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1.
Plant Physiol ; 195(3): 2323-2338, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38478585

RESUMO

Hydroxylated monoterpenes (HMTPs) are differentially emitted by tomato (Solanum lycopersicum) plants resisting bacterial infection. We have studied the defensive role of these volatiles in the tomato response to bacteria, whose main entrance is through stomatal apertures. Treatments with some HMTPs resulted in stomatal closure and pathogenesis-related protein 1 (PR1) induction. Particularly, α-terpineol induced stomatal closure in a salicylic acid (SA) and abscisic acid-independent manner and conferred resistance to bacteria. Interestingly, transgenic tomato plants overexpressing or silencing the monoterpene synthase MTS1, which displayed alterations in the emission of HMTPs, exhibited changes in the stomatal aperture but not in plant resistance. Measures of both 2-C-methyl-D-erythritol-2,4-cyclopyrophosphate (MEcPP) and SA levels revealed competition for MEcPP by the methylerythritol phosphate (MEP) pathway and SA biosynthesis activation, thus explaining the absence of resistance in transgenic plants. These results were confirmed by chemical inhibition of the MEP pathway, which alters MEcPP levels. Treatments with benzothiadiazole (BTH), a SA functional analog, conferred enhanced resistance to transgenic tomato plants overexpressing MTS1. Additionally, these MTS1 overexpressors induced PR1 gene expression and stomatal closure in neighboring plants. Our results confirm the role of HMTPs in both intra- and interplant immune signaling and reveal a metabolic crosstalk between the MEP and SA pathways in tomato plants.


Assuntos
Monoterpenos , Doenças das Plantas , Estômatos de Plantas , Plantas Geneticamente Modificadas , Ácido Salicílico , Solanum lycopersicum , Solanum lycopersicum/microbiologia , Solanum lycopersicum/genética , Solanum lycopersicum/metabolismo , Ácido Salicílico/metabolismo , Monoterpenos/metabolismo , Doenças das Plantas/microbiologia , Doenças das Plantas/imunologia , Estômatos de Plantas/fisiologia , Estômatos de Plantas/efeitos dos fármacos , Hidroxilação , Tiadiazóis/farmacologia , Regulação da Expressão Gênica de Plantas , Fosfatos Açúcares/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Pseudomonas syringae/patogenicidade , Pseudomonas syringae/fisiologia , Eritritol/análogos & derivados , Eritritol/metabolismo , Resistência à Doença/genética , Resistência à Doença/efeitos dos fármacos
2.
Int J Mol Sci ; 25(11)2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38892410

RESUMO

The cancer stem cell (SC) theory proposes that a population of SCs serves as the driving force behind fundamental tumor processes, including metastasis, recurrence, and resistance to therapy. The standard of care for patients with stage III and high-risk stage II colorectal cancer (CRC) includes surgery and adjuvant chemotherapy. Fluoropyrimidines and their combination with oxaliplatin increased the cure rates, being able to eradicate the occult metastatic SC in a fraction of patients. The treatment for unresectable metastatic CRC is based on chemotherapy, antibodies to VEGF and EGFR, and tyrosine-kinase inhibitors. Immunotherapy is used in MSI-H tumors. Currently used drugs target dividing cells and, while often effective at debulking tumor mass, these agents have largely failed to cure metastatic disease. SCs are generated either due to genetic and epigenetic alterations in stem/progenitor cells or to the dedifferentiation of somatic cells where diverse signaling pathways such as Wnt/ß-catenin, Hedgehog, Notch, TGF-ß/SMAD, PI3K/Akt/mTOR, NF-κB, JAK/STAT, DNA damage response, and Hippo-YAP play a key role. Anti-neoplastic treatments could be improved by elimination of SCs, becoming an attractive target for the design of novel agents. Here, we present a review of clinical trials assessing the efficacy of targeted treatment focusing on these pathways in CRC.


Assuntos
Neoplasias Colorretais , Células-Tronco Neoplásicas , Humanos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/patologia , Terapia de Alvo Molecular , Transdução de Sinais/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Animais
3.
Geriatr Nurs ; 59: 278-295, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39094351

RESUMO

This comprehensive review assessed the psychometric properties of abbreviated versions of the Caregiver Burden Instrument (ZBI-22). Initially, 40 articles that met the inclusion criteria were identified through a systematic search of four databases. Additionally, 26 articles were included through manual searches, totaling 66 articles in the analysis. Different versions of instruments measuring caregiver burden were examined, considering item variability and differences in factor structures. Although most measures exhibited satisfactory content validity, as well as construct validity supported by high internal consistencies, it is important to note that measurement invariance, criterion validity and test-retest reliability were not established for all measures analyzed. Furthermore, structural validity was not satisfactory for all versions. Research and clinical practice could benefit from a standardized approach that allows for a more accurate and consistent assessment of caregiver strain.

4.
New Phytol ; 239(6): 2292-2306, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37381102

RESUMO

Carotenoids are photoprotectant pigments and precursors of hormones such as strigolactones (SL). Carotenoids are produced in plastids from geranylgeranyl diphosphate (GGPP), which is diverted to the carotenoid pathway by phytoene synthase (PSY). In tomato (Solanum lycopersicum), three genes encode plastid-targeted GGPP synthases (SlG1 to SlG3) and three genes encode PSY isoforms (PSY1 to PSY3). Here, we investigated the function of SlG1 by generating loss-of-function lines and combining their metabolic and physiological phenotyping with gene co-expression and co-immunoprecipitation analyses. Leaves and fruits of slg1 lines showed a wild-type phenotype in terms of carotenoid accumulation, photosynthesis, and development under normal growth conditions. In response to bacterial infection, however, slg1 leaves produced lower levels of defensive GGPP-derived diterpenoids. In roots, SlG1 was co-expressed with PSY3 and other genes involved in SL production, and slg1 lines grown under phosphate starvation exuded less SLs. However, slg1 plants did not display the branched shoot phenotype observed in other SL-defective mutants. At the protein level, SlG1 physically interacted with the root-specific PSY3 isoform but not with PSY1 and PSY2. Our results confirm specific roles for SlG1 in producing GGPP for defensive diterpenoids in leaves and carotenoid-derived SLs (in combination with PSY3) in roots.


Assuntos
Diterpenos , Solanum lycopersicum , Solanum lycopersicum/genética , Geranil-Geranildifosfato Geranil-Geraniltransferase/genética , Geranil-Geranildifosfato Geranil-Geraniltransferase/metabolismo , Farnesiltranstransferase , Carotenoides/metabolismo , Isoformas de Proteínas , Folhas de Planta/metabolismo
5.
Cult Health Sex ; : 1-16, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38056488

RESUMO

Research documents how abortion can be emotionally difficult and stigmatising, but generally has not considered whether and how involvement in abortion may be a source of positive emotions, including pleasure, belonging and even joy. The absence of explorations that start from the possibility of abortion pleasure and joy represents an epistemic foreclosure. Moreover, it highlights how social science literature has tended to emphasise the negative aspects of abortion care in ways that produce or amplify normative negative associations. In this paper, we investigate the positive emotions, pleasure and joy of abortion involvement by drawing on interviews conducted in 2019 with 28 abortion accompaniers in Argentina, Chile, and Ecuador about their experiences accompanying abortions after 17 weeks' gestation. Abortion accompaniment is a response to unsafe and/or inaccessible abortion whereby volunteer activists guide abortion seekers through a medication abortion. Interviewees described how the practice of accompaniment generated positive emotions by building a feminist community, shared intimacy among women, and witnessing aborting people claim their strength. Importantly, these positive emotional experiences of involvement with abortion were not distinct from the broader marginalisation of abortion but were, instead, rooted in its marginalisation.

6.
Mod Pathol ; 35(5): 601-608, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34839351

RESUMO

Triple-negative breast cancer (TNBC) with high tumour-infiltrating lymphocytes (TILs) has been associated with a promising prognosis. To better understand the prognostic value of immune cell subtypes in TNBC, we characterised TILs and the interaction between tumour cells and immune cell subtypes. A total of 145 breast cancer tissues were stained by multiplex immunofluorescence (mIF), including panel 1 (PD-L1, PD-1, CD3, CD8, CD68 and CK) and panel 2 (Foxp3, Granzyme B, CD45RO, CD3, CD8 and CK). Phenotypes were analysed and quantified by pathologists using InForm software. We found that in the ER-negative (ER <1% and HER2-negative) group and the ER/PR-low positive (ER 1-9% and HER2-negative) group, 11.2% and 7.1% of patients were PD-L1+ by the tumour cell score, 29.0% and 28.6% were PD-L1+ by the modified immune cell score and 30.8% and 32.1% were PD-L1+ by the combined positive score. We combined ER-negative and ER/PR-low positive cases for the survival analysis since a 10% cut-off is often used in clinical practice for therapeutic purposes. The densities of PD-L1+ tumour cells (HR: 0.366, 95% CI: 0.138-0.970; p = 0.043) within the tumour compartment and CD3+ immune cells in the total area (tumour and stromal compartments combined) (HR: 0.213, 95% CI: 0.070-0.642; p = 0.006) were favourable prognostic biomarkers for overall survival (OS) in TNBC. The density of effector/memory cytotoxic T cells (CD3+CD8+CD45RO+) in the tumour compartment was an independent prognostic biomarker for OS (HR: 0.232, 95% CI: 0.086-0.628; p = 0.004) and DFS (HR: 0.183, 95% CI: 0.1301-0.744; p = 0.009) in TNBC. Interestingly, spatial data suggested that patients with a higher density of PD-L1+ tumour cells had shorter cell-cell distances from tumour cells to cytotoxic T cells (p < 0.01). In conclusion, we found that phenotyping tumour immune cells by mIF is highly informative in understanding the immune microenvironment in TNBC. PD-L1+ tumour cells, total T cells and effector/memory cytotoxic T cells are promising prognostic biomarkers in TNBC.


Assuntos
Memória Imunológica , Neoplasias de Mama Triplo Negativas , Antígeno B7-H1 , Biomarcadores Tumorais , Complexo CD3/imunologia , Linfócitos T CD8-Positivos/patologia , Humanos , Antígenos Comuns de Leucócito/imunologia , Linfócitos do Interstício Tumoral , Prognóstico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Microambiente Tumoral
7.
Methods ; 171: 86-96, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31128238

RESUMO

The global shortage of donor corneas for transplantation has led to corneal bioengineering being investigated as a method to generate transplantable tissues. Decellularized corneas are among the most promising materials for engineering corneal tissue since they replicate the complex structure and composition of real corneas. Decellularization is a process that aims to remove cells from organs or tissues resulting in a cell-free scaffold consisting of the tissues extracellular matrix. Here different decellularization techniques are described, including physical, chemical and biological methods. Analytical techniques to confirm decellularization efficiency are also discussed. Different cell sources for the recellularization of the three layers of the cornea, recellularization methods used in the literature and techniques used to assess the outcome of the implantation of such scaffolds are examined. Studies involving the application of decellularized corneas in animal models and human clinical studies are discussed. Finally, challenges for this technology are explored involving scalability, automatization and regulatory affairs.


Assuntos
Córnea/crescimento & desenvolvimento , Matriz Extracelular/transplante , Engenharia Tecidual/tendências , Alicerces Teciduais/química , Animais , Bioengenharia/métodos , Córnea/patologia , Matriz Extracelular/química , Humanos , Modelos Animais , Doadores de Tecidos
8.
Gastroenterol Hepatol ; 43(3): 117-125, 2020 Mar.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31810793

RESUMO

BACKGROUND: At present only monoclonal EIA (enzyme-immunoassay) stool antigen-tests have obtained optimal accuracy in the diagnosis of Helicobacter pylori. Our aim was to evaluate the accuracy of two stool antigen-tests, the validated Premier Platinum HpSA PLUS (EIA test) and the newly available ImmunoCard STAT! HpSA HD (rapid test) for the initial diagnosis and the confirmation of eradication of H. pylori infection. PATIENTS AND METHODS: Patients with indication of H. pylori diagnosis, or confirmation after treatment were included. Data were coded to protect personal data and ensure blindness between tests. Accuracy was considered as coincident diagnosis with the gold standard (13C-urea breath test, UBT). The EIA was used as a bench standard. All stool tests were performed in duplicate. RESULTS: 264 patients completed the protocol (100 naïve, 164 post-eradication). Average age was 52 years, 61% women, 11% ulcer. Positive diagnoses by UBT were 41% for naïve and 17% for post-eradication. Overall ImmunoCard and EIA accuracies were respectively 91% (95%C.I.=88-94%) and 89% (86-93%), sensitivities 72% (67-78%) and 72% (67-78%), and specificities 98% (96-100%), and 95% (92-97%). Concordance between ImmunoCard and EIA was 95% (93-98%). DISCUSSION: Our results indicate that the newly available ImmunoCard rapid stool antigen-test achieves 90% accuracy, with high specificity but suboptimal sensitivity. The ImmunoCard attained equivalent accuracies as the EIA bench standard, with 95% concordance.


Assuntos
Antígenos de Bactérias/análise , Fezes/microbiologia , Infecções por Helicobacter/diagnóstico , Helicobacter pylori/imunologia , Imunoensaio/métodos , Técnicas Imunoenzimáticas/métodos , Kit de Reagentes para Diagnóstico , Idoso , Área Sob a Curva , Testes Respiratórios , Dispepsia/microbiologia , Fezes/química , Feminino , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Úlcera Péptica/microbiologia , Estudos Prospectivos , Curva ROC , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
9.
Molecules ; 24(6)2019 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-30875724

RESUMO

Ochratoxin A (OTA) is a mycotoxin produced in the secondary metabolism of fungus belonging to the genus Aspergillus and Penicillium. In this study, the employment of oriental mustard flour (OMF) as an ingredient in a packaged sauce was evaluated for the generation in situ of the antimicrobial compound allyl isothiocyanate (AITC) in order to preserve pita bread contaminated with Penicillium verrucosum VTT D-01847, an OTA producer, in an active packaging system. Four different concentrations (8, 16, 33 and 50 mg/g) were tested. Mycelium formation, mycotoxin production, AITC absorbed by the food matrix, and volatilization kinetics were studied for each concentration. The results obtained were compared with bread treated with the commercial additive calcium propionate (E-282). The results showed a shelf life increase of two and three days with the employment of 33 and 50 mg/g of OMF, with a significant reduction of the fungal population (3.1 and 5.7 logs, respectively) in comparison with the control experiment. The use of 16 and 33 mg/g of OMF in the sauce formulation decreased the concentration of OTA in the bread samples while no OTA production was detected employing 50 mg/g of OMF.


Assuntos
Antifúngicos/química , Armazenamento de Alimentos , Isotiocianatos/química , Ocratoxinas/química , Antifúngicos/farmacologia , Aspergillus/efeitos dos fármacos , Aspergillus/patogenicidade , Pão/microbiologia , Farinha/microbiologia , Microbiologia de Alimentos , Conservantes de Alimentos , Humanos , Isotiocianatos/farmacologia , Mostardeira/química , Micélio/efeitos dos fármacos , Micélio/patogenicidade , Ocratoxinas/farmacologia , Penicillium/efeitos dos fármacos , Penicillium/patogenicidade
10.
Cancer ; 123(18): 3617-3627, 2017 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28543182

RESUMO

BACKGROUND: Greater than 40% of renal cell carcinoma (RCC) cases in the United States are attributed to excessive body weight. Moreover, obesity also may be linked to RCC prognosis. However, the molecular mechanisms underlying these associations are unclear. In the current study, the authors evaluated the role of promoter methylation in obesity-related genes in RCC tumorigenesis and disease recurrence. METHODS: Paired tumors (TU) and normal adjacent (N-Adj) tissues from 240 newly diagnosed and previously untreated white patients with RCC were examined. For the discovery phase, 63 RCC pairs were analyzed. An additional 177 RCC pairs were evaluated for validation. Pyrosequencing was used to determine CpG methylation in 20 candidate obesity-related genes. An independent data set from The Cancer Genome Atlas also was analyzed for functional validation. The association between methylation and disease recurrence was analyzed using multivariate Cox proportional hazards models and Kaplan-Meier survival analysis. RESULTS: Methylation in neuropeptide Y (NPY), leptin (LEP), and leptin receptor (LEPR) was significantly higher in TU compared with N-Adj tissues (P<.0001) in both the discovery and validation groups. High methylation in LEPR was associated with an increased risk of disease recurrence (hazard ratio, 3.15; 95% confidence interval, 1.23-8.07 [P = .02]). Patients with high methylation in LEPR had a shorter recurrence-free survival compared with patients in the low-methylation group (log-rank P = 2.25 × 10-3 ). In addition, high LEPR methylation in TU was associated with more advanced features (P≤.05). Consistent with the findings of the current study, lower LEPR expression in TU compared with N-Adj tissues (P = 1.00 × 10-3 ) was found in data from The Cancer Genome Atlas. CONCLUSIONS: Somatic alterations of promoter methylation in the NPY, LEP, and LEPR genes are involved in RCC tumorigenesis. Furthermore, LEPR methylation appears to be associated with RCC recurrence. Future research to elucidate the biology underlying this association is warranted. Cancer 2017;123:3617-27. © 2017 American Cancer Society.


Assuntos
Carcinoma de Células Renais/genética , Ilhas de CpG/genética , Metilação de DNA/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/genética , Receptores para Leptina/genética , Idoso , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Estudos de Coortes , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Leptina/genética , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neuropeptídeo Y/genética , Obesidade/genética , Prognóstico , Regiões Promotoras Genéticas , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , Análise de Sobrevida
11.
BMC Pregnancy Childbirth ; 17(Suppl 2): 350, 2017 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-29143680

RESUMO

BACKGROUND: This paper analyzes the strategies used by activist health professionals in Argentina who justify providing abortion despite legal restrictions on the procedure. These "insider activists" make a case for abortion rights by linking pregnancy termination to a woman's ability to exert agency at a key point in her reproductive life, and argue that refusing women access to the procedure constitutes a grievous health risk. This argument frames pregnancy termination as an issue of empowerment and also as a medical necessity. METHODS: This article is based on ethnographic research conducted in Argentina in 2013 and 2015, which includes in-depth interviews with abortion activists and health professionals and ethnographic observation at activist events and in clinics. RESULTS: During the period of my field research, the medical staff in one clinic shifted from abortion counseling, based on a harm reduction model, to legal pregnancy termination, a new mode of abortion provision where they directly provided abortions based on the legal health exception. These insider activists formalized the latter approach by creating a diagnostic instrument that frames women's "bio-psycho-social" reasons for wishing to terminate a pregnancy as medically justified. CONCLUSIONS: The clinical practice analyzed in this article raises important questions about the potential for health professionals to take on an activist role by making safe abortion accessible, even in a context where the procedure is highly restricted.


Assuntos
Aborto Legal/psicologia , Serviços de Planejamento Familiar/legislação & jurisprudência , Ativismo Político , Poder Psicológico , Direitos Sexuais e Reprodutivos/psicologia , Aborto Legal/legislação & jurisprudência , Argentina , Feminino , Humanos , Gravidez , Direitos Sexuais e Reprodutivos/legislação & jurisprudência , Direitos da Mulher/legislação & jurisprudência
13.
Molecules ; 19(4): 4654-68, 2014 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-24739928

RESUMO

A physio-pathological feature of diabetes mellitus is a significant reduction of ß-pancreatic cells. The growth, differentiation and function maintenance of these cells is directed by transcription factors. Nkx6.1 is a key transcription factor for the differentiation, neogenesis and maintenance of ß-pancreatic cells. We reported that silymarin restores normal morphology and endocrine function of damaged pancreatic tissue after alloxan-induced diabetes mellitus in rats. The aim of this study was to analyze the effect of silymarin on Nkx6.1 transcription factor expression and its consequence in ß cells neogenesis. Sixty male Wistar rats were partially pancreatectomized and divided into twelve groups. Six groups were treated with silymarin (200 mg/Kg p.o) for periods of 3, 7, 14, 21, 42 and 63 days. Additionally, an unpancreatectomized control group was used. Nkx6.1 and insulin gene expression were assessed by RT-PCR assay in total pancreatic RNA. ß-Cell neogenesis was determined by immunoperoxidase assay. Silymarin treated group showed an increase of Nkx6.1 and insulin genic expression. In this group, there was an increment of ß-cell neogenesis in comparison to pancreatectomized untreated group. Silymarin treatment produced a rise in serum insulin and serum glucose normalization. These results suggest that silymarin may improve the reduction of ß pancreatic cells observed in diabetes mellitus.


Assuntos
Proteínas de Homeodomínio/agonistas , Células Secretoras de Insulina/efeitos dos fármacos , Insulina/agonistas , Pancreatectomia , Substâncias Protetoras/farmacologia , Silimarina/farmacologia , Animais , Glicemia/metabolismo , Contagem de Células , Proliferação de Células , Diabetes Mellitus , Modelos Animais de Doenças , Expressão Gênica , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Técnicas Imunoenzimáticas , Insulina/genética , Insulina/metabolismo , Células Secretoras de Insulina/citologia , Células Secretoras de Insulina/metabolismo , Masculino , Ratos , Ratos Wistar
14.
Macromol Biosci ; 24(1): e2300109, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37401723

RESUMO

Developing biomaterials for corneal repair and regeneration is crucial for maintaining clear vision. The cornea, a specialized tissue, relies on corneal keratocytes, that respond to their mechanical environment. Altering stiffness affects keratocyte behavior, but static stiffness alone cannot capture the dynamic properties of in vivo tissue. This study proposes that the cornea exhibits time-dependent mechanical properties, similar to other tissues, and aims to replicate these properties in potential therapeutic matrices. First, the cornea's stress relaxation properties are investigated using nanoindentation, revealing 15% relaxation within 10 seconds. Hydrogel dynamicity is then modulated using a specially formulated alginate-PEG and alginate-norbornene mixture. The tuning of the hydrogel's dynamicity is achieved through a photoinitiated norbornene-norbornene dimerization reaction, resulting in relaxation times ranging from 30 seconds to 10 minutes. Human primary corneal keratocytes are cultured on these hydrogels, demonstrating reduced αSMA (alpha smooth muscle actin) expression and increased filopodia formation on slower relaxing hydrogels, resembling their native phenotype. This in vitro model can enable the optimization of stress relaxation for various cell types, including corneal keratocytes, to control tissue formation. Combining stress relaxation optimization with stiffness assessment provides a more accurate tool for studying cell behavior and reduces mechanical mismatch with native tissues in implanted constructs.


Assuntos
Alginatos , Hidrogéis , Humanos , Hidrogéis/farmacologia , Alginatos/farmacologia , Compostos de Sulfidrila , Córnea , Norbornanos , Engenharia Tecidual/métodos
15.
Microorganisms ; 12(5)2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38792714

RESUMO

It was in the 1800s when the first public publications about the infection and treatment of gonorrhoea were released. However, the first prevention programmes were only published a hundred years later. In the 1940s, the concept of vaccination was introduced into clinical prevention programmes to address early sulphonamide resistance. Since then, tons of publications on Neisseria gonorrhoeae are undisputed, around 30,000 publications today. Currently, the situation seems to be just as it was in the last century, nothing has changed or improved. So, what are we doing wrong? And more importantly, what might we do? The review presented here aims to review the current situation regarding the resistance mechanisms, prevention programmes, treatments, and vaccines, with the challenge of better understanding this special pathogen. The authors have reviewed the last five years of advancements, knowledge, and perspectives for addressing the Neisseria gonorrhoeae issue, focusing on new therapeutic alternatives.

16.
Materials (Basel) ; 17(13)2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38998374

RESUMO

Understanding the interactions in hybrid systems based on graphene and functional oxides is crucial to the applicability of graphene in real devices. Here, we present a study of the structural defects occurring on graphene during the early stages of the growth of CoO, tailored by the electronic coupling between graphene and the substrate in which it is supported: as received pristine graphene on polycrystalline copper (coupled), cleaned in ultra-high vacuum conditions to remove oxygen contamination, and graphene transferred to SiO2/Si substrates (decoupled). The CoO growth was performed at room temperature by thermal evaporation of metallic Co under a molecular oxygen atmosphere, and the early stages of the growth were investigated. On the decoupled G/SiO2/Si samples, with an initial low crystalline quality of graphene, the formation of a CoO wetting layer is observed, identifying the Stranski-Krastanov growth mode. In contrast, on coupled G/Cu samples, the Volmer-Weber growth mechanism is observed. In both sets of samples, the oxidation of graphene is low during the early stages of growth, increasing for the larger coverages. Furthermore, structural defects are developed in the graphene lattice on both substrates during the growth of CoO, which is significantly higher on decoupled G/SiO2/Si samples mainly for higher CoO coverages. When approaching the full coverage on both substrates, the CoO islands coalesce to form a continuous CoO layer with strip-like structures with diameters ranging between 70 and 150 nm.

17.
Hortic Res ; 11(1): uhad248, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38239809

RESUMO

Biotic and abiotic stresses can severely limit crop productivity. In response to drought, plants close stomata to prevent water loss. Furthermore, stomata are the main entry point for several pathogens. Therefore, the development of natural products to control stomata closure can be considered a sustainable strategy to cope with stresses in agriculture. Plants respond to different stresses by releasing volatile organic compounds. Green leaf volatiles, which are commonly produced across different plant species after tissue damage, comprise an important group within volatile organic compounds. Among them, (Z)-3-hexenyl butyrate (HB) was described as a natural inducer of stomatal closure, playing an important role in stomatal immunity, although its mechanism of action is still unknown. Through different genetic, pharmacological, and biochemical approaches, we here uncover that HB perception initiates various defence signalling events, such as activation of Ca2+ permeable channels, mitogen-activated protein kinases, and production of Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-mediated reactive oxygen species. Furthermore, HB-mediated stomata closure was found to be independent of abscisic acid biosynthesis and signalling. Additionally, exogenous treatments with HB alleviate water stress and improve fruit productivity in tomato plants. The efficacy of HB was also tested under open field conditions, leading to enhanced resistance against Phytophthora spp. and Pseudomonas syringae infection in potato and tomato plants, respectively. Taken together, our results provide insights into the HB signalling transduction pathway, confirming its role in stomatal closure and plant immune system activation, and propose HB as a new phytoprotectant for the sustainable control of biotic and abiotic stresses in agriculture.

18.
J Gastrointest Oncol ; 14(2): 692-704, 2023 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-37201039

RESUMO

Background: The combination of trifluridine and tipiracil is indicated in patients with metastatic colorectal cancer previously treated or non-candidates to chemotherapy and biological therapies. This study in routine clinical practice aimed to describe the effectiveness and safety of trifluridine and tipiracil and identify prognostic factors in patients with metastatic colorectal cancer in Spain. Methods: This analysis was a retrospective, observational, multicenter study that included patients aged ≥18 years who had received treatment with trifluridine/tipiracil for metastatic colorectal cancer in third- or subsequent lines. Results: Overall, 294 were evaluated. Trifluridine/tipiracilmedian (minimum, maximum) treatment duration was 3.5 (1.0-29.0) months, and 128 (43.5%) patients received subsequent treatments. One hundred (34%) patients showed disease control rate, and the median progression-free survival and overall survival from trifluridine/tipiracil treatment onset were 3.7 and 7.5 months, respectively. The most frequently reported adverse events were asthenia (all grades, 57.9%) and neutropenia (all grades, 51.3%). A 39.1% and 4.4% of the participants had a dose reduction and a treatment interruption due to toxicity. Patients with age ≥65 years, low tumor burden, ≤2 metastasis sites, treatment dose reduction, neutropenia, and ≥6 cycles, had significantly higher overall survival, progression-free survival, and response rate. Conclusions: This real-life study indicates that trifluridine/tipiracil shows effectiveness and safety in treating patients with metastatic colorectal cancer. The results show a profile of metastatic colorectal cancer patients with previously unknown prognostic factors who have a more significant benefit from treatment with trifluridine/tipiracil in routine clinical practice.

19.
Front Cell Infect Microbiol ; 13: 1266685, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37842006

RESUMO

Introduction: The emergence of resistance and interference mechanisms to phage infection can hinder the success of bacteriophage-based applications, but the significance of these mechanisms in phage therapy has not been determined. This work studies the emergence of Salmonella isolates with reduced susceptibility to a cocktail of three phages under three scenarios: i) Salmonella cultures (LAB), ii) biocontrol of cooked ham slices as a model of food safety (FOOD), and iii) oral phage therapy in broilers (PT). Methods: S. Typhimurium ATCC 14028 RifR variants with reduced phage susceptibility were isolated from the three scenarios and conventional and molecular microbiology techniques were applied to study them. Results and discussion: In LAB, 92% of Salmonella isolates lost susceptibility to all three phages 24 h after phage infection. This percentage was lower in FOOD, with 4.3% of isolates not susceptible to at least two of the three phages after seven days at 4°C following phage treatment. In PT, 9.7% and 3.3 % of isolates from untreated and treated broilers, respectively, displayed some mechanism of interference with the life cycle of some of the phages. In LAB and FOOD scenarios, resistant variants carrying mutations in rfc and rfaJ genes involved in lipopolysaccharide synthesis (phage receptor) were identified. However, in PT, the significant decrease of EOP, ECOI, and burst size observed in isolates was prompted by lateral gene transfer of large IncI1 plasmids, which may encode phage defense mechanisms. These data indicate that the acquisition of specific conjugative plasmids has a stronger impact than mutagenesis on the emergence of reduced phage-susceptibility bacteria in certain environments. In spite of this, neither mechanism seems to significantly impair the success of Salmonella biocontrol and oral phage therapy.


Assuntos
Bacteriófagos , Terapia por Fagos , Fagos de Salmonella , Animais , Bacteriófagos/genética , Fagos de Salmonella/genética , Galinhas , Transferência Genética Horizontal , Mutagênese , Bactérias
20.
Cells ; 12(15)2023 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-37566010

RESUMO

The human lifespan has increased over the past century; however, healthspans have not kept up with this trend, especially cognitive health. Among nutrients for brain function maintenance, long-chain omega-3 polyunsaturated fatty acids (ω-3 LCPUFA): DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid) must be highlighted, particularly structured forms of EPA and DHA which were developed to improve bioavailability and bioactivity in comparison with conventional ω-3 supplements. This study aims to elucidate the effect of a structured triglyceride form of DHA (DHA-TG) on the healthspan of aged C. elegans. Using a thrashing assay, the nematodes were monitored at 4, 8, and 12 days of adulthood, and DHA-TG improved its motility at every age without affecting lifespan. In addition, the treatment promoted antioxidant capacity by enhancing the activity and expression of SOD (superoxide dismutase) in the nematodes. Lastly, as the effect of DHA-TG was lost in the DAF-16 mutant strain, it might be hypothesized that the effects of DHA need DAF-16/FOXO as an intermediary. In brief, DHA-TG exerted a healthspan-promoting effect resulting in both enhanced physical fitness and increased antioxidant defense in aged C. elegans. For the first time, an improvement in locomotive function in aged wild-type nematodes is described following DHA-TG treatment.


Assuntos
Ácidos Docosa-Hexaenoicos , Ácidos Graxos Ômega-3 , Humanos , Animais , Adulto , Idoso , Ácidos Docosa-Hexaenoicos/farmacologia , Ácidos Docosa-Hexaenoicos/metabolismo , Antioxidantes/farmacologia , Caenorhabditis elegans/metabolismo , Triglicerídeos
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