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1.
Biomedicines ; 12(9)2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39335498

RESUMO

Glaucoma is the second leading cause of blindness worldwide and is, in most cases, a consequence of elevated intraocular pressure (IOP), ultimately resulting in the death of retinal ganglion cells (RGCs). Current treatments are mostly focused on normalizing IOP, but we propose the additional use of neuroprotective agents, including methylene blue (MB), to block the loss of RGCs. Wistar rats were subjected to episcleral vein cauterization (EVC) in the left eye while the right eye was sham-operated. One week later, they were divided into two groups, which were injected with either 2.0 mg/kg MB or phosphate-buffered saline (PBS), twice a day, for 7 days. Fifteen days after surgery, rats were tested with scotopic electroretinography (ERG) or pattern electroretinography (PERG). After sacrifice, the number of RGCs and the thickness of the inner retina (IR) were evaluated both in the peripheral and central areas of the retina. Scotopic ERG showed a marked reduction (p < 0.0001) on the a- and b-wave amplitude and oscillatory potential (OP) complexity of the eyes subjected to EVC. These parameters were significantly (p < 0.01) restored by the application of MB. PERG indicated that EVC was responsible for a very significant decrease in N2 amplitude (p < 0.0001) and prolongation of N2 implicit time (p < 0.0001). Treatment with MB significantly restored N2 amplitude (p < 0.0001). In parallel with the ERG results, morphological analysis showed a significant loss of RGCs (p < 0.0001) and IR thickness (p < 0.0001) in both the peripheral and central retinas subjected to EVC, which was significantly prevented (p < 0.0001) by MB treatment. We have shown that MB treatment can be effective in preventing physiological and morphological hallmarks of optic neuropathy in a model of ocular hypertension, which faithfully recapitulates human open-angle glaucoma. Due to its high safety profile, this drug could therefore represent a new pharmacologic strategy to prevent vision loss in glaucoma patients.

2.
Nutrients ; 16(16)2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39203769

RESUMO

The aim of our cross-sectional and longitudinal study is to assess the relationship between daytime and night-time sleep duration and health-related quality of life (HRQoL) in adults with metabolic syndrome after a 1-year healthy lifestyle intervention. Analysis of the data from 2119 Spanish adults aged 55-75 years from the PREDIMED-Plus study was performed. Sleep duration was assessed using a wrist-worn accelerometer. HRQoL was measured using the SF-36 questionnaire. Linear regression models adjusted for socioeconomic and lifestyle factors and morbidity were developed. In cross-sectional analyses, participants with extreme night-time sleep duration categories showed lower physical component summary scores in Models 1 and 2 [ß-coefficient (95% confidence interval) <6 h vs. 7-9 h: -2, 3 (-3.8 to -0.8); p = 0.002. >9 h vs. 7-9 h: -1.1 (-2.0 to -0.3); p = 0.01]. Participants who sleep less than 7 h a night and take a nap are associated with higher mental component summary scores [ß-coefficient (95% confidence interval) 6.3 (1.3 to 11.3); p = 0.01]. No differences between night-time sleep categories and 12-month changes in HRQoL were observed. In conclusion, in cross-sectional analyses, extremes in nocturnal sleep duration are related to lower physical component summary scores and napping is associated with higher mental component summary scores in older adults who sleep less than 7 h a night.


Assuntos
Síndrome Metabólica , Qualidade de Vida , Sono , Humanos , Idoso , Pessoa de Meia-Idade , Masculino , Feminino , Estudos Longitudinais , Sono/fisiologia , Síndrome Metabólica/psicologia , Síndrome Metabólica/epidemiologia , Estudos Transversais , Espanha/epidemiologia , Fatores de Tempo , Inquéritos e Questionários , Acelerometria , Estilo de Vida Saudável , Duração do Sono
3.
Pharmaceutics ; 16(7)2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-39065577

RESUMO

The E6 and E7 oncoproteins of high-risk types of human papillomavirus (HR-HPV) are crucial for the development of cervical cancer (CC). Small interfering RNAs (siRNAs) are explored as novel therapies that silence these oncogenes, but their clinical use is hampered by inefficient delivery systems. Modification (pegylation) with polyethylene glycol (PEG) of liposomal siRNA complexes (siRNA lipoplexes) may improve systemic stability. We studied the effect of siRNA targeting HPV16 E6, delivered via cationic liposomes (lipoplexes), on cellular processes in a cervical carcinoma cell line (CaSki) and its potential therapeutic use. Lipoplexes-PEG-HPV16 E6, composed of DOTAP, Chol, DOPE, and DSPE-PEG2000 were prepared. The results showed that pegylation (5% DSPE-PEG2000) provided stable siRNA protection, with a particle size of 86.42 ± 3.19 nm and a complexation efficiency of over 80%; the siRNA remained stable for 30 days. These lipoplexes significantly reduced HPV16 E6 protein levels and restored p53 protein expression, inhibiting carcinogenic processes such as proliferation by 25.74%, migration (95.7%), and cell invasion (97.8%) at concentrations of 20 nM, 200 nM, and 80 nM, respectively. In conclusion, cationic lipoplexes-PEG-HPV16 E6 show promise as siRNA carriers for silencing HPV16 E6 in CC.

4.
Front Immunol ; 15: 1433185, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39081320

RESUMO

Tumor related angiogenesis is an attractive target in cancer therapeutic research due to its crucial role in tumor growth, invasion, and metastasis. Different agents were developed aiming to inhibit this process; however they had limited success. Cancer vaccines could be a promising tool in anti-cancer/anti-angiogenic therapy. Cancer vaccines aim to initiate an immune response against cancer cells upon presentation of tumor antigens which hopefully will result in the eradication of disease and prevention of its recurrence by inducing an efficient and long-lasting immune response. Different vaccine constructs have been developed to achieve this and they could include either protein-based or nucleic acid-based vaccines. Nucleic acid vaccines are simple and relatively easy to produce, with high efficiency and safety, thus prompting a high interest in the field. Different DNA vaccines have been developed to target crucial regulators of tumor angiogenesis. Most of them were successful in pre-clinical studies, mostly when used in combination with other therapeutics, but had limited success in the clinic. Apparently, different tumor evasion mechanisms and reduced immunogenicity still limit the potential of these vaccines and there is plenty of room for improvement. Nowadays, mRNA cancer vaccines are making remarkable progress due to improvements in the manufacturing technology and represent a powerful potential alternative. Apart from their efficiency, mRNA vaccines are simple and cheap to produce, can encompass multiple targets simultaneously, and can be quickly transferred from bench to bedside. mRNA vaccines have already accomplished amazing results in cancer clinical trials, thus ensuring a bright future in the field, although no anti-angiogenic mRNA vaccines have been described yet. This review aims to describe recent advances in anti-angiogenic DNA vaccine therapy and to provide perspectives for use of revolutionary approaches such are mRNA vaccines for anti-angiogenic treatments.


Assuntos
Vacinas Anticâncer , Neoplasias , Neovascularização Patológica , Vacinas de mRNA , Humanos , Vacinas Anticâncer/imunologia , Vacinas Anticâncer/uso terapêutico , Neoplasias/imunologia , Neoplasias/terapia , Neovascularização Patológica/imunologia , Animais , Vacinas de DNA/imunologia , Antígenos de Neoplasias/imunologia , Angiogênese
5.
Environ Toxicol Pharmacol ; 110: 104521, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39069195

RESUMO

The ability of organophosphate pesticides to disturb immune function has been demonstrated by in vivo and in vitro studies, but evidence of such effects on humans remains scarce. To assess the association between organophosphate pesticides exposure and cytokine levels in Mexican flower workers, a cross-sectional study was carried out. A questionnaire was provided to 121 male flower workers, and urine and blood samples were collected. Using gas chromatography, urinary concentrations of dialkylphosphate metabolites were determined. The serum cytokine levels, IL-4, IL-5, IL-6, IL-8, and IL-10, were measured using multiplex analysis, and levels of INF-γ and TNF-α by ELISA. We found that a higher dialkylphosphate concentration decreased the pro-inflammatory cytokines INF-γ (ß = -0.63; 95 % CI: -1.22, -0.05), TNF-α (ß= -1.18; 95 % CI: -2.38, 0.02), and IL-6 (ß= -0.59; 95 % CI: -1.29, 0.12), and increased IL-10 (ß=0.56; 95 % CI: 0.02, 1.09), the main anti-inflammatory cytokine, suggesting an imbalance of the immune response in flower workers.


Assuntos
Citocinas , Exposição Ocupacional , Praguicidas , Humanos , México , Masculino , Exposição Ocupacional/análise , Adulto , Citocinas/sangue , Praguicidas/urina , Praguicidas/sangue , Praguicidas/toxicidade , Pessoa de Meia-Idade , Estudos Transversais , Flores , Adulto Jovem , Compostos Organofosforados/urina , Organofosfatos/urina , Organofosfatos/sangue
6.
Nutrients ; 16(13)2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38999747

RESUMO

BACKGROUND: The COVID-19 lockdown represented an immense impact on human health, which was characterized by lifestyle and dietary changes, social distancing and isolation at home. Some evidence suggests that these consequences mainly affected women and altered relevant ongoing clinical trials. The aim of this study was to evaluate the status and changes in diet, physical activity (PA), sleep and self-reported health status (SRH) as perceived by older adult men and women with metabolic syndrome during the COVID-19 lockdown. METHODS: We analyzed data from 4681 Spanish adults with metabolic syndrome. We carried out a telephone survey during May and June 2020 to collect information on demographics, dietary habits, PA, sleep, SRH and anthropometric data. RESULTS: The mean age of participants was 64.9 years at recruitment, and 52% of participants were men. Most participants (64.1%) perceived a decrease in their PA during confinement. Regarding gender-specific differences, a higher proportion of women than men perceived a decrease in their PA (67.5% vs. 61.1%), Mediterranean diet adherence (20.9% vs. 16.8%), sleep hours (30.3% vs. 19.1%), sleep quality (31.6% vs. 18.2%) and SRH (25.9% vs. 11.9%) (all p < 0.001). CONCLUSIONS: The COVID-19 lockdown affected women more negatively, particularly their self-reported diet, PA, sleep and health status.


Assuntos
COVID-19 , Exercício Físico , Nível de Saúde , Estilo de Vida , Síndrome Metabólica , Autorrelato , Humanos , Masculino , Feminino , COVID-19/epidemiologia , COVID-19/prevenção & controle , Pessoa de Meia-Idade , Idoso , Espanha/epidemiologia , Síndrome Metabólica/epidemiologia , Fatores Sexuais , Fatores de Risco Cardiometabólico , SARS-CoV-2 , Quarentena , Dieta Mediterrânea/estatística & dados numéricos , Sono , Dieta
7.
Angew Chem Int Ed Engl ; 63(37): e202407131, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-38935849

RESUMO

Pancreatic cancer is one of the deadliest cancers worldwide, mainly due to late diagnosis. Therefore, there is an urgent need for novel diagnostic approaches to identify the disease as early as possible. We have developed a diagnostic assay for pancreatic cancer based on the detection of naturally occurring tumor associated autoantibodies against Mucin-1 (MUC1) using engineered glycopeptides on nanoparticle probes. We used a structure-guided approach to develop unnatural glycopeptides as model antigens for tumor-associated MUC1. We designed a collection of 13 glycopeptides to bind either SM3 or 5E5, two monoclonal antibodies with distinct epitopes known to recognize tumor associated MUC1. Glycopeptide binding to SM3 or 5E5 was confirmed by surface plasmon resonance and rationalized by molecular dynamics simulations. These model antigens were conjugated to gold nanoparticles and used in a dot-blot assay to detect autoantibodies in serum samples from pancreatic cancer patients and healthy volunteers. Nanoparticle probes with glycopeptides displaying the SM3 epitope did not have diagnostic potential. Instead, nanoparticle probes displaying glycopeptides with high affinity for 5E5 could discriminate between cancer patients and healthy controls. Remarkably, the best-discriminating probes show significantly better true and false positive rates than the current clinical biomarkers CA19-9 and carcinoembryonic antigen (CEA).


Assuntos
Autoanticorpos , Glicopeptídeos , Mucina-1 , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/sangue , Mucina-1/imunologia , Mucina-1/sangue , Mucina-1/química , Glicopeptídeos/imunologia , Glicopeptídeos/química , Autoanticorpos/sangue , Autoanticorpos/imunologia , Autoanticorpos/química , Nanopartículas Metálicas/química , Ouro/química , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/química , Nanopartículas/química
8.
Infect Dis (Lond) ; : 1-8, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38913347

RESUMO

BACKGROUND: Until 2005, when a single dose of vaccine was implemented in one-year-old children, the Hepatitis A virus (HAV) was responsible for approximately 90% of acute hepatitis cases in the paediatric population in Argentina. However, despite vaccination success, sporadic outbreaks of HAV still occur among adults. This study aimed to assess the seroepidemiology of HAV in Argentina, analysing IgG and IgM antibodies against HAV in a large population, both vaccinated and unvaccinated. METHODS: The study included 16,982 patients attending a hospital from 2001 to 2023. The cohort was divided into two groups: 16,638 individuals who were not reached by the vaccination program implemented in 2005 and 344 children who were covered by the universal vaccination. RESULTS: Anti-HAV IgG was detected in 56.7% of cases. The rate was significantly higher in individuals born after 2005 (77.7%) compared to those born before (56.3%), p < 0.001. The age groups 19-40 and 41-60 years showed the anti-HAV IgG lowest rates. On the other hand, 100/3956 cases (2.5%) with suspected acute hepatitis were positive for Anti-HAVIgM. Notably, none of these were born after the mandatory vaccine rollout. CONCLUSIONS: The study of this large cohort contributes to the understanding of the seroepidemiology of HAV. Although the implementation of the vaccine achieved its main goal, the age segment between 19 and 60 years does not reach the estimated threshold to achieve herd immunity. These findings reveal the importance of targeting vaccination campaigns, provide essential insights for public health planning, and guide future immunisation strategies against HAV in Argentina.

9.
Heliyon ; 10(9): e30430, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38726117

RESUMO

Non-linear pyroelectric energy harvesting using ferroelectric thin films exhibits high energy conversion, primarily due to their large breakdown field compared to bulks. Here, we report the pyroelectric energy conversion potential of lead scandium tantalate, Pb(Sc1/2Ta1/2)O3 (PST) thin film fabricated on a c-sapphire substrate using chemical solution deposition. To enable the application of high electric field and to assess the pyroelectric energy conversion performance, interdigitated electrodes were deposited on the PST thin film. A maximum harvested energy density of 9.1 J cm-3 per cycle was deduced from polarization measurements in films undergoing an Olsen cycle between 0 °C and 150 °C when the electric field was varied between 50 and 1500 kV/cm. Furthermore, PST thin films can reach up to 27 % of Carnot efficiency for a temperature interval of 10 K between 30 °C and 40 °C. This study highlights the significance of PST thin films for electro-thermal energy harvesting and promising opportunities for enhancing the conversion efficiency and power density using thin films or thin film multi-layer capacitors in the future for thermal energy harvesting.

10.
Antioxidants (Basel) ; 13(5)2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38790641

RESUMO

This work aimed to elucidate how O3 pollution causes a loss of regulation in the immune response in both the brain and the intestine. In this work, we studied the effect of exposing rats to low doses of O3 based on the association between the antioxidant response of superoxide dismutase (SOD) levels and the nuclear factor kappa light chains of activated B cells (NFκB) as markers of inflammation. Method: Seventy-two Wistar rats were used, divided into six groups that received the following treatments: Control and 7, 15, 30, 60, and 90 days of O3. After treatment, tissues were extracted and processed using Western blotting, biochemical, and immunohistochemical techniques. The results indicated an increase in 4-hydroxynonenal (4HNE) and Cu/Zn-SOD and a decrease in Mn-SOD, and SOD activity in the substantia nigra, jejunum, and colon decreased. Furthermore, the translocation of NFκB to the nucleus increased in the different organs studied. In conclusion, repeated exposure to O3 alters the regulation of the antioxidant and inflammatory response in the substantia nigra and the intestine. This indicates that these factors are critical in the loss of regulation in the inflammatory response; they respond to ozone pollution, which can occur in chronic degenerative diseases.

11.
Clin Chim Acta ; 557: 117895, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38561063

RESUMO

The discovery of new diagnostic tools for the early detection of diseases with poor prognosis such as pancreatic adenocarcinoma (PAC) is of high importance. The results from a control-case study (20 PAC patients, 19 healthy controls) for the search of new biomarkers of pancreatic cancer based in differences in the serum volatolome are presented in this work. Volatolomics were performed following a non-targeted HS-SPME-GC/MS approach, and a total of 433 volatile organic compounds (VOCs) was detected in the human serum samples. Of these, 125 VOC indexes showed a significant variation when controls and patients were compared (p-value < 0.05). Bonferroni corrected p-values < 0.05 were found for 40 features. PCA analysis showed the control-PAC discrimination capability of VOCs in serum, and PLS-DA was performed to select the best candidate biomarkers for the diagnosis of PAC. For the 40 selected VOCs, calculated areas under the curve (AUC) ranged from 0.98 to 0.85, and 11 of them were successfully validated using an independent set of samples (5 PAC patients, 5 healthy controls). Four of the proposed PAC biomarkers were identified as toluene, 2-ethyl-1-hexanol, pentylbenzene, and butoxymethylbenzene. Combinations of the identified PAC biomarkers were tested and showed AUC > 0.90, with the more promising candidate being butoxymethylbenzene (AUC = 0.98).


Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Compostos Orgânicos Voláteis , Humanos , Adenocarcinoma/diagnóstico , Biomarcadores , Neoplasias Pancreáticas/diagnóstico , Estudos de Caso Único como Assunto , Compostos Orgânicos Voláteis/análise , Estudos de Casos e Controles
12.
Radiol Case Rep ; 19(7): 2729-2734, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38680744

RESUMO

Stenosis of the portal vein is one of the main complications after hepatobiliar and pancreatic surgery, with a reported incidence of 19.6% after pancreaticoduodenectomy and 3% after liver transplant. It is associated with the intraoperative resection of the portal vein, local recurrence of the primary tumor and radiotherapy. The portal lesion secondary to bile drainage catheter insertion is extremely rare or unusual, with few cases described in the literature. This article describes 2 cases: the first of a male patients 49 years old post-operative to liver transplant with partial portal thrombosis and stenosis of the mesoportal joint, and the second a female patient 50 years old with history of cholecystectomy, exploration of the bile duct and placement of Kehr "T" tube with secondary portal lesion. The 2 cases were successfully treated through minimally invasive procedures by an interventionist radiologist.

13.
Cancers (Basel) ; 16(5)2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38473321

RESUMO

Non-coding RNAs provide new opportunities to identify biomarkers that properly classify cancer patients. Here, we study the biomarker status of the mitochondrial long non-coding RNAs, MDL1 and MDL1AS. Expression of these genes was studied in public transcriptomic databases. In addition, a cohort of 69 locally advanced rectal cancer (LARC) patients with a follow-up of more than 5 years was used to determine the prognostic value of these markers. Furthermore, cell lines of colorectal (HCT116) and breast (MDA-MB-231) carcinoma were employed to study the effects of downregulating MDL1AS in vitro. Expression of MDL1AS (but not MDL1) was significantly different in tumor cells than in the surrounding tissue in a tumor-type-specific context. Both MDL1 and MDL1AS were accurate biomarkers for the 5-year survival of LARC patients (p = 0.040 and p = 0.007, respectively) with promising areas under the curve in the ROC analyses (0.820 and 0.930, respectively). MDL1AS downregulation reduced mitochondrial respiration in both cell lines. Furthermore, this downregulation produced a decrease in growth and migration on colorectal cells, but the reverse effects on breast cancer cells. In summary, MDL1 and MDL1AS can be used as reliable prognostic biomarkers of LARC, and MDL1AS expression provides relevant information on the diagnosis of different cancers.

14.
J Interferon Cytokine Res ; 44(6): 281-289, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38516906

RESUMO

Chronic low-grade inflammation (CLI) is implicated in the development of multiple metabolic diseases. The gut microbiota (GM) activates different signaling pathways and induces phenotypic changes, offering an exciting opportunity to treat CLI. We evaluated the mediation of waist circumference on the association of GM with serum cytokines. In this cross-sectional study of 331 children, we measured 5 gut bacterial species, namely, Lactobacillus (L.) casei, L. paracasei, L. reuteri, Staphylococcus (S.) aureus, and Akkermansia (A.) muciniphila, as well as anthropometry, serum cytokines, and other covariates. We evaluated adjusted regression models, path analysis, and structural equation modeling to obtain path coefficients (PCs) for direct, indirect (waist circumference-mediated), and total effects. We found that L. paracasei was directly associated with lower interleukin-10 (IL-10) levels (PC = -173.5 pg/mL). We also observed indirect associations between S. aureus with lower adiponectin levels (PC = -0.1 µg/mL and -0.09 µg/mL). Finally, A. muciniphila was indirectly associated with higher adiponectin levels (PC = 0.1 µg/mL). Our findings suggest the importance of considering the GM composition and waist circumference when evaluating inflammatory-related factors, providing a basis for future research to identify potential strategies to intervene in inflammatory processes and prevent metabolic diseases in childhood. [Figure: see text].


Assuntos
Microbioma Gastrointestinal , Inflamação , Circunferência da Cintura , Humanos , Masculino , Feminino , Criança , Estudos Transversais , Análise de Mediação , Citocinas/sangue , Citocinas/metabolismo , Adolescente
15.
Nat Commun ; 15(1): 1890, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38424073

RESUMO

Integration of thin-film oxide piezoelectrics on glass is imperative for the next generation of transparent electronics to attain sensing and actuating functions. However, their crystallization temperature (above 650 °C) is incompatible with most glasses. We developed a flash lamp process for the growth of piezoelectric lead zirconate titanate films. The process enables crystallization on various types of glasses in a few seconds only. The functional properties of these films are comparable to the films processed with standard rapid thermal annealing at 700 °C. A surface haptic device was fabricated with a 1 µm-thick film (piezoelectric e33,f of -5 C m-2). Its ultrasonic surface deflection reached 1.5 µm at 60 V, sufficient for its use in surface rendering applications. This flash lamp annealing process is compatible with large glass sheets and roll-to-roll processing and has the potential to significantly expand the applications of piezoelectric devices on glass.

16.
Nurs Rep ; 14(1): 287-302, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38391067

RESUMO

(1) Background: The aim of this study was to review the scope of the existing scientific literature on creating safe and inclusive healthcare environments for transgender people and provide an overview of the resources and nursing skills required to do so. (2) Methods: With the research question in mind, an exploratory search of six databases was conducted to identify all relevant primary studies. After screening and selection of articles based on the inclusion and exclusion criteria, a total of 41 articles were included and reviewed. (3) Results: The results were classified under four headings: the training of health professionals, the creation of safe spaces, the nurse as facilitator, and best care practice. Most of the evidence indicates that it is essential for nurses and other healthcare staff to be trained in specific skills to provide comprehensive, high-quality care to transgender people; however, there is a lack of material and human resources to do so. (4) Conclusions: The trans-inclusive care competent nurse should use neutral language that respects the person's preferred name and pronouns in a safe healthcare environment that offers and ensures warmth, respect, and inclusivity in the care provided. This study was registered with the Open Science Framework (OSF) on 9 January 2024 (osf.io/rpj6a).

17.
Int Arch Occup Environ Health ; 97(3): 291-302, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38270603

RESUMO

OBJECTIVE: Occupational exposure to pesticides is a known risk for disrupting cellular immune response in flower workers due to their use of multiple chemical products, poor work conditions, and inadequate protection. Recently, the analysis of pesticide use patterns has emerged as an alternative to studying exposure to mixtures of these products. This study aimed to evaluate the association between exposure to different patterns of pesticide use and the cytokine profile of flower workers in the State of Mexico and Morelos, Mexico. METHODS: A cross-sectional study was carried out on a population of 108 flower workers. Serum levels of IL-4, IL-5, IL-6, IL-8, IL-10 cytokines were analyzed by means of multiplex analysis, and TNF-α and IFN-γ using an ELISA test. Pesticide use patterns were generated by principal components analysis. RESULTS: The analysis revealed that certain patterns of pesticide use, combining insecticides and fungicides, were associated with higher levels of pro-inflammatory cytokines, particularly IL-6 and IFN-γ. CONCLUSION: These findings indicate that pesticides may possess immunotoxic properties, contributing to increased inflammatory response. However, further comprehensive epidemiological studies are needed to establish a causal relationship.


Assuntos
Exposição Ocupacional , Praguicidas , Humanos , Praguicidas/toxicidade , Citocinas , Estudos Transversais , México/epidemiologia , Interleucina-6 , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise , Flores/química
18.
JACS Au ; 4(1): 150-163, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38274250

RESUMO

Mucin-1 (MUC1) glycopeptides are exceptional candidates for potential cancer vaccines. However, their autoantigenic nature often results in a weak immune response. To overcome this drawback, we carefully engineered synthetic antigens with precise chemical modifications. To be effective and stimulate an anti-MUC1 response, artificial antigens must mimic the conformational dynamics of natural antigens in solution and have an equivalent or higher binding affinity to anti-MUC1 antibodies than their natural counterparts. As a proof of concept, we have developed a glycopeptide that contains noncanonical amino acid (2S,3R)-3-hydroxynorvaline. The unnatural antigen fulfills these two properties and effectively mimics the threonine-derived antigen. On the one hand, conformational analysis in water shows that this surrogate explores a landscape similar to that of the natural variant. On the other hand, the presence of an additional methylene group in the side chain of this analog compared to the threonine residue enhances a CH/π interaction in the antigen/antibody complex. Despite an enthalpy-entropy balance, this synthetic glycopeptide has a binding affinity slightly higher than that of its natural counterpart. When conjugated with gold nanoparticles, the vaccine candidate stimulates the formation of specific anti-MUC1 IgG antibodies in mice and shows efficacy comparable to that of the natural derivative. The antibodies also exhibit cross-reactivity to selectively target, for example, human breast cancer cells. This investigation relied on numerous analytical (e.g., NMR spectroscopy and X-ray crystallography) and biophysical techniques and molecular dynamics simulations to characterize the antigen-antibody interactions. This workflow streamlines the synthetic process, saves time, and reduces the need for extensive, animal-intensive immunization procedures. These advances underscore the promise of structure-based rational design in the advance of cancer vaccine development.

19.
Case Rep Oncol Med ; 2024: 5093727, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38264474

RESUMO

Peritoneal cancer is the invasion by malignant cells of serous membrane that lines the abdominal cavity, the viscera, and the coelom of the amniotes. Histologically, it is indistinguishable from ovarian counterpart, although in the former, it commonly involves the ovary only superficially, or it may totally lack an ovarian component, but with extensive involvement of the peritoneum, calcified perihepatic peritoneal nodules, or involvement of the omentum, in most cases. The current study describes the case of a 54-year-old female patient referring a history of colitis and dairy intolerance. A transvaginal ultrasound and a computed tomography (CT) scan revealed a tumor measuring 70 × 61 × 63 mm. CA-125 serum levels were 880 U/ml. Laparotomy surgery was indicated, and tumor was found at the level of the rectovaginal septum without evidence of metastasis. Tumor dissection and protective colostomy with loop sigmoid colon were performed. A pathological study gave a diagnosis of a high-grade peritoneal serous carcinoma with a micropapillary pattern. The present study describes the case of papillary serous peritoneal cancer presented as a single tumor mass without extensive involvement of the peritoneum. Additionally, the need for routine tests for its diagnosis and documenting hormonal alterations as the cause of its origin are suggested.

20.
Histol Histopathol ; 39(4): 447-462, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37694837

RESUMO

Primary cilia act as cellular sensors for multiple extracellular stimuli and regulate many intracellular signaling pathways in response. Here we investigate whether the cold-shock proteins (CSPs), CIRP and RBM3, are present in the primary cilia and the physiological consequences of such a relationship. R28, an immortalized retinal precursor cell line, was stained with antibodies against CIRP, RBM3, and ciliary markers. Both CSPs were found in intimate contact with the basal body of the cilium during all stages of the cell cycle, including migrating with the centrosome during mitosis. In addition, the morphological and physiological manifestations of exposing the cells to hypothermia and shear stress were investigated. Exposure to moderately cold (32°C) temperatures, the hypothermia mimetic small molecule zr17-2, or to shear stress resulted in a significant reduction in the number and length of primary cilia. In addition, shear stress induced expression of CIRP and RBM3 in a complex pattern depending on the specific protein, flow intensity, and type of flow (laminar versus oscillatory). Flow-mediated CSP overexpression was detected by qRT-PCR and confirmed by Western blot, at least for CIRP. Furthermore, analysis of public RNA Seq databases on flow experiments confirmed an increase of CIRP and RBM3 expression following exposure to shear stress in renal cell lines. In conclusion, we found that CSPs are integral components of the centrosome and that they participate in cold and shear stress sensing.


Assuntos
Hipotermia , Humanos , Hipotermia/genética , Hipotermia/metabolismo , Cílios/metabolismo , Proteínas e Peptídeos de Choque Frio/metabolismo , Proteínas de Ligação a RNA/metabolismo , Centrossomo/metabolismo
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