RESUMO
Metal-modulated croconium dyes with multimodal-imaging and synergistic therapy in the tumor microenvironment have exhibited great potential in tumor theranostics. However, their unideal structure optimization always weakened the efficacy of near-infrared fluorescence-photoacoustic (NIRF/PA) imaging and photothermal therapy (PTT). Here, we screened croconium dye containing two indole groups with better NIRF/PA imaging and PTT in their family, linked to two morpholine rings, and obtained CR-736, as a lysosome-targeting and Fe3+-modulated agent. The established CR-736-Fe3+ nanoplatform was accurately delivered to the breast tumor site, released CR-736 and Fe3+ in the lower acidic lysosome microenvironment, and activated pH-responsive NIRF/PA/magnetic resonance imaging and PTT. Furthermore, ferroptosis generated hydroxyl free radicals and lipid peroxide by consuming GSH and H2O2 by dint of the accumulation of Fe3+ in tumor cells, which resulted in the inhibition of the expression of heat shock proteins and the concomitant recovery of PTT. The synergistic therapy of PTT, ferroptosis, and chemodynamics was further optimized to the maximal extent in tumor lysosome acidic microenvironment and proved both in vitro and a mouse tumor model. This study opens a new avenue in designing excellent and unique croconium-based nanoplatforms, synergizing multiple tumor theranostic methods, and further optimizing the theranostic effects in tumor microenvironment.
RESUMO
Two rhenium compounds: cis-tetrachlorotetrabenzimidazoldirhenium(iii) chloride - I and tetrabenzimidazoldioxorhenium(v) - II have been synthesized and characterized. X-ray data are presented for the new complex II. I and II show strong emission that has been used to investigate their interaction with several non-canonical DNA structures. Both compounds have a quenching effect on the fluorescence intensity upon addition of the investigated oligonucleotides; I was more selective for binding G4-than II. Association constant values obtained for I and II with G-quadruplexes reached 106 M-1, which suggests a strong interaction between both complexes and these sequences. FRET-melting assays show that I and II have a rather high level of stabilization of ckit1 and ckit2 quadruplexes. I is toxic against macrophages RAW267.7 only in high concentrations, while complex II shows no toxicity against these cells. I and II accumulate inside cells in different degrees. Molecular dynamic simulation studies have provided insights into the binding modes of II with ckit1 and ckit2 G-quadruplexes. The results obtained show the DNA binding activity of the rhenium complexes and their ability to be players in the anti-cancer fight since they can bind to non-canonical DNA forms in oncogene promoters, accumulate in some cancer cells, and influence the cancer cells microenvironment.
RESUMO
Introducción: El quiste dentígero es un quiste odontogénico, casi siempre asociado a la corona de un diente retenido. Sus ubicaciones más frecuentes son la zona de tercer molar inferior y canino superior. Objetivo: Caracterizar la presentación de un quiste dentígero en un paciente adulto. Presentación de caso: Se presentó el caso de una paciente de 27 años de edad que acude a consulta por presentar sensación de opresión, dolor e inflamación en región de tercer molar inferior izquierdo. Al examen oral se observa tejido dentario en correspondencia con molar 38 parcialmente brotado con ligero edema de la mucosa a su alrededor. En radiografía panorámica se observa imagen radiolúcida en relación con cara mesial del 38 con discreto halo radiopaco, redondeada, compatible con un quiste dentígero. Conclusiones: Un diagnóstico a tiempo de estas lesiones constituye la clave para un tratamiento exitoso y menos invasivo, lo cual evitaría complicaciones mayores como la malignización, el crecimiento exagerado que puede ocasionar deformidad facial y la disfunción masticatoria permanente(AU)
Introduction: Dentigerous cyst is an odontogenic cyst, almost always associated with the crown of a retained tooth. Its most frequent locations are the areas of the lower third molar and the upper canine. Objective: To characterize the presentation of a dentigerous cyst in an adult patient. Case presentation: The case is presented of a 27-year-old female patient who came to the clinic with a sensation of pressure, pain and inflammation in the region of the lower left third molar. Oral examination permits to observe some dental tissue corresponding with molar 38 partially erupted with slight edema of the surrounding mucosa. Panoramic radiograph shows a radiolucent image related to the mesial side of 38, with a discrete radiopaque halo, rounded, compatible with a dentigerous cyst. Conclusions: A timely diagnosis of these lesions is the key to a successful and less invasive treatment, which would avoid major complications, such as malignization, the exaggerated growth that can cause facial deformity and permanent masticatory dysfunction(AU)
Assuntos
Humanos , Feminino , Adulto , Radiografia Panorâmica/métodos , Cisto Dentígero/diagnósticoRESUMO
The study presents 'G4-QuadScreen', a user-friendly computational tool for identifying MTDLs against G4s. Also, it offers a few hit MTDLs based on in silico and in vitro approaches. Multi-tasking QSAR models were developed using linear discriminant analysis and random forest machine learning techniques for predicting the responses of interest (G4 interaction, G4 stabilization, G4 selectivity, and cytotoxicity) considering the variations in the experimental conditions (e.g., G4 sequences, endpoints, cell lines, buffers, and assays). A virtual screening with G4-QuadScreen and molecular docking using YASARA (AutoDock-Vina) was performed. G4 activities were confirmed via FRET melting, FID, and cell viability assays. Validation metrics demonstrated the high discriminatory power and robustness of the models (the accuracy of all models is ~>90% for the training sets and ~>80% for the external sets). The experimental evaluations showed that ten screened MTDLs have the capacity to selectively stabilize multiple G4s. Three screened MTDLs induced a strong inhibitory effect on various human cancer cell lines. This pioneering computational study serves a tool to accelerate the search for new leads against G4s, reducing false positive outcomes in the early stages of drug discovery. The G4-QuadScreen tool is accessible on the ChemoPredictionSuite website.
RESUMO
Metallo-phthalocyanines (MPc) are common photosensitizers with ideal photophysical and photochemical properties. Also, these molecules have shown to interact with non-canonical nucleic acid structures, such as G-quadruplexes, and modulate oncogenic expression in cancer cells. Herein, we report the synthesis and characterisation of two metallo-phthalocyanines containing either zinc (ZnPc) or nickel (NiPc) in the central aromatic core and four alkyl ammonium lateral chains. The interaction of both molecules with G-quadruplex DNA was assessed by UV-Vis, fluorescence and FRET melting experiments. Both molecules bind strongly to G-quadruplexes and stabilise these structures, being NiPc the most notable G-quadruplex stabiliser. In addition, the photosensitizing ability of both metal complexes was explored by the evaluation of the singlet oxygen generation and their photoactivation in cells. Only ZnPc showed a high singlet oxygen generation either by direct observation or by indirect evaluation using a DPBF dye. The cellular evaluation showed mainly cytoplasmic localization of ZnPc and a decrease of the IC50 values of the cell viability of ZnPc upon light activation of two orders of magnitude. Two metallo-phthalocyanines containing zinc and nickel within the aromatic core have been investigated as G-quadruplex stabilizers and photosensitizers. NiPc shows a high G4 binding but negligible photosensitizing ability while ZnPc exhibits a moderate binding to G-quadruplex together with a high potency to generate singlet oxygen and photocytotoxicity. The interaction with G4s and capacity to be photosensitized is associated with the geometry adopted by the central metal core of the phthalocyanine scaffold.
Assuntos
Antineoplásicos , Quadruplex G , Compostos Organometálicos , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Oxigênio Singlete/química , Níquel , Antineoplásicos/química , Compostos Organometálicos/química , Zinco/química , Compostos de ZincoRESUMO
An exact equation to relate the optical path differences (OPD) with its transversal aberration components (TAC) is determined. The OPD-TAC equation reproduces the Rayces formula and introduces the coefficient for the longitudinal aberration. The defocus orthonormal Zernike polynomial (Z DF) is not a solution for the OPD-TAC equation since the obtained longitudinal defocus depends on the ray height on the exit pupil, meaning that it cannot be interpreted as a defocus. In order to find an exact expression for OPD defocus, first, a general relationship between the wavefront shape and its OPD is established. Second, an exact formula for the defocus OPD is established. Finally, it is proved that only the exact defocus OPD is an exact solution of the exact OPD-TAC equation.
RESUMO
Metal complexes have gained a huge interest in the biomedical research in the last decade because of the access to unexplored chemical space with regards to organic molecules and to present additional functionalities to act simultaneously as diagnostic and therapeutic agents. Herein, we evaluated the interaction of two polytopic polyaza ligands and their zinc complexes with DNA and RNA by UV thermal denaturation, fluorescence and circular dichroism spectroscopic assays. The zinc coordination was investigated by X-ray diffraction and afforded the structure of the binuclear zinc complex of PYPOD. Thermal denaturation of DNA and RNA and fluorimetry analysis revealed preferential binding of the zinc-PHENPOD complexes towards GC-containing DNA in contrast to the free ligands. On the other hand, PYPOD metal complexes, compared to the free ligand, stabilized AT-based DNA (B-form) better than AU-RNA (A-form). With regards to single stranded RNA, the binuclear complex of PHENPOD and the free ligand can efficiently identify polyadenylic acid (poly A) among other RNA sequences by circular dichroism spectroscopy. The antimicrobial activity in S. aureus and E. coli bacteria showed the highest activity for the free ligands and their trinuclear zinc complexes. This work can provide valuable insights into the impact of the nuclearity of polytopic polyaza ligands in the binding to DNA/RNA and the antimicrobial effect.
Assuntos
Anti-Infecciosos , Complexos de Coordenação , DNA de Cadeia Simples , RNA/química , Complexos de Coordenação/química , Zinco/química , Ligantes , Escherichia coli , Staphylococcus aureus , DNA/química , Anti-Infecciosos/químicaRESUMO
Through the methodology of optical surface design based on concentric rings, this paper proposes the design of freeform mirrors, initially by employing segmented rings, each of them with different spherical radii of curvature, and then by employing segmented conic rings with different conic constants in each of the segments. These surfaces will then produce the desired images. For the case of segmented spherical rings, mathematical expressions were deduced to obtain the image points as a function of the radii of curvature. Furthermore, it is shown that in the case where conic rings were used, there is a decrease in spherical aberration, which allows the manipulation of the generated image. Finally, several proposals are presented for the design of mirrors to generate both the desired size of the image and the desired distribution of energy, together with their analyses.
RESUMO
Two fluorescent and non-toxic spirobifluorene molecules bearing either positive (Spiro-NMe3) or negative (Spiro-SO3) charged moieties attached to the same aromatic structure have been investigated as binders for DNA. The novel Spiro-NMe3 containing four alkylammonium substituents interacts with G-quadruplex (G4) DNA structures and shows preference for G4s over duplex by means of FRET melting and fluorescence experiments. The interaction is governed by the charged substituents of the ligands as deduced from the lower binding of the sulfonate analogue (Spiro-SO3). On the contrary, Spiro-SO3 exhibits higher binding affinity to duplex DNA structure than to G4. Both molecules show a moderate quenching of the fluorescence upon DNA binding. The confocal microscopy evaluation shows the internalization of both molecules in HeLa cells and their lysosomal accumulation.
Assuntos
Quadruplex G , Humanos , Células HeLa , DNA/química , Corantes , LigantesRESUMO
Two new ligands (TPB3P and TPB3Py) showing a strong stabilisation effect and good selectivity for G4 over duplex DNAs have been synthesised. The ligands hold three analogous polyamine pendant arms (TPA3P and TPA3Py) but differ in the central aromatic core, which is a triphenylbenzene moiety instead of a triphenylamine moiety. Both TPB3P and TPB3Py exhibit high cytotoxicity in MCF-7, LN229 and HeLa cancer cells in contrast to TPA-based ligands, which exhibit no significant cytotoxicity. Moreover, the most potent G4 binders have been encapsulated in liposomes and AS1411 aptamer-targeted liposomes reaching nanomolar IC50 values for the most cytotoxic systems.
Assuntos
Antineoplásicos , Quadruplex G , Neoplasias , Humanos , Lipossomos , Antineoplásicos/farmacologia , Células HeLa , DNA , LigantesRESUMO
Introducción: Con el advenimiento de la pandemia por la enfermedad de la COVID-19 ha sido necesario reorganizar los servicios de salud y modificar en cierta medida la indicación quirúrgica en la colecistitis aguda. Objetivo: Caracterizar la colecistostomía como una alternativa segura y eficaz para la resolución de la colecistitis aguda litiásica en pacientes en los que no está indicada la cirugía, portador o no de la COVID-19. Métodos: Se realizó una revisión descriptiva narrativa desde el 2019 hasta el 2021 de las fuentes primarias y secundarias que abordan este tema; fue este período de tiempo en el que se desarrolló la pandemia provocada por SARS-Cov 2. Se usaron el Google Chrome y las bases de datos electrónicas MEDLINE/PubMed, INDEXMEDICUS y fuentes de información en revistas basadas en evidencias como ACP Journal Best Evidence y Cochrane. Desarrollo: El impacto de la crisis sanitaria sobre los servicios quirúrgicos se traduce en la cancelación de las colecistectomías electivas en el 97,6 por ciento de los centros. Esta decisión no es inocua, puesto que se ha estimado un riesgo anual de desarrollar complicaciones del 1-3 por ciento en la colelitiasis sintomática. Conclusiones: La colecistostomía es el método más acertado a utilizar para la resolución de la colecistitis aguda litiásica en pacientes en los que no está indicada la cirugía, con mala respuesta al tratamiento médico y sin tener la completa seguridad de que el paciente es o no portador de la COVID-19(AU)
Introduction: With the arrival of the COVID-19 pandemic, to reorganize health services has been necessary, as well as to modify, to a certain extent, the surgical indication for acute cholecystitis. Objective: To characterize cholecystostomy as a safe and effective alternative for the resolution of acute lithiasic cholecystitis in patients with no surgical indication, whether or not they have COVID-19. Methods: A narrative-descriptive review was carried out from 2019 to 2021 of primary and secondary sources addressing this topic; this time period marked the development of the pandemic caused by SARS-CoV-2. Google Chrome was used, together with the electronic databases MEDLINE/PubMed and INDEXMEDICUS, as well as sources of information in evidence-based journals, such as ACP Journal Best Evidence and Cochrane. Development: The impact of the health crisis over surgical services is translated into the cancellation of elective cholecystectomies in 97.6 percent of the centers. This decision is not innocuous, since an annual risk of developing complications has been estimated at 1-3 percent for symptomatic cholelithiasis. Conclusions: Cholecystostomy is the most successful method to be used for the resolution of acute lithiasic cholecystitis in patients with no surgical indication or poor response to medical treatment, without complete certainty as to whether or not the patient has COVID-19(AU)
Assuntos
Humanos , Colecistectomia/métodos , Colecistite Aguda/etiologia , COVID-19/epidemiologia , Epidemiologia DescritivaRESUMO
Introducción: El ser humano siempre ha tratado de solucionar los defectos óseos en los maxilares, tanto para corregir defectos postraumáticos como para aportar tejido en lechos donde se colocarán implantes dentales. Objetivos: Demostrar las ventajas del uso del injerto de hueso autólogo de tibia en la reconstrucción de defectos postraumáticos de los maxilares. Presentación del caso: Paciente masculino de 21 años de edad, con trauma en el tercio medio facial debido a un golpe de alto impacto. Las fracturas produjeron deformidad traumática residual en el hemimaxilar derecho. El daño del contorno facial afectó la estética y la función masticatoria del paciente. Se intervino quirúrgicamente para colocar injerto autólogo de tibia en el área afectada. Conclusiones: Los injertos óseos autólogos constituyen una alternativa importante para el tratamiento rehabilitador en pacientes con deformidad traumática residual. Esta cirugía asegura la aceptación del injerto y una baja morbilidad en los pacientes.
Introduction: The human being has always tried to solve bone defects in the jaws, both to correct post-traumatic defects and to provide tissue in beds where dental implants will be placed. Objectives: To demonstrate the advantages of the use of autologous bone graft from the tibia in the reconstruction of post-traumatic defects of the maxillae. Case report: This was a 21-year-old male patient with trauma to the middle third of the face due to a high-impact blow. The fractures produced residual traumatic deformity in the right hemimaxilla. The damage to the facial contour affected the patient's aesthetics and masticatory function. Surgery was performed to place an autologous tibial graft in the affected area. Conclusions: Autologous bone grafts are an important alternative for rehabilitation treatment in patients with residual traumatic deformity. This surgery ensures graft acceptance and low patient morbidity.
RESUMO
RESUMEN Fundamento el traumatismo torácico es un cuadro clínico complejo que puede comprometer la vida del paciente. Por ello es de interés su estudio y análisis. Objetivo caracterizar los pacientes con traumatismo torácico en el servicio de Cirugía General. Métodos estudio descriptivo, prospectivo, de serie de casos, que incluyó a pacientes que ingresaron con el diagnóstico de traumatismo torácico, en el servicio de Cirugía General del Hospital General Universitario Dr. Gustavo Aldereguía Lima, de Cienfuegos, en el período enero/2019 a diciembre/2020. Las variables analizadas fueron: edad, sexo, comorbilidades, exámenes imagenológicos, agente causal, lesión torácica, tipo de tratamiento, tipo de traumatismo torácico y estado al egreso. Resultados el trauma de tórax fue más frecuente en el sexo masculino, a partir de la cuarta década de vida en pacientes sanos. El examen imagenológico más usado fue la radiografía simple de tórax; y el agente causal predominante, la herida por arma blanca. Las lesiones torácicas más frecuentes resultaron el enfisema subcutáneo y el hemoneumotorax, así como la pleurostomía fue el tipo de tratamiento más usado. Predominó el traumatismo torácico aislado, siendo las lesiones abdominales las más asociadas. La mayoría de los pacientes egresaron vivos. Conclusión el trauma torácico constituye una patología altamente desafiante, por lo complejas que pueden llegar a ser las lesiones derivadas de él; se presenta con mayor frecuencia en hombres sanos. Cuando se asocia a otras lesiones aumenta la mortalidad.
Background chest trauma is a complex clinical picture that can compromise the patient's life. Therefore, its study and analysis is of interest. Objective to characterize patients with chest trauma in the General Surgery service. Methods descriptive, prospective, case series study which included patients admitted with a diagnosis of chest trauma, in the General Surgery Service at the Dr. Gustavo Aldereguía Lima General University Hospital, Cienfuegos, from January 2019 to December2020. The analyzed variables were: age, sex, comorbidities, imaging tests, causal agent, chest injury, type of treatment, type of chest trauma, and discharge status. Results chest trauma was more frequent in males, from the fourth decade of life in healthy patients. The most used imaging test was the simple chest X-ray; and the predominant causal agent, the stab wound. The most frequent chest injuries were subcutaneous emphysema and hemopneumothorax, and pleurostomy was the most used type of treatment. Isolated chest trauma prevailed, with abdominal injuries being the most associated. Most of the patients were discharged alive. Conclusion thoracic trauma constitutes a highly challenging pathology, due to how complex the injuries derived from it can become; It occurs more frequently in healthy men. When associated with other injuries, mortality increases.
RESUMO
In a previous paper [Appl. Opt. 61, C20 (2022)] it was proven that for a circular exit pupil and any optical path differences, the border of any spot diagram is integrated by the caustic surface and/or marginal rays. In this paper, the previous results are extended to annular (circular an elliptical) as well as hexagonal (single and segmented) exit pupils. Several examples of wavefronts affected by linear combinations of orthonormal Zernike aberrations are shown.
RESUMO
In this paper, it is proven that for any optical system with a circular exit pupil and wavefronts affected by any aberrations, the borders of all leaving rays are caustic surfaces and/or marginal rays. Several examples are shown for wavefronts affected by linear combinations of Zernike aberrations.
RESUMO
Chagas disease (CD) is a tropical and potentially fatal infection caused by Trypanosoma cruzi. Although CD was limited to Latin America as a silent disease, CD has become widespread as a result of globalization. Currently, 6-8 million people are infected worldwide, and no effective treatment is available. Here, we identify new effective agents against T. cruzi. In short, 16 aryl polyamines were screened in vitro against different T. cruzi strains, and lead compounds were evaluated in vivo after oral administration in both the acute and chronic infections. The mode of action was also evaluated at the energetic level, and its high activity profile could be ascribed to a mitochondria-dependent bioenergetic collapse and redox stress by inhibition of the Fe-SOD enzyme. We present compound 15 as a potential compound that provides a step forward for the development of new agents to combat CD.
RESUMO
Antimicrobial photodynamic therapy has emerged as a powerful approach to tackle microbial infections. Photodynamic therapy utilises a photosensitiser, light, and oxygen to generate singlet oxygen and/or reactive oxygen species in an irradiated tissue spot, which subsequently react with nearby biomolecules and destroy the cellular environment. Due to the possibility to irradiate in a very precise location, it can be used to eradicate bacteria, fungus, and parasites upon light activation of the photosensitiser. In this regard, natural products are low-cost molecules capable of being obtained in large quantities, and some of them can be used as photosensitisers. Alkaloids are the largest family among natural products and include molecules with a basic nature and aromatic rings. For this study, we collected the naturally occurring alkaloids used to treat microorganism infections using a photodynamic inactivation approach. We gathered their main photophysical properties (excitation/emission wavelengths, quantum yields, and oxygen quantum yield) which characterise the ability to efficiently photosensitise. In addition, we described the antibacterial activity of alkaloids upon irradiation and the mechanisms involved in the microorganism killing. This review will serve as a reference source to obtain the main information on alkaloids used in antimicrobial photodynamic therapy.
RESUMO
RESUMEN El íleo biliar es una causa poco frecuente de obstrucción intestinal mecánica. Generalmente se ve en pacientes adultos mayores del sexo femenino con antecedentes de ser portadores de litiasis vesicular, representando solamente del 1 al 6% de las obstrucciones intestinales diagnosticadas. Se presenta el caso de una paciente femenina de 66 años de edad con antecedentes de presentar cólicos a repetición por litiasis vesicular, la cual acude al cuerpo de guardia de nuestro centro por dolor abdominal vómitos y distención abdominal. Se comprobó en el acto quirúrgico la presencia de un íleo biliar. Se concluye que entre las causas infrecuentes de oclusión intestinal mecánica podemos citar el íleo biliar, lo cual lo corrobora el hecho de que en el servicio de cirugía de nuestro centro solo tenemos dos casos anteriores reportados.
ABSTRACT Gallstone ileus is a rare cause of mechanical bowel obstruction. It is generally seen in older female patients with a history of being carriers of gallstones, representing only 1 to 6% of diagnosed intestinal obstructions. A case of a 66-years-old female patient with a history of recurrent colic due to gallstones, who came to the guardhouse of the hospital for abdominal pain, vomiting and abdominal distention, it is presented. The presence of a gallstone ileus was verified in the surgical act. It is concluded that among the infrequent causes of mechanical intestinal occlusion can be mentioned gallstone ileus, which is corroborated by the fact that in the surgery service of the hospital only have two previous reported cases.
RESUMO
Nanoparticles for medical use should be non-cytotoxic and free of bacterial contamination. Upconversion nanoparticles (UCNPs) coated with cucurbit[7]uril (CB[7]) made by combining UCNPs free of oleic acid, here termed bare UCNPs (UCn), and CB[7], i.e., UC@CB[7] nanohybrids, could be used as photoactive inorganic-organic hybrid scaffolds for biological applications. UCNPs, in general, are not considered to be highly toxic materials, but the release of fluorides and lanthanides upon their dissolution may cause cytotoxicity. To identify potential adverse effects of the nanoparticles, dehydrogenase activity of endothelial cells, exposed to various concentrations of the UCNPs, was determined. Data were verified by measuring lactate dehydrogenase release as the indicator of loss of plasma membrane integrity, which indicates necrotic cell death. This assay, in combination with calcein AM/Ethidium homodimer-1 staining, identified induction of apoptosis as main mode of cell death for both particles. The data showed that the UCNPs are not cytotoxic to endothelial cells, and the samples did not contain endotoxin contamination. Higher cytotoxicity, however, was seen in HeLa and RAW 264.7 cells. This may be explained by differences in lysosome content and particle uptake rate. Internalization of UCn and UC@CB[7] nanohybrids by cells was demonstrated by NIR laser scanning microscopy.