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1.
Front Cell Infect Microbiol ; 14: 1362765, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38562963

RESUMO

Cestodes use own lipid-binding proteins to capture and transport hydrophobic ligands, including lipids that they cannot synthesise as fatty acids and cholesterol. In E. granulosus s.l., one of these lipoproteins is antigen B (EgAgB), codified by a multigenic and polymorphic family that gives rise to five gene products (EgAgB8/1-5 subunits) assembled as a 230 kDa macromolecule. EgAgB has a diagnostic value for cystic echinococcosis, but its putative role in the immunobiology of this infection is still poorly understood. Accumulating research suggests that EgAgB has immunomodulatory properties, but previous studies employed denatured antigen preparations that might exert different effects than the native form, thereby limiting data interpretation. This work analysed the modulatory actions on macrophages of native EgAgB (nEgAgB) and the recombinant form of EgAg8/1, which is the most abundant subunit in the larva and was expressed in insect S2 cells (rEgAgB8/1). Both EgAgB preparations were purified to homogeneity by immunoaffinity chromatography using a novel nanobody anti-EgAgB8/1. nEgAgB and rEgAgB8/1 exhibited differences in size and lipid composition. The rEgAgB8/1 generates mildly larger lipoproteins with a less diverse lipid composition than nEgAgB. Assays using human and murine macrophages showed that both nEgAgB and rEgAgB8/1 interfered with in vitro LPS-driven macrophage activation, decreasing cytokine (IL-1ß, IL-6, IL-12p40, IFN-ß) secretion and ·NO generation. Furthermore, nEgAgB and rEgAgB8/1 modulated in vivo LPS-induced cytokine production (IL-6, IL-10) and activation of large (measured as MHC-II level) and small (measured as CD86 and CD40 levels) macrophages in the peritoneum, although rEgAgB8/1 effects were less robust. Overall, this work reinforced the notion that EgAgB is an immunomodulatory component of E. granulosus s.l. Although nEgAgB lipid's effects cannot be ruled out, our data suggest that the EgAgB8/1 subunit contributes to EgAgB´s ability to regulate the inflammatory activation of macrophages.


Assuntos
Echinococcus granulosus , Humanos , Animais , Camundongos , Echinococcus granulosus/genética , Echinococcus granulosus/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/metabolismo , Ativação de Macrófagos , Lipoproteínas/genética , Lipoproteínas/metabolismo , Macrófagos , Citocinas/metabolismo
2.
Arch Ital Urol Androl ; 95(4): 11897, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38193227

RESUMO

BACKGROUND: Most men diagnosed with prostate cancer will be candidates for active treatment and 20 to 50% of patients treated with organ preserving strategies recur within the prostate. Optimal treatment of recurrence is controversial. Prostate cryosurgery has been increasingly used as primary, recurrence and focal treatment for prostate cancer. METHODS: We analysed 55 patients submitted to cryotherapy as salvage treatment after recurrence. RESULTS: Study population presented with a mean age of 70.9 ± 6.2 years, mean initial PSA of 7.6 ng/ml and average prostate volume by ultrasound of 43.2 ± 14.7 grams. Mean follow-up was of 18.0 months. Biochemical free survival at one year of follow-up was of 85%. CONCLUSIONS: Cryotherapy can be an effective and safe treatment for recurrence after primary curative treatment failure.


Assuntos
Crioterapia , Neoplasias da Próstata , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Neoplasias da Próstata/terapia , Próstata , Pelve , Terapia de Salvação
3.
Int J Parasitol Parasites Wildl ; 23: 100904, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38261956

RESUMO

Bats have been reported as reservoir host of Leishmania spp. worldwide, mostly by molecular detection. However, it is still unclear whether bats act as reservoirs of Leishmania infantum to sandflies vectors. In this sense, the investigation of amastigotes forms in the target organs, and the characterization of their associated inflammation, may help to clarify the epidemiological importance of bats in endemic areas for leishmaniasis. The aim of this work was to investigate the host-parasite relationships under microscopic evaluation and predict the epidemiological role of two phyllostomid bats species naturally infected by L. infantum in an endemic area for human leishmaniasis. Fragments of skin, liver and spleen of L. infantum positive and negative bats (Artibeus planirostris and Carollia perspicillata) by qPCR, were studied by histological and immunohistochemical techniques. Both groups, positive and negative, did not show differences in the histopathological study, presenting only discrete tissue changes. Liver and skin showed mild inflammatory reactions. Findings on spleen consisted of reactivity of the lymphoid follicles, expressive presence of apoptotic cells and macrophages containing abundant phagocytic cells debris. We did not find amastigote forms in tissues by histological and IHC techniques in positive qPCR bats. Our results allow us to hypothesize that phyllostomid bats seem to have an important role in reducing the risk of transmission, possibly acting as dead-end host.

4.
Arch Ital Urol Androl ; 95(3): 11567, 2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37791556

RESUMO

INTRODUCTION: Infertility, the inability to conceive, constitutes a major problem in modern societies. It affects 10 to 15 percent of couples in the United States. Evaluation of infertile men is usually complex and often demands a testicular biopsy. MATERIALS AND METHODS: We reviewed all azoospermic men submitted to testicular biopsy, in our center, during infertility investigation between January 2015 and December 2021. RESULTS: A total of 117 patients with a mean age of 36.5 was considered. Biopsy was positive, as defined by the presence of viable spermatozoids by microscopy, in 48.7% of patients (n = 57). Patients were divided in two separate groups based on positive (PB) or negative biopsy (NB) and compared. PB-group had normal serum total testosterone levels and higher than NB-group (3.7 ng/mL vs. 2.85 ng/mL, p = 0.021), and normal serum FSH levels and lower than NB-group (6.0 mIU/mL vs. 16.0 mIU/mL, p < 0.001). The groups were similar concerning serum LH levels (3.9 mIU/mL vs. 6.3 mIU/mL, p = 0.343. CONCLUSIONS: Predicting outcomes of testicular biopsy is a difficult task. Our study found that men with normal testicular volume, normal levels of testosterone and FSH and those with type 1 diabetes mellitus had a higher probability of positive testicular biopsy.


Assuntos
Infertilidade Masculina , Hormônio Luteinizante , Testículo , Adulto , Humanos , Masculino , Biópsia , Hormônio Foliculoestimulante , Infertilidade Masculina/etiologia , Testículo/patologia , Testosterona
5.
Sci Rep ; 13(1): 16762, 2023 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-37798436

RESUMO

Advanced head and neck squamous cell carcinoma (HNSCC) patients have been treated with cisplatin (CDDP) chemoradiation, and the variability of treatment effects has been attributed to single nucleotide variants (SNVs) in genes of metabolic pathways. This study investigated the roles of GSTM1, GSTT1, GSTP1 c.313A>G, XPC c.2815A>C, XPD c.934G>A and c.2251A>C, XPF c.2505T>C, ERCC1 c.354C>T, MLH1 c.93G>A, MSH2 c.211+9C>G, MSH3 c.3133G>A, EXO1 c.1765G>A, TP53 c.215G>C, CASP3 c.-1191A>G and c.-182-247G>T, FAS c.-1378G>A and c.-671A>G and FASL c.-844C>T SNVs in outcome of 109 patients treated with CDDP chemoradiation. Genotypes were identified in genomic DNA by PCR-based methods. Conventional criteria and tests analyzed response and survival. Patients with XPC c.2815AC or CC had 3.43 times more chances of presenting partial response or stable disease. Patients with FAS c.-671GG, GSTM1 present plus XPC c.2815AA, or plus XPD c.934GG, or plus XPD c.2251AA, or plus TP53 c.215GC or CC, and XPD c.2251AA plus XPF c.2505TT had up to 2.70 and 2.37 times more chances of presenting tumor progression and evolving to death, respectively. Our data indicate, for the first time, preliminary evidence that combined SNVs of CDDP metabolism act as independent prognostic factors and can be used to select patients for distinct treatments.


Assuntos
Cisplatino , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/induzido quimicamente , Cisplatino/uso terapêutico , Polimorfismo de Nucleotídeo Único , Genótipo , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/genética , Redes e Vias Metabólicas
6.
Vet Med Sci ; 9(6): 2443-2446, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37669416

RESUMO

This report presents anatomo-histopathological, immunohistochemical and molecular analyses of an asymptomatic female dog naturally infected with Leishmania (Leishmania) infantum and her four pups. In addition to routine serological tests, the mother's positivity was confirmed by real-time PCR of a bone marrow sample; the placenta and ovaries, however, were negative with the same analysis. The pups presented no positivity in any of the techniques used. It is suggested that the gestational period and factors related to the female's immunological condition cause greater variability in the occurrence of vertical infection.


Assuntos
Doenças do Cão , Leishmania infantum , Leishmaniose Visceral , Gravidez , Cães , Feminino , Animais , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/veterinária , Leishmaniose Visceral/epidemiologia , Doenças do Cão/diagnóstico , Doenças do Cão/epidemiologia , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Feto
7.
Sci Rep ; 13(1): 15151, 2023 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-37704663

RESUMO

Caffeine and trigonelline are found in Coffea arabica, and show antioxidant roles and growth and development functions. However, there are no reports on trigonelline and caffeine in relation to coffee rooting. The aim was to evaluate the impact of application of indole-3-butyric acid (IBA) and melatonin on caffeine and trigonelline at different stages of adventitious rooting in cuttings. In addition, to study the correlation between these metabolites and H2O2, phenols, and antioxidant enzymes. Four treatments (Control, melatonin 21 µM (M21), melatonin 43 µM (M43), and IBA 7380 µM (IBA)) were used, with four replications. The growth and biochemical parameters of the antioxidant system were performed in induction, initiation, and extension rooting stages. Higher concentrations of trigonelline and caffeine quantified in the induction and initiation stages were positively correlated with higher percentage of rooted cuttings. Trigonelline and caffeine were positively correlated with H2O2 in all stages of development of adventitious roots. The correlations of trigoneline and caffeine with phenols and antioxidant enzymes reveal different profiles, depending on the phases. The results indicate that IBA and melatonin increase trigonelline and caffeine during the induction and initiation of adventitious roots in Coffea arabica cuttings, which is correlated with a higher percentage of rooted cuttings.


Assuntos
Coffea , Melatonina , Cafeína , Antioxidantes , Peróxido de Hidrogênio , Fenóis
8.
J Inorg Biochem ; 245: 112227, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37156056

RESUMO

Some hydrazones and Schiff bases derived from isatin, an endogenous oxindole formed in the metabolism of tryptophan, were obtained to investigate their effects on in vitro aggregation of ß-amyloid peptides (Aß), macromolecules implicated in Alzheimer's disease. Some hydrazone ligands, prepared by condensation reactions of isatin with hydrazine derivatives, showed a large affinity binding to the synthetic peptides Aß, particularly to Aß1-16. Measurements by NMR spectroscopy indicated that those interactions occur mainly at the metal binding site of the peptide, involving His6, His13, and His14 residues, and that hydrazone E-diastereoisomer interacts preferentially with the amyloid peptides. Experimental results were consistent with simulations using a docking approach, where it is demonstrated that the amino acid residues Glu3, His6, His13, and His14 are those that mostly interact with the ligands. Further, these oxindole-derived ligands can efficiently chelate copper(II) and zinc(II) ions, forming moderate stable [ML] 1:1 species. The corresponding formation constants were determined by UV/Vis spectroscopy, by titrations of the ligands with increasing amounts of metal salts, and the obtained log K values were in the range 2.74 to 5.11. Both properties, good affinity for amyloid peptides, and reasonably good capacity of chelating biometal ions, like copper and zinc, can explain the efficient inhibition of Aß fragments aggregation, as shown by experiments carried out with the oxindole derivatives in the presence of metal ions.


Assuntos
Doença de Alzheimer , Isatina , Humanos , Peptídeos beta-Amiloides/química , Oxindóis , Cobre/química , Ligantes , Metais , Doença de Alzheimer/metabolismo , Zinco/química , Íons , Fragmentos de Peptídeos/química
9.
RSC Adv ; 13(14): 9715-9719, 2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36968063

RESUMO

A novel strategy of improving cytotoxicity against metastatic melanoma cells using an oxindolimine copper(ii) complex immobilized and dimerized on a modified Polyhedral Oligomeric Silsesquioxane (POSS) matrix was developed, as revealed by electron paramagnetic resonance (EPR) spectroscopy. An assured correlation between continuous-wave (CW) and pulsed EPR spectroscopies provided a complete characterization of the actual active species, its coordination environment, as well as the efficiency/selectivity of the bioconjugate materials.

10.
J Chromatogr A ; 1690: 463788, 2023 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-36649666

RESUMO

For the first time, a very simple and fast method combining the use of a guard column coupled to tandem mass spectrometry (guard column-MS/MS) has been proposed for the determination of plasticizer metabolites in urine. Briefly, samples (1.0 mL) were submitted to enzymatic hydrolysis for 10 min, filtered, diluted 1/10 v/v with ultrapure water and directly injected into the system. A fast run of only 2 min (3 min including the injection cycle) allowed the determination of 19 analytes. Enzymatic hydrolysis, filtering material, and guard column-MS/MS conditions were optimized. Intra-day precision at the low-level concentration (expressed as relative standard deviation, %RSD) obtained from the analysis of synthetic urine samples varied between 11 and 20%. Limits of quantification ranged from 2.8 to 60 ng/mL. Trueness values, calculated as apparent recoveries, ranged from 70 to 135%. To correct for matrix effects, analyte concentrations in real urine were quantified by the standard addition method. To confirm the results obtained by guard column-MS/MS, an ultra(high)-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method was also applied (total chromatographic run time 17 min, including column re-equilibration). Concentrations measured with both methods were in good agreement. Hence, we propose the use of guard column-MS/MS to analyse a large number samples in a very short time (semi-quantification), and apply the chromatographic analysis only to those samples with levels close to/higher than the concentrations equivalent to the safe maximum daily intakes of the parent compounds (confirmation). This double strategy (semi-quantification by guard column-MS/MS and confirmation-when needed-by UHPLC-MS/MS) implies important savings in time and money.


Assuntos
Plastificantes , Espectrometria de Massas em Tandem , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos
11.
J Inorg Biochem ; 240: 112099, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36584559

RESUMO

Studies on the immobilization of oxindolimine­copper(II) or zinc(II) complexes [ML] in synthetic beidellite (BDL) clay were developed to obtain a suitable inorganic carrier capable of promoting the modified-release of metallopharmaceuticals. Previous investigations have shown that the studied metal complexes are promising antitumor agents, targeting DNA, mitochondria, and some proteins. They can bind to DNA, causing oxidative damage via formation of reactive oxygen species (ROS). In mitochondria they lead to a decrease in membrane potential, acting as decoupling agents, and therefore efficiently inducing apoptosis. Additionally, they inhibit human topoisomerase IB and cyclin dependent kinases, proteins involved in the cell cycle. BDL clays in the sodium form were synthesized under hydrothermal conditions and characterized by a set of physicochemical techniques while the BDL-[ML] hybrid materials were prepared by ion exchange method. The characterization of pristine clay and the obtained hybrids were performed by Infrared, Raman, electron paramagnetic resonance and energy dispersive X-ray spectroscopies, thermogravimetric analysis, scanning electron microscopy, X-ray powder diffraction, specific surface area, zeta potential and surface ionic charge measurements. The [ML] release assays under the same cell incubation conditions were performed monitoring metals by X-ray fluorescence. The BDL-[CuL] hybrid materials were stable and able to derail tumor HeLa cells, with corresponding IC50 values in the 0.11-0.41 mg mL-1 range. By contrast, the analogous hybrid samples of zinc(II) and the pristine BDL proved to be non-toxic facing the same cells. These results indicate a promising possibility of using synthetic beidellite as a carrier of such antitumor metal complexes.


Assuntos
Antineoplásicos , Complexos de Coordenação , Humanos , Argila , Células HeLa , Complexos de Coordenação/química , Zinco/química , DNA/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química
12.
J Inorg Biochem ; 239: 112047, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36428157

RESUMO

Currently the only drug available to treat Chagas disease in Brazil is benznidazole (BZN). Therefore, there is an urgent need to discover and develop new anti- Trypanosoma cruzi candidates. In our continuous effort to enhance clinical antiparasitic drugs using synergistic strategy, BZN was coordinated to silver and copper ions to enhance its effectiveness to treat that illness. In this work, the syntheses of four novel metal-BZN complexes, [Ag(BZN)2]NO3·H2O (1), [CuCl2(BZN)(H2O)]·1/2CH3CN (2), [Ag(PPh3)2(BZN)2]NO3·H2O (3), and [Cu(PPh3)2(BNZ)2]NO3·2H2O (4), and their characterization using multiple analytical and spectroscopic techniques such as Infrared (FTIR), Nuclear Magnetic Resonance (1H, 13C, 31P), UV-Visible (UV-Vis), Electron Paramagnetic Resonance (EPR), conductivity and elemental analysis are described. IC50 (Half-maximal inhibitory concentration) values of Ag-BZN compounds are about five to ten times lower than benznidazole itself in both proliferation stages of the parasite (epimastigotes and amastigotes). The cytotoxicity of both compounds in human cells (fibroblasts and hepatocytes) are comparable to BZN, indicating that Ag-BZN complexes can be more selective than BZN.


Assuntos
Anti-Infecciosos , Doença de Chagas , Nitroimidazóis , Tripanossomicidas , Trypanosoma cruzi , Humanos , Prata/farmacologia , Cobre/farmacologia , Cobre/uso terapêutico , Antiparasitários/farmacologia , Tripanossomicidas/farmacologia , Tripanossomicidas/uso terapêutico , Doença de Chagas/tratamento farmacológico , Nitroimidazóis/farmacologia , Anti-Infecciosos/uso terapêutico
13.
Res Vet Sci ; 154: 84-88, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36512978

RESUMO

The aim of this study was to evaluate de immunoexpression of ezrin in gastric cells of domestic cats infected with Helicobacter spp. and with chronic gastritis. Twenty paraffin-embedded gastric samples were selected based on previous positive results for Helicobacter spp. in the Rapid Urease Test, Warthin-Starry staining and cytology. Haematoxylin-eosin stained sections was done to evaluate inflammatory cell infiltrates. Immunohistochemical analysis was done using anti-Helicobacter pylori and anti-Ezrin antibodies. The analysis of inflammatory infiltrates revealed 8/20 (40%) in score 0, 11/20 (55%) in score 1 and 1/20 (5%) in score 2. The labelling observed in the immunohistochemical analysis using anti-Helicobacter spp. antibody showed no samples with score 0; 4/20 (20%) with score 1; 7/20 35% with score 2 and 9/20 (45%) with score 3. Ezrin overexpression on the cytoplasm of parietal cells was revealed in 18 out of 20 samples (90%). Of these, 10 cases (45%) achieved the score 1; 6 cases (30%) the score 2 and 2 cases (10%) the score 3. On the surface and pit cells there was an increase in Ezrin immnoexpression in 12 out of the 20 samples (60%), of which 8 samples (40%) achieved the score 1 and 4 samples (20%) the score 2. No sample were classified in score 3. Statistically significant differences (p = 0.026) were observed between the inflammatory infiltrate in the gastric mucosa and the immunoexpression of Ezrin in the cytoplasm of parietal cells. It was concluded that ezrin had an increased immunoexpression in the gastric mucosa of cats with chronic gastritis.


Assuntos
Doenças do Gato , Gastrite , Helicobacter pylori , Helicobacter , Animais , Gatos , Doenças do Gato/metabolismo , Mucosa Gástrica , Gastrite/veterinária , Gastrite/metabolismo
14.
Artigo em Inglês | MEDLINE | ID: mdl-36293669

RESUMO

A fast methodology for the determination of monohydroxy polycyclic aromatic hydrocarbons in human urine using a fully automated microextraction by packed sorbent coupled to a gas chromatograph-mass spectrometer is reported. Sample preparation requires simple hydrolysis, centrifugation, filtration, and dilution. The method does not require a derivatization step prior to analysis with gas chromatography and allows the measurement of up to three samples per hour after hydrolysis. Quantitation is carried out by a one-point standard addition allowing the determination of 6 analytes with good limits of detection (10.1-39.6 ng L-1 in water and 0.5-19.4 µg L-1 in urine), accuracy (88-110%) and precision (2.1-23.4% in water and 5.1-19.0% in urine) values. This method has been successfully applied to the analysis of six urine samples (three from smoker and three from non-smoker subjects), finding significant differences between both types of samples. Results were similar to those found in the literature for similar samples, which proves the applicability of the methodology.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Poluentes Químicos da Água , Humanos , Hidrocarbonetos Policíclicos Aromáticos/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Microextração em Fase Sólida/métodos , Poluentes Químicos da Água/análise , Água/química , Limite de Detecção
15.
Front Psychiatry ; 13: 976831, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36177218

RESUMO

The Personality Inventory for DSM-5 - Self Reported Form (PID-5-SRF) operationalizes Criterion B of the personality alternative model of DSM-5 Section III and has already been cross-culturally adapted to many countries. The objective is to present evidence of validity and reliability of the Brazilian version of PID-5 (pencil-and-paper) in a Brazilian community sample. The sample was composed of 730 individuals from the general population [67.8% women, aged 33.84 (SD = ±15.2), 69.5% ≥ 12 years of schooling]. The participants were recruited in academic, organizational, healthcare, and business facilities in three Brazilian states. The snowball method was used. The PID-5 Brazilian version and the Revised NEO-Five Factor Inventory (NEO-FFI-R) were individually applied, and the retest was applied 30 days after. Satisfactory internal consistency (facets α ≥0.51; domains α ≥0.82) and test-retest reliability (facets ICC ≥ 0.45; domains ICC ≥0.76) were found, but a floor effect was verified in 97.7% of the items. Regarding convergent validity, strong correlations were found between the PID-5 and the NEO-FFI-R domains (r = -0.44 to 0.70). Ten facets did not fit the unidemensional structure. Confirmatory Factor Analyses did not present adequate goodness of fit, and Exploratory Analyses indicated that a five-factor model is more appropriate, though it presents some peculiarities concerning the original model. PID-5 also presented satisfactory goodness of fit to the personality hierarchical model. Generally, the instrument's psychometric indicators favor its use in the Brazilian context. However, some aspects demand attention, and more specific studies should be conducted to verify the impact of reverse-scored items, floor effect, and peculiarities of its internal structure (some facets' multidimensionality and interstitiality) concerning the original model.

16.
Fish Shellfish Immunol ; 128: 505-522, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35985628

RESUMO

Sturgeons are chondrostean fish of high economic value and critically endangered due to anthropogenic activities, which has led to sturgeon aquaculture development. Russian sturgeon (Acipenser gueldenstaedtii), the second most important species reared for caviar, is successfully farmed in subtropical countries, including Uruguay. However, during the Uruguayan summer, sturgeons face intolerable warmer temperatures that weaken their defences and favour infections by opportunistic pathogens, increasing fish mortality and farm economic losses. Since innate immunity is paramount in fish, for which the liver plays a key role, we used deep RNA sequencing to analyse differentially expressed genes in the liver of Russian sturgeons exposed to chronic heat stress and challenged with Aeromonas hydrophila. We assembled 149.615 unigenes in the Russian sturgeon liver transcriptome and found that metabolism and immune defence pathways are among the top five biological processes taking place in the liver. Chronic heat stress provoked profound effects on liver biological functions, up-regulating genes related to protein folding, heat shock response and lipid and protein metabolism to meet energy demands for coping with heat stress. Besides, long-term exposure to heat stress led to cell damage triggering liver inflammation and diminishing liver ability to mount an innate response to A. hydrophila challenge. Accordingly, the reprogramming of liver metabolism over an extended period had detrimental effects on fish health, resulting in weight loss and mortality, with the latter increasing after A. hydrophila challenge. To our knowledge, this is the first transcriptomic study describing how chronic heat-stressed sturgeons respond to a bacterial challenge, suggesting that liver metabolism alterations have a negative impact on the innate anti-bacterial response.


Assuntos
Infecções Bacterianas , Peixes , Adaptação Psicológica , Animais , Peixes/metabolismo , Resposta ao Choque Térmico , Lipídeos
17.
J Inorg Biochem ; 234: 111881, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35691262

RESUMO

To further explore the structural features and potential antibacterial and antitumor activities of polynuclear CuII coordination compounds with nalidixic acid (nx) derivatives, new complexes bearing nx hydrazones with N-pyridinyl moieties substituted at positions 2 and 3 (h2py and h3py) were synthesized. Complexes [Cu3(C18H16N5O2)2(C18H17N5O2)2(H2O)]4BF4∙H2O (1), and [Cu3(C18H16N5O2)2(C18H17N5O2)2(H2O)3]4BF4∙3H2O (%) (2) were synthesized using h2py and h3py with Cu(BF4)2∙nH2O as precursor, whereas the [Cu(C18H17N5O2)Cl2]∙0.5H2O complex (3) was synthesized with h2py and CuCl2∙2H2O. Crystallographic studies of complex 1, showed that coordination of hydrazones to CuII occurs by tridentate modes of type κ3(O,N,N') as well as bidentate modes of type κ2(O',N″). Complexes 1, 2 and 3 had their antiproliferative activities evaluated in vitro against a panel of tumor cells by the determination of GI50 values. Complexes 1 and 2 were more active than complex 3, suggesting an effect of the complex charge on their activities. The interactions of such complexes towards bovine serum albumin (BSA) and DNA plasmid (pGEX-4 T1) were investigated using fluorescence spectroscopy and gel electrophoresis. All complexes were shown to interact with the DNA model as metallonucleases, but no interaction with BSA was observed. DNA molecular docking of complex 1 encompassing both its trinuclear (TN) form and a possible mononuclear (MN) derivative suggests that naphthyridyl ring performs π-stacking interactions with DNA. The TN species were also shown to be possible minor groove binders.


Assuntos
Antineoplásicos , Complexos de Coordenação , Antineoplásicos/química , Antineoplásicos/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Cobre/química , Cristalografia por Raios X , DNA/química , Hidrazonas/farmacologia , Simulação de Acoplamento Molecular , Ácido Nalidíxico , Piridinas/química , Piridinas/farmacologia , Soroalbumina Bovina/química
18.
J Inorg Biochem ; 233: 111834, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35500350

RESUMO

A series of new transition metal coordination polymers, [Zn(Ac)2(FLZ)2]n (1), [Zn(FLZ)2(Cl)2]n (2), {[Zn(FLZ)2](NO3)2}n (3), [Cu(FLZ)2(CH3COO)4]n (4), {[Cu(FLZ)2Cl2]}n (5) and {[Cu(FLZ)2](NO3)2}n (6), were synthesized by the reaction of fluconazole (FLZ) with the respective zinc or copper salts under mild conditions. The molecular structure of these compounds was elucidated by several analytical and spectroscopy techniques such as elemental analyses, 1H and 13C{1H} nuclear magnetic resonance, electronic paramagnetic resonance, and infrared spectroscopy. Single-crystal X-ray diffraction confirmed the structure of the compounds 2, 4, 5 and 6 in solid state. The antichagasic activity of these compounds was evaluated against different forms of Trypanosoma cruzi. Compound 2 exhibited the highest activity against intracellular amastigotes. The ultrastructural changes in epimastigotes and intracellular amastigotes were investigated. These promising biological results demonstrated that the zinc or copper coordination polymers can form very active anti-parasitic compounds. The resulting compounds are more effective than the free azole drug and, consequently, great candidates for the treatment of Chagas disease.


Assuntos
Doença de Chagas , Complexos de Coordenação , Doença de Chagas/tratamento farmacológico , Complexos de Coordenação/química , Cobre/química , Cristalografia por Raios X , Fluconazol/farmacologia , Fluconazol/uso terapêutico , Humanos , Polímeros/química , Zinco/química
20.
Sci Rep ; 12(1): 1487, 2022 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-35087079

RESUMO

The native marmoset of the Southeastern Atlantic Forest in Brazil is among the 25 most endangered primates of the world. Hybridization with alien species is one of its main threats registered since the early 2000s based on phenotype, so far, without genetic confirmation. Using uniparental molecular markers, we analyzed 18 putative hybrids, captured from 2004 to 2013 in different localities of the Atlantic Forest. A nine base pair deletion in the SRY gene of C. aurita was used to investigate paternal ancestry. Maternal ancestry was assessed by DNA sequencing of ca. 455 bp from the COX2 gene. Hybridization was confirmed for 16 out of the 18 marmosets since they inherited COX2 haplotypes of the alien C. penicillata or C. jacchus and the SRY deletion specific to C. aurita. Two individuals inherited both parental lineages of C. aurita, which is probably related to backcrossing or hybrid interbreeding. The direction of hybridization of females with the matrilineal lineage of invasive species with males descending from the native lineage was predominant in our sampling. This is the first time that hybridization between C. aurita and invasive species has been confirmed through genetic analysis.


Assuntos
Callithrix/genética , Hibridização Genética , Espécies Introduzidas , Animais , Brasil , Ciclo-Oxigenase 2/genética , DNA Mitocondrial , Feminino , Marcadores Genéticos , Técnicas de Genotipagem/métodos , Padrões de Herança , Masculino , Filogenia
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