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1.
Rev. enferm. UERJ ; 32: e74624, jan. -dez. 2024.
Artigo em Inglês, Espanhol, Português | LILACS-Express | LILACS | ID: biblio-1554378

RESUMO

Objetivo: analisar o desenvolvimento da enfermagem traumato-ortopédica a partir da primeira turma de residentes de um hospital especializado. Método: o estudo seguiu a metodologia histórica com abordagem qualitativa. As fontes foram documentos escritos e orais. Resultados: trabalhar em uma instituição especializada foi o ponto de partida para a busca por especialização de enfermeiras atuantes no cuidado traumato-ortopédico, que perceberam o saber/poder adquirido no trabalho assistencial, além da intenção de qualificar a assistência e elevar o hospital a instituto. Estratégias empregadas reúnem a busca por parcerias com instituições universitárias e associativas, além da criação de uma associação própria. Considerações finais: a enfermagem traumato-ortopédica ampliou seu espaço científico ao criar um curso de especialização com uma unidade acadêmica. Foi possível delimitar o poder acadêmico e institucional da enfermagem na instituição de saúde pela formação de enfermeiras especialistas constituindo um grupo de reconhecido pelo saber científico.


Objective: to analyze the development of trauma and orthopedic nursing care from the very first class of residents of a specialized hospital. Method: historical methodology study with a qualitative approach. The sources consisted of written and oral documents. Results: working in a specialized institution was the starting point for nurses who were seeking specialization in the field of trauma and orthopedic care as they noticed the power-knowledge acquired through care work, plus they were willing to improve assistance and take the hospital up to an institute level. Strategies used include the search for partnerships with universities and associative-type institutions, in addition to creating their own association. Final considerations: trauma and orthopedic nursing care expanded its scientific space by creating a specialization course together with an academic unit. It was possible to define the academic and institutional power of the nursing staff in the health institution by considering the training process of its nurse specialists, who consisted of a group recognized for their scientific knowledge.


Objetivo: analizar el desarrollo de la enfermería traumatológica ortopédica a partir del primer grupo de residentes de un hospital especializado. Método: estudio con metodología histórica con un enfoque cualitativo. Las fuentes fueron documentos escritos y orales. Resultados: el trabajo en una institución especializada fue el punto de partida para la búsqueda de la especialización de las enfermeras que trabajaban en la atención traumatológica ortopédica, quienes notaron el saber/poder adquirido en el trabajo asistencial, además de la intención de cualificar la atención y elevar el hospital al nivel de instituto. Las estrategias empleadas incluyen la búsqueda de alianzas con instituciones universitarias y asociaciones, y la creación de una asociación propia. Consideraciones finales: la enfermería traumatológica ortopédica amplió su espacio científico mediante la creación de un curso de especialización con una unidad académica. Se logró delimitar el poder académico e institucional de la enfermería en la institución de salud a través de la formación de enfermeros especialistas, que es un grupo reconocido por el conocimiento científico.

2.
Biomacromolecules ; 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39235263

RESUMO

Paediatric acute myeloid leukemia (AML) is a heterogeneous hematological malignancy still heavily reliant on traditional chemotherapeutic approaches. Combination treatments have shown to be a superior approach, but their success is often hindered by side effects and different drugs' pharmacokinetics. Here, we investigated ABT-737 and Purvalanol A as a potential drug pairing for pediatric AML and described the development of CD33-targeted polymeric nanoparticles (NPs) to enable their simultaneous targeted codelivery. Separate drug encapsulation within poly(lactic-co-glycolic acid) (PLGA) NPs was optimized prior to coencapsulation of both drugs at a synergistic ratio in PEGylated PLGA NPs. The therapeutic effects of formulations were evaluated in a panel of pediatric AML cells, and dual drug-loaded NPs (dual NPs) demonstrated significantly enhanced apoptotic cell death. Moreover, conjugation to gemtuzumab resulted in improved NP binding and internalization in CD33-positive cells. Finally, CD33-targeted dual-loaded NPs showed enhanced cytotoxicity to CD33-positive AML cells via CD33-mediated targeted drug delivery.

3.
Toxicol Appl Pharmacol ; 492: 117085, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39236990

RESUMO

The significant rise in cancer survivorship stands out as one of the most notable achievements of modern science. However, this comes with a significant burden, as cancer treatment is not without adverse effects. Lately, there has been a growing focus on cognitive dysfunction associated with cancer treatment, often referred to as 'chemobrain'. It significantly impacts the quality of life for cancer survivors. The underlying mechanisms studied so far usually focus on neurons, while other cells of the central nervous system are often overlooked. This review seeks to place the hypothesis that glial cells may play a role in the development of chemotherapy-induced cognitive dysfunction. It summarizes the primary mechanisms proposed to date while underscoring the existing gaps in this research field. Inflammation and release of pro-inflammatory mediators by M1 microglia and A1 astrocytes are the most prevalent findings after chemotherapy. However, activation of A1 astrocytes by some chemotherapeutic agents may contribute to neuronal degeneration, alterations in synaptic branches, as well as glutamate excitotoxicity, which can contribute to cognitive impairment. Furthermore, the reduction in the number of oligodendrocytes after chemotherapy may also impact the myelin sheath, contributing to 'chemobrain'. Furthermore, some chemotherapeutic drugs activate M1 microglia, which is associated with decreased neuroplasticity and, possibly, cognitive impairment. In conclusion, data regarding the effects of chemotherapy on glial cells are scarce, and it is essential to understand how these cells are affected after cancer treatment to enable reliable therapeutic or preventive actions on cancer-treated patients.

4.
Biology (Basel) ; 13(8)2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39194522

RESUMO

Proteomics can be a robust tool in protein identification and regulation, allowing the discovery of potential biomarkers. In clinical practice, the management of endometrial cancer can be challenging. Thus, identifying promising markers could be beneficial, helping both in diagnosis and prognostic stratification, even predicting the response to therapy. Therefore, this manuscript systematically reviews the existing evidence of the proteomic profile of human endometrial cancer. The literature search was conducted via Medline (through PubMed) and the Web of Science. The inclusion criteria were clinical, in vitro, and in vivo original studies reporting proteomic analysis using all types of samples to map the human endometrial cancer proteome. A total of 55 publications were included in this review. Most of the articles carried out a proteomic analysis on endometrial tissue, serum and plasma samples, which enabled the identification of several potential diagnostic and prognostic biomarkers. In addition, eight articles were analyzed regarding the identified proteins, where three studies showed a strong correlation, sharing forty-five proteins. This analysis also allowed the identification of the 10 most frequently reported proteins in these studies: EGFR, PGRMC1, CSE1L, MYDGF, STMN1, CASP3 ANXA2, YBX1, ANXA1, and MYH11. Proteomics-based approaches pointed out potential diagnostic and prognostic candidates for endometrial cancer. However, there is a lack of studies exploring novel therapeutic targets.

5.
Free Radic Biol Med ; 224: 23-38, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39151835

RESUMO

Remote ischemic conditioning (RIC) is a procedure consisting of short cycles of ischemia applied in a limb that activates endogenous protection in distant organs, such as the brain. Despite the promising outcomes of RIC, the biochemical factors governing inter-organ communication remain largely unexplored, particularly in humans. A pilot study on 20 healthy humans was performed to identify potential circulating biochemical factors involved in RIC signalling. Blood was collected before and immediately, 4 and 22 h after the end of RIC. To characterize the responses triggered by RIC, a combination of biochemical and proteomic analysis, along with functional in vitro tests in human cells, were performed. RIC did not alter the levels of nitric oxide, bilirubin and cell-free mitochondrial DNA. In contrast, carboxyhaemoglobin levels increased following RIC at all time points and young subset, suggesting endogenous production of carbon monoxide that is a cytoprotective gasotransmitter. Additionally, the levels of glutathione and cysteinylglycine bound to proteins also increased after RIC, while glutathione catabolism decreased. Plasma proteomic analysis identified overall 828 proteins. Several steps of statistical analysis (Student's t-test, repeated measures ANOVA, with Holm corrected pairwise p-values <0.05 threshold and fold change higher or lower than 100 %) leaded to the identification of 9 proteins with altered circulating levels in response to RIC at 4h and 22h. All 9 proteins are from extracellular space or exosomes, being involved in inflammation, angiogenesis or metabolism control. In addition, RIC-conditioned plasma from young subjects protected microglial cell culture against inflammatory stimuli, indicating an anti-inflammatory effect of RIC. Nevertheless, other functional tests in neurons or endothelial cells had no effect. Overall, we present some evidence for RIC-induced anti-inflammatory and antioxidant responses in healthy human subjects, in particular in young subjects. This study is a first step towards the disclosure of signalling factors involved in RIC-mediated inter-organ communication.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38953141

RESUMO

Fecal immunochemical test (FIT) followed by colonoscopy in positive cases is commonly used for population-based colorectal cancer (CRC) screening. However, specificity of FIT for CRC is not ideal, and has poor performance for advanced adenoma detection. Fecal Fusobacterium nucleatum (Fn) detection has been proposed as a potential non-invasive biomarker for CRC and advanced adenoma detection. We aimed to evaluate the diagnostic performance of Fn detection using droplet digital PCR (ddPCR) in FIT samples from individuals enrolled in a CRC screening program with colorectal adenoma or cancer. We evaluated Fn presence in DNA isolated from FIT leftover material of 300 participants in a CRC Screening Program using ddPCR. The Fn DNA amount was classified as Fn-low/negative and Fn-high, and the association with patients clinicopathological features and accuracy measurements was calculated. Fn high levels were more prevalent in FIT-positive (47.2%n=34 of72) than FIT-negative samples (28.9%, n=66 of 228) (p<0.04). Among FIT-positive samples, high Fn levels were significantly more frequent in cancer patients (CA, n=8) when compared to normal (NT, n=16) (p=0.02), non-advanced adenomas (NAA, n=36) (p=0.01), and advanced adenomas (AA, n=12) (p=0.01). Performance analysis of Fn in FIT-positive samples for colorectal cancer detection yielded an AUC of 0.8203 (CI: 0.6464-0.9942), with high sensitivity (100%) and specificity of 50%%. Concluding, we showed the feasibility of detecting Fn in FIT leftovers using the ultrasensitive ddPCR technique. Furthermore, we highlighted the potential use of Fn levels in fecal samples to ameliorate CRC detection.

7.
Pathogens ; 13(7)2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39057816

RESUMO

Sewage surveillance can be used as an effective complementary tool for detecting pathogens in local communities, providing insights into emerging threats and aiding in the monitoring of outbreaks. In this study using qPCR and whole genomic sewage surveillance, we detected the Mpox virus along with other viruses, in municipal and hospital wastewaters in Belo Horizonte, Brazil over a 9-month period (from July 2022 until March 2023). MPXV DNA detection rates varied in our study, with 19.6% (11 out of 56 samples) detected through the hybrid capture method of whole-genome sequencing and 20% (12 out of 60 samples) through qPCR. In hospital wastewaters, the detection rate was higher, at 40% (12 out of 30 samples) compared to 13.3% (4 out of 30 samples) in municipal wastewaters. This variation could be attributed to the relatively low number of MPXV cases reported in the city, which ranged from 106 to 341 cases during the study period, and the dilution effects, given that each of the two wastewater treatment plants (WWTP) investigated serves approximately 1.1 million inhabitants. Additionally, nine other virus families were identified in both hospitals and municipal wastewaters, including Adenoviridade, Astroviridae, Caliciviridae, Picornaviridade, Polyomaviridae, Coronaviridae (which includes SARS-CoV-2), Herspesviridae, Papillomaviridae and Flaviviridae (notably including Dengue). These findings underscore the potential of genomic sewage surveillance as a robust public health tool for monitoring a wide range of viruses circulating in both community and hospitals environments, including MPXV.

8.
Sci Rep ; 14(1): 17166, 2024 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-39060284

RESUMO

The cellular response to cisplatin was assessed in human osteosarcoma cells, using synchrotron-based (SR) Fourier Transform InfraRed nanospectroscopy (nano-FTIR) at the MIRIAM beamline B22 of Diamond Light Source (UK). This label-free mapping method delivered simultaneous morphological and biochemical information on a subcellular level (i.e. 100 s nanometer or better). Based on specific spectral biomarkers, the main biochemical constituents affected by the drug were identified at distinct locations within the cell´s inner body. Cisplatin was shown to have a noteworthy effect on proteins, mostly within the cytoplasm. A clear drug impact on cellular lipids was also observed. Within current literature on s-SNOM, this nanospectroscopy work represents a first successful application in life sciences providing full fingerprint nano-FTIR spectra across intact human cancer cells.


Assuntos
Antineoplásicos , Cisplatino , Síncrotrons , Humanos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Cisplatino/farmacologia , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Osteossarcoma/tratamento farmacológico
9.
Braz J Microbiol ; 55(3): 3021-3025, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38878258

RESUMO

Emerald tree boas (Corallus batesii) are boids that in situ occurs in forested habitats in the Amazon Basin. The mycobacterial species can infect reptiles but the species Mycolicibacterium fortuitum was identified only in feces samples of ex situ Python regius and was isolated from granulomatous lesions of an ex situ Iguana iguana when was still part of the genus Mycobacterium. This article aims to report a mycobacteria infection case in a female Corallus batesii kept under human care. The animal presented apathy and 2 months of anorexia, being found dead. The necropsy revealed presence of tracheal and pulmonary nodules besides multifocal, bacterial, granulomatous pneumonia. After Fite-Faraco histochemical staining, immunohistochemistry, semi-nested polymerase chain reaction (PCR) and genetic sequencing the Mycolicibacterium fortuitum complex was diagnosed with 99.54% of nucleotide similarity. This mycobacterial species was already pointed out as an important nosocomial pathogen and more studies are necessary to explore their zoonotic potential.


Assuntos
Boidae , Mycobacterium fortuitum , Animais , Feminino , Mycobacterium fortuitum/isolamento & purificação , Mycobacterium fortuitum/genética , Mycobacterium fortuitum/classificação , Boidae/microbiologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Infecções por Mycobacterium não Tuberculosas/veterinária , Evolução Fatal , Filogenia
10.
Dent Mater ; 40(9): 1353-1363, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38876826

RESUMO

OBJECTIVE: To fabricate and characterize an innovative gelatin methacryloyl/GelMA electrospun scaffold containing the citrus flavonoid naringenin/NA with osteogenic and anti-inflammatory properties. METHODS: GelMA scaffolds (15 % w/v) containing 0/Control, 5, 10, or 20 % of NA w/w were obtained via electrospinning. The chemical composition, fiber morphology/diameter, swelling/degradation profile, and NA release were investigated. Cytotoxicity, cell proliferation, adhesion and spreading, total protein/TP production, alkaline phosphatase/ALP activity, osteogenic genes expression (OCN, OPN, RUNX2), and mineralized nodules deposition/MND with human alveolar bone-derived mesenchymal stem cells (aBMSCs) seeded on the scaffolds were assessed. Moreover, aBMSCs seeded on the scaffolds and stimulated with tumor necrosis factor-alpha/TNF-α were submitted to collagen, nitric oxide/NO, interleukin/IL-1α, and IL-6 production assessment. Data were analyzed using ANOVA and t-student/post-hoc tests (α = 5 %). RESULTS: NA-laden scaffolds presented increased fiber diameter, lower swelling capacity, and faster degradation profile over 28 days (p < 0.05). NA release was detected over time. Cell adhesion and spreading, and TP production were similar between GelMA and GelMA+NA5 % scaffolds, while cell proliferation, ALP activity, OCN/OPN/RUNX2 gene expression, and MND were higher for GelMA+NA5 % scaffolds (p < 0.05). Cells seeded on control scaffolds and TNF-α-stimulated presented higher levels of NO, IL-1α/IL-6, and lower levels of collagen (p < 0.05). In contrast, cells seeded on GelMA+NA5 % scaffolds showed downregulation of inflammatory markers and higher collagen synthesis (p < 0.05). SIGNIFICANCE: GelMA+NA5 % scaffold was cytocompatible, stimulated aBMSCs proliferation and differentiation, and downregulated inflammatory mediators' synthesis, suggesting its therapeutic effect as a multi-target bifunctional scaffold with osteogenic and anti-inflammatory properties for bone tissue engineering.


Assuntos
Proliferação de Células , Flavanonas , Gelatina , Metacrilatos , Osteogênese , Alicerces Teciduais , Alicerces Teciduais/química , Gelatina/química , Humanos , Flavanonas/farmacologia , Flavanonas/química , Osteogênese/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Metacrilatos/química , Células-Tronco Mesenquimais/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Fosfatase Alcalina/metabolismo , Adesão Celular/efeitos dos fármacos , Células Cultivadas , Fator de Necrose Tumoral alfa , Engenharia Tecidual , Subunidade alfa 1 de Fator de Ligação ao Core
11.
Cancers (Basel) ; 16(11)2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38893151

RESUMO

Endometrial cancer is one of the most common gynaecological malignancies. Although often diagnosed at an early stage, there is a subset of patients with recurrent and metastatic disease for whom current treatments are not effective. Cancer stem cells (CSCs) play a pivotal role in triggering tumorigenesis, disease progression, recurrence, and metastasis, as high aldehyde dehydrogenase (ALDH) activity is associated with invasiveness and chemotherapy resistance. Therefore, this study aimed to evaluate the effects of ALDH inhibition in endometrial CSCs. ECC-1 and RL95-2 cells were submitted to a sphere-forming protocol to obtain endometrial CSCs. ALDH inhibition was evaluated through ALDH activity and expression, sphere-forming capacity, self-renewal, projection area, and CD133, CD44, CD24, and P53 expression. A mass spectrometry-based proteomic study was performed to determine the proteomic profile of endometrial cancer cells upon N,N-diethylaminobenzaldehyde (DEAB). DEAB reduced ALDH activity and expression, along with a significant decrease in sphere-forming capacity and projection area, with increased CD133 expression. Additionally, DEAB modulated P53 expression. Endometrial cancer cells display a distinct proteomic profile upon DEAB, sharing 75 up-regulated and 30 down-regulated proteins. In conclusion, DEAB inhibits ALDH activity and expression, influencing endometrial CSC phenotype. Furthermore, ALDH18A1, SdhA, and UBAP2L should be explored as novel molecular targets for endometrial cancer.

12.
Heliyon ; 10(11): e31608, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38868005

RESUMO

Doxorubicin (DOX) is an anthracycline used to treat a wide range of tumours. Despite its effectiveness, it is associated with a long range of adverse effects, of which cognitive deficits stand out. The present study aimed to assess the neurologic adverse outcome pathways of two clinically relevant cumulative doses of DOX. Adult male CD-1 mice received biweekly intraperitoneal administrations for 3 weeks until reaching cumulative doses of 9 mg/kg (DOX9) or 18 mg/kg (DOX18). Animals were euthanized one week after the last administration, and biomarkers of oxidative stress and brain metabolism were evaluated in the whole brain. Coronal sections of fixed brains were used for specific determinations of the prefrontal cortex (PFC) and hippocampal formation (HF). In the whole brain, DOX18 tended to disrupt the antioxidant defences, affecting glutathione levels and manganese superoxide dismutase expression. Considering the regional analysis, DOX18 increased the volume of all brain areas evaluated, while GFAP-immunoreactive astrocytes decreased in the dentate gyrus (DG) and increased in the CA3 region of HF, both in a dose-dependent manner. Concerning the apoptosis pathway, whereas Bax increased in the DOX9 group, it decreased in the DOX18 group. Only in the latter group did Bcl-2 levels also decrease. While p53 only increased in the CA3 region of the DOX9 group, AIF increased in the PFC and DG of DOX18. Finally, phosphorylation of Tau decreased with the highest DOX dose in DG and CA3, while TNF-α levels increased in CA1 of DOX18. Our results indicate new pathways not yet described that could be responsible for the cognitive impairments observed in treated patients.

13.
J Med Primatol ; 53(3): e12716, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38831476

RESUMO

Neotropical primates rarely exhibit active tuberculosis. A brown howler monkey was found injured in an urban area. Histopathology revealed granulomatous inflammation in the lungs, lymph nodes, and liver. Immunohistochemistry and molecular analysis confirmed the presence of Mycobacterium tuberculosis complex. The findings highlight the importance of TB surveillance in nonhuman primates.


Assuntos
Alouatta , Doenças dos Macacos , Mycobacterium tuberculosis , Tuberculose , Animais , Doenças dos Macacos/microbiologia , Doenças dos Macacos/patologia , Brasil , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose/veterinária , Tuberculose/microbiologia , Tuberculose/patologia , Masculino , Feminino
14.
medRxiv ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38699364

RESUMO

Tobacco smoke, alone or combined with alcohol, is the predominant cause of head and neck cancer (HNC). Here, we further explore how tobacco exposure contributes to cancer development by mutational signature analysis of 265 whole-genome sequenced HNC from eight countries. Six tobacco-associated mutational signatures were detected, including some not previously reported. Differences in HNC incidence between countries corresponded with differences in mutation burdens of tobacco-associated signatures, consistent with the dominant role of tobacco in HNC causation. Differences were found in the burden of tobacco-associated signatures between anatomical subsites, suggesting that tissue-specific factors modulate mutagenesis. We identified an association between tobacco smoking and three additional alcohol-related signatures indicating synergism between the two exposures. Tobacco smoking was associated with differences in the mutational spectra and repertoire of driver mutations in cancer genes, and in patterns of copy number change. Together, the results demonstrate the multiple pathways by which tobacco smoke can influence the evolution of cancer cell clones.

15.
Spectrochim Acta A Mol Biomol Spectrosc ; 317: 124389, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-38710137

RESUMO

Over the years, osteosarcoma therapy has had a significative improvement with the use of a multidrug regime strategy, increasing the survival rates from less than 20 % to circa 70 %. Different types of development of new antineoplastic agents are critical to achieve irreversible damage to cancer cells, while preserving the integrity of their healthy counterparts. In the present study, complexes with two and three Pd(II) centres linked by the biogenic polyamines: spermine (Pd2SpmCl4) and spermidine (Pd3Spd2Cl6) were tested against non-malignant (osteoblasts, HOb) and cancer (osteosarcoma, MG-63) human cell lines. Either alone or in combination according to the EURAMOS-1 protocol, they were used versus cisplatin as a drug reference. By evaluating the cytotoxic effects of both therapeutic approaches (single and drug combination) in HOb and MG-63 cell lines, the selective anti-tumoral potential is assessed. To understand the different treatments at a molecular level, Synchrotron Radiation Fourier Transform Infrared and Raman microspectroscopies were applied. Principal component analysis and hierarchical cluster analysis are applied to the vibrational data, revealing the major metabolic changes caused by each drug, which were found to rely on DNA, lipids, and proteins, acting as biomarkers of drug-to-cell impact. The main changes were observed for the B-DNA native conformation to either Z-DNA (higher in the presence of polynuclear complexes) or A-DNA (preferably after cisplatin exposure). Additionally, a higher effect upon variation in proteins content was detected in drug combination when compared to single drug administration proving the efficacy of the EURAMOS-1 protocol with the new drugs tested.


Assuntos
Antineoplásicos , Osteossarcoma , Análise Espectral Raman , Humanos , Osteossarcoma/tratamento farmacológico , Osteossarcoma/patologia , Osteossarcoma/metabolismo , Análise Espectral Raman/métodos , Antineoplásicos/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Vibração , Espermina/farmacologia , Espermina/química , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Neoplasias Ósseas/metabolismo , Espermidina/farmacologia , Espermidina/química , Análise de Componente Principal , Sobrevivência Celular/efeitos dos fármacos
17.
ACS Pharmacol Transl Sci ; 7(5): 1650-1663, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38751616

RESUMO

Type 1 diabetes (T1D) is characterized by insufficient insulin secretion due to ß-cell loss. Despite exogenous insulin administration being a lifesaving treatment, many patients still experience severe glycemic lability. For these patients, a ß-cell replacement strategy through pancreas or pancreatic islet transplantation is the most physiological approach. However, donors' scarcity and the need for lifelong immunosuppressive therapy pose some challenges. This study proposes an innovative biomimetic pancreas, comprising ß- and α-cells differentiated from human induced pluripotent stem cells (hiPSCs) embedded in a biofunctional matrix with glucose-responsive nanoparticles (NPs) encapsulating a glucagon-like peptide 1 (GLP-1) analogue, which aims to enhance the glucose responsiveness of differentiated ß-cells. Herein, glucose-sensitive pH-responsive NPs encapsulating exenatide or semaglutide showed an average size of 145 nm, with 40% association efficiency for exenatide-loaded NPs and 55% for semaglutide-loaded NPs. Both peptides maintained their secondary structure after in vitro release and showed a similar effect on INS-1E cells' insulin secretion. hiPSCs were differentiated into ß- and α-cells, and insulin-positive cells were obtained (82%), despite low glucose responsiveness, as well as glucagon-positive cells (17.5%). The transplantation of the developed system in diabetic mice showed promising outcomes since there was an increase in the survival rate of those animals. Moreover, diabetic mice transplanted with cells and exenatide showed a decrease in their glucose levels. Overall, the biomimetic pancreas developed in this work showed improvements in diabetic mice survival rate, paving the way for new cellular therapies for T1D that explore the synergy of nanomedicines and stem cell-based approaches.

18.
Nutrients ; 16(8)2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38674905

RESUMO

Over the past few decades, people in Saudi Arabia have become less inclined to adopt active lifestyles and healthy eating habits due to the increasing use of digital technologies such as social media. The objective of this online-based cross-sectional study was to assess the role of social media food advertisements and physical activity on eating behaviors among the general population in Saudi Arabia (n = 471). Data were collected through a structured questionnaire, which consisted of four parts: (i) sociodemographic information, (ii) attitude towards social media, (iii) eating behaviors-related information, and (iv) exposure to and engagement with social media advertisements. The study's outcome variable, eating behaviors (healthy vs. unhealthy), was assessed using the following question: "Are you on a healthy diet (such as a balanced diet, keto, or low carb)?" A multiple binary logistic regression analysis was performed to investigate the factors that influence unhealthy eating behaviors. Approximately 79.6% of the participants had unhealthy eating behaviors. Participants who were not involved in daily physical activity were more likely to have unhealthy eating behaviors compared to their counterparts (adjusted odds ratio, AOR = 4.86). Participants who watched food ads on social media channels 1-3 times a week (AOR = 2.58) or daily (AOR = 3.49) were more likely to have unhealthy eating behaviors than their counterparts. Participants whose appetite to try foods increases always (AOR = 1.42) or usually (AOR = 2.88) after viewing ads on social media were more likely to have unhealthy eating behaviors. These findings suggest that policymakers should take immediate action to regulate food advertising policy to promote a healthy food environment across the country. Saudis should be encouraged to engage in more physical activity, which could support the maintenance of healthy eating patterns and lifestyles.


Assuntos
Publicidade , Exercício Físico , Comportamento Alimentar , Mídias Sociais , Humanos , Arábia Saudita , Mídias Sociais/estatística & dados numéricos , Masculino , Feminino , Adulto , Comportamento Alimentar/psicologia , Publicidade/métodos , Publicidade/estatística & dados numéricos , Estudos Transversais , Pessoa de Meia-Idade , Adulto Jovem , Inquéritos e Questionários , Dieta Saudável/psicologia , Dieta Saudável/estatística & dados numéricos , Adolescente , Comportamentos Relacionados com a Saúde
19.
Lett Appl Microbiol ; 77(5)2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38658187

RESUMO

Species from Candida parapsilosis complex are frequently found in neonatal candidemia. The antifungal agents to treat this infection are limited and the occurrence of low in vitro susceptibility to echinocandins such as micafungin has been observed. In this context, the chaperone Hsp90 could be a target to reduce resistance. Thus, the objective of this research was to identify isolates from the C. parapsilosis complex and verify the action of Hsp90 inhibitors associated with micafungin. The fungal identification was based on genetic sequencing and mass spectrometry. Minimal inhibitory concentrations were determined by broth microdilution method according to Clinical Laboratory and Standards Institute. The evaluation of the interaction between micafungin with Hsp90 inhibitors was realized using the checkerboard methodology. According to the polyphasic taxonomy, C. parapsilosis sensu stricto was the most frequently identified, followed by C. orthopsilosis and C. metapsilosis, and one isolate of Lodderomyces elongisporus was identified by genetic sequencing. The Hsp90 inhibitor geladanamycin associated with micafungin showed a synergic effect in 31.25% of the isolates, a better result was observed with radicicol, which shows synergic effect in 56.25% tested yeasts. The results obtained demonstrate that blocking Hsp90 could be effective to reduce antifungal resistance to echinocandins.


Assuntos
Antifúngicos , Candida parapsilosis , Candidemia , Proteínas de Choque Térmico HSP90 , Micafungina , Humanos , Recém-Nascido , Antifúngicos/farmacologia , Benzoquinonas/farmacologia , Candida parapsilosis/efeitos dos fármacos , Candida parapsilosis/isolamento & purificação , Candida parapsilosis/genética , Candidemia/microbiologia , Farmacorresistência Fúngica , Sinergismo Farmacológico , Equinocandinas/farmacologia , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Proteínas de Choque Térmico HSP90/metabolismo , Proteínas de Choque Térmico HSP90/genética , Lactamas Macrocíclicas/farmacologia , Lipopeptídeos/farmacologia , Micafungina/farmacologia , Testes de Sensibilidade Microbiana
20.
BMJ Case Rep ; 17(4)2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38604742

RESUMO

This is a case of primary hyperparathyroidism in a female teenager with multiple fractures and severe bone manifestations. The histopathology revealed atypical parathyroid adenoma, an exceedingly rare form of hyperparathyroidism; its main differential diagnosis is parathyroid carcinoma, as it shares both clinical and histological characteristics with it, in addition to its still uncertain malignant potential.


Assuntos
Hiperparatireoidismo , Neoplasias das Paratireoides , Humanos , Adolescente , Feminino , Neoplasias das Paratireoides/diagnóstico , Neoplasias das Paratireoides/diagnóstico por imagem , Glândulas Paratireoides/diagnóstico por imagem , Glândulas Paratireoides/patologia , Osso e Ossos/patologia
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