus and pregnancy-specific urinary incontinence. Urine and blood samples were collected from pregnant women between 24 and 28 weeks of gestation. The serotonin concentration and cytokine IL-10 levels were evaluated in plasma and urine. In the total blood and urine, the viscosity was evaluated in the presence and absence of exogenous serotonin and IL-10. The plasma serotonin levels decreased, while the urine serotonin levels increased in the normoglycemic incontinent (NG-I), hyperglycemic continent (GDM-C), and hyperglycemic incontinent (GDM-I) groups. The IL-10 in the plasma decreased in the GDM-I group and was higher in the urine in the NG-I and GDM-I groups. The blood viscosity was higher, independently of urinary incontinence, in the GDM groups. The serotonin increased the blood viscosity from women with GDM-C and urine in the NG-I, GDM-C, and GDM-I groups. Blood and urine in the presence of IL-10 showed a similar viscosity in all groups studied. Also, no difference was observed in the viscosity in either the blood or urine when in the presence of serotonin and IL-10. These findings suggest that serotonin and IL-10 have the potential to reduce blood viscosity in pregnant women with gestational diabetes and specific urinary incontinence, maintaining values similar to those in normoglycemic women's blood.

Correlation between melatonin concentration and cytokines in cervical mucus in positive samples for the presence of human papillomavirus.

The human papillomavirus (HPV) is the main causative agent of cervical cancer, characterized by neoplastic lesions in the cervix. Based on the morphology of the cells of the uterine cervix, the findings are classified as negative intraepithelial lesions for malignancies, low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions (HSILs), atypical squamous cells of undetermined significance and atypical squamous cells of undetermined significance without excluding HSILs (ASCs-H). The progression of neoplastic lesions is related to the cervix's microenvironmental inflammatory process and mediated by the expression and stimulation of cytokines. Cervical mucus is a viscous liquid secretion composed of proteins, inorganic components, pro-and anti-inflammatory agents, and an important protective barrier. This study aimed to quantify and correlate cytokines IL-6, IL-8, and IL-10 and Melatonin in cervical mucus. According to the results, a decrease in MLT was observed in LSIL, HSI, and ASC-H groups than in the NILM group. The cytokines IL-6 and IL-8 showed greater expression in the LSIL and HSIL groups than the NILM group. HSIL group showed a negative correlation between the MLT and IL-6 and IL-8 concentrations. In the ASC-US group, IL8 level was positively correlated to MLT levels. We suggest that IL-6, IL-8, and MLT levels in HSIL groups are decisive for the progression of neoplastic lesions in HPV infections. New cervical cancer treatment strategies may include cytokine and melatonin control targets for effective immunotherapy.

Human colostrum action against Giardia lamblia infection influenced by hormones and advanced maternal age.

Children are more susceptible to Giardia lamblia infection. Cells and hormones contained in human colostrum have an immunoprotective action against giardiasis, but the effects of advanced maternal age on these components are poorly understood. This study analyzed the colostrum of older women to determine melatonin and cortisol levels besides the participation of these hormones on the functional activity of phagocytes against G. lamblia. Colostrum samples were collected from younger (18 to 35 years old) and older (over 36 years old) lactating women. Colostrum samples were subjected to melatonin and cortisol determination, immunophenotyping, quantification of superoxide release, and assessment of phagocytic rate and microbicidal activity of phagocytes treated with hormones and in the presence of G. lamblia. Colostrum from mothers of advanced age contained higher melatonin and cortisol levels and a lower rate of cells expressing CD14+ and CD15+. In the colostru of these older mothers, melatonin increased superoxide release by phagocytes. In both groups, superoxide release by phagocytes treated with cortisol was higher in the presence of G. lamblia. In colostrum from mothers of advanced age, mononuclear (MN) phagocytes treated with melatonin showed higher phagocytosis of G. lamblia and higher microbicidal index. In younger mothers, MN and polymorphonuclear (PMN) colostrum phagocytes exhibited higher rates of G. lamblia elimination when treated with both melatonin and cortisol. In older mothers, cortisol and melatonin regulation for the functional activity of colostrum phagocytes against G. lamblia may represent an additional defense mechanism, relevant for the protection and treatment of parasitic infections in breastfed children.

Effects of barium chloride adsorbed to polyethylene glycol (PEG) microspheres on co-culture of human blood mononuclear cell and breast cancer cell lines (MCF-7).

This study investigated the effects of BaCl2 adsorbed to polyethylene glycol (PEG) microspheres on human blood mononuclear cells (MN) co-cultured with breast cancer cell lines (MCF-7). The MCF-7 cells were obtained from the American Type Culture Collection and the blood mononuclear (MN) cells from volunteer donors. MN cells, MCF-7 cells and their co-culture (MN and MCF-7 cells) were pre-incubated for 24 h with or without 25 and 1000 pg L-1 BaCl2 (Ba25 and Ba1000), PEG microspheres or 25 and 1000 pg L-1 BaCl2 adsorbed to PEG microspheres (PEG-Ba25 and PEG-Ba1000). Rheological parameters and apoptosis were determined. Fluorescence microscopy and flow cytometry analyses revealed that BaCl2 was able to adsorb the PEG microspheres. The blood flow and viscosity curves were similar among the treatments. In general, apoptosis rates increased in co-cultured cells, co-cultured cells incubated with Ba25 and with PEG-Ba25, but the highest rates were observed in co-cultured cells incubated with PEG-Ba1000. In conclusion, BaCl2 adsorbed to PEG microspheres exhibited dose-dependent antitumor effects against human MCF-7 breast cancer cells co-cultured with MN cells, thereby offering a possible therapeutic alternative for treating this disease provided they are administered at very low concentrations.

The Effect of Melatonin Adsorbed to Polyethylene Glycol Microspheres on the Survival of MCF-7 Cells.

Although melatonin exhibits oncostatic properties such as antiproliferative effects, the oral bioavailability of this hormone is less than 20%. Modified drug release systems have been used to improve the pharmacological efficiency of drugs. These systems can change the pharmacokinetics and biodistribution of the associated drugs. Thus, this study investigated the effect of melatonin adsorbed to polyethylene glycol (PEG) microspheres on MCF-7 human breast cancer cells. The MCF-7 cells were obtained from the American Type Culture Collection. MCF-7 cells were preincubated for 24 h with or without melatonin (100 ng/ml), PEG microspheres or melatonin adsorbed to PEG microspheres (100 ng/ml). Viability, intracellular calcium release and apoptosis in MCF-7 cells were determined by flow cytometry. MCF-7 cells incubated with melatonin adsorbed to PEG microspheres showed a lower viability rate (40.0 ± 8.3 with melatonin adsorbed to PEG microspheres compared to 54.1 ± 7.3 with melatonin; 81.8 ± 12.5 with PEG microsphere and 92.7 ± 4.1 with medium), increased spontaneous intracellular Ca2+ release (27.0 ± 8.6 with melatonin adsorbed to PEG microspheres compared to 21.5 ± 13.4 with melatonin; 10.1 ± 5.4 with PEG microsphere and 9.1 ± 5.6 with medium) and increased apoptosis index (51.2 ± 2.7 with melatonin adsorbed to PEG microspheres compared to 36.0 ± 2.1 with melatonin; 4.9 ± 0.5 with PEG microsphere and 3.1 ± 0.6 with medium). The results indicate that melatonin adsorbed to PEG microspheres exerts antitumor effects on human MCF-7 breast cancer cells. However, clinical tests must be performed to confirm the use of melatonin adsorbed to PEG microspheres as an alternative therapy against cancer.

Bioactive compounds of honey from different regions of Brazil: the effect of simulated gastrointestinal digestion on antioxidant and antimicrobial properties.

Monofloral and multifloral honey produced in different regions may have different bioactive compounds and antioxidant capacities, resulting in changes in the antimicrobial activity of honey. However, many of these compounds degrade due to the extreme digestion conditions, which may inhibit the antimicrobial activity. Given this context, this study aimed to describe the bioactive compounds of honey produced in Brazil and verify if honey samples from different botanical and geographical origins differ in bioactive compounds, and if honey maintains its antimicrobial activity after digestion simulation. Multivariate analysis was used to identify characteristics that differentiated the honey samples according to the botanical and geographical origin criteria. The amount of the bioactive compounds varied significantly: the total phenolic compound content varied from 20.49 to 101.44 mg GAE per 100 g, flavonoids varied from 1.41 to 13.52 mg QE per 100 g, phenolic acids varied from 13.61 to 56.41 mg CAE per 100 g, and carotenoids varied from 0.66 to 4.27 mg ß-carotene per g. Multifloral honey (H22) produced in the dry season of northeastern Brazil presented the highest bioactive compound concentration except for the carotenoid content. HPLC-MS analysis showed the presence of six hydroxybenzoic acids, four hydroxycinnamic acids, eight flavonols, three flavanones, two flavones and two isoflavonoids; Pterodon pubescens monofloral honey (H14) from midwestern Brazil stood out in terms of the carotenoid content. All analyzed honey samples exhibited antimicrobial activity against Staphylococcus aureus and Escherichia coli bacteria before digestive process simulation, and bacteria were inhibited during in vitro digestion; this activity decreased during the simulation of the oral phase, remained in the gastric phase, and disappeared in the intestinal phase.

The role of cytokines in the functional activity of phagocytes in blood and colostrum of diabetic mothers.

Immune response changes induced by diabetes are a risk factor for infections during pregnancy and may modify the development of the newborn's immune system. The present study analyzed colostrum and maternal and cord blood of diabetic women to determine (1) the levels of the cytokines IFN- γ and TGF- ß and (2) phagocytic activity after incubation with cytokines. Methods. Colostrum and maternal and cord blood samples were classified into normoglycemic (N = 20) and diabetic (N = 19) groups. Cytokine levels, superoxide release, rate of phagocytosis, bactericidal activity, and intracellular Ca(2+) release by phagocytes were analyzed in the samples. Irrespective of glycemic status, IFN- γ and TGF- ß levels were not changed in colostrum and maternal and cord blood. In maternal blood and colostrum, superoxide release by cytokine-stimulated phagocytes was similar between the groups. Compared to spontaneous release, superoxide release was stimulated by IFN- γ and TGF- ß in normoglycemic and diabetic groups. In the diabetic group, cord blood phagocytes incubated with IFN- γ exhibited higher phagocytic activity in response to EPEC, and maternal blood exhibited lower microbicidal activity. These data suggest that diabetes interferes in maternal immunological parameters and that IFN- γ and TGF- ß modulate the functional activity of phagocytes in the colostrum, maternal blood, and cord blood of pregnant diabetic women.

Application of bioinformatics in chronobiology research.

Bioinformatics and other well-established sciences, such as molecular biology, genetics, and biochemistry, provide a scientific approach for the analysis of data generated through "omics" projects that may be used in studies of chronobiology. The results of studies that apply these techniques demonstrate how they significantly aided the understanding of chronobiology. However, bioinformatics tools alone cannot eliminate the need for an understanding of the field of research or the data to be considered, nor can such tools replace analysts and researchers. It is often necessary to conduct an evaluation of the results of a data mining effort to determine the degree of reliability. To this end, familiarity with the field of investigation is necessary. It is evident that the knowledge that has been accumulated through chronobiology and the use of tools derived from bioinformatics has contributed to the recognition and understanding of the patterns and biological rhythms found in living organisms. The current work aims to develop new and important applications in the near future through chronobiology research.

Integration of nutrigenomics, melatonin, serotonin and inflammatory cytokines in the pathophysiology of pregnancy-specific urinary incontinence in women with gestational diabetes mellitus.

Gestational diabetes mellitus is an important public health problem and has been associated with the development of pregnancy-specific urinary incontinence. The interaction is related to hyperglycemia, and inflammatory and hormonal patterns, which favor functional alterations in different organs and systems. Several genes associated with human diseases have been identified and partially characterized. Most of these genes are known to cause monogenic diseases. However, about 3 % of diseases do not fit the monogenic theory due to the complex interactions between multiple genes and environmental factors, as in chronic metabolic diseases such as diabetes. The nutritional, immunological, and hormonal patterns associated with changes in maternal metabolism may influence and contribute to greater susceptibility to urinary tract disorders. However, early systematic reviews have not yielded consistent findings for these associations. This literature review summarizes important new findings from integrating nutrigenomics, hormones, and cytokines in women with Gestational diabetes mellitus and pregnancy-specific urinary incontinence. Changes in maternal metabolism due to hyperglycemia can generate an inflammatory environment with increased inflammatory cytokines. This environment modulated by inflammation can alter tryptophan uptake through food and thus influence the production of serotonin and melatonin. As these hormones seem to have protective effects against smooth muscle dysfunction and to restore the impaired contractility of the detrusor muscle, it is assumed that these changes may favor the onset of urinary incontinence specific to pregnancy.

Effects of Doxycycline Treatment on Hematological Parameters, Viscosity, and Cytokines in Canine Monocytic Ehrlichiosis.

This study aimed to analyze the hematological parameters, blood viscosity, and cytokines of dogs infected by Ehrlichia canis untreated and treated with doxycycline. Initially, 47 dogs were examined, and 36 were suspected to have canine monocytic ehrlichiosis, which was confirmed through molecular polymerase chain reaction tests. This study consisted of 25 dogs, with 11 being healthy and 14 testing positive for E. canis. The dogs were divided into experimental groups based on their test results, including a control group of healthy dogs (N = 11), a group of infected dogs without treatment (N = 7), and a group of infected dogs treated with doxycycline (N = 7) at a 10 mg/kg dose every 12 h for 28 days. Blood samples were taken to determine hematological parameters, viscosity, and cytokine levels. It was observed that, regardless of doxycycline treatment, there was a reduction in total leukocytes and lymphocytes in infected dogs with Ehrlichia canis. The eosinophils and platelets decreased in dogs with Ehrlichia canis infections without treatment. Monocytes, eosinophils, and platelets increased when the dogs were treated with doxycycline. Regardless of treatment, infected dogs' blood viscosity was lower than uninfected dogs. Infected dogs showed lower TNF-α and increased IL-1ß. There was a correlation between the blood viscosity with the cytokines IL-10 and IL-12 in the infected dogs. The eosinophil count correlated with TNF-α in the group of infected and untreated dogs. In conclusion, treating dogs with monocytic ehrlichiosis using doxycycline can increase platelet and eosinophil levels but may also increase IL-1ß and monocyte levels, exacerbating inflammation. Therefore, evaluating viscosity and cytokine levels is important when treating dogs with this condition.

Transfer of maternal immunity to newborns of diabetic mothers.

This study was carried out with hyperglycemic pregnant women to investigate the transfer of antibody classes to newborns across the placenta or by colostrum and the functional activity of phagocytes in maternal blood, cord blood, and colostrum from diabetes mothers. Samples from maternal blood, cord blood, and colostrum were collected from 20 normoglycemic and 20 hyperglycemic pregnant women. We determined antibodies levels, superoxide release, phagocytosis and bactericidal activity of phagocytes. We demonstrated that IgG levels in cord blood were higher in the hyperglycemic group. IgA and IgM levels were higher in maternal than in cord blood samples. Plasma antibody levels were lower in hyper- than in normoglycemic women. The colostrum of diabetic mothers had lower IgA and IgG levels. Colostrum and maternal blood phagocytes when exposed to EPEC increased the superoxide release. Cord blood phagocytes of hyperglycemic group, independently of bacteria, had higher superoxide release. Colostrum and blood phagocytes from diabetic group exhibited some phagocytic and microbicidal activity in response to EPEC. Mononuclear phagocytes from cord blood had the lowest phagocytosis, and bactericidal activity for EPEC, regardless of glycemic status. These data showed that hyperglycemia altered IgG transfer across the placenta and decreases immunoglobulin levels in maternal blood and colostrum.

Bioactive compounds of pequi pulp and oil extracts modulate antioxidant activity and antiproliferative activity in cocultured blood mononuclear cells and breast cancer cells.

BACKGROUND: Pequi (Caryocar brasiliense Camb.) is a fruit from Brazilian Cerrado rich in bioactive compounds, such as phytosterols and tocopherols, which can modulate the death of cancer cells. OBJECTIVE: In the present study, the main bioactive compounds of hydrophilic and lipophilic extracts of pequi oil and pulp were identified and were verified if they exert modulatory effects on oxidative stress of mononuclear cells cocultured with MCF-7 breast cancer cells. STUDY DESIGN: Identification and quantification of the main compounds and classes of bioactive compounds in pequi pulp and oil, hydrophilic, and lipophilic extracts were performed using spectroscopy and liquid chromatographic methods, while the beneficial effects, such as antioxidant capacity in vitro, were determined using methods based on single electron transfer reaction or hydrogen atom transfer, while for antioxidant and antiproliferative activities ex vivo, 20 healthy volunteers were recruited. Human peripheral blood mononuclear cells (MN) were collected, and cellular viability assay by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide), superoxide anion evaluation, and CuZn-superoxide dismutase determination (CuZn-SOD) in MN cells, MCF-7 cells, and coculture of MN cells and MCF-7 cells in the presence and absence of pequi pulp or oil hydrophilic and lipophilic extracts were performed. RESULTS: In the hydrophilic extract, the pequi pulp presented the highest phenolic content, while in the oil lipophilic extract, it had the highest content of carotenoids. The main phytosterol in pequi oil was ß-sitosterol (10.22 mg/g), and the main tocopherol was γ-tocopherol (26.24 µg/g sample). The extracts that had highest content of bioactive compounds stimulated blood mononuclear cells and also improved SOD activity. By evaluating the extracts against MCF-7 cells and coculture, they showed cytotoxic activity. CONCLUSION: The results support the anticarcinogenic activity of pequi extracts, in which the pequi pulp hydrophilic extracts presented better immunomodulatory potential.

Resistin Modulates the Functional Activity of Colostral Macrophages from Mothers with Obesity and Diabetes.

BACKGROUND: Obesity and diabetes are major public health problems. Resistin is an adipokine that links the two diseases. There are few reports regarding colostrum cells and resistin from mothers with obesity and diabetes. Thus, this study aimed to determine the functional activity of macrophages present in the breast milk and colostrum of diabetic mothers with obesity and the effects of resistin on these cells. METHODS: The women were divided according to BMI and glycemic status into normal weight non-diabetic, obese non-diabetic, normal weight type 2 diabetic, or obese type 2 diabetic groups. ELISA determined the resistin in colostrum. The cell subsets and apoptosis were determined by flow cytometry and the functional activity of cells by fluorescence microscopy. RESULTS: The resistin levels were higher in the colostrum from diabetic mothers with obesity. The frequencies of CD14+ cells and cells expressing CD95+, independent of resistin treatment, were higher in the colostrum from diabetic mothers with obesity. The frequency of cells expressing CD14+CD95+ was higher in cells not treated with resistin in the colostrum from diabetic mothers with obesity. Apoptosis, irrespective of the presence of resistin, increased, whereas microbicidal activity decreased in cells from diabetic mothers with obesity. CONCLUSION: The data suggest that hyperglycemia associated with low-grade inflammation caused by obesity affects the percentage of cells expressing CD14+CD95+, death by apoptosis, and microbicidal indices; meanwhile, resistin restored the microbicidal activity of colostrum cells.

Effects of Cytokines IFN-γ and TGF-ß on the Functional Activity of Blood Mononuclear Cells against Giardia lamblia.

BACKGROUND: This study aimed to analyze cultures of mononuclear (MN) cells with Giardia lamblia to determine the levels of the cytokines IFN-γ and TGF-ß and the functional activity of MN cells after incubation with cytokines. METHODS: This study was conducted in 2018 in Barra do Garças, Mato Grosso State, Brazil. Blood samples were collected from 60 healthy volunteer donors to obtain leukocytes. The levels of IFN-γ and TGF-ß were quantified in trophozoite cell culture supernatants. Superoxide release, phagocytosis, microbicidal activity, apoptosis and intracellular calcium release were analyzed. RESULTS: The cytokines evaluated were detected in the culture supernatant of MN cells and G. lamblia. Regardless of the type of cytokine, MN cells increased superoxide release in the presence of G. lamblia. Phagocytosis, microbicidal activity and apoptosis were higher when MN phagocytes were treated with cytokines. The highest microbicidal activity and apoptosis rates were observed in MN cells cultured with TGF-ß. IFN-γ increased the release of intracellular calcium by MN phagocytes. CONCLUSION: Cytokines play a beneficial role in the host by activating MN cells against G. lamblia. In addition, phagocytosis causes G. lamblia death and that the modulation of the functional activity of blood MN phagocytes by cytokines is an alternative mechanism for eliminating G. lamblia.

Melatonin Hormone Acts on Cells of Maternal Blood and Placenta From Diabetic Mothers.

Changes in glucose metabolism of diabetic mothers affect immunological components, proinflammatory factors, and placental hypervascularization that can induce cell death. The hormone melatonin has been identified as a potential modulating agent. The aim of this study was to analyze the oxidative process and the apoptosis in maternal blood and placental cells modulated by melatonin from diabetic mothers. The groups were 40 pregnant women divided into non-diabetic (ND) and type 2 diabetes mellitus (T2DM) groups. Blood and placental cells were obtained by density gradient and maintained in culture treated or not with melatonin (100 ng/mL) for 24 h (37°C, 5% CO2). Oxidative stress was evaluated by superoxide release and CuZn superoxide dismutase (SOD). Apoptosis was assessed by flow cytometry. Maternal hyperglycemia increased superoxide release and apoptosis in MN cells from maternal blood and reduced SOD level and SOD/O2- ratio. Melatonin reduced oxidative stress and apoptosis rates in MN cells in the blood of diabetic mothers. There was a reduction in SOD and SOD/O2- ratio in the placental extravillous layer, and melatonin restored the concentrations of this enzyme. There was greater superoxide release, reduced SOD/O2- ratio, and apoptosis in MN cells placental villous layer. Melatonin increased apoptosis rates in the placental villous layer from hyperglycemic mothers. These data suggest that hyperglycemia altered the processes oxidative in blood and placenta from hyperglycemic mothers. These changes reflected in the mechanisms of induction of apoptosis, especially in the vascularized layers of the placenta, and were modulated by melatonin.

Modulatory role of melatonin on superoxide release by spleen macrophages isolated from alloxan-induced diabetic rats.

UNLABELLED: The aim of this study was to evaluate the modulatory effect of melatonin on superoxide release by spleen macrophages isolated from alloxan-induced diabetic insulin treated or non-treated rats. METHODS: Blood glucose, body weight, CuZn-superoxide dismutase concentration, and superoxide release by spleen macrophages were evaluated. RESULTS: The spontaneous superoxide release from the macrophages of the control group was lower when compared to diabetic rats without insulin treatment. Melatonin (MLT) significantly increased the superoxide release in the control group (11.5 +/- 1.5 with MLT x 6.8 +/- 1.0 without MLT). The macrophages from diabetic rats treated with insulin exhibited a decreased superoxide release (7.0 +/- 2.4), when compared to superoxide release of the macrophages from diabetic rats without insulin (14.7 +/- 3.7). CuZn-SOD concentrations were increased in both diabetic groups. CONCLUSION: The pineal hormone melatonin in physiological concentration can stimulate natural immunity since it triggers the superoxide release from the macrophages, an important anti-infectious mechanism. On the other side, melatonin had antioxidant effects in the macrophages from insulin-treated alloxan-induced diabetic rats (Tab. 1, Fig. 2, Ref. 51).

Dental implant surfaces treated with phosphoric acid can modulate cytokine production by blood MN cells.

The study characterizes dental implant surfaces treated with phosphoric acid to assess the effects of acid treatment on blood cells and correlate them with cytokine levels. The implant surfaces examined were divided into untreated metal surface (US; n = 50), metal surface treated with phosphoric acid (ATS; n = 50) and cement surface (CS; n = 50) groups. The samples were characterized by scanning electron microscopy (SEM) and rheometry. The implants were incubated with human blood mononuclear cells for 24 h, with surface rinsing in the ATS treatment. Cell viability was determined by colorimetric methods and cytokines in the culture supernatant were quantified using flow cytometry. In the ATS group, the surface porosity and contact surface were increased and plaques were observed on the surface. The blood flow and viscosity curves were similar among the treatments, and the high cell viability rates indicate the biocompatibility of the materials used. An increase in the levels of IL-2, IL-4, IL-6, IL-10 and TNF-α was observed in the ATS and CS groups. There were positive correlations between IL-10 and IL-2 levels and between IL-10 and IL-4 levels in the culture supernatant of the ATS group. The results suggest that implant surface treatment with phosphoric acid activates the production of inflammatory cytokines. The increased cytokine levels can modulate the immune response, thereby improving biofunctional processes and promoting the success of dental implants.