Publications by authors named "Maíra Galdino da Rocha Pitta"

66 Publications

Synthesis, anticancer activity and mechanism of action of new phthalimido-1,3-thiazoles derivatives.

Chem Biol Interact 2021 Jul 22:109597. Epub 2021 Jul 22.

Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, 50740-520, Recife, PE, Brazil. Electronic address:

In this work, 22 new compounds were obtained and evaluated for their cytotoxic activity on peripheral blood mononuclear cells (PBMC) and eight different tumor cell lines. All compounds displayed IC values above 100 μM when assayed against PBMCs. The cytotoxic assays in tumor cell lines revealed that sub-series of phthalimido-bis-1,3-thiazoles (5a-f) exhibited the best anti-tumor activity profile, presenting viability values below 59 %. As a result, the IC value was calculated for compounds 5a-f and 4c, and compounds 5b and 5e were selected for further assays due to their best ICs. Considering the results presented by the sub-series 5a-f, the importance of the 1,3-thiazole ring in improving the anti-tumor activity was pointed out. Together, the results highlighted the anti-tumor activity of phthalimido-bis-1,3-thiazoles derivatives.
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http://dx.doi.org/10.1016/j.cbi.2021.109597DOI Listing
July 2021

Development, Characterization, and Immunomodulatory Evaluation of Carvacrol-loaded Nanoemulsion.

Molecules 2021 Jun 25;26(13). Epub 2021 Jun 25.

Laboratory of Synthesis and Drug Delivery, State University of Paraiba, João Pessoa, PB 58071-160, Brazil.

Carvacrol (CV) is an essential oil with numerous therapeutic properties, including immunomodulatory activity. However, this effect has not been studied in nanoemulsion systems. The objective of this study was to develop an innovative carvacrol-loaded nanoemulsion (CVNE) for immunomodulatory action. The developed CVNE comprised of 5% / oily phase (medium chain triglycerides + CV), 2% / surfactants (Tween 80/Span 80), and 93% / water, and was produced by ultrasonication. Dynamic light scattering over 90 days was used to characterize CVNE. Cytotoxic activity and quantification of cytokines were evaluated in peripheral blood mononuclear cell (PBMC) culture supernatants. CVNE achieved a drug loading of 4.29 mg/mL, droplet size of 165.70 ± 0.46 nm, polydispersity index of 0.14 ± 0.03, zeta potential of -10.25 ± 0.52 mV, and good stability for 90 days. CVNE showed no cytotoxicity at concentrations up to 200 µM in PBMCs. CV diminished the production of IL-2 in the PBMC supernatant. However, CVNE reduced the levels of the pro-inflammatory cytokines IL-2, IL-17, and IFN-γ at 50 µM. In conclusion, a stable CVNE was produced, which improved the CV immunomodulatory activity in PBMCs.
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http://dx.doi.org/10.3390/molecules26133899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8271444PMC
June 2021

PA-Int5: An isatin-thiosemicarbazone derivative that exhibits anti-nociceptive and anti-inflammatory effects in Swiss mice.

Biomed Rep 2021 Jul 26;15(1):61. Epub 2021 May 26.

Research Laboratory of Clinical Biochemistry, Department of Clinical and Toxicological Analysis, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte 59012-570, Brazil.

Pain and inflammation are symptoms of various diseases, and they can be modulated by different pathways, thus highlighting the importance of investigating the therapeutic effects of novel compounds. Previous studies have shown that isatin-thiosemicarbazone exhibits antitumor, antifungal antibacterial and other biological properties. Based on the wide range of biological effects of these compounds, the aim of the present study was to investigate the central nervous system (CNS) performance, and the anti-nociceptive and anti-inflammatory activity of (Z)-2-(5-nitro-2-oxoindolin-3-ilidene)-N-hydroazinecarbothioamide (PA-Int5) in treated mice. Three doses of PA-Int5 were tested orally (1.0, 2.5 and 5.0 mg/kg) in the nociceptive and inflammatory animal models. Additionally, the potential sedative effects of PA-Int5 (5 mg/kg, oral gavage) were investigated using an open field and rotarod tests, to exclude any possible unspecific effects of the nociceptive assays. Anti-nociceptive activity was assessed using the acetic acid-induced abdominal contortion and formalin tests, whereas anti-inflammatory activity was assessed using a carrageenan-induced paw edema and zymosan-induced air-pouch models. PA-Int5 (5 mg/kg) induced anti-nociceptive activity in the abdominal contortion model. In the formalin test, PA-Int5 (at 2.5 and 5 mg/kg) reduced nociception in the second phase. At the higher dose tested, PA-Int5 did not affect spontaneous locomotion or motor coordination. The data revealed that at all doses tested, the compound significantly reduced paw edema following carrageenan administration. In the zymosan-induced air-pouch model, PA-Int5 potently inhibited leukocyte migration and protein levels at the site of inflammation. When combined, the results revealed, for the first time, that PA-Int5 exhibited anti-nociceptive and anti-inflammatory activities, and highlights its potential, as well that of other derivatives, as novel candidates for pain relief.
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http://dx.doi.org/10.3892/br.2021.1437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165752PMC
July 2021

Interleukin-18 in Brazilian Rheumatoid Arthritis Patients: Can Leflunomide Reduce It?

Autoimmune Dis 2021 10;2021:6672987. Epub 2021 May 10.

Laboratory of Immunomodulation and New Therapeutic Approaches (LINAT), Research Group on Immunomodulation and New Therapeutic Approaches Suely Galdino (Nupit SG), Federal University of Pernambuco, Recife, Brazil.

Objectives: Rheumatoid arthritis affects about 1% of the world's population. This is a chronic autoimmune disease. It is predominant in females with progressive joint damage. Immune cells are involved, especially Th1/Th17 lymphocytes and their inflammatory cytokines. These proteins have different functions in the immune system, such as IL-16 is a chemotactic factor; IL-18 can activate NFB transcription producing inflammatory proteins; IL-31 can activate the JAK/STAT pathway which leads to the production of inflammatory factors in chronic diseases; IL-33 promotes IL-16 secretion which causes lymphocyte recruitment, and IL-32 and IL-34 appear to increase TNF secretion by macrophages activation in AR. The aim of this study was to evaluate serum levels of IL-16, IL-18, IL-31, IL-32, IL-33, and IL-34 and compare them with the severity and treatment of RA patients if there are any correlations.

Methods: A total of 140 RA patients and 40 healthy donors were recruited from the Department of Rheumatology at Hospital das Clínicas from the Federal University of Pernambuco. 60 AR patients were naïve for any treatment. Serum cytokine levels were determined using an ELISA kit.

Results: Serum IL-16 ( = 0.0491), IL-18 ( < 0.0001), IL-31 ( = 0.0004), and IL-32 ( = 0.0040) levels were significantly increased in RA patients compared with healthy donors. It was observed that patients using leflunomide had the lowest IL-18 levels, close to controls levels ( = 0.0064).

Conclusion: IL-16, IL-18, IL-31, and IL-32 are increased in the serum of RA patients. IL-18 is at lower levels in those AR who are taking leflunomide as treatment.
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http://dx.doi.org/10.1155/2021/6672987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131162PMC
May 2021

Genetic variants in are related to lower galectin-3 serum levels and clinical outcomes in systemic sclerosis patients: A case-control study.

Autoimmunity 2021 Jun 11;54(4):187-194. Epub 2021 May 11.

Laboratório de Imunomodulação e Novas Abordagens Terapêuticas (LINAT), Núcleo de Pesquisa em Inovação Terapêutica - Suely Galdino (NUPIT-SG), Universidade Federal de Pernambuco (UFPE), Recife, PE, Brazil.

Introduction: Systemic sclerosis (SSc) is a rare complex disease characterized by vascular damage, autoimmunity, and extensive skin and internal organs fibrosis. Galectin-3 (Gal-3) is encoded by gene (Lectin, Galactoside-Binding, Soluble, 3; 14q22.3) and it has been reported to play a central role in self-tolerance, inflammation, and fibrosis.

Objective: To investigate associations among single nucleotide polymorphisms (SNPs) and serum levels Gal-3 and SSc susceptibility and their clinical features.

Methods: A case-control study with 88 patients and 151 matched controls was performed. variants were analyzed by the TaqMan real-time polymerase chain reaction (PCR) system whereas Gal-3 serum levels were measured by sandwich enzyme linked immunosorbent assay (ELISA). Associations among genotypes, clinical features, and Gal-3 levels were performed by univariable and multivariable analysis through statistical packages.

Results: The rs4652 A/C genotype was more frequent in SSc patients than controls according to overdominant model [OR 1.89 (CI 95% 1.01 - 3.52);  = .046]. Also, rs4652 C/C polymorphic genotype was associated with lower patient Gal-3 levels ( = .03) and control group ( = 0.005), as noted by generalized linear model (GLM). The rs1009977 G/T controls showed higher Gal-3 levels than wild-type and polymorphic genotypes ( = .03); however, in SSc patients, no difference was found. None of the SNPs or Gal-3 levels was associated with clinical manifestations in SSc patients. Considering only the SSc group, GLM analysis pointed rs4652 and rs2075601, pulmonary arterial hypertension (PAH), myopathy, and health assessment questionnaire (HAQ) and scleroderma health assessment questionnaire (SHAQ) as important predictors for Gal-3 levels.

Conclusion: The rs4652 A/C was more frequent in SSc patients and related to lower Gal-3 levels. These findings were corroborated through a GLM to estimate Gal-3 values. Also, by model equations, Gal-3 levels may be predicted by HAQ, SHAQ, PAH, myopathy, and rs4652 and rs2075601 factors. In these ways, we suggest that galectins may be promising biomarkers to identify susceptibility to SSc as well as to identify HAQ, SHAQ, PAH, and myopathy outcomes.
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http://dx.doi.org/10.1080/08916934.2021.1919881DOI Listing
June 2021

Unveiling the pathogenesis of perineural invasion from the perspective of neuroactive molecules.

Biochem Pharmacol 2021 Jun 8;188:114547. Epub 2021 Apr 8.

Biochemistry Department, Federal University of Pernambuco, Recife, Brazil.

Perineural invasion (PNI) is characterized by an encounter between the cancer cells and neuronal fibers and holds an extremely poor prognosis for malignant tumors. The exact molecular mechanism behind PNI yet remains to be explored. However, it is worth-noting that an involvement of the neuroactive molecules plays a major part in this process. A complex signaling network comprising the interplay between immunological cascades and neurogenic molecules such as tumor-derived neurotrophins, neuromodulators, and growth factors constitutes an active microenvironment for PNI associated with malignancy. The present review aims at discussing the following points in relation to PNI: a) Communication between PNI and neuroplasticity mechanisms can explain the pathophysiology of poor, short and long-term outcomes in cancer patients; b) Neuroactive molecules can significantly alter the neurons and cancer cells so as to sustain PNI progression; c) Finally, careful manipulation of neurogenic pathways and/or their crosstalk with the immunological molecules implicated in PNI could provide a potential breakthrough in cancer therapeutics.
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http://dx.doi.org/10.1016/j.bcp.2021.114547DOI Listing
June 2021

Immunopositivity for Siglec-15 in gastric cancer and its association with clinical and pathological parameters.

Eur J Histochem 2021 Mar 4;65(1). Epub 2021 Mar 4.

Laboratório de Imunomodulação e Novas Abordagens Terapêuticas - LINAT / Núcleo de Pesquisa em Inovação Terapêutica Suely Galdino - NUPIT SG, Universidade Federal de Pernambuco, Recife.

The sialic acid-binding immunoglobulin-type lectin Siglec-15 is a promising target to cancer immunotherapy in several tumor types. The present study aimed to investigate Siglec-15 expression in gastric cancer (GC) patient tissue and to evaluate its clinical value. Siglec-15 expression was evaluated by immunohistochemistry with 71 patients. Siglec-15 staining was observed in tumor cells of 53 (74.64%) patients, with significant association with histologic classification and angiolymphatic invasion (p<0.05). Immunohistochemistry analysis also detected Siglec-15 in tumor-associated stroma cells (macrophages/myeloid cells). There was no significant association with outcomes parameters. Siglec-15 expression in well differentiated histological GC tissues and in the tumor microenvironment are potential targets to be further investigated as a novel prognostic factor for GC.
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http://dx.doi.org/10.4081/ejh.2021.3174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967265PMC
March 2021

Investigation of a new oxazolidine derivative in human resistance acute leukemia cells: deciphering its mechanism of action by label-free proteomic.

Naunyn Schmiedebergs Arch Pharmacol 2021 06 21;394(6):1153-1166. Epub 2021 Jan 21.

Research Center for Therapeutic Innovation (NUPIT-SG), Federal University of Pernambuco, Professor Moraes Rêgo s/n, Cidade Universitária, Recife, Pernambuco, 50670-901, Brazil.

The present study aimed to evaluate the mechanism of action of the antineoplastic activity of an oxazolidine derivative, LPSF/NB-3 (5-(4-cloro-benzilideno)-3-etil-2-tioxo-oxazolidin-4-ona). Cytotoxicity assays were performed in peripheral blood mononuclear cells (PBMCs) and resistant acute leukemia cell line (HL-60/MX1) by the MTT method. LPSF/NB-3 exhibited cytotoxicity in HL-60/MX1, but it was not toxic to healthy cells in the highest dose tested (100 μM). The protein extract of HL-60/MX1 cells treated with LPSF/NB-3 was subjected to proteomic analysis using two-dimensional chromatography coupled to mass spectrometry. We could identify a total of 2652 proteins, in which 633 were statistically modulated. Within the group of protein considered for the quantitative analysis with the established criteria, 262 were differentially expressed, 146 with increased expression and 116 with decreased expression in the sample treated with LPSF/NB-3 compared to the control. The following differentially expressed pathways were found: involving regulation of the cytoskeleton, DNA damage, and transduce cellular signals. Networks that were highlighted are related to the immune system. The ELISA technique was used to assess the immunomodulatory potential of LPSF/NB-3 in PBMCs. We observed significant decrease of IFNγ (p < 0.01) and dose-response pattern of the cytokines IL-6, IL-17A, IL-22, and IL-10. Therefore, results suggest that LPSF/NB-3 appears to modulate important pathways, including cell cycle and immune system regulatory pathways.
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http://dx.doi.org/10.1007/s00210-020-02024-8DOI Listing
June 2021

Evaluation of IL-33 and IL-34 Plasma Levels in a Cohort of Multiple Myeloma Patients in Northeast Brazil.

J Interferon Cytokine Res 2020 11;40(11):540-541

Research Center for Therapeutic Innovation (NUPIT-SG), Federal University of Pernambuco, Recife, Pernambuco, Brazil.

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http://dx.doi.org/10.1089/jir.2020.0100DOI Listing
November 2020

Galectin-3 Expression in Pancreatic Cell Lines Under Distinct Autophagy-Inducing Stimulus.

Microsc Microanal 2020 12;26(6):1187-1197

Immunomodulation and New Therapy Approaches Laboratory (LINAT), Biochemistry Department, Federal University of Pernambuco (UFPE), Cidade Universitária, Recife, Pernambuco50670-901, Brazil.

Hypoxia and nutrient deprivation are responsible for inducing malignant behavior in neoplastic cells. In these conditions, metabolic stress leads the cells to enhance their autophagic flux and to activate key molecules for homeostasis maintenance. Galectin-3 (Gal-3) is upregulated in pancreatic cancer and it is activated under the hypoxic atmosphere. We aimed to analyze the most effective autophagic-inducing conditions in pancreatic ductal adenocarcinoma cells and the effect exerted under these conditions in association with hypoxia on the Gal-3 expression. Gal-3 and the microtubule-associated protein light chain 3 beta (LC3) were accessed through western blot and immunofluorescence. Degradative vacuole quantification was analyzed by transmission electronic microscopy, and inhibition of Gal-3 was performed using siRNA. According to the analyses, the most effective conditions in the inducement of autophagy for PANC-1 and MIA PaCa-2 cells were nutritional deprivation and complete amino acid/glucose deprivation, respectively. PANC-1 cells presented higher Gal-3 when they were submitted to 24 h of nutritional deprivation alone and simultaneously nutritional and oxygen deprivation. Inhibition of Gal-3 causes a decrease of LC3 levels in all experimental conditions. These results confirm that Gal-3 is modulated by microenvironment factors and the possibility of Gal-3 participating in an adaptive response from PDAC cells to extreme conditions.
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http://dx.doi.org/10.1017/S1431927620024526DOI Listing
December 2020

New Oxazolidines Inhibit the Secretion of IFN-γ and IL-17 by PBMCS from Moderate to Severe Asthmatic Patients.

Med Chem 2021 ;17(3):289-297

Laboratorio de Imunomodulacao e Novas Abordagens Terapeuticas (LINAT), Nucleo de Pesquisa em Inovacao Terapeutica Suely Galdino (NUPIT-SG), Universidade Federal de Pernambuco, Recife, PE, Brazil.

Background: Moderate to severe asthma could be induced by diverse proinflammatory cytokines, as IL-17 and IFN-γ, which are also related to treatment resistance and airway hyperresponsiveness. Oxazolidines emerged as a novel approach for asthma treatment, since some chemical peculiarities were suggested by previous studies.

Objective: The present study aimed to evaluate the IL-17A and IFN-γ modulatory effect of two new oxazolidine derivatives (LPSF/NB-12 and -13) on mononucleated cells of patients with moderate and severe asthma.

Methods: The study first looked at potential targets for oxazolidine derivatives using SWISS-ADME. After the synthesis of the compounds, cytotoxicity and cytokine levels were analyzed.

Results: We demonstrated that LPSF/NB-12 and -13 reduced IFN-γ and IL-17 production in peripheral blood mononucleated cells from asthmatic patients in a concentrated manner. Our in silico analysis showed the neurokinin-1 receptor as a common target for both compounds, which is responsible for diverse proinflammatory effects of moderate and severe asthma.

Conclusion: The work demonstrated a novel approach against asthma, which deserves further studies of its mechanisms of action.
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http://dx.doi.org/10.2174/1573406416666200910151950DOI Listing
June 2021

A Spatio-Temporal Analysis of the Environmental Correlates of COVID-19 Incidence in Spain.

Geogr Anal 2020 Jun 8. Epub 2020 Jun 8.

Núcleo de Pesquisa em Inovação Terapêutica NUPIT/UFPE Universidade Federal de Pernambuco Recife Brazil.

The novel SARS-CoV2 has disrupted health systems and the economy, and public health interventions to slow its spread have been costly. How and when to ease restrictions to movement hinges in part on whether SARS-CoV2 will display seasonality due to variations in temperature, humidity, and hours of sunshine. Here, we address this question by means of a spatio-temporal analysis in Spain of the incidence of COVID-19, the disease caused by the virus. Use of spatial Seemingly Unrelated Regressions (SUR) allows us to model the incidence of reported cases of the disease per 100,000 population as an interregional contagion process, in addition to a function of temperature, humidity, and sunshine. In the analysis we also control for GDP per capita, percentage of older adults in the population, population density, and presence of mass transit systems. The results support the hypothesis that incidence of the disease is lower at higher temperatures and higher levels of humidity. Sunshine, in contrast, displays a positive association with incidence of the disease. Our control variables also yield interesting insights. Higher incidence is associated with higher GDP per capita and presence of mass transit systems in the province; in contrast, population density and percentage of older adults display negative associations with incidence of COVID-19.
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http://dx.doi.org/10.1111/gean.12241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300768PMC
June 2020

Increased serum levels of galectin-9 in patients with chikungunya fever.

Virus Res 2020 09 18;286:198062. Epub 2020 Jun 18.

Programa de Pós-Graduação em Inovação Terapêutica (PPGIT)/ UFPE, Brazil; Núcleo de Pesquisa em Inovação Terapêutica - Sueli Galdino (Nupit-SG), Brazil.

Chikungunya fever (CHIKF) is an arboviral disease that has caused an epidemic burst of chronic inflammatory joint disease in Latin America in the last few years. Efforts are being spent in understanding the mechanisms by which it may cause such articular damage and in determining possible biomarkers of the disease. Galectins (GAL) are a family of animal lectins with an affinity for beta-galactosides. They have multiple functions including working as receptors in innate immunity and as a control for inflammatory responses in both innate and adaptive immunity. They regulate functions of immune cells, such as lymphocytes and macrophages, which have a main role in the chikungunya inflammatory process. Galectins are also involved in chronification of viral diseases, participate in the immunopathogenesis of chronic joint diseases such as rheumatoid arthritis, and have a role in inflammation in other arboviral diseases, such as dengue. Thus, we intended to determine the serum levels of galectin-1, -3, -4, -7, and -9 in patients with subacute and chronic articular manifestations of CHIKF and to evaluate their associations with clinical manifestations. We evaluated 44 patients with clinical manifestations of CHIKF and serological confirmation with IgM and/or IgG chikungunya virus (CHIKV) antibodies. Forty-nine age- and gender-matched healthy individuals served as controls. Anti-CHIKV IgM and IgG antibodies and galectins serum levels were measured by ELISA. We found higher levels of GAL-9 (patients median 2192 [1500-2631] pg/mL, controls median 46.88 [46.88-46.88] pg/mL, p < 0.0001) and lower levels of GAL-3 (patients median 235.5 [175.5-351.8] pg/mL, controls median 2236.0 [1256.0-2236.0] pg/mL, p < 0.0001) in patients than in controls. There was no statistical difference in levels of GAL-1, -4 and -7 between patients and control groups. There was no difference in GAL-9 serum levels between patients with subacute or chronic symptoms (median 2148 [1500-2722] pg/mL x 2212 [1844-2500] pg/mL, p = 0.3626). A significant association of GAL-9 with joint stiffness, both in its duration and intensity, was found. These results may reflect the participation of GAL-9 in the immunopathogenesis of the inflammatory process in chikungunya fever, as morning stiffness may reflect the systemic inflammatory process.
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http://dx.doi.org/10.1016/j.virusres.2020.198062DOI Listing
September 2020

Increased levels of the soluble oncostatin M receptor (sOSMR) and glycoprotein 130 (sgp130) in systemic sclerosis patients and associations with clinical parameters.

Immunobiology 2020 05 22;225(3):151964. Epub 2020 May 22.

Laboratório de Imunomodulação e Novas Abordagens Terapêuticas, Núcleo de Pesquisa em Inovação Terapêutica, Universidade Federal de Pernambuco, Recife, PE, Brazil. Electronic address:

Objective: The objective of the present study was to evaluate the serum levels of soluble oncostatin M (OSM), OSM receptor (sOSMR) and glycoprotein130 (sgp130) in patients with systemic sclerosis (SSc), and the possible associations and correlations with clinical parameters.

Methods: Serum levels of OSM, sOSMR and sgp130 were evaluated by ELISA in eighty-four SSc patients and eighty-four healthy volunteers.

Results: SSc patients had significantly elevated levels of sOSMR and sgp130 when compared with healthy individuals (p < 0.0001 and p = 0.025, respectively). Diffuse cutaneous SSc and limited cutaneous SSc patients also presented higher levels of sOSMR when compared with healthy individuals (p = 0.003 and p = 0.0001, respectively). Patients with digital ulcers presented higher levels of sOSMR when compared to those without ulcers (p = 0.034). However, sOSMR levels were lower in patients with esophageal dysfunction than patients without this involvement (p = 0.038). OSM levels were undetectable in serum from SSc patients and healthy volunteers.

Conclusion: Serum levels of sOSMR and sgp130 are elevated in patients with systemic sclerosis. In addition, associations were observed with important clinical manifestations, suggesting that sOSMR is a candidate biomarker of this disease. More studies are needed to clarify the functions of IL-6 family cytokines in systemic sclerosis.
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http://dx.doi.org/10.1016/j.imbio.2020.151964DOI Listing
May 2020

Atorvastatin inhibits IL-17A, TNF, IL-6, and IL-10 in PBMC cultures from patients with severe rheumatoid arthritis.

Immunobiology 2020 05 30;225(3):151908. Epub 2020 Jan 30.

Laboratory of Immunomodulation and New Therapeutic Approaches (LINAT), Suely-Galdino Therapeutic Innovation Research Center (NUPIT-SG), Federal University of Pernambuco (UFPE), Recife, PE, Brazil.

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint damage, and it may present with comorbidities at the systemic level. The Th1/Th2/Th17 CD4 lymphocyte imbalance produces inflammatory cytokines, which begin to act, injuring joint tissue. Atorvastatin is a cholesterol- lowering drug with a range of biological effects including anti-inflammatory potential. Patients with rheumatoid arthritis who used statins exhibited clinical improvement. However, the mechanism is not fully understood. Therefore, we aimed to evaluate the RA immunomodulatory activity of atorvastatin.

Methods: Peripheral blood mononuclear cells (PBMCs) of RA patients and healthy donors were exposed to atorvastatin in different concentrations following a cytotoxicity assay. Th1, Th2, and Th17 cytokines profiles were evaluated in the culture supernatant by cytometric bead array (CBA). Data were analyzed using the Wilcoxon test, and differences were considered significant when p < 0.05.

Results: Atorvastatin showed no toxicity at the tested doses in RA PBMC cultures, and at 10μM, it showed the most significant results, reducing IL-17A (p = 0.002), TNF (p = 0.002), and IL-6 (p = 0.008) supernatant levels. The outcomes also revealed that only patients with more severe disease activity and those sensitive to corticoid treatments were responders to atorvastatin in vitro.

Conclusion: These findings suggest the potential immunomodulatory action of atorvastatin as a mechanism in rheumatoid arthritis treatment.
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http://dx.doi.org/10.1016/j.imbio.2020.151908DOI Listing
May 2020

Sensitivity and specificity of Interleukin 29 in patients with rheumatoid arthritis and other rheumatic diseases.

Immunol Lett 2020 04 16;220:38-43. Epub 2020 Jan 16.

Laboratório de Imunomodulação e Novas Abordagens Terapêuticas, Núcleo de Pesquisa em Inovação Terapêutica, Universidade Federal de Pernambuco, Recife-PE, Brazil. Electronic address:

Background: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic and progressive inflammation that can cause a high degree of disability in affected individuals. Proinflammatory cytokines play central roles in the development of degradative and inflammatory responses in RA. IL-29 has been identified in RA and reported as a biomarker of the disease.

Objective: To analyze serum levels and accuracy of IL-29 in RA patients compared to healthy subjects and patients with other rheumatic diseases.

Methods: IL-29 serum levels were measured in 121 patients with RA, 53 patients with systemic lupus erythematosus (SLE), 60 patients with systemic sclerosis (SSc), 29 patients with fibromyalgia (FM), 50 patients with osteoarthritis (OA) and 68 healthy individuals as controls. IL-29 levels in serum were investigated by ELISA. Sensitivity, specificity and likelihood ratios (LR) for having RA were calculated.

Results: Serum levels of IL-29 were increased in RA patients 113.6 (IQR = 31.25-308.5) pg/ml compared to non-RA patients (SLE, SSc, OA, and FM) (31.25 pg/ml) and healthy controls (31.25 pg/ml, p < 0.001). The IL-29 cut-off values to distinguish patients with RA from non-RA patients were 61.11 pg/ml (sensitivity 57.02, specificity 92.71, LR: 7.82) and for all subjects 32.96 pg/ml (sensitivity 64.46, specificity 87.31, LR: 5.08). Additionally, IL-29 correlated negatively with age (r=-0189, p = 0.038) and disease duration (-0.192, p = 0.037). Interestingly, IL-29 correlated positively with neutrophil count in RA patients positive for rheumatoid factor (r = 0.259, p = 0.022).

Conclusion: IL-29 is higher in the serum of patients with RA compared to non-RA subjects and may have potential for use as a biological marker.
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http://dx.doi.org/10.1016/j.imlet.2020.01.004DOI Listing
April 2020

Overexpression of UDP-Glucose 4-Epimerase Is Associated with Differentiation Grade of Gastric Cancer.

Dis Markers 2019 20;2019:6325326. Epub 2019 Nov 20.

Laboratório de Imunomodulação e Novas Abordagens Terapêuticas-LINAT/Núcleo de Pesquisa em Inovação Terapêutica Suely Galdino-NUPIT SG, Universidade Federal de Pernambuco, Recife, PE, Brazil.

The UDP-glucose 4-epimerase (GALE) is a glycosyltransferase, which acts on protein and lipid glycosylation in normal and neoplastic cells. This study is aimed at investigating the differential tissue expression of GALE and its possible association with clinical-pathological parameters and the outcome of gastric adenocarcinoma patients. Seventy-one patients were evaluated in relation to GALE expression by immunohistochemistry. Our results showed that 48 (67.6%) patients were GALE positive and 23 (32.4%) negative. Positive staining was present on well-differentiated and moderate-differentiated histological grade of gastric adenocarcinomas ( < 0.0001). There was no significant association with outcome parameters ( > 0.05). Besides that, our results corroborated with the validation cohort analysis, where the expression of GALE mRNA was also associated with the histological grade ( < 0.001). These results suggest a possible use of this enzyme as a biomarker for well and moderately differentiated tumors.
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http://dx.doi.org/10.1155/2019/6325326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6886318PMC
May 2020

Galectin-9 gene (LGALS9) polymorphisms are associated with rheumatoid arthritis in Brazilian patients.

PLoS One 2019 10;14(10):e0223191. Epub 2019 Oct 10.

Laboratory of Immunomodulation and New Therapeutic Approaches (LINAT), Suely-Galdino Therapeutic Innovation Research Center (NUPIT-SG), Federal University of Pernambuco (UFPE), Recife, Pernambuco, Brazil.

Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation and hyperplasia, as well as cartilage and bone destruction. Several proteins are associated with the pathogenesis of the disease. Galectin-9 belongs to the family of lectins that are involved in various biological processes and have anti-inflammatory activity.

Objective: To investigate associations between the SNPs of the GAL-9 gene (LGALS9) and serum levels in rheumatoid arthritis patients. We extracted DNA from 356 subjects, 156 RA patients and 200 healthy controls from northeastern Brazil. Three polymorphisms (rs4795835, rs3763959, and rs4239242) in the LGALS9 gene were selected and genotyped using TaqMan SNP genotyping assay. Serum concentrations of galectin-9 were analyzed by ELISA.

Results: The rs4239242 TT genotype showed a positive association with RA (p = 0.0032, odds ratio = 0.28), and heterozygous TC were prevalent in the control group compared to RA patients (p = 0.0001, odds ratio = 7.99). Galectin-9 serum levels were significantly increased in RA patients compared to the control group (p<0.0001). Patients in remission had high levels of galectin compared to the moderate activity group (p<0.0001). Regarding the Clinical Disease Activity Index (CDAI), patients in remission or low activity presented high levels of galectin when compared to patients in severity (p<0.0001). Patients performing moderate activity had a significant value compared to patients who were in high disease severity (p = 0.0064). Interestingly, the AG genotype (rs3763959) has been associated with a higher presence of bone erosion in RA patients (p = 0.0436). The SNP rs4239242 TT genotype showed a positive association with RA in comparison to the control group. The AG genotype (rs3763959) has been associated with a higher presence of bone erosion in RA patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0223191PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6786579PMC
March 2020

Design, synthesis and pharmacological evaluation of CVIB, a codrug of carvacrol and ibuprofen as a novel anti-inflammatory agent.

Int Immunopharmacol 2019 Nov 31;76:105856. Epub 2019 Aug 31.

Laboratory of Synthesis and Drug Delivery, State University of Paraiba, João Pessoa, PB 58071-160, Brazil; Post-Graduation Program in Natural and Synthetic Bioactive Products, Federal University of Paraiba, João Pessoa, PB 58051-900, Brazil. Electronic address:

The search for new drugs with anti-inflammatory properties remains a challenge for modern medicine. Among the various strategies for drug discovery, deriving new chemical entities from known bioactive natural and/or synthetic compounds remains a promising approach. Here, we designed and synthesized CVIB, a codrug developed by association of carvacrol (a phenolic monoterpene) with ibuprofen (a non-steroidal anti-inflammatory drug). In silico pharmacokinetic and physicochemical properties evaluation indicated low aqueous solubility (LogP ≥5.0). Nevertheless, the hybrid presented excellent oral bioavailability, gastrointestinal tract absorption, and low toxicity. CVIB did not present cytotoxicity in peripheral blood mononuclear cells (PBMCs), and promoted a significant reduction in IL-2, IL-10, IL-17, and IFN-γ cytokine levels in vitro. The LD was estimated to be approximately 5000 mg/kg. CVIB was stable and detectable in human plasma after 24 h. In vivo anti-inflammatory evaluations revealed that CVIB at 10 and 50 mg/kg i.p. caused a significant decrease in total leukocyte count (p < 0.01) and provoked a significant reduction in IL-1β (p < 0.01). CVIB at 10 mg/kg i.p. efficiently decreased inflammatory parameters better than the physical mixture (carvacrol + ibuprofen 10 mg/kg i.p.). The results suggest that the codrug approach is a good option for drug design and development, creating the possibility of combining NSAIDs with natural products in order to obtain new hybrid drugs may be useful for treatment of inflammatory diseases.
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http://dx.doi.org/10.1016/j.intimp.2019.105856DOI Listing
November 2019

Galectin-1, -4, and -7 Were Associated with High Activity of Disease in Patients with Rheumatoid Arthritis.

Autoimmune Dis 2019 22;2019:3081621. Epub 2019 Jul 22.

Laboratory of Immunomodulation and New Therapeutic Approaches (LINAT), Suely-Galdino Therapeutic Innovation Research Center (NUPIT-SG), Federal University of Pernambuco (UFPE), Recife, PE, Brazil.

Background: Due to the variety of functions that galectins (Gal) possess, it is clear that they participate in the pathogenesis of rheumatoid arthritis (RA). Although some studies demonstrate their functions, there is still no correlation with the clinical data of the disease, having the physiological meaning still unknown.

Objectives: To compare serum levels of Gal-1, -4, and -7 in patients with RA and healthy controls and to correlate them with clinical parameters.

Methods: Serum samples were collected from patients with RA and healthy donors to determine the serum levels of Gal-1, -4, and -7.

Results: Serum levels of Gal-1, -4, and -7 were significantly higher in RA patients compared to controls. We evaluated disease activity (CDAI) with serum levels of galectins and found that patients who were high in disease activity had high levels of galectin compared to the moderate activity group. Galectin-4 had higher levels in patients who were in high activity when compared to the group in remission or low activity. Evaluating the activity of the individual disease (DAS28), patients in high individual activity had high levels of Gal-4 when compared to the group in remission or low activity. We also found an association between positive rheumatoid factor and Gal-1 and Gal-4 levels.

Conclusion: Our results show for the first time the relationship between serum levels of galectin and the clinical parameters of patients with RA. Demonstrating their role in pathogenesis, new studies with galectins are needed to assess how they function as a biomarker in RA.
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http://dx.doi.org/10.1155/2019/3081621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6681614PMC
July 2019

CCL3, IL-7, IL-13 and IFNγ transcripts are increased in skin's biopsy of systemic sclerosis.

Exp Dermatol 2019 10 3;28(10):1172-1175. Epub 2019 Jul 3.

Laboratório de Imunomodulação e Novas Abordagens Terapêuticas, Núcleo de Pesquisa em Inovação Terapêutica, Universidade Federal de Pernambuco, Recife, Brazil.

Although several cytokines and chemokines have been investigated as possible mediators of fibrosis in systemic sclerosis (SSc), specific correlation between cytokines and organ involvement have not been found yet, and a cytokine profile characteristic of SSc is far to be identified. We studied the profile of antifibrotic and profibrotic transcripts involved in skin of SSc patients. The mRNA expression was detected by fluorescence-based quantitative real-time PCR (qPCR) in skin's biopsies from 14 patients with SSc and 5 healthy controls. PDGF-A, CTGF, CCL3, IL-6, IL-13, IL-7, IFNγ, IL-17, IL-22 and RORc were analysed in these samples. CCL3, IL-7, IL-13 and IFN-γ were more expressed in skin's biopsy of patients with SSc (P = 0.0002, P = 0.0082, P = 0.0243, P = 0.0335, respectively) when compared with healthy controls. We also found a positive correlation between CCL3 and IL-7 transcripts (P = 0.0050 r = 0.7187). Furthermore, we observed that patients with lung involvement had lower expression of PDGF-A (P = 0.0385). We found an increase in IL-7, IFN-γ, CCL3 and IL-13 relative mRNA expressions on the skin's biopsy of patients with SSc, and a positive correlation between IL-7 and CCL3. These molecules are involved in the pathogenesis of SSc, and how their interactions occur should be the subject of further studies.
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http://dx.doi.org/10.1111/exd.13982DOI Listing
October 2019

IL-27 in patients with Chikungunya fever: A possible chronicity biomarker?

Acta Trop 2019 Aug 7;196:48-51. Epub 2019 May 7.

Serviço de Reumatologia - Hospital das Clínicas da Universidade Federal de Pernambuco, Núcleo de Pesquisa em Inovação Terapêutica Suely Galdino (Nupit-SG)/ UFPE, Endereço: Av. Prof. Moraes Rego, 1235 - Cidade Universitária, Recife, PE, CEP: 50670-901, Brazil.

Background/purpose: Although many patients with chikungunya virus disease (CHIKVD), an arboviral disease characterized by sudden fever and incapacitating poliartralgia, develop chronic articular symptoms, the mechanisms involved in CHIKVD's chronification and its possible biomarkers remain poorly understood. Interleukin (IL)-17A, IL-21, IL-22, IL-29, and transforming growth factor (TGF)-β have been implicated in the pathogenesis of other inflammatory joint diseases, including rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Since chronic manifestations of CHIKVD share many clinical and immunological characteristics with those diseases, we assessed the serum levels of those cytokines and analyzed their associations with clinical manifestations in patients with CHIKVD.

Methods: We evaluated 45 patients (36 female, mean age: 55.2 ± 13.8 years) with CHIKVD serologically confirmed by enzyme-linked immunosorbent assay (ELISA), articular manifestations upon evaluation, and no previous history of inflammatory rheumatologic diseases, along with 49 healthy age- and sex-matched controls. We tested anti-Chikungunya IgM and IgG antibodies and measured IL-17A, IL-21, IL-22, IL-27, IL-29, and TGF-β serum levels with specific ELISA kits.

Results: IL-27, IL-17A, and IL-29 appeared in most patients but not in controls. IL-27 serum levels were higher in patients with chronic symptoms (median: 523.0 pg/mL [62.5-1,048]) than in ones in the acute or subacute stage (median: 62.5 pg/mL [62.5-483.8], p = .008). In patients with CHIKVD, we found significant correlations between IL-27 levels and tender joint counts (r = .32, p = .006), along with associations between IL-17A levels and swollen joint counts (r = .315, p = .0352). Furthermore, patients with arthritis had higher IL-17A levels (median: 23.14 pg/mL [20.6-25.86]) than ones without (median: 20.29 pg/mL [3.91-22.43], p = .0352). We did not detect IL-22 in either group or IL-21 in patients with CHIKVD.

Conclusion: Serum levels of IL-17A, IL-27, and IL-29 were high in patients with CHIKVD and had important associations with articular manifestations, which might indicate the inflammatory nature of Chikungunya infection in patients with joint symptoms and the roles of those cytokines in the disease's pathophysiology.
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http://dx.doi.org/10.1016/j.actatropica.2019.05.005DOI Listing
August 2019

Dexamethasone inhibits cytokine production in PBMC from systemic sclerosis patients.

Inflammopharmacology 2019 Aug 8;27(4):723-730. Epub 2019 May 8.

Laboratório de Imunomodulação e Novas Abordagens Terapêuticas, Núcleo de Pesquisa em Inovação Terapêutica, Universidade Federal de Pernambuco, Avenida Professor Moraes Rêgo, 1235, Cidade Universitária, Recife, PE, 50670-901, Brazil.

Glucocorticoids (GC) are widely used in the treatment of SSc, although there is not much evidence to prove the benefits offered by these drugs in this disease. In this study, we evaluated the effects of a GC on cytokine production in peripheral blood mononuclear cells (PBMC) of SSc patients. The effect of dexamethasone (DEX) was evaluated in PBMC of 21 SSc patients and 10 healthy volunteers after stimulation of cells with anti-CD3 and anti-CD28. Cytokines IL-2, IL-4, IL-6, IL-10, IL-17A, IL-17F, IFN-γ, TNF, and IL-1β were quantified in the culture supernatant by CBA or ELISA. Of the patients evaluated in this study, 8 (38%) were taking corticosteroids, and esophageal dysfunction was more frequent in these patients when compared to those who did not take corticosteroids. DEX (1.000 nM) treatment in PBMC of SSc patients stimulated with anti-CD3 and anti-CD28 promoted a significant reduction in IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ, TNF, IL-1β (p < 0.001 for all), and IL-17F (p = 0.023) cytokines levels. We did not observe differences in response to in vitro treatment with DEX between groups of patients taking or not taking corticosteroids. In PBMC from healthy volunteers, we observed that DEX treatment significantly reduced IL-4, IFN-γ (p = 0.003 for both), IL-6, IL-10, IL-17A, and TNF (p = 0.002 for all) cytokines. These results show that DEX treatment in PBMC of SSc patients reduced the production of important cytokines involved in the pathogenesis of the disease, suggesting a possible mechanism of action of the CG in the treatment of SSc.
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http://dx.doi.org/10.1007/s10787-019-00600-wDOI Listing
August 2019

Portulaca elatior root contains a trehalose-binding lectin with antibacterial and antifungal activities.

Int J Biol Macromol 2019 Apr 22;126:291-297. Epub 2018 Dec 22.

Departamento de Bioquímica, Centro de Biociências, Universidade Federal de Pernambuco, Recife, Pernambuco, Brazil. Electronic address:

Lectins are carbohydrate-binding proteins broadly distributed in plants and have several biological functions, including antimicrobial action. Portulaca elatior is a Caatinga plant whose chemical composition and biotechnological potential have not been extensively studied. In this work, a lectin was isolated from P. elatior root extract and evaluated for antimicrobial activity. The P. elatior root lectin (PeRoL) showed native molecular mass of 33 kDa, pI 3.8 and is comprised of two subunits of 15 kDa linked by disulfide bonds. No sequence similarities with Viridiplantae proteins were observed. The PeRoL hemagglutinating activity (HA) was not affected by heating and was detected in a pH ranging from 4.0 to 8.0. Trehalose was identified as an endogenous inhibitor of PeRoL present in the roots. Bacteriostatic activity was detected against Enterococcus faecalis, Pseudomonas aeruginosa and Staphylococcus aureus (minimal inhibitory concentration of 8.1, 32.5 and 4.06 μg/mL, respectively). PeRoL induced the death of Candida albicans, Candida parapsilosis, Candida krusei, and Candida tropicalis cells, with a minimal fungicidal concentration of 16 μg/mL. The lectin (100 μg/mL) was not cytotoxic to human peripheral blood mononuclear cells (PBMCs) and did not show hemolytic activity. In conclusion, the roots of P. elatior contain a trehalose-binding, thermostable, and antimicrobial lectin.
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http://dx.doi.org/10.1016/j.ijbiomac.2018.12.188DOI Listing
April 2019

Novel betulin derivatives inhibit IFN-γ and modulates COX-2 expression.

Nat Prod Res 2020 Jun 22;34(12):1702-1711. Epub 2018 Dec 22.

Laboratory of Immunomodulation and New Therapeutic Approaches (LINAT), Research Center Innovation Therapeutics Suely Galdino (NUPIT-SG), Federal University of Pernambuco, Recife, Brazil.

Betulin () is a pentacyclic triterpenes, obtained from natural sources and with several biological activities described, such as anti-tumoral and anti-inflammatory activities. The esterification at hydroxyl group (C-3 and C-28) resulted in five new ester derivatives with different numbers of carbons or halogens (chlorine and fluorine). Among these derivatives, two ( e ) were able to significantly decrease IFN-g (*p = 0.0391; **p = 0.0156) and modulated the expression of COX-2 better than Dexamethasone (). Regarding to cytotoxic assay, the best results were obtained for without modifications, with emphasis on tumoral cell lines Raji and MCF-7. The derivatives and showed immunomodulation activity (for the cytokines IFN-g). The presence of chorine in seems to be important for the ability of modulate COX-2 expression, since the ester chloride derivative at 100 μM is more powerful inhibitor of COX-2 than .
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http://dx.doi.org/10.1080/14786419.2018.1528581DOI Listing
June 2020

Potential Therapeutic Agents Against Par-4 Target for Cancer Treatment: Where Are We Going?

Curr Drug Targets 2019 ;20(6):635-654

Laboratory of Immunomodulation and New Therapeutical Approaches, Research Centre for Therapeutic Innovation Suely Galdino (NUPIT-SG), Federal University of Pernambuco, Recife, PE, Brazil.

One of the greatest challenges of cancer therapeutics nowadays is to find selective targets successfully. Prostate apoptosis response-4 (Par-4) is a selective tumor suppressor protein with an interesting therapeutic potential due to its specificity on inducing apoptosis in cancer cells. Par-4 activity and levels can be downregulated in several tumors and cancer cell types, indicating poor prognosis and treatment resistance. Efforts to increase Par-4 expression levels have been studied, including its use as a therapeutic protein by transfection with adenoviral vectors or plasmids. However, gene therapy is very complex and still presents many hurdles to be overcome. We decided to review molecules and drugs with the capacity to upregulate Par-4 and, thereby, be an alternative to reach this druggable target. In addition, Par-4 localization and function are reviewed in some cancers, clarifying how it can be used as a therapeutic target.
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http://dx.doi.org/10.2174/1389450120666181126122440DOI Listing
July 2020

Correction to: Statins Inhibit Cytokines in a Dose-Dependent Response in Patients with Systemic Sclerosis.

Inflammation 2019 04;42(2):412

Laboratório de Imunomodulação e Novas Abordagens Terapêuticas Suely Galdino, Universidade Federal de Pernambuco, Recife, Brazil.

One of the author's surname was incorrect. Anderson Ferreira de Almeida should be captured as Anderson Rodrigues de Almeida. The correct name is now presented above.
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http://dx.doi.org/10.1007/s10753-018-0916-2DOI Listing
April 2019

In vitro and in silico studies of antioxidant activity of 2-thiazolylhydrazone derivatives.

J Mol Graph Model 2019 01 12;86:106-112. Epub 2018 Oct 12.

Department of Pharmaceutical Products, Pharmacy Faculty, Federal University of Minas Gerais, 6627 Antônio Carlos AVE, 31270-901, Belo Horizonte, Minas Gerais, Brazil. Electronic address:

The antioxidant potential of a series of thiazolylhydrazone derivatives was investigated using three different methods namely DPPH, ABTS and FRAP assays. In general, the tested compounds showed higher or comparable activity to that of curcumin, used as positive control. Chemometric analyses demonstrated that the presence of hydrazone moiety is required for the activity of this class of compounds. From these results, compound 4 was identified as the most promising molecule and was then selected for further studies. The antiproliferative effect of compound 4 was evaluated, being active in three (T47D, MDA-MB-231 and SKMEL) of the six cancer cell lines tested, with IC values ranging from 15.9 to 31.3 μM. Compound 4 exhibited no detectable cytotoxic effect on peripheral blood mononuclear cells (PBMC) when tested at a concentration of 100 μM, demonstrating good selectivity. From these results, it is possible to infer that there is a correlation between antioxidant capacity and anticancer effects.
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http://dx.doi.org/10.1016/j.jmgm.2018.10.007DOI Listing
January 2019

Statins Inhibit Cytokines in a Dose-Dependent Response in Patients with Systemic Sclerosis.

Inflammation 2019 Apr;42(2):407-411

Laboratório de Imunomodulação e Novas Abordagens Terapêuticas Suely Galdino, Universidade Federal de Pernambuco, Recife, Brazil.

Although statins have been successfully administered in the treatment of hypercholesterolemia and cardiovascular disease due to their lipid-lowering and anti-atherosclerotic action, they have shown immunomodulatory effects in several studies with immune-mediated diseases. The aim of this study was to investigate the effects of statins treatment on Th1, Th2, and Th17 cytokines production from stimulated peripheral blood mononuclear cells (PBMCs) obtained from Systemic Sclerosis (SSc) patients. We recruited 21 patients classified according to the American College of Rheumatology criteria for SSc for PBMCs culture analysis. Cytokine levels (IL-2, IL-4, IL-6, IL-10, TNF, IFN-γ, IL-17A, and IL-17F) were quantified by ELISA or CBA, and patients were assessed for clinical and exam's variables. Simvastatin and atorvastatin at 50 μM promoted reduction in all cytokine levels with statistical significance, except for IL-6, which had its reduction only induced by the use of simvastatin. Statins, particularly simvastatin, appear to have an immunosuppressive effect in reducing all cytokine secretion levels from PBMCs of SSc in a dose-dependent manner.
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http://dx.doi.org/10.1007/s10753-018-0907-3DOI Listing
April 2019

Losartan, but not Enalapril and Valsartan, Inhibits the Expression of IFN-γ, IL-6, IL-17F and IL-22 in PBMCs from Rheumatoid Arthritis Patients.

Open Rheumatol J 2018 18;12:160-170. Epub 2018 Sep 18.

Laboratory of Immunomodulation and New Therapeutic Approaches (LINAT), Nucleus of Research in Immunomodulation and New Therapeutic Approaches Suely Galdino (Nupit SG), Federal University of Pernambuco (UFPE), Recife, Brazil.

Background: Rheumatoid Arthritis (RA) is a chronic and inflammatory disease that affects about 1% of the world's population. Almost 70% of RA patients have a cardiovascular disease such as Systemic Arterial Hypertension (SAH). Inflammatory cytokines are clearly involved in the pathogenesis of RA and correlated with SAH.

Objective: It is necessary to understand whether the antihypertensive drugs have a dual effect as immunomodulators and which one is the best choice for RA SAH patients.

Methods: Peripheral Blood Mononuclear Cells (PBMCs) from 16 RA patients were purified and stimulated or not stimulated with anti-CD3 and anti-CD28 mAB and were treated with Enalapril, Losartan and Valsartan at 100μM. Patients were evaluated for clinical and laboratory variables including measures of disease activity by Clinical Disease Activity Index (CDAI) and Disease Activity Score (DAS28). Cytokines were quantified by ELISA sandwich.

Results: Losartan was able to reduce levels of IFN-γ ( = 0.0181), IL-6 ( = 0.0056), IL-17F (0.0046) and IL-22 ( = 0.0234) in RA patients. In addition, patients in remission and mild score (DAS28<3.2 and CDAI<10) had a better response to treatment. On the other hand, patients in moderate and severe activity had poor response to Losartan in cytokine inhibition.

Conclusion: PBMCs from RA patients are responsive in inhibiting proinflammatory cytokines using Losartan better than Enalapril and Valsartan and it could be a better antihypertensive choice for patients with RA and systemic arterial hypertension treatment.
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http://dx.doi.org/10.2174/1874312901812010160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151964PMC
September 2018
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