Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 876
Filtrar
1.
Artículo en Inglés, Español | MEDLINE | ID: mdl-38851565

RESUMEN

INTRODUCTION: The incidence of hip fracture in the elderly is on the rise, occasionally accompanied by concurrent upper limb fractures. Our investigation aims to determine whether these patients experience poorer functional outcomes, prolonged hospitalization, or higher mortality rates when compared to those with isolated hip fracture. MATERIAL AND METHODS: We retrospectively reviewed 1088 elderly patients admitted to our centre with hip fracture between January 2017 and March 2020. We recorded the presence of concomitant fractures and their treatment. We analyzed the duration of hospital stay, in-hospital mortality and function. RESULTS: We identified 63 patients with concomitant upper limb fracture (5.6%). Among them, 93.7% were women, and the average age was 86.4 years. 80.9% of the upper limb fractures were distal radius or proximal humerus. Patients with concomitant fracture had increased length of stay (mean, 19.6 vs 12.8, p=0.002), decreased proportion of patients returning to their own home at discharge (23.6% vs 26.3%, p=0.042) and increased in-hospital mortality rate (9.5% vs 5.9%, p=0.003). CONCLUSIONS: Patients with concomitant upper limb fracture require a longer length of stay and exhibit an elevated in-hospital mortality rate. Furthermore, this condition is associated with a reduced short-term functional recovery, thereby decreasing the chances of the patient returning home upon hospital discharge.

2.
Int J Environ Health Res ; : 1-12, 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38842028

RESUMEN

Various exogenous factors, such as microbiological and chemical contamination condition food security. Salmonella Typhimurium (S. Typhimurium) is the cause of salmonellosis. This bacterium utilizes phagocytosis to create bacterial reservoirs. On the other hand, exposure to chemical contaminants, such as pesticides, increases susceptibility to numerous infections. Therefore, this research aims to evaluate the effect of co-exposure to diazoxon and S. Typhimurium on the in vitro infection dynamics. For this purpose, human mononuclear cells were pre-exposed in vitro to diazoxon and then challenged with S. Typhimurium at 1, 8, and 24 h. Bacterial internalization, actin polymerization, and reactive oxygen species (ROS) were analyzed. Obtained data show that mononuclear cells previously exposed to diazoxon exhibit greater internalization of S. Typhimurium. Likewise, greater ROS production and an increase in actin polymerization were observed. Therefore, in the proposed scenario, obtained data suggest that co-exposure to diazoxon and S. Typhimurium increases susceptibility to acquiring an illness.

3.
PeerJ Comput Sci ; 10: e2095, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38855217

RESUMEN

Mixed integer nonlinear programming (MINLP) addresses optimization problems that involve continuous and discrete/integer decision variables, as well as nonlinear functions. These problems often exhibit multiple discontinuous feasible parts due to the presence of integer variables. Discontinuous feasible parts can be analyzed as subproblems, some of which may be highly constrained. This significantly impacts the performance of evolutionary algorithms (EAs), whose operators are generally insensitive to constraints, leading to the generation of numerous infeasible solutions. In this article, a variant of the differential evolution algorithm (DE) with a gradient-based repair method for MINLP problems (G-DEmi) is proposed. The aim of the repair method is to fix promising infeasible solutions in different subproblems using the gradient information of the constraint set. Extensive experiments were conducted to evaluate the performance of G-DEmi on a set of MINLP benchmark problems and a real-world case. The results demonstrated that G-DEmi outperformed several state-of-the-art algorithms. Notably, G-DEmi did not require novel improvement strategies in the variation operators to promote diversity; instead, an effective exploration within each subproblem is under consideration. Furthermore, the gradient-based repair method was successfully extended to other DE variants, emphasizing its capacity in a more general context.

4.
J Phys Chem Lett ; 15(21): 5747-5753, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38775633

RESUMEN

The use of electric fields applied across magnetic heterojunctions that lack spatial inversion symmetry has been previously proposed as a nonmagnetic means of controlling localized magnetic moments through spin-orbit torques (SOT). The implementation of this concept at the single-molecule level has remained a challenge, however. Here, we present first-principles calculations of SOT in a single-molecule junction under bias and beyond linear response. Employing a self-consistency scheme invoking density functional theory and nonequilibrium Green's function theory including spin-orbit interaction, we compute the change of the magnetization with the bias voltage and the associated current-induced SOT. Within the linear regime our quantitative estimates for the SOT in single-molecule junctions yield values similar to those known for magnetic interfaces. Our findings contribute to an improved microscopic understanding of SOT in single molecules.

5.
Hum Vaccin Immunother ; 20(1): 2347019, 2024 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-38807261

RESUMEN

Influenza A viruses pose a significant threat to global health, impacting both humans and animals. Zoonotic transmission, particularly from swine and avian species, is the primary source of human influenza outbreaks. Notably, avian influenza viruses of the H5N1, H7N9, and H9N2 subtypes are of pandemic concern through their global spread and sporadic human infections. Preventing and controlling these viruses is critical due to their high threat level. Vaccination remains the most effective strategy for influenza prevention and control in humans, despite varying vaccine efficacy across strains. This review focuses specifically on pandemic preparedness for avian influenza viruses. We delve into vaccines tested in animal models and summarize clinical trials conducted on H5N1, H7N9, and H9N2 vaccines in humans.


Asunto(s)
Aves , Vacunas contra la Influenza , Gripe Aviar , Gripe Humana , Pandemias , Animales , Vacunas contra la Influenza/inmunología , Vacunas contra la Influenza/administración & dosificación , Humanos , Gripe Humana/prevención & control , Gripe Humana/epidemiología , Gripe Humana/inmunología , Gripe Aviar/prevención & control , Gripe Aviar/epidemiología , Pandemias/prevención & control , Desarrollo de Vacunas , Subtipo H7N9 del Virus de la Influenza A/inmunología , Subtipo H9N2 del Virus de la Influenza A/inmunología , Subtipo H5N1 del Virus de la Influenza A/inmunología , Ensayos Clínicos como Asunto , Modelos Animales de Enfermedad , Vacunación , Preparación para una Pandemia
6.
Artículo en Inglés | MEDLINE | ID: mdl-38814543

RESUMEN

PURPOSE: Determine if the gene expression profiles of ovarian support cells (OSCs) and cumulus-free oocytes are bidirectionally influenced by co-culture during in vitro maturation (IVM). METHODS: Fertility patients aged 25 to 45 years old undergoing conventional ovarian stimulation donated denuded immature oocytes for research. Oocytes were randomly allocated to either OSC-IVM culture (intervention) or Media-IVM culture (control) for 24-28 h. The OSC-IVM culture condition was composed of 100,000 OSCs in suspension culture with human chorionic gonadotropin (hCG), recombinant follicle stimulating hormone (rFSH), androstenedione, and doxycycline supplementation. The Media-IVM control lacked OSCs and contained the same supplementation. A limited set of in vivo matured MII oocytes were donated for comparative evaluation. Endpoints consisted of MII formation rate, morphological and spindle quality assessment, and gene expression analysis compared to in vitro and in vivo controls. RESULTS: OSC-IVM resulted in a statistically significant improvement in MII formation rate compared to the Media-IVM control, with no apparent effect on morphology or spindle assembly. OSC-IVM MII oocytes displayed a closer transcriptomic maturity signature to IVF-MII controls than Media-IVM control MII oocytes. The gene expression profile of OSCs was modulated in the presence of oocytes, displaying culture- and time-dependent differential gene expression during IVM. CONCLUSION: The OSC-IVM platform is a novel tool for rescue maturation of human oocytes, yielding oocytes with improved nuclear maturation and a closer transcriptomic resemblance to in vivo matured oocytes, indicating a potential enhancement in oocyte cytoplasmic maturation. These improvements on oocyte quality after OSC-IVM are possibly occurring through bidirectional crosstalk of cumulus-free oocytes and ovarian support cells.

7.
J Virol ; 98(5): e0054924, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38624241

RESUMEN

As an Argentine scientist, the defunding of CONICET and INTA feels like a blow to progress and our future. Despite free education, these cuts force talented researchers to seek opportunities abroad. Argentina's history of scientific achievement, from Nobel Prizes to COVID-19 vaccines, is at risk. Defunding science weakens our ability to solve problems and compete globally.


Asunto(s)
Investigación Biomédica , Humanos , Argentina , Investigación Biomédica/economía , Investigación Biomédica/educación , Ciencia/economía , Ciencia/educación , Fuga de Cerebros
8.
PLoS One ; 19(4): e0302031, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38603692

RESUMEN

Chronic neuroinflammation is characterized by increased blood-brain barrier (BBB) permeability, leading to molecular changes in the central nervous system that can be explored with biomarkers of active neuroinflammatory processes. Magnetic resonance imaging (MRI) has contributed to detecting lesions and permeability of the BBB. Ultra-small superparamagnetic particles of iron oxide (USPIO) are used as contrast agents to improve MRI observations. Therefore, we validate the interaction of peptide-88 with laminin, vectorized on USPIO, to explore BBB molecular alterations occurring during neuroinflammation as a potential tool for use in MRI. The specific labeling of NPS-P88 was verified in endothelial cells (hCMEC/D3) and astrocytes (T98G) under inflammation induced by interleukin 1ß (IL-1ß) for 3 and 24 hours. IL-1ß for 3 hours in hCMEC/D3 cells increased their co-localization with NPS-P88, compared with controls. At 24 hours, no significant differences were observed between groups. In T98G cells, NPS-P88 showed similar nonspecific labeling among treatments. These results indicate that NPS-P88 has a higher affinity towards brain endothelial cells than astrocytes under inflammation. This affinity decreases over time with reduced laminin expression. In vivo results suggest that following a 30-minute post-injection, there is an increased presence of NPS-P88 in the blood and brain, diminishing over time. Lastly, EAE animals displayed a significant accumulation of NPS-P88 in MRI, primarily in the cortex, attributed to inflammation and disruption of the BBB. Altogether, these results revealed NPS-P88 as a biomarker to evaluate changes in the BBB due to neuroinflammation by MRI in biological models targeting laminin.


Asunto(s)
Barrera Hematoencefálica , Laminina , Animales , Barrera Hematoencefálica/diagnóstico por imagen , Barrera Hematoencefálica/metabolismo , Laminina/metabolismo , Enfermedades Neuroinflamatorias , Células Endoteliales/metabolismo , Inflamación/diagnóstico por imagen , Inflamación/metabolismo , Imagen por Resonancia Magnética/métodos
9.
Med Clin (Barc) ; 2024 Apr 19.
Artículo en Inglés, Español | MEDLINE | ID: mdl-38643026

RESUMEN

INTRODUCTION: Peripheral arterial disease is a marker of vascular damage that is diagnosed by measuring the ankle-brachial index. The aim of this study was to determine the validity and agreement of the MESI ABPI-MD and Microlife WatchBP® office-ABI oscillometric devices with respect to the gold standard arterial Doppler. MATERIALS AND METHODS: Observational, cross-sectional, descriptive study of inpatients who underwent ABI measurement with the three devices. Values are considered normal between 1-1.4, indeterminate between 0.91-0.99 and pathological ≤0.9 and >1.4. RESULTS: A total of 187 patients (54.4% male) with a mean age of 66 years were included. The Doppler results were inferior to those of the oscillometric devices (median [IQR] 1.1 [0.2] vs. 1.2 [0.2], P<.05), with no significant differences between the automated devices (P=.29 for the right lower limb and P=.342 for the left lower limb). Both devices had high specificity (96.5-99.2%) and low sensitivity (29.5-45.4%). The correlation of the results was good-moderate for MESI and moderate for Microlife. The agreement between the two was acceptable-moderate. CONCLUSION: Automated oscillometric devices could be useful in asymptomatic patients as an alternative to arterial Doppler.

10.
Int J Inj Contr Saf Promot ; : 1-20, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38647115

RESUMEN

As the elderly population grows, there is a greater concern for their safety on the roads. This is particularly important for elderly pedestrians who are more vulnerable to accidents. In Spain, one of the most aged countries in the world, the elderly accounted for 70% of all pedestrian deaths in 2019. In this study, the focus was on analysing the occurrence of elderly pedestrian-vehicle collisions in Spanish municipalities and how it is related to the built environment. The study used the hurdle negative binomial model to analyse the number of elderly and non-elderly pedestrian accidents per municipality in 2016-2019. The exploratory analysis showed that cities above 50,000 inhabitants were safer for the elderly, and larger provincial capitals had lower elderly pedestrian traffic accident rates. The occurrence of all pedestrian traffic accidents was linked to the socio-demographic features. For elderly pedestrians, land use was found to be influential, with a lower proportion of land covered by manufacturing and service activities linked to a smaller number of accidents. Results showed that improving road safety for older pedestrians may not necessarily compromise the situation for the rest of population. Hence, policymakers should focus on infrastructure improvements adapted to the needs of elderly pedestrians.

12.
Eur J Orthop Surg Traumatol ; 34(4): 1851-1863, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38431896

RESUMEN

INTRODUCTION: The purposes of this study were to analyze and compare the functional outcomes and radiological changes around the press-fit humeral components in two contemporary medialized reverse total shoulder arthroplasty (RTSA) systems at a minimum of 5-year follow-up. MATERIALS AND METHODS: Between December 2003 and December 2015, 249 consecutive RTSAs were performed at our hospital. Of these, 68 primary uncemented RTSA met our inclusion criteria. The Constant-Murley score (CMS), the modified Constant score, a visual analog scale (VAS) and active shoulder range of motion (ROM) were measured pre- and postoperatively. Radiological assessment was performed by plain radiographs at a minimum of 5 years postoperatively. RESULTS: At a mean follow-up of 80.2 months, there was no significant difference (p = .59) between the postoperative functional scores and range of motion of the two groups (Delta Xtend and Lima SMR). Radiological data of stress-shielding were observed in 38 patients (55.9%) being slightly more frequent in the Lima SMR group (21 patients) than in the Delta Xtend group (17 patients) (p = .62). CONCLUSIONS: Our study shows that the good functional results are similar between the two uncemented RTSA systems used and that they do not depend on the presence of radiological changes (stress-shielding) in the humeral stem at a minimum 5-year follow-up.


Asunto(s)
Artroplastía de Reemplazo de Hombro , Húmero , Radiografía , Rango del Movimiento Articular , Prótesis de Hombro , Humanos , Artroplastía de Reemplazo de Hombro/métodos , Femenino , Masculino , Estudios de Seguimiento , Anciano , Radiografía/métodos , Persona de Mediana Edad , Húmero/diagnóstico por imagen , Húmero/cirugía , Diseño de Prótesis , Resultado del Tratamiento , Articulación del Hombro/cirugía , Articulación del Hombro/diagnóstico por imagen , Articulación del Hombro/fisiopatología , Estudios Retrospectivos
13.
Hip Int ; : 11207000241239624, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38529883

RESUMEN

INTRODUCTION: Ceramic-on-ceramic bearings have been widely used since their introduction in the 1970s. First-generation ceramics have very high fracture (breakage) rates. To overcome this, in the 1990s, modular cotyloid insert designs were developed, consisting of a ceramic and polyethylene composite (sandwich-type) liner; however, high implant fracture rates were observed in the medium term. We aimed to estimate the cumulative incidences of revision surgery (implant failure) and implant failure due to fractures, survival rates (time-to-revision surgery and time-to-fracture), and the long-term clinical and radiological outcomes in our series. METHODS: This was an observational, longitudinal, ambispective, single-centre study based on patients who underwent primary total hip arthroplasty (THA) using a sandwich-type liner (Cerasul), only available in our tertiary hospital between January 1999 and December 2002. Cumulative incidences were estimated and the 95% confidence interval (95% CI) was calculated. The Kaplan-Meier method was used to assess the time-to-revision surgery and time-to-fracture. RESULTS: 54 patients (49 men) were included, accounting for 59 sandwich-type linear implants. The mean (range) age was 47.4 (22-57) years. The primary THA indications were osteoarthritis (28 patients), osteonecrosis (14), childhood pathology sequelae (11), and inflammatory arthritis (6). The cumulative incidence of revision surgery by implants was 8.5% (5/59, 95% CI, 3.5-19.2%), 9.3% by patients (5/54, 95% CI, 4.0-19.9%), and 5.1% by implant fractures (3/59, 95%CI, 1.7-13.9%). The median (Interquartile Range, IQR) time-to-revision surgery was 158 (72.5-161) months, and the time to fracture was 182 (138-215) months. All primary THAs had good clinical and long-term survival outcomes. All implants had signs of solid fixation. CONCLUSIONS: After a 20-year follow-up period, the polyethylene-ceramic sandwich-type liner showed a long survival rate and low cumulative incidence of implant fracture; however, implant fractures remain the main complication. Orthopaedic surgeons should be aware that some patients still have this type of prosthesis and must be capable of responding quickly if a fracture occurs.

14.
J Leukoc Biol ; 2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38547424

RESUMEN

The physiological and molecular responses of leukocytes are altered by organophosphate pesticides (OPs). Some reports have shown that diazinon (DZN) causes immunotoxic effects; diazoxon (DZO), the oxon metabolite of DZN, is attributed to influence the immune response by affecting the leukocyte cholinergic system. In this study, the in vitro effects of DZO on molecules involved in cell signaling (cAMP, IP3, DAG, JAK1, and STAT3), which play a crucial role in the activation, differentiation, and survival of leukocytes, were evaluated. Data indicate that DZO leads to a decrease in cAMP concentration and an increase in basal IP3 levels. However, DZO does not affect basal levels of JAK1 and STAT3 phosphorylation. Instead, DZO inhibits leukocyte responsiveness to PMA and ionomycin, substances that, under normal conditions, enhance JAK/STAT signaling. These findings demonstrate that DZO significantly affects key molecular parameters related to cell signaling.

15.
Methods Cell Biol ; 184: 97-103, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38555161

RESUMEN

Current strategies to undermine the deleterious influence of myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment (TME) are lacking effective clinical solutions, in large part, due to insufficient knowledge on susceptible cellular and molecular targets. We describe here the application of biomimetic microfabricated platforms designed to analyze migratory phenotypes of MDSCs in the tumor niche ex vivo, which may enable accelerated therapeutic discovery. By mimicking the guided structural cues present in the physiological architecture of the TME, aligned microtopography substrates can elucidate potential interventions on migratory phenotypes of MDSCs at the single clonal level. Coupled with cellular and molecular biology analysis tools, our approach employs real-time tracking analysis of cell motility to probe the dissemination characteristics of MDSCs under guided migration conditions. These methods allow us to identify cellular subpopulations of interest based on their disseminative and suppressive capabilities. By doing so, we illustrate the potential of applying microscale engineering tools, in concert with dynamic live cell imaging and bioanalysis methods to uncover novel exploitable motility targets for advancing cancer therapy discovery. The inherent simplicity and extended application to a variety of contexts in tumor-associated cell migration render this method widely accessible to existing biological laboratory conditions and interests.


Asunto(s)
Células Supresoras de Origen Mieloide , Neoplasias , Humanos , Células Supresoras de Origen Mieloide/patología , Biomimética , Neoplasias/patología , Fenotipo , Microambiente Tumoral
16.
J Subst Use Addict Treat ; 161: 209341, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38490334

RESUMEN

BACKGROUND: North America has been in an unrelenting overdose crisis for almost a decade. British Columbia (BC), Canada declared a public health emergency due to overdoses in 2016. Risk Mitigation Guidance (RMG) for prescribing pharmaceutical opioids, stimulants and benzodiazepine alternatives to the toxic drug supply ("safer supply") was implemented in March 2020 in an attempt to reduce harms of COVID-19 and overdose deaths in BC during dual declared public health emergencies. Our objective was to describe early implementation of RMG among prescribers in BC. METHODS: We conducted a convergent mixed methods study drawing population-level linked administrative health data and qualitative interviews with 17 prescribers. The Consolidated Framework for Implementation Research (CFIR) informs our work. The study utilized seven linked databases, capturing the characteristics of prescribers for people with substance use disorder to describe the characteristics of those prescribing under the RMG using univariate summary statistics and logistic regression analysis. For the qualitative analysis, we drew on interpretative descriptive methodology to identify barriers and facilitators to implementation. RESULTS: Analysis of administrative databases demonstrated limited uptake of the intervention outside large urban centres and a highly specific profile of urban prescribers, with larger and more complex caseloads associated with RMG prescribing. Nurse practitioners were three times more likely to prescribe than general practitioners. Qualitatively, the study identified five themes related to the five CFIR domains: 1) RMG is helpful but controversial; 2) Motivations and challenges to prescribing; 3) New options and opportunities for care but not enough to 'win the arms race'; 4) Lack of implementation support and resources; 5) Limited infrastructure. CONCLUSIONS: BC's implementation of RMG was limited in scope, prescriber uptake and geographic scale up. Systemic, organizational and individual barriers and facilitators point to the importance of engaging professional regulatory colleges, implementation planning and organizational infrastructure to ensure effective implementation and adaptation to context.


Asunto(s)
COVID-19 , Humanos , Colombia Británica/epidemiología , COVID-19/epidemiología , Sobredosis de Droga/tratamiento farmacológico , Analgésicos Opioides/envenenamiento , Analgésicos Opioides/efectos adversos , Trastornos Relacionados con Sustancias/epidemiología , Benzodiazepinas/provisión & distribución , Benzodiazepinas/uso terapéutico , Benzodiazepinas/envenenamiento , Investigación Cualitativa , Femenino , Masculino
17.
Br J Cancer ; 130(10): 1670-1678, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38486123

RESUMEN

BACKGROUND: The Colorectal Cancer Subtyping Consortium established four Consensus Molecular Subtypes (CMS) in colorectal cancer: CMS1 (microsatellite-instability [MSI], Immune), CMS2 (Canonical, epithelial), CMS3 (Metabolic), and CMS4 (Mesenchymal). However, only MSI tumour patients have seen a change in their disease management in clinical practice. This study aims to characterise the proteome of colon cancer CMS and broaden CMS's clinical utility. METHODS: One-hundred fifty-eight paraffin samples from stage II-III colon cancer patients treated with adjuvant chemotherapy were analysed through DIA-based mass-spectrometry proteomics. RESULTS: CMS1 exhibited overexpression of immune-related proteins, specifically related to neutrophils, phagocytosis, antimicrobial response, and a glycolytic profile. These findings suggested potential therapeutic strategies involving immunotherapy and glycolytic inhibitors. CMS3 showed overexpression of metabolic proteins. CMS2 displayed a heterogeneous protein profile. Notably, two proteomics subtypes within CMS2, with different protein characteristics and prognoses, were identified. CMS4 emerged as the most distinct group, featuring overexpression of proteins related to angiogenesis, extracellular matrix, focal adhesion, and complement activation. CMS4 showed a high metastatic profile and suggested possible chemoresistance that may explain its worse prognosis. CONCLUSIONS: DIA proteomics revealed new features for each colon cancer CMS subtype. These findings provide valuable insights into potential therapeutic targets for colorectal cancer subtypes in the future.


Asunto(s)
Neoplasias del Colon , Proteómica , Humanos , Proteómica/métodos , Neoplasias del Colon/patología , Neoplasias del Colon/genética , Neoplasias del Colon/metabolismo , Femenino , Masculino , Pronóstico , Anciano , Persona de Mediana Edad , Inestabilidad de Microsatélites , Quimioterapia Adyuvante , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética
18.
Anticancer Res ; 44(3): 1201-1208, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38423672

RESUMEN

BACKGROUND/AIM: Enzyme-mediated grafting of poly (gallic acid) (PGAL) and L-arginine and a-L-lysine onto PGAL produces reactive oxygen species (ROS)-suppressor multiradical molecules with low cytotoxicity, high thermostability and water solubility with cancer treatment potential. This study examined the anticancer effects of these molecules in hepatic (HepG2, ATCC HB-8065), breast (MCF7, ATCC HTB-22), and prostate (PC-3, ATCC CRL-1435 and DU 145, ATCC HTB-81) cancer cell lines, as well as in fibroblasts from healthy human skin as control cells. MATERIALS AND METHODS: PGAL was synthesized by the oxidative polymerization of the naturally abundant GA using laccase from Trametes versicolor. Insertions of amino acids L-arginine and α-L-lysine on the PGAL chain were carried out by microwave. The cells of dermal fibroblast (Fb) were obtained from primary skin cultures and isolated from skin biopsies. The cancer cells lines of hepatic (HepG2), breast (MCF7), and prostate (PC-3, DU 145) were obtained from ATCC. The viability of the cancer cells and the primary culture was obtained by the MTT assay. Proliferation was demonstrated by crystal violet assay. Cell migration was determined by Wound healing assay. Finally, cell cycle analysis was carried out with cells. RESULTS: The results show that 200 µg/ml of PGAL cultured in vitro with prostate cancer cells decreased viability, proliferation, and migration, as well as arrested cells in the G1 and S phases of the cell cycle. In contrast, the dermal fibroblasts and the hepatic line remained unaffected. The random grafting of L-Arg and a-L-Lys onto the PGAL chain also decreased the viability of prostate cancer cells. CONCLUSION: PGAL and PGAL-grafted amino acids are potential adjuvants for prostate cancer treatment, with improved physicochemical characteristics compared to GA.


Asunto(s)
Ácido Gálico , Neoplasias de la Próstata , Salicilatos , Masculino , Humanos , Ácido Gálico/farmacología , Lisina , Trametes , Neoplasias de la Próstata/patología , Células MCF-7 , Arginina/farmacología , Proliferación Celular
19.
Microbiol Spectr ; 12(3): e0338623, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38299860

RESUMEN

Since the 1990s, endemic North American swine influenza A viruses (swFLUAVs) contained an internal gene segment constellation, the triple reassortment internal gene (TRIG) cassette. In 2009, the H1N1 pandemic (pdmH1N1) virus spilled back into swine but did not become endemic. However, the pdmH1N1 contributed the matrix gene (pdmM) to the swFLUAVs circulating in the pig population, which replaced the classical swine matrix gene (swM) found in the TRIG cassette, suggesting the pdmM has a fitness benefit. Others have shown that swFLUAVs containing the pdmM have greater transmission efficiency compared to viruses containing the swM gene segment. We hypothesized that the matrix (M) gene could also affect disease and utilized two infection models, resistant BALB/c and susceptible DBA/2 mice, to assess pathogenicity. We infected BALB/c and DBA/2 mice with H1 and H3 swFLUAVs containing the swM or pdmM and measured lung virus titers, morbidity, mortality, and lung histopathology. H1 influenza strains containing the pdmM gene caused greater morbidity and mortality in resistant and susceptible murine strains, while H3 swFLUAVs caused no clinical disease. However, both H1 and H3 swFLUAVs containing the pdmM replicated to higher viral titers in the lungs and pdmM containing H1 viruses induced greater histological changes compared to swM H1 viruses. While the surface glycoproteins and other gene segments may contribute to swFLUAV pathogenicity in mice, these data suggest that the origin of the matrix gene also contributes to pathogenicity of swFLUAV in mice, although we must be cautious in translating these conclusions to their natural host, swine. IMPORTANCE: The 2009 pandemic H1N1 virus rapidly spilled back into North American swine, reassorting with the already genetically diverse swFLUAVs. Notably, the M gene segment quickly replaced the classical M gene segment, suggesting a fitness benefit. Here, using two murine models of infection, we demonstrate that swFLUAV isolates containing the pandemic H1N1 origin M gene caused increased disease compared to isolates containing the classical swine M gene. These results suggest that, in addition to other influenza virus gene segments, the swFLUAV M gene segment contributes to pathogenesis in mammals.


Asunto(s)
Subtipo H1N1 del Virus de la Influenza A , Gripe Humana , Infecciones por Orthomyxoviridae , Enfermedades de los Porcinos , Porcinos , Ratones , Animales , Humanos , Subtipo H1N1 del Virus de la Influenza A/genética , Modelos Animales de Enfermedad , Ratones Endogámicos DBA , Infecciones por Orthomyxoviridae/patología , Mamíferos
20.
Nat Commun ; 15(1): 1439, 2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38365892

RESUMEN

Metal-metal contacts, though not yet widely realized, may provide exciting opportunities to serve as tunable and functional interfaces in single-molecule devices. One of the simplest components which might facilitate such binding interactions is the ferrocene group. Notably, direct bonds between the ferrocene iron center and metals such as Pd or Co have been demonstrated in molecular complexes comprising coordinating ligands attached to the cyclopentadienyl rings. Here, we demonstrate that ferrocene-based single-molecule devices with Fe-Au interfacial contact geometries form at room temperature in the absence of supporting coordinating ligands. Applying a photoredox reaction, we propose that ferrocene only functions effectively as a contact group when oxidized, binding to gold through a formal Fe3+ center. This observation is further supported by a series of control measurements and density functional theory calculations. Our findings extend the scope of junction contact chemistries beyond those involving main group elements, lay the foundation for light switchable ferrocene-based single-molecule devices, and highlight new potential mechanistic function(s) of unsubstituted ferrocenium groups in synthetic processes.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...