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1.
Clin Genitourin Cancer ; 22(5): 102154, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-39094286

RESUMO

INTRODUCTION: Platinum-based chemotherapy (CTX) has historically been the primary treatment for advanced urothelial cancer (aUC), with limited alternative options. The therapeutic landscape experienced a paradigm shift following the results of the EV-302 and Checkmate-901 trials, which led to the approval of Enfortumab vedotin plus pembrolizumab (EV-P) as the preferred first-line treatment, and nivolumab plus CTX for those unable to receive the preferred regimen. Currently, further investigations are underway to explore PD-1 and PD-L1 inhibitors in the initial treatment of aUC. PATIENTS AND METHODS: We conducted a systematic search across PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) comparing immune checkpoint inhibitors (ICI)-CTX combinations versus CTX alone as first-line treatment for advanced UC. Employing a random-effects model, we pooled hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: Our analysis encompassed 3 RCTs, involving 2162 participants, with 51.16% randomized to combination therapy with platinum-based CTX. Compared to CTX alone, immune-chemotherapy significantly improved overall survival (HR 0.84; 95% CI 0.75-0.93; P < .01), progression-free survival (HR 0.78; 95% CI 0.70-0.86; P < .01), and objective response rate (RR 1.20; 95% CI 1.06-1.36; P < .01), while elevating the risk of immune-related adverse events (P-value = .02). CONCLUSION: In this meta-analysis of RCTs, ICI plus CTX demonstrated a significant association with improved survival at the expense of an increased risk of immune-related adverse events. Therefore, our findings suggest that this combination should be considered as an initial treatment for aUC in platinum-eligible patients who cannot receive EV-P.

3.
Arch Oral Biol ; 166: 106047, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39024694

RESUMO

OBJECTIVE: To assess the effect of naltrexone on oral mucosal healing using a traumatic ulcer model DESIGN: Wistar rats (n = 112) received distilled water (control) or naltrexone (0.5, 10, or 50 mg/kg/day). Ulcers were induced on the buccal mucosa using a round skin biopsy punch (diameter 6 mm). Euthanasia was performed on days 1, 3, 7, and 14. Healing was assessed by ulcer area, histological scores, histomorphometric analysis (number of polymorphonuclears, mononuclears, and fibroblasts), and collagen percentage. Immunohistochemistry for TLR-2, TLR-4, NF-kB, and CD31 was evaluated. Nociceptive threshold was measured daily. RESULTS: The 50 mg/kg group showed reduced ulcer area on days 1 (p < 0.001), 3 (p < 0.05), and 14 (p < 0.01). In this group, there was, on day 14, an increase in the percentage of reepithelization (p = 0.043) and collagen (p < 0.05), an increase in connective tissue maturation (p = 0.016), and on day 7 an increase in fibroblasts (p < 0.001). The 10 mg/kg dose reduced the ulcer area on day 1 (p < 0.001). The 50 mg/kg group showed lower expression of TLR-4 (p < 0.001) on day 1, NF-kB on days 1 (p < 0.05) and 14 (p < 0.05), and CD31 on day 14 (p < 0.05). The 0.5 and 10 mg/kg doses reduced TLR-4 expression on day 1 (p < 0.05; p < 0.01, respectively). Nociceptive threshold increased in the 50 mg/kg group (p < 0.01). CONCLUSION: Naltrexone enhanced traumatic oral ulcer healing by reducing TLR-4/NF-kB signaling and promoting fibroblast proliferation and collagen deposition. Additionally, naltrexone reduced pain in rats.


Assuntos
Mucosa Bucal , NF-kappa B , Naltrexona , Úlceras Orais , Ratos Wistar , Receptor 4 Toll-Like , Cicatrização , Animais , Receptor 4 Toll-Like/metabolismo , Naltrexona/farmacologia , NF-kappa B/metabolismo , Úlceras Orais/tratamento farmacológico , Úlceras Orais/patologia , Ratos , Cicatrização/efeitos dos fármacos , Masculino , Mucosa Bucal/efeitos dos fármacos , Mucosa Bucal/metabolismo , Mucosa Bucal/lesões , Regulação para Baixo , Modelos Animais de Doenças , Imuno-Histoquímica , Fibroblastos/efeitos dos fármacos , Colágeno/metabolismo , Receptor 2 Toll-Like/metabolismo , Transdução de Sinais/efeitos dos fármacos
4.
Imaging Sci Dent ; 54(2): 211-220, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38948192

RESUMO

Non-secretory multiple myeloma (NSMM) is a rare cancer of plasma cells characterized by the absence of detectable monoclonal M protein in the blood or urine. A 57-year-old woman presented with mandibular pain but without intraoral swelling. Imaging studies revealed multiple osteolytic lesions in her mandible and pronounced root resorption of the left mandibular second molar. Biopsy results showed atypical plasmacytoid cells positive for anti-kappa, CD138, MUM1, and CD79a antibodies, but negative for anti-lambda and CD20. These results were indicative of a malignant plasma cell neoplasm. No abnormalities were revealed by free light chain assay or by serum or urine protein electrophoresis, leading to a diagnosis of NSMM. The patient began chemotherapy in conjunction with bisphosphonate therapy and achieved remission following treatment. This case underscores the critical role of dentists in the early detection and prevention of NSMM complications, as the disease can initially present in the oral cavity.

5.
Int J Pharm ; 661: 124439, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38972520

RESUMO

Liposomes functionalized with monoclonal antibodies offer targeted therapy for cancer, boasting advantages like sustained drug release, enhanced stability, passive accumulation in tumors, and interaction with overexpressed receptors on cancer cells. This study aimed to develop and characterize anti-EGFR immunoliposomes loaded with cabazitaxel and assess their properties against prostate cancer in vitro and in vivo. Using a Box-Behnken design, a formulation with soy phosphatidylcholine, 10% cholesterol, and a 1:20 drug-lipid ratio yielded nanometric particle size, low polydispersity and high drug encapsulation. Immunoliposomes were conjugated with cetuximab through DSPE-PEG-Maleimide lipid anchor. Characterization confirmed intact antibody structure and interaction with EGFR receptor following conjugation. Cabazitaxel was dispersed within the liposomes in the amorphous state, confirmed by solid-state analyses. In vitro release studies showed slower cabazitaxel release from immunoliposomes. Immunoliposomes had enhanced cabazitaxel cytotoxicity in EGFR-overexpressing DU145 cells without affecting non-tumor L929 cells. Cetuximab played an important role to improve cellular uptake in a time-dependent fashion in EGFR-overexpressing prostate cancer cells. In vivo, immunoliposomes led to significant tumor regression, improved survival, and reduced weight loss in xenograft mice. While cabazitaxel induced leukopenia, consistent with clinical findings, histological analysis revealed no evident toxicity. In conclusion, the immunoliposomes displayed suitable physicochemical properties for cabazitaxel delivery, exhibited cytotoxicity against EGFR-expressing prostate cancer cells, with high cell uptake, and induced significant tumor regression in vivo, with manageable systemic toxicity.


Assuntos
Cetuximab , Liberação Controlada de Fármacos , Receptores ErbB , Lipossomos , Neoplasias da Próstata , Taxoides , Ensaios Antitumorais Modelo de Xenoenxerto , Masculino , Animais , Receptores ErbB/imunologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Humanos , Linhagem Celular Tumoral , Taxoides/administração & dosagem , Taxoides/farmacocinética , Taxoides/farmacologia , Taxoides/química , Cetuximab/administração & dosagem , Camundongos , Camundongos Nus , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Antineoplásicos/química , Polietilenoglicóis/química , Polietilenoglicóis/administração & dosagem , Tamanho da Partícula , Sistemas de Liberação de Medicamentos
6.
Front Pharmacol ; 15: 1390187, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38860172

RESUMO

Introduction: Caffeine and the selective A2A receptor antagonist SCH58261 both have ergogenic properties, effectively reducing fatigue and enhancing exercise capacity. This study investigates in male Swiss mice the interaction between adenosine A2A receptors and dopamine D2 receptors controlling central fatigue, with a focus on the striatum where these receptors are most abundant. Methods: We employed DPCPX and SCH58261 to antagonize A1 and A2A receptors, caffeine as a non-competitive antagonist for both receptors, and haloperidol as a D2 receptor antagonist; all compounds were tested upon systemic application and caffeine and SCH58261 were also directly applied in the striatum. Behavioral assessments using the open field, grip strength, and treadmill tests allowed estimating the effect of treatments on fatigue. Results and discussion: The results suggested a complex interplay between the dopamine and adenosine systems. While systemic DPCPX had little effect on motor performance or fatigue, the application of either caffeine or SCH58261 was ergogenic, and these effects were attenuated by haloperidol. The intra-striatal administration of caffeine or SCH58261 was also ergogenic, but these effects were unaffected by haloperidol. These findings confirm a role of striatal A2A receptors in the control of central fatigue but suggest that the D2 receptor-mediated control of the ergogenic effects of caffeine and of A2A receptor antagonists might occur outside the striatum. This prompts the need of additional efforts to unveil the role of different brain regions in the control of fatigue.

7.
Clin Transl Oncol ; 2024 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-38909323

RESUMO

There is growing evidence about how physical activity can improve cancer care. Unfortunately, exercise is still not widely prescribed to oncology patients, despite the benefit it brings. For this to occur, it is necessary for a multidisciplinary approach involving different types of healthcare professionals, given that each treatment be tailored for each single case. Besides incorporating appropriate infrastructures and referral pathways, we need to integrate exercise into healthcare practice, which ameliorates patients' quality of life and treatment side effects. From the Spanish Society of Medical Oncology (SEOM), and through the Exercise and Cancer Working Group, we indicate considerations, analyze patient care scenarios, and propose a referral pathway algorithm for exercise prescription, taking in account the patient's needs. In later sections of this paper, we describe how this algorithm could be implemented, and how the exercise programs should be built, including the physical activity contents, the settings, and the delivery mode. We conclude that professionals, infrastructures, and organizations should be available at every assistance level to create programs providing adequate exercise training for cancer patients.

8.
Toxicol In Vitro ; 99: 105883, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38936442

RESUMO

Melanoma is a type of tumor skin with high metastatic potential. Reconstructed human skin, development for pre-clinic assay, are make using primary human cells, but with same limitations. The aim this study was to characterize a cell culture model, with structure similar to human skin containing melanoma cells entirely from cell lines. Reconstructed skin with melanoma were development using human fibroblasts (MRC5), human epidermal keratinocytes (HaCat), and human melanoma (SK-MEL-28) embedded in collagen type I. The structure was characterized by hematoxylin-eosin stained, as well as points of melanoma cell invasion, which was associated with activity of MMPs (MMP-2 and MMP-9) by zymographic method. Then, the gene expression of the target molecular mechanisms involved in melanoma progression were evaluated. Here, the model development showed a region epidermis organized and separated from the dermis, with fibroblast cells confined and melanoma cells form delimited area invasion. MMP-2 and MMP-9 were identified during of cell culture and gene expression of BRAF, NRAS, and Vimentin was confirmed. The proposed model provides one more opportunity to study in vitro tumor biology of melanoma and also to allows the study of new drugs with more reliable results then whats we would find in vivo.


Assuntos
Fibroblastos , Metaloproteinase 2 da Matriz , Metaloproteinase 9 da Matriz , Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/patologia , Melanoma/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Neoplasias Cutâneas/patologia , Fibroblastos/metabolismo , Fibroblastos/efeitos dos fármacos , Linhagem Celular Tumoral , Pele/metabolismo , Pele/patologia , Invasividade Neoplásica , Queratinócitos/efeitos dos fármacos , Linhagem Celular , Vimentina/metabolismo , Vimentina/genética
9.
Pharmaceuticals (Basel) ; 17(6)2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38931414

RESUMO

Polymersomes, self-assembled nanoparticles composed of amphiphilic block copolymers, have emerged as promising versatile nanovesicles with various applications, such as drug delivery, medical imaging, and diagnostics. The integration of click chemistry reactions, specifically the copper [I]-catalysed azide-alkyne cycloaddition (CuAAC), has greatly expanded the functionalisation and bioconjugation capabilities of polymersomes and new drugs, being this synergistic combination explored in this review. It also provides up-to-date examples of previous incorporations of click-compatible moieties (azide and alkyne functional groups) into polymer building blocks, enabling the "click" attachment of various functional groups and ligands, delving into the diverse range of click reactions that have been reported and employed for polymersome copolymer synthesis and the modification of polymersome surfaces, including ligand conjugation and surface modification. Overall, this review explores the current state-of-the-art of the combinatory usage, in recent years, of polymersomes with the click chemistry reaction, highlighting examples of studies of their synthesis and functionalisation strategies.

10.
J Oral Pathol Med ; 53(5): 321-330, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38693618

RESUMO

BACKGROUND: To evaluate the presence of myofibroblasts (MFs) in the development of lip carcinogenesis, through the correlation of clinical, histomorphometric and immunohistochemical parameters, in actinic cheilitis (ACs) and lower lip squamous cell carcinomas (LLSCCs). METHODS: Samples of ACs, LLSCCs, and control group (CG) were prepared by tissue microarray (TMA) for immunohistochemical TGF-ß, α-SMA, and Ki-67 and histochemical hematoxylin and eosin, picrosirius red, and verhoeff van gieson reactions. Clinical and microscopic data were associated using the Mann-Whitney, Kruskal-Wallis/Dunn, and Spearman correlation tests (SPSS, p < 0.05). RESULTS: ACs showed higher number of α-SMA+ MFs when compared to CG (p = 0.034), and these cells were associated with the vertical expansion of solar elastosis (SE) itself (p = 0.027). Areas of SE had lower deposits of collagen (p < 0.001), immunostaining for TGF-ß (p < 0.001), and higher density of elastic fibers (p < 0.05) when compared to areas without SE. A positive correlation was observed between high-risk epithelial dysplasia (ED) and the proximity of SE to the dysplastic epithelium (p = 0.027). LLSCCs showed a higher number of α-SMA+ MFs about CG (p = 0.034), as well as a reduction in the deposition of total collagen (p = 0.009) in relation to ACs and CG. There was also a negative correlation between the amount of α-SMA+ cells and the accumulation of total collagen (p = 0.041). Collagen and elastic density loss was higher in larger tumors (p = 0.045) with nodal invasion (p = 0.047). CONCLUSIONS: Our findings show the possible role of MFs, collagen fibers, and elastosis areas in the lip carcinogenesis process.


Assuntos
Carcinoma de Células Escamosas , Queilite , Matriz Extracelular , Neoplasias Labiais , Miofibroblastos , Humanos , Queilite/patologia , Queilite/metabolismo , Neoplasias Labiais/patologia , Neoplasias Labiais/metabolismo , Miofibroblastos/patologia , Carcinoma de Células Escamosas/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Matriz Extracelular/patologia , Idoso , Fator de Crescimento Transformador beta , Adulto , Actinas , Imuno-Histoquímica , Antígeno Ki-67 , Colágeno , Tecido Elástico/patologia
11.
Front Vet Sci ; 11: 1372023, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38711535

RESUMO

The increased fish consumption by the growing human population in the world translates into an increase in fish waste. The reintroduction of these fish by-products into food and feed chains presents economic benefits and contributes to counteracting their negative environmental impact. Under this context, the present study aimed to evaluate the effects of the dietary inclusion of fish hydrolysate and oil obtained from fish waste (experimental diet) in substitution of shrimp hydrolysate and salmon oil (control diet) mainly imported from third countries on palatability, apparent total tract digestibility, fecal characteristics and metabolites, blood fatty acid profile, flatulence, and coat quality of adult dogs. A two-bowl test was performed to evaluate palatability by the pairwise comparison between the two diets. A feeding trial was conducted according to a crossover design with two diets (control and experimental diets), six adult Beagle dogs per diet, and two periods of 6 weeks each. The replacement of shrimp hydrolysate and salmon oil with fish hydrolysate and oil did not affect the first diet approach and taste, as well as the intake ratio. Generally, the digestibility of dry matter, nutrients, and energy was not affected by diet, but the intake of digestible crude protein (CP) and ether extract was higher, respectively, with the control and the experimental diet. The higher intake of eicosapentaenoic acid and docosahexaenoic acid with the experimental diet was reflected in a higher content of these long-chain polyunsaturated fatty acids and the omega-3 index of red blood cells, but it did not affect coat quality. The significantly higher intake of digestible CP with the control diet might have contributed to the higher fecal ammonia-N and valerate concentrations. Daily fecal output and characteristics were similar between diets. Overall, results suggest that fish hydrolysate and oil from the agrifood industry might constitute sustainable functional ingredients for dog feeding while adding value for wild fisheries, aquaculture, and fish farming under a circular economy approach and reducing dependence on imports from third countries with a high carbon footprint.

13.
Front Genet ; 15: 1361418, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38606359

RESUMO

Eucalyptus dunnii is one of the most important Eucalyptus species for short-fiber pulp production in regions where other species of the genus are affected by poor soil and climatic conditions. In this context, E. dunnii holds promise as a resource to address and adapt to the challenges of climate change. Despite its rapid growth and favorable wood properties for solid wood products, the advancement of its improvement remains in its early stages. In this work, we evaluated the performance of two single nucleotide polymorphism, (SNP), genotyping methods for population genetics analysis and Genomic Selection in E. dunnii. Double digest restriction-site associated DNA sequencing (ddRADseq) was compared with the EUChip60K array in 308 individuals from a provenance-progeny trial. The compared SNP set included 8,011 and 19,008 informative SNPs distributed along the 11 chromosomes, respectively. Although the two datasets differed in the percentage of missing data, genome coverage, minor allele frequency and estimated genetic diversity parameters, they revealed a similar genetic structure, showing two subpopulations with little differentiation between them, and low linkage disequilibrium. GS analyses were performed for eleven traits using Genomic Best Linear Unbiased Prediction (GBLUP) and a conventional pedigree-based model (ABLUP). Regardless of the SNP dataset, the predictive ability (PA) of GBLUP was better than that of ABLUP for six traits (Cellulose content, Total and Ethanolic extractives, Total and Klason lignin content and Syringyl and Guaiacyl lignin monomer ratio). When contrasting the SNP datasets used to estimate PAs, the GBLUP-EUChip60K model gave higher and significant PA values for six traits, meanwhile, the values estimated using ddRADseq gave higher values for three other traits. The PAs correlated positively with narrow sense heritabilities, with the highest correlations shown by the ABLUP and GBLUP-EUChip60K. The two genotyping methods, ddRADseq and EUChip60K, are generally comparable for population genetics and genomic prediction, demonstrating the utility of the former when subjected to rigorous SNP filtering. The results of this study provide a basis for future whole-genome studies using ddRADseq in non-model forest species for which SNP arrays have not yet been developed.

14.
World J Gastrointest Oncol ; 16(4): 1119-1133, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38660635

RESUMO

Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide, being the third most commonly diagnosed malignancy and the second leading cause of cancer-related deaths globally. Despite the progress in screening, early diagnosis, and treatment, approximately 20%-25% of CRC patients still present with metastatic disease at the time of their initial diagnosis. Furthermore, the burden of disease is still expected to increase, especially in individuals younger than 50 years old, among whom early-onset CRC incidence has been increasing. Screening and early detection are pivotal to improve CRC-related outcomes. It is well established that CRC screening not only reduces incidence, but also decreases deaths from CRC. Diverse screening strategies have proven effective in decreasing both CRC incidence and mortality, though variations in efficacy have been reported across the literature. However, uncertainties persist regarding the optimal screening method, age intervals and periodicity. Moreover, adherence to CRC screening remains globally low. In recent years, emerging technologies, notably artificial intelligence, and non-invasive biomarkers, have been developed to overcome these barriers. However, controversy exists over the actual impact of some of the new discoveries on CRC-related outcomes and how to effectively integrate them into daily practice. In this review, we aim to cover the current evidence surrounding CRC screening. We will further critically assess novel approaches under investigation, in an effort to differentiate promising innovations from mere novelties.

15.
J Equine Vet Sci ; 135: 105050, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38527562

RESUMO

A 25-year-old female mule weighing 336 kg was referred with a history of lethargy, abdominal discomfort, anorexia, and constipation in the previous 24 hours. On admission, decreased intestinal borborygmi and distended small intestinal loops were detected by auscultation and rectal palpation, respectively. On rectal examination a firm, irregular surface, and pedunculated mass were detected in the middle-caudal region of the abdomen. Transrectal ultrasonography revealed the mass was highly vascularized with heterogeneous tissue density. On exploratory celiotomy two neoplastic masses were observed, one in the jejunoileal junction obstructing the intestinal flow and the second in the dorsal part of the jejunal mesentery, unable to be exposed and resected. An enterectomy was conducted, and the intestinal mass was removed. The mass was pale with hemorrhagic areas and 12 cm in diameter. Histopathology and immunohistochemistry confirmed a diagnosis of enteric associated T cell lymphoma subtype 2. The mule died suddenly 43 days later.


Assuntos
Equidae , Linfoma de Células T , Feminino , Animais , Linfoma de Células T/veterinária , Ultrassonografia
16.
Arch Oral Biol ; 161: 105937, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38442471

RESUMO

OBJECTIVE: To evaluate the role of induced nitric oxide synthase (iNOS) in nociception/orofacial discomfort in rats submitted to tooth whitening with hydrogen peroxide (H2O2). DESIGN: Wistar rats were divided into three groups (n = 24/group): a sham group not submitted to whitening treatment, a saline group submitted to whitening treatment, and a test group submitted to whitening treatment and blockade of iNOS with aminoguanidine 50 mg/kg/day. After 24 and 48 h, and 7 days, the animals were euthanized to collect trigeminal ganglia and maxillae to histomorphometric analysis (size of neuronal bodies and percentage of pulp area filled by vessels) and behavior/nociception (Grimace scales, scratching and biting counting, weight loss and nociception assay). ANOVA-1- or - 2-way tests were used (p < 0.05, GraphPadPrism 5.0). RESULTS: The aminoguanidine-treated group showed a reduction in nociceptive threshold in the masseteric region (p < 0.001), Grimace scale scores (p < 0.001), number of scratching (p = 0.011) and body mass loss (p = 0.007). After 24 and 48 h of tooth bleaching, the saline group showed a significant increase in the mean area of the blood vessels (p = 0.020) and iNOS immunostaining in odontoblasts (p = 0.002) and non-odontoblasts cells (p = 0.025). Aminoguanidine reversed both increases. Tooth bleaching reduced the mean area of neuronal bodies, and aminoguanidine significantly reversed it (p = 0.019), but an increase in GFAP immunostaining in neuronal bodies did not reduce after seven-days or after aminoguanidine treatment (p = 0.003). CONCLUSION: iNOS blockage by aminoguanidine plays an important role in nociception and orofacial discomfort by control of inflammation in dental pulp after tooth bleaching with hydrogen peroxide (H2O2) 35%.


Assuntos
Guanidinas , Clareadores Dentários , Clareamento Dental , Ratos , Animais , Peróxido de Hidrogênio/farmacologia , Nociceptividade , Óxido Nítrico , Ratos Wistar , Óxido Nítrico Sintase
17.
Redox Biol ; 71: 103122, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38490068

RESUMO

Typical two-cysteine peroxiredoxins (2-Cys-PRXs) are H2O2-metabolizing enzymes whose activity relies on two cysteine residues. Protists of the family Trypanosomatidae invariably express one cytosolic 2-Cys-PRX (cPRX1). However, the Leishmaniinae sub-family features an additional isoform (cPRX2), almost identical to cPRX1, except for the lack of an elongated C-terminus with a Tyr-Phe (YF) motif. Previously, cytosolic PRXs were considered vital components of the trypanosomatid antioxidant machinery. Here, we shed new light on the properties, functions and relevance of cPRXs from the human pathogen Leishmania infantum. We show first that LicPRX1 is sensitive to inactivation by hyperoxidation, mirroring other YF-containing PRXs participating in redox signaling. Using genetic fusion constructs with roGFP2, we establish that LicPRX1 and LicPRX2 can act as sensors for H2O2 and oxidize protein thiols with implications for signal transduction. Third, we show that while disrupting the LicPRX-encoding genes increases susceptibility of L. infantum promastigotes to external H2O2in vitro, both enzymes are dispensable for the parasites to endure the macrophage respiratory burst, differentiate into amastigotes and initiate in vivo infections. This study introduces a novel perspective on the functions of trypanosomatid cPRXs, exposing their dual roles as both peroxidases and redox sensors. Furthermore, the discovery that Leishmania can adapt to the absence of both enzymes has significant implications for our understanding of Leishmania infections and their treatment. Importantly, it questions the conventional notion that the oxidative response of macrophages during phagocytosis is a major barrier to infection and the suitability of cPRXs as drug targets for leishmaniasis.


Assuntos
Leishmania , Leishmaniose , Parasitos , Animais , Humanos , Peroxirredoxinas/metabolismo , Cisteína/metabolismo , Peróxido de Hidrogênio/metabolismo , Parasitos/metabolismo , Oxirredução
18.
Food Chem ; 446: 138820, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38430763

RESUMO

This study has innovative aspects related to the use of sequential inoculation technique in the coffee bean fermentation process: the inoculation of Lactiplantibacillus plantarum followed by Saccharomyces cerevisiae, in the fermentation of coffee fruit for the production of specialty natural coffees. The objective was to evaluate the effect of this technique and of the total fermentation time on the sensory attributes of the coffee beverage and on the organic acid profile, bioactive compounds, and fatty acid profile of the beans. The fermentation of coffee fruit with sequential inoculation resulted in greater acidity of the beverage and contributed to increases of up to 2 points in coffee fermented. The total fermentation time was directly related to the organic acid content, and the longer the total fermentation time was, the greater the organic acid content. The fatty acid content and bioactive compound content showed little variation among treatments.


Assuntos
Frutas , Saccharomyces cerevisiae , Fermentação , Ácidos Graxos
19.
Artigo em Inglês | MEDLINE | ID: mdl-38433146

RESUMO

Chronic use of omeprazole has been linked to central effects alongside with the global concern of increasing appearance of neuropsychiatric disorders. This study aimed to identifying behavioral, inflammatory, and oxidative stress alterations after long-term administration of omeprazole. C57BL/6 mice were divided in groups: OME and Sham, each received either solutions of omeprazole or vehicle, administered for 28 days by gavage. Results observed in the omeprazole-treated mice: Decrease in the crossing parameter in the open field, no change in the motor performance assessed by rotarod, an immobility time reduction in the forced swimming test, improved percentage of correct alternances in the Ymaze and an exploration time of the novel object reduction in the novel object recognition. Furthermore, a reduced weight gain and hippocampal weight were observed. There was an increase in the cytokine IL1-ß levels in both prefrontal cortex (PFC) and serum, whereas TNF-α increased only in the PFC. Nitrite levels increased in the hippocampus (HP) and PFC, while malondialdehyde (MDA) and glutathione (GSH) levels decreased. These findings suggest that omeprazole improves depressive-like behavior and working memory, likely through the increase in nitrite and reduction in MDA levels in PFC and HP, whereas, the impairment of the recognition memory is more likely to be related to the reduced hippocampal weight. The diminished weight gain might be associated with the IL-1ß increased levels in the peripheral blood. Altogether, omeprazole showed to have the potential to impact at central level and inflammatory and oxidative parameters might exert a role between it.

20.
Food Chem ; 444: 138608, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38325081

RESUMO

Mixed starter cultures of lactic acid bacteria and yeasts used in the production of fermented foods, including coffee, can improve the sensory quality and food safety. The objective of this study was to evaluate the effects of fermentation of coffee with inoculation of Lactiplantibacillus plantarum followed by Saccharomyces cerevisiae and the effects of fermentation time on the aroma and flavor of the coffee beverage and on the volatile composition of the roasted coffee beans. The coffee was fermented for 48 h or 96 h after inoculation of Lactiplantibacillus plantarum followed by inoculation of Saccharomyces cerevisiae or the respective controls. The aroma and flavor of the coffee beverage fermented with sequential inoculation showed complexity, with a predominance of fruity and fermented sensory notes. Forty-seven volatile compounds were identified. In addition, the sequentially inoculated coffees had greater formation of volatiles and led to greater perception of fruity and fermented flavor and aroma.


Assuntos
Frutas , Saccharomyces cerevisiae , Fermentação , Frutas/microbiologia , Odorantes
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