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1.
Cureus ; 16(4): e57620, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38707090

RESUMEN

Purple urine bag syndrome (PUBS) is a rare manifestation of urinary tract infection (UTI) characterized by bluish-purple discoloration of urine, typically seen in patients with long-term urinary catheters. It occurs due to the bacterial metabolism of dietary tryptophan into indole, which is converted into indoxyl sulfate in the liver and then excreted in the urine, where it reacts with catheter materials under alkaline conditions. Risk factors include chronic constipation, advanced age, female gender, dehydration, and recurrent UTIs. Morganella morganii is one of the bacteria commonly implicated. Although usually benign, PUBS can signal underlying UTIs, especially in asymptomatic patients. The case presented involves an 81-year-old woman with a history of urothelial carcinoma and a monoJ catheter since pelvic exenteration and ureterostomy. She presented with blue-colored urine in the collection bag; she was asymptomatic, but the urinalysis had leukocytes, nitrites and alkaline pH, and the uroculture was positive for M. morganii. Antibiotic therapy resolved the symptoms initially, but recurrence prompted further treatment and optimization of constipation management. PUBS, although rare, poses risks, especially in vulnerable populations. Identification of risk factors and causative agents is crucial for effective treatment, typically involving catheter replacement, antimicrobial therapy, and constipation correction. Prevention focuses on minimizing catheter use, regular replacement, and hygiene optimization. Early recognition and management in primary care settings can prevent complications and reduce patient and caregiver distress. In conclusion, PUBS is a visually evident condition that may serve as an early indication of UTI, particularly in patients with chronic catheterization. Treatment and prevention strategies should be tailored to individual risk factors to prevent the recurrence or persistence of the syndrome. Awareness among healthcare professionals and patients is essential for timely diagnosis and management. The presented case demonstrates the importance of primary care in managing complex conditions and highlights the close patient-physician relationship in such settings.

2.
Neuropathology ; 2024 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-38736183

RESUMEN

Medulloblastoma (MB) is the most prevalent malignant brain tumor in children, known for its heterogeneity and treatment-associated toxicity, and there is a critical need for new therapeutic targets. We analyzed the somatic mutation profile of 15 driver genes in 69 Latin-Iberian molecularly characterized medulloblastomas using the Illumina TruSight Tumor 15 panel. We classified the variants based on their clinical impact and oncogenicity. Among the patients, 66.7% were MBSHH, 13.0% MBWNT, 7.3% MBGrp3, and 13.0% MBGrp4. Among the 63 variants found, 54% were classified as Tier I/II and 31.7% as oncogenic/likely oncogenic. We observed 33.3% of cases harboring at least one mutation. TP53 (23.2%, 16/69) was the most mutated gene, followed by PIK3CA (5.8%, 4/69), KIT (4.3%, 3/69), PDGFRA (2.9%, 2/69), EGFR (1.4%, 1/69), ERBB2 (1.4%, 1/69), and NRAS (1.4%, 1/69). Approximately 41% of MBSHH tumors exhibited mutations, TP53 (32.6%) being the most frequently mutated gene. Tier I/II and oncogenic/likely oncogenic TP53 variants were associated with relapse, progression, and lower survival rates. Potentially actionable variants in the PIK3CA and KIT genes were identified. Latin-Iberian medulloblastomas, particularly the MBSHH, exhibit higher mutation frequencies than other populations. We corroborate the TP53 mutation status as an important prognostic factor, while PIK3CA and KIT are potential therapeutic targets.

3.
Braz J Microbiol ; 55(1): 639-646, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38214875

RESUMEN

Iron (Fe) is the fourth most abundant element on the planet, and iron-oxidising bacteria (FeOB) play an important role in the biogeochemical cycle of this metal in nature. FeOB stands out as Fe oxidisers in microaerophilic environments, and new members of this group have been increasingly discussed in the literature, even though their isolation can still be challenging. Among these bacteria is the Gallionellaceae family, mainly composed of neutrophilic FeOB, highlighting Gallionella ferruginea, and nitrite-oxidiser genera. In the previous metagenomic study of the biofilm and sediments of the cooling system from the Irapé hydroelectric power plant (HPP-Irapé), 5% of the total bacteria sequences were related to Gallionellaceae, being 99% unclassified at genus level. Thus, in the present study, a phylogenetic tree based on this family was constructed, in order to search for shared and unique Gallionellaceae signatures in a deep phylogenetic level affiliation and correlated them with geomorphologic characteristics. The results revealed that Gallionella and Ferrigenium were ubiquitous reflecting their ability to adapt to various locations in the power plant. The cave was considered a hotspot for neutrophilic FeOB since it harboured most of the Gallionellaceae diversity. Microscopic biosignatures were detected only in the CS1 sample, which presented abundance of the stalk-forming Ferriphaselus and of the sheath-forming Crenothrix. Further studies are required to provide more detailed insights on Gallionellaceae distribution and diversity patterns in hydroelectric power plants, particularly its biotechnological potential in this industry.


Asunto(s)
Gallionellaceae , Gallionellaceae/genética , Filogenia , Hierro , Metales , Metagenómica , Oxidación-Reducción
4.
J Biol Rhythms ; 39(1): 68-78, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37846856

RESUMEN

Newborn infants' circadian systems are not completely developed and rely on external temporal cues for synchronizing their biological rhythms to the environment. In neonatal intensive care units (NICUs), lighting is usually continuous or irregular and infants are exposed to artificial light at night, which can have negative health consequences. Therefore, the aim of this study was to evaluate the impact of the use of individual light protection equipment at night on the development and growth of preterm neonates. Infants born at less than 37 gestational weeks who no longer needed constant intensive care were admitted into a newborn nursery and randomized to either use eye masks at night (intervention, n = 21) or not (control, n = 20). Infants who used eye protection at night were discharged earlier than those in the control group (8 [5] vs 12 [3.75] days; p < 0.05). A greater variation within the day in heart rate was observed in the intervention group, with lower values of beats per minute at 1400 and 2000 h. There was no significant difference in weight gain between groups. In view of our results and of previous findings present in the literature, we suggest that combining a darkened environment at night with individual light protection devices creates better conditions for the development of preterm infants in the NICU. In addition, eye masks are an affordable and simple-to-use tool that can reduce hospitalization costs by decreasing the number of days spent in the NICU.


Asunto(s)
Recien Nacido Prematuro , Unidades de Cuidado Intensivo Neonatal , Humanos , Recién Nacido , Ritmo Circadiano , Alta del Paciente , Aumento de Peso
5.
Animals (Basel) ; 13(20)2023 Oct 19.
Artículo en Inglés | MEDLINE | ID: mdl-37893982

RESUMEN

Limnoperna fortunei, the golden mussel, is a bivalve mollusk considered an invader in South America. This species is responsible for ecological and economic damages due to its voluminous fouling capability. Chemical biocides such as MXD-100™ and sodium dichloroisocyanurate (NaDCC) are often used to control L. fortunei infestations in hydraulic systems. Thus, we proposed to investigate the effects of different periods (24, 48 and 72 h) of exposure to MXD-100™ (0.56 mg L-1) and NaDCC (1.5 mg L-1) on the gills of L. fortunei through morphological and molecular analyses. NaDCC promoted progressive morphological changes during the analyzed periods and only an upregulation of SOD and HSP70 expression during the first 24 h of exposure. MXD-100™ led to severe morphological changes from the first period of exposure, in addition to an upregulation of SOD, CAT, HSP70 and CYP expression during the first 24 h. In contrast, MXD-100™ led to a downregulation of CAT transcription between 24 and 48 h. In static conditions, NaDCC causes lethal damage after 72 h of exposure, and that exposure needs to be continuous to achieve the control of the species. Meanwhile, the MXD-100™ treatment presented several effects during the first 24 h, showing acute toxicity in a shorter period of time.

6.
Biomolecules ; 13(10)2023 09 25.
Artículo en Inglés | MEDLINE | ID: mdl-37892126

RESUMEN

Neurodegenerative diseases (NDs) are characterized by progressive and irreversible neuronal loss, accompanied by a range of pathological pathways, including aberrant protein aggregation, altered energy metabolism, excitotoxicity, inflammation, and oxidative stress. Some of the most common NDs include Alzheimer's Disease (AD), Parkinson's Disease (PD), Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS), and Huntington's Disease (HD). There are currently no available cures; there are only therapeutic approaches that ameliorate the progression of symptoms, which makes the search for new drugs and therapeutic targets a constant battle. Cyanobacteria are ancient prokaryotic oxygenic phototrophs whose long evolutionary history has resulted in the production of a plethora of biomedically relevant compounds with anti-inflammatory, antioxidant, immunomodulatory, and neuroprotective properties, that can be valuable in this field. This review summarizes the major NDs and their pathophysiology, with a focus on the anti-neurodegenerative properties of cyanobacterial compounds and their main effects.


Asunto(s)
Cianobacterias , Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Humanos , Enfermedades Neurodegenerativas/metabolismo , Estrés Oxidativo , Enfermedad de Parkinson/tratamiento farmacológico , Antioxidantes/farmacología , Cianobacterias/metabolismo
7.
Molecules ; 28(14)2023 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-37513486

RESUMEN

Alzheimer's disease (AD) is well-known among neurodegenerative diseases for the decline of cognitive functions, making overall daily tasks difficult or impossible. The disease prevails as the most common form of dementia and remains without a well-defined etiology. Being considered a disease of multifactorial origin, current targeted treatments have only managed to reduce or control symptoms, and to date, only two drugs are close to being able to halt its progression. For decades, natural compounds produced by living organisms have been at the forefront of research for new therapies. Mushrooms, which are well-known for their nutritional and medicinal properties, have also been studied for their potential use in the treatment of AD. Natural products derived from mushrooms have shown to be beneficial in several AD-related mechanisms, including the inhibition of acetylcholinesterase (AChE) and ß-secretase (BACE 1); the prevention of amyloid beta (Aß) aggregation and neurotoxicity; and the prevention of Tau expression and aggregation, as well as antioxidant and anti-inflammatory potential. Several studies in the literature relate mushrooms to neurodegenerative diseases. However, to the best of our knowledge, there is no publication that summarizes only AD data. In this context, this review aims to link the therapeutic potential of mushrooms to AD by compiling the anti-AD potential of different mushroom extracts or isolated compounds, targeting known AD-related mechanisms.


Asunto(s)
Agaricales , Enfermedad de Alzheimer , Enfermedades Neurodegenerativas , Humanos , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Agaricales/metabolismo , Acetilcolinesterasa/metabolismo
8.
Braz J Microbiol ; 54(3): 1547-1557, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37301793

RESUMEN

Microfouling can have significant economic impacts for hydroelectric power plants. However, knowledge concerning the composition and metabolism of microbial biofilm in cooling systems remains scarce. We examined the metagenome present in a cooling system, comprising a filter (F) and heat exchanger (HE), in the Nova Ponte hydroelectric power plant in Brazil, to identify bacteria and pathways that could be targeted to monitor and control biofilm formation. Our data revealed that the microfouling sample from heat exchanger 1 (HEM1), with porous consistency, presented enriched bacterial members not frequently described as biofilm formers in cooling systems, besides it has been shown to be an autoinducer repression pathway. Furthermore, the microfouling sample from heat exchanger 2 (HEM2), with gelatinous consistency, seemed to be an established biofilm, containing enriched bacterial groups such as Desulfotomaculum and Crenothrix and autoinducers, with biotechnological relevance in industrial biofilms. The results demonstrate that biofilm composition will vary depending on different abiotic conditions and the antifouling strategy used, including type of compound, concentration, and frequency of use. Therefore, all these variables must be evaluated when a power plant is affected by microbial slime in the cooling system. Our findings could help to define strategies for efficient and ecofriendly measures to contain microfouling in power plants.


Asunto(s)
Incrustaciones Biológicas , Incrustaciones Biológicas/prevención & control , Biopelículas , Bacterias/genética , Brasil , Percepción de Quorum
9.
Cancer Med ; 12(15): 15854-15867, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37338022

RESUMEN

BACKGROUND: Colorectal cancer (CRC) screening can help to reduce its incidence and mortality. Noninvasive strategies, such as plasma analysis of epigenetic alterations, can constitute important biomarkers of CRC detection. OBJECTIVE: This study aimed to evaluate the plasma methylation status of SEPT9 and BMP3 promoters as biomarkers for detection of CRC and its precursor lesions in a Brazilian population. METHODS: Plasma samples from 262 participants of the CRC screening program of Barretos Cancer Hospital who had a positive fecal occult blood test and underwent colonoscopy and cancer patients were analyzed. Participants were grouped according to the worst lesion detected in the colonoscopy. Cell-free circulating DNA (cfDNA) was bisulfite treated followed by the analysis of SEPT9 and BMP3 methylation status using a droplet digital PCR system (ddPCR). The best methylation cutoff value for group discrimination was calculated by receiver operating characteristic (ROC) curve analysis. RESULTS: Among the 262 participants, 38 were diagnosed with CRC, 46 with advanced adenomas 119 with nonadvanced adenomas, three with sessile serrated lesions, and 13 with hyperplastic polyps. In 43 participants, no lesion was detected in the colonoscopy and were used as controls. The CRC group showed the highest cfDNA concentration (10.4 ng/mL). For the SEPT9 gene, a cutoff of 2.5% (AUC = 0.681) that discriminates between CRC and the control group resulted in CRC sensitivity and specificity of 50% and 90%, respectively. Concerning the BMP3 gene, a cutoff of 2.3% (AUC = 0.576) showed 40% and 90% of sensitivity and specificity for CRC detection, respectively. Combining SEPT9, BMP3 status, and age over 60 years resulted in a better performance for detecting CRC (AUC = 0.845) than the individual gene models, yielding 80% and 81% of sensitivity and specificity, respectively. CONCLUSION: The present study suggests that a combination of SEPT9 and BMP3 plasma methylation, along with age over 60 years, showed the highest performance in detecting CRC in a Brazilian population. These noninvasive biomarkers can potentially serve as useful tools for CRC screening programs.


Asunto(s)
Adenoma , Ácidos Nucleicos Libres de Células , Neoplasias Colorrectales , Humanos , Persona de Mediana Edad , Detección Precoz del Cáncer , Brasil/epidemiología , Metilación de ADN , Septinas/genética , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genética , Sensibilidad y Especificidad , Adenoma/diagnóstico , Adenoma/genética , Biomarcadores de Tumor/genética , Proteína Morfogenética Ósea 3/genética
10.
Front Oncol ; 13: 1133363, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37007070

RESUMEN

Background: Testicular Germ Cell Tumors (TGCT) are the most common cancer among young adult men. The TGCT histopathology is diverse, and the frequency of genomic alterations, along with their prognostic role, remains largely unexplored. Herein, we evaluate the mutation profile of a 15-driver gene panel and copy number variation of KRAS in a large series of TGCT from a single reference cancer center. Materials and methods: A cohort of 97 patients with TGCT, diagnosed at the Barretos Cancer Hospital, was evaluated. Real-time PCR was used to assess copy number variation (CNV) of the KRAS gene in 51 cases, and the mutation analysis was performed using the TruSight Tumor 15 (Illumina) panel (TST15) in 65 patients. Univariate analysis was used to compare sample categories in relation to mutational frequencies. Survival analysis was conducted by the Kaplan-Meier method and log-rank test. Results: KRAS copy number gain was a very frequent event (80.4%) in TGCT and presented a worse prognosis compared with the group with no KRAS copy gain (10y-OS, 90% vs. 81.5%, p = 0.048). Among the 65 TGCT cases, different variants were identified in 11 of 15 genes of the panel, and the TP53 gene was the most recurrently mutated driver gene (27.7%). Variants were also detected in genes such as KIT, KRAS, PDGFRA, EGFR, BRAF, RET, NRAS, PIK3CA, MET, and ERBB2, with some of them potentially targetable. Conclusion: Although larger studies incorporating collaborative networks may shed the light on the molecular landscape of TGCT, our findings unveal the potential of actionable variants in clinical management for applying targeted therapies.

11.
Procedia Comput Sci ; 219: 1349-1356, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36968667

RESUMEN

With the current evolution of health digitalization driven by the COVID-19 pandemic, it is expected that teleconsultations - specifically, synchronous audio consultations (by telephone) or video-based (video calls) between health professionals (Doctors and Nurses) and patients - will be more used in Primary Health Care. The provision of health care through teleconsultations must be evaluated by the quality management of health organizations to ensure that the needs of patients are met. For this reason, this study was carried out under the objective of identifying indicators to create a culture of Patient-Centered Care (PCC) in teleconsultations in Primary Health Care. The methodology followed was based on the Delphi method. The research aimed to analyze the suitability of 48 indicators (organized in Donabedian's quality dimensions) to assess the implementation of PCC in Primary Health Care. Despite all indicators were viewed as very important, the disparity in responses was significant. Future research should extend this study by involving other groups of experts (like academics who study the subject and members of patient associations).

12.
Mol Ecol ; 32(23): 6507-6522, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36541038

RESUMEN

Coccolithophores have global ecological and biogeochemical significance as the most important calcifying marine phytoplankton group. The structure and selection of prokaryotic communities associated with the most abundant coccolithophore and bloom-forming species, Emiliania huxleyi, are still poorly known. In this study, we assessed the diversity of bacterial communities associated with an E. huxleyi bloom in the Celtic Sea (Eastern North Atlantic), exposed axenic E. huxleyi cultures to prokaryotic communities derived from bloom and non-bloom conditions, and followed the dynamics of their microbiome composition over one year. Bloom-associated prokaryotic communities were dominated by SAR11, Marine group II Euryarchaeota and Rhodobacterales and contained substantial proportions of known indicators of phytoplankton bloom demises such as Flavobacteriaceae and Pseudoalteromonadaceae. The taxonomic richness of bacteria derived from natural communities associated with axenic E. huxleyi rapidly shifted and then stabilized over time. The succession of microorganisms recruited from the environment was consistently dependent on the composition of the initial bacterioplankton community. Phycosphere-associated communities derived from the E. huxleyi bloom were highly similar to one another, suggesting deterministic processes, whereas cultures from non-bloom conditions show an effect of stochasticity. Overall, this work sheds new light on the importance of the initial inoculum composition in microbiome recruitment and elucidates the temporal dynamics of its composition and long-term stability.


Asunto(s)
Haptophyta , Microbiota , Haptophyta/genética , Fitoplancton/genética , Organismos Acuáticos , Bacterias , Microbiota/genética
13.
J Nat Prod ; 85(12): 2753-2768, 2022 12 23.
Artículo en Inglés | MEDLINE | ID: mdl-36382951

RESUMEN

Investigation of a pine bark extract for bioactive proanthocyanidin oligomers resulted in the isolation of structurally related dimeric seco B-type procyanidin derivatives, 1-5. This includes scalemic mixtures of gambiriin A1 (1a) and A2 (2a) and their newly described optical antipodes, ent-gambiriin A1 (1b) and ent-gambiriin A2 (2b), respectively, as well as a racemic mixture of the newly described (ent-)gambiriin A5 (3a/3b). Furthermore, the study now fully characterizes the previously reported optically pure dimers gambiriin B1 (4) and gambirflavan D1 (5), and characterized the novel seco B-type procyanidin trimer, 6 (gambirifuran C1). Thermal conversion of catechin in aqueous solution provided further evidence for the structures of 1-6 and led to the purification of semisynthetic 1a and 2a as well as additional dimers 7-10. Elucidating the structures of the natural dimers, 1-5, from comprehensive NMR and ECD data and synthetic evidence provided crucial reference points for establishing the structure of the seco B-type procyanidin trimer, 6. Serving as assigned building blocks, data from the dimers supported the 3D structural assignment of 6 based on NMR substituent chemical shift differences (s.c.s., syn. ΔδC) and component-based empirical ECD calculations. Within the newly characterized series of PAC-related molecules, 5 exhibited high dentin biomodification potential. In addition, considering the nomenclature issues and plausible biosynthetic pathways of this group of compounds led to a consolidated nomenclature of all currently known seco B-type procyanidins. These findings, thereby, expand the chemical space of bioactive catechin oligomers, which have promise as agents for the natural enhancement of dental biomaterials. Finally, the current knowledge of the chemical space of seco B-type procyanidin derivatives was compiled to the level of absolute configuration.


Asunto(s)
Biflavonoides , Catequina , Pinus , Proantocianidinas , Proantocianidinas/química , Catequina/química , Biflavonoides/química
14.
J Agric Food Chem ; 70(39): 12456-12468, 2022 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-36134876

RESUMEN

To enable translational studies, a scalable preparative isolation scheme was developed for underivatized cocoa (Theobroma cacao) proanthocyanidins (PACs), affording six all-B-type oligomeric PACs, including a new tetramer 4. Their structures, including absolute configuration, were unambiguously established by comprehensive spectroscopic and chemical methods. Evaluation of the PACs' dentin biomodification properties employed dynamic mechanical and infrared spectroscopic analyses in dentin bioassay models. PAC treatment enhanced the biomechanical strength of dentin by 5- to 15-fold compared to untreated dentin. Among the PAC agents, the pentamer, cinnamtannin A3 (6), led to the highest complex modulus value of 131 MPa, whereas the "branched" tetramer, 4, showed the lowest, yet still significant bioactivity. This study of specifically singly linked medium-length oligomeric PACs indicates that the linkage site is paramount in determining the potency of these PACs as dentin biomodifiers.


Asunto(s)
Cacao , Proantocianidinas , Antioxidantes/análisis , Cacao/química , Dentina/química , Proantocianidinas/química
15.
Sci Data ; 9(1): 565, 2022 09 13.
Artículo en Inglés | MEDLINE | ID: mdl-36100598

RESUMEN

The biogeography of bacterial communities is a key topic in Microbial Ecology. Regarding continental water, most studies are carried out in the northern hemisphere, leaving a gap on microorganism's diversity patterns on a global scale. South America harbours approximately one third of the world's total freshwater resources, and is one of these understudied regions. To fill this gap, we compiled 16S rRNA amplicon sequencing data of microbial communities across South America continental water ecosystems, presenting the first database µSudAqua[db]. The database contains over 866 georeferenced samples from 9 different ecoregions with contextual environmental information. For its integration and validation we constructed a curated database (µSudAqua[db.sp]) using samples sequenced by Illumina MiSeq platform with commonly used prokaryote universal primers. This comprised ~60% of the total georeferenced samples of the µSudAqua[db]. This compilation was carried out in the scope of the µSudAqua collaborative network and represents one of the most complete databases of continental water microbial communities from South America.


Asunto(s)
Microbiota , Bacterias/genética , Bases de Datos Genéticas , Secuenciación de Nucleótidos de Alto Rendimiento , Microbiota/genética , ARN Ribosómico 16S/genética , América del Sur , Microbiología del Agua
16.
J Dent ; 127: 104310, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36167234

RESUMEN

OBJECTIVES: To compare the biodegradability, mechanical behavior, and physicochemical features of the collagen-rich extracellular matrix (ECM) of artificial caries-affected dentin (ACAD), natural caries-affected dentin (NCAD) and sound dentin (SD). METHODS: Dentin specimens from human molars were prepared and assigned into groups according to the type of dentin: ACAD, NCAD, or SD. ACAD was produced by incubation of demineralized SD with Streptococcus mutans in a chemically defined medium (CDM) with 1% sucrose for 7 days at 37 °C under anaerobic conditions. Specimens were assessed to determine collagen birefringence, biodegradability, mechanical behavior, and chemical composition. Data were individually processed and analyzed by ANOVA and post-hoc tests (α = 0.05). RESULTS: CDM-based biofilm challenge reduced loss, storage, and complex moduli in ACAD (p < 0.001), while the damping capacity remained unaffected (p = 0.066). Higher red and lower green birefringence were found in ACAD and NCAD when compared with SD (p < 0.001). Differently to ACAD, SD and NCAD presented higher biodegradability to exogenous proteases (p = 0.02). Chemical analysis of the integrated areas of characteristic bands that assess mineral quality (carbonate/phosphate and crystallinity index), mineral to matrix (phosphate/amide I) and post-translational modifications (amide III/CH2, pentosidine/CH2, and pentosidine/amide III) (p<0.05) showed that NCAD was significantly different from SD while ACAD exhibited intermediate values. CONCLUSIONS: CDM-based biofilm challenge produced a dentin ECM with decreased mechanical properties and increased collagen maturity. The compositional and structural conformation of the ACAD suggested that CDM-based biofilm challenge showed potential to produce artificial lesions by revealing a transitional condition towards mimicking critical features of NCAD. CLINICAL SIGNIFICANCE: This study highlights the importance of developing a tissue that mimics the features of natural caries-affected dentin ECM for in vitro studies. Our findings suggested the potential of a modified biofilm challenge protocol to produce and simulate a relevant substrate, such as caries-affected dentin.


Asunto(s)
Caries Dental , Recubrimientos Dentinarios , Humanos , Recubrimientos Dentinarios/química , Dentina/química , Susceptibilidad a Caries Dentarias , Caries Dental/patología , Colágeno/análisis , Fosfatos , Amidas/análisis
17.
Front Med (Lausanne) ; 9: 821094, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35935795

RESUMEN

Background/aims: Combination products are therapeutic and/or diagnostic products that can combine drugs and medical devices and which increasing complexity has raised new regulatory framework challenges. To reach the market, a combination product must be classified based on the principal mode of action (PMOA). However, research and technological progress has been leading to the development of novel combination products with no clearly defined PMOA, emphasizing the lack of a systematization process, thus challenging the correct classification of these products. To illustrate the regulatory challenge, two case studies are discussed: innovative combination products with PMOA that can change due to an external stimulus, specifically custom-made 3D-printed scaffolds with incorporated medicinal substances. Methods: Data was collected through computational search engines, regulatory agencies and equally relevant associations. The analysis of the data resulted on this state-of-the-art review, a description of the decision-making process by the regulatory authorities, and case studies analysis that culminated in the proposal of a decision-tree scheme. Findings: Current regulations do not fully address complex combination products namely personalized 3D-printed scaffolds. Two merged regulatory approaches are suggested along with the schematization of the rational assisted by a decision-tree tool. Conclusion: Combination products have become increasingly sophisticated, which has furthered the need to develop multidisciplinary collaborations within the health sector to adapt to these innovative healthcare solutions as well as with regulators to overcome the challenges posed for their classification.

18.
J Cancer Res Clin Oncol ; 148(10): 2893-2910, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35922694

RESUMEN

PURPOSE: Prostate cancer (PCa) is the 4th most diagnosed cancer and the 8th leading cause of cancer-related death worldwide. Currently, clinical risk stratification models including factors like PSA levels, Gleason score, and digital rectal examination are used for this purpose. There is a need for novel biomarkers that can distinguish between indolent and aggressive pathology and reduce the risk of overdiagnosis/overtreatment. Liquid biopsy has a non-invasive character, can lead to less morbidity and provide new biomarkers, such as miRNAs, that regulate diverse important cellular processes. Here, we report an extended revision about the role of cell-free and exosomal miRNAs (exomiRNAs) as biomarkers for screening, diagnosis, prognosis, or treatment of PCa. METHODS: A comprehensive review of the published literature was conducted focusing on the usefulness, advantages, and clinical applications of cell-free and exomiRNAs in serum and plasma. Using PubMed database 53 articles published between 2012 and 2021 were selected and discussed from the perspective of their use as diagnostic, prognostic and therapeutic biomarkers for PCa. RESULTS: We identify 119 miRNAs associated with PCa development and the cell-free and exosomal miR-21, miR-141, miR-200c, and miR-375 were consistently associated with progression in multiple cohorts/studies. However, standardized experimental procedures, and well-defined and clinically relevant cohort studies are urgently needed to confirm the biomarker potential of cell-free and exomiRNAs in serum or plasma. CONCLUSION: Cell-free and exomiRNAs in serum or plasma are promising tools for be used as non-invasive biomarkers for diagnostic, prognosis, therapy improvement and clinical outcome prediction in PCa patients.


Asunto(s)
MicroARNs , Neoplasias de la Próstata , Biomarcadores de Tumor/genética , Humanos , Biopsia Líquida , Masculino , MicroARNs/genética , Pronóstico , Antígeno Prostático Específico , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología
19.
MethodsX ; 9: 101764, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35813160

RESUMEN

The use of iron oxide nanoparticles for the synthesis of adsorbents materials with application in contaminated water remediation is based on both their magnetic and adsorption properties. Poly(styrene-co-divinylbenzene) - Poly(Sty-co-DVB)microparticles are widely known for this use and the addition of magnetite comes to add magnetic properties, however it should not limit the functionalization processes for formation of cationic and/or anionic resins. Thus, there is a concern about the stability of magnetite in acidic environments, as required by the sulfonation process, for example. Furthermore, the synthesis of composites with magnetic nanoparticles is a challenge due to the strong magnetic dipole interactions between particles resulting from the high specific surface area, making them susceptible to aggregation. As well as oxidation during the synthesis process can compromise the structure of the initial magnetic material. In this sense, the present work validated processes for the synthesis of Poly(Sty-co-DVB)/magnetite microparticles that sought, as a final result, the incorporation of magnetite aiming to preserve its initial structural conformation. Thus, started from original synthesis method aimed at the production of Poly(Sty-co-DVB) microparticles without magnetite, to methods in which magnetite nanoparticles is added through two distinct processes, different regarding the use or not of oleic acid in its preparation. In this method article we show:•Combination of methods to preserve the structure of magnetite in the Poly(Sty-co-DVB)/magnetite composite.•Simple method of adding magnetite to the Poly(Sty-co-DVB)/magnetite composite synthesis process.•Magnetite treatment method with oleic acid in Poly(Sty-co-DVB)/magnetite composite synthesis. The samples were characterized using Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and Mössbauer spectroscopy to evaluate the chemical modifications that were introduced in the original synthesis method.

20.
Mol Biol Rep ; 49(9): 9079-9087, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35708863

RESUMEN

BACKGROUND: There is an ongoing search for molecular markers that are specific, sensitive, and able to predict the stage of prostate cancer (PCa), which is the second most prevalent type of cancer in men worldwide. This study examined whether different single nucleotide polymorphisms (SNPs) were reliable markers of susceptibility to and prognosis of PCa in a sample of Brazilian patients. METHODS AND RESULTS: DNA samples were extracted from peripheral blood cells of 283 PCa patients and matched with samples from healthy controls. Single nucleotide polymorphisms (SNPs in four genes (BCL-2-rs2279115, CASP3-rs4647603, CASP9-rs1052571, and NKX3-1-rs11781886) were genotyped by real-time PCR using the TaqMan® probe. Odds Ratios with 95% confidence intervals were calculated for allelic and genotypic frequencies. The association between polymorphic variants, risk of developing PCa, and clinicopathological characteristics was analyzed by univariate and multivariate logistic regression analysis. SNPs in CASP3, CASP9, and NKX3-1 genes, either alone or in combination (BCL-2+NKX3-1 and CASP3+NKX3-1) were associated with the risk of developing PCa. Genotypes and tumor histopathological data indicated that the BCL-2, NKX3-1, and CASP3 allelic variants, either alone or combined in pairs, were associated with a poor prognosis of PCa. CONCLUSIONS: Genetic polymorphisms in CASP3, NKX3-1, and BCL-2 genes were associated with susceptibility to PCa. The SNPs in the three genes alone and the SNP in the BCL-2 gene combined with the other two genes were strongly associated with adverse outcomes in PCa patients and are promising candidates for molecular markers for PCa prognosis.


Asunto(s)
Genes bcl-2 , Neoplasias de la Próstata , Estudios de Casos y Controles , Caspasa 3/genética , Caspasa 9/genética , Predisposición Genética a la Enfermedad , Proteínas de Homeodominio/genética , Humanos , Masculino , Polimorfismo de Nucleótido Simple/genética , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Proteínas Proto-Oncogénicas c-bcl-2/genética , Factores de Transcripción/genética
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