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1.
Indian J Surg Oncol ; 15(1): 168-171, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38511017

RESUMEN

Testicular mixed germ cell tumors (TMGCTs) are rare malignant tumors comprising of two or more types of germ cell tumors. Their onset may be undetectable and the patient may first present with symptoms of metastasis. We hereby report a case of a young male who presented with respiratory discomfort and had no symptoms of primary testicular tumor. CT-guided FNAC lung revealed mainly necrotic, keratinous debris with a focus of chondromyxoid stroma. Differential diagnoses of components of teratoma, squamous cell carcinoma and inclusion cyst was considered. FNAC was reported out for the possible presence of teratoma components. Retrospectively, physical examination and subsequent USG revealed testicular tumor. The case led to a diagnostic dilemma as the patient presented with no prior history suggestive of metastasis from testicular mixed germ cell tumor. The aim of the current case report is to alert the pathologists and clinicians about this uncommon clinical presentation and diagnostic relevance of FNA. It highlights that FNA lung revealing keratinous material should always be searched for the possibility of teratoma component.

2.
Indian J Surg Oncol ; 15(1): 145-148, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38511037

RESUMEN

Peritoneal malignant mesothelioma is an uncommon neoplasm with a poor prognosis. We hereby report a case of a 20-year-old male, first diagnosed on biopsy with axillary lymph node metastasis. He presented with abdominal pain and axillary lymphadenopathy, with no history of asbestos exposure. CECT showed peritoneal thickening and ascites. Ascitic fluid cytology showed reactive morphology. The diagnosis of metastatic deposits of malignant mesothelioma was made on histopathology and confirmed by immunohistochemistry. Tumor cells were immune-reactive for CK 5/6, calretinin, D2-40, and WT1 and negative for TTF1, CK 20, and CD 3. This case report has two important highlights-(i) unusual presentation with axillary lymph node metastasis leading to diagnostic dilemma in a young male with no asbestos exposure history and (ii) confirmatory diagnostic role of IHC in Peritoneal malignant mesothelioma.

3.
Chem Res Toxicol ; 36(12): 1834-1863, 2023 12 18.
Artículo en Inglés | MEDLINE | ID: mdl-38059476

RESUMEN

Edibles are the only source of nutrients and energy for humans. However, ingredients of edibles have undergone many physicochemical changes during preparation and storage. Aging, hydrolysis, oxidation, and rancidity are some of the major changes that not only change the native flavor, texture, and taste of food but also destroy the nutritive value and jeopardize public health. The major reasons for the production of harmful metabolites, chemicals, and toxins are poor processing, inappropriate storage, and microbial spoilage, which are lethal to consumers. In addition, the emergence of new pollutants has intensified the need for advanced and rapid food analysis techniques to detect such toxins. The issue with the detection of toxins in food samples is the nonvolatile nature and absence of detectable chromophores; hence, normal conventional techniques need additional derivatization. Mass spectrometry (MS) offers high sensitivity, selectivity, and capability to handle complex mixtures, making it an ideal analytical technique for the identification and quantification of food toxins. Recent technological advancements, such as high-resolution MS and tandem mass spectrometry (MS/MS), have significantly improved sensitivity, enabling the detection of food toxins at ultralow levels. Moreover, the emergence of ambient ionization techniques has facilitated rapid in situ analysis of samples with lower time and resources. Despite numerous advantages, the widespread adoption of MS in routine food safety monitoring faces certain challenges such as instrument cost, complexity, data analysis, and standardization of methods. Nevertheless, the continuous advancements in MS-technology and its integration with complementary techniques hold promising prospects for revolutionizing food safety monitoring. This review discusses the application of MS in detecting various food toxins including mycotoxins, marine biotoxins, and plant-derived toxins. It also explores the implementation of untargeted approaches, such as metabolomics and proteomics, for the discovery of novel and emerging food toxins, enhancing our understanding of potential hazards in the food supply chain.


Asunto(s)
Micotoxinas , Espectrometría de Masas en Tándem , Humanos , Espectrometría de Masas en Tándem/métodos , Toxinas Marinas , Análisis de los Alimentos , Estándares de Referencia
4.
J Phys Chem C Nanomater Interfaces ; 127(44): 21768-21776, 2023 Nov 09.
Artículo en Inglés | MEDLINE | ID: mdl-37969924

RESUMEN

The conjugation of ionic gold with bacterial antibodies makes it possible to induce a specific interaction between targeted bacteria and the surface of a GaAs/AlGaAs biochip. The process of immobilization is based on a galvanic displacement reaction (GDR) involving electron transfer between GaAs and Au3+ ions that leads to the formation of a Au-Ga alloy anchoring bacteria to the biochip surface. The GDR-based immobilization of Escherichia coli on biochips comprising a stack of GaAs/AlGaAs nanolayers (dGaAs = 12 nm, dAlGaAs = 10 nm) was confirmed by X-ray photoelectron spectroscopy and atomic force microscopy-based infrared experiments. We report the successful application of this approach for highly sensitive detection of E. coli with a digital photocorrosion (DIP) biosensor. The photoluminescence (PL) monitored DIP of GaAs/AlGaAs nanolayers results in the formation of a PL intensity maximum whose temporal appearance depends on the electric charge transfer between bacteria and the biochip. The formation of a robust bacteria-biochip interface achieved with the GDR process allowed us to observe the role of bacteria on the temporal position of a PL intensity maximum related to the etching of two pairs of GaAs/AlGaAs nanolayers extending up to 24 nm below the biochip surface. We demonstrate the attractive detection of E. coli at 250 CFU/mL, and we discuss the potential of this approach for designing a family of biosensors addressing the quasi-continuous monitoring of a water environment for the presence of pathogenic bacteria.

5.
Cureus ; 15(6): e41183, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37525774

RESUMEN

Insulin autoimmune syndrome is a rare cause of recurrent hypoglycemic episodes that can mimic various other pathological problems leading to unnecessary diagnostic assessments and interventions. Here, we report a case of a healthy non-diabetic male in his 50s presenting with recurrent episodes of hypoglycemia with no prior exposure to exogenous insulin. During a 72-hour fasting test, his glucose levels reached 22 mg/dl within less than three hours. The lab tests showed insulin of 1000 µIU/mL and C-peptide of 4.99 ng/ml. On further evaluation, high titers of insulin autoantibodies (IAA) >100 U/ml (normal = <10 U/ml) were consistent with insulin autoimmune syndrome diagnosis. This case thus highlights the importance of including IAA titers in first-line investigations for hypoglycemia in a non-diabetic patient with strikingly high blood insulin levels.

6.
Anal Chim Acta ; 1270: 341444, 2023 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-37311616

RESUMEN

Nitric oxide (NO) is a ubiquitous, gaseous, free radical signaling molecule which plays a key role in physiological and pathological processes. Literature reports revealed that the conventional methods such as colorimetry, electron paramagnetic resonance (EPR), electrochemical etc. to detect NO are costly, time consuming and lack resolution, particularly in aqueous or biological system. Thus, in this context, herein we have developed covalently linked biomass derived carbon quantum dots (CQDs) and naphthalimide based nano sensor system for FRET based ratiometric detection of nitric oxide (NO) in pure aqueous media. The CQDs derived from orange peels were characterized using UV-visible absorption, fluorescence spectroscopy, PXRD, TEM, FT-IR and zeta potential studies. Further, the obtained CQDs were functionalized with amine functionality, and subsequently linked with naphthalimide derivative (5) using terephthaldehyde through covalent bond formation. The conjugation of naphthalimide (5) and functionalized CQDs was studied using DLS, zeta potential, FT-IR and time resolved fluorescence spectroscopy. The excitation of developed nano sensor system at λex 360 nm results in fluorescence emission at λem 530 nm which establishes the FRET pair between the CQDs and naphthalimide unit. However, in the presence of NO, the observed FRET pair abolishes due to the cleavage of NO susceptible imine bond. The developed sensor demonstrates high selectivity towards NO with limit of detection (LOD) and limit of quantification (LOQ) of 15 nM and 50 nM respectively. Further, the developed sensor system was also utilized for indirect detection of nitrite (NO2-) in food samples for food safety and monitoring.


Asunto(s)
Puntos Cuánticos , Óxido Nítrico , Nitritos , Naftalimidas , Biomasa , Transferencia Resonante de Energía de Fluorescencia , Espectroscopía Infrarroja por Transformada de Fourier , Carbono , Colorantes , Carne
7.
Cureus ; 15(4): e38146, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37252459

RESUMEN

The focus of this review is to examine therapeutic interventions which may be used to increase bone mineral density (BMD), reduce bone loss, and ultimately reduce complications in obese patients prior to total joint replacement (TJR). It is recommended that obese patients lose weight prior to surgery to reduce post-surgical complications, but weight loss can also increase bone loss and fracture risk in older individuals. In this review, we investigate potential therapies to improve bone density and reduce bone loss including exercise therapy, parathyroid hormone (PTH), estrogen, bisphosphonate, and calcitonin treatment in obese patients prior to TJR. Our review of existing literature found that treatment with PTH increased total body BMD in both men and women with osteoporosis; exercise therapy in combination with weight loss prevents the weight loss-induced increase in bone turnover and attenuates the weight loss-induced decrease in BMD; and estrogen, bisphosphonate, and calcitonin reduce bone resorption.

8.
Anal Methods ; 15(14): 1826-1835, 2023 04 06.
Artículo en Inglés | MEDLINE | ID: mdl-36971227

RESUMEN

Ochratoxin A (OTA), a mycotoxin formed by various fungi, such as Aspergillus and Penicillium species, is dangerous to human health. Thus, to circumvent the risk of OTA ingestion, the recognition and quantification of OTA levels are of great significance. A perusal of the literature has revealed that the integration of DNA/Carbon Quantum Dot (CQD)-based hybrid systems may exhibit the unique electronic and optical properties of nanomaterials/nanoarchitecture and consequent recognition properties. Herein, we developed the CQDs@DNA-based hybrid nanoarchitecture system for the selective detection of OTA, which exhibits modulation in the emission spectrum after interaction with OTA, with a significant binding constant (Ka = 3.5 × 105 M-1), a limit of detection of 14 nM, limit of quantification of 47 nM and working range of 1-10 µM. The mechanism for sensing the OTA has been corroborated using fluorescence, UV-visible absorption spectroscopy, and FTIR techniques, demonstrating the binding mode of CQD@DNA hybrid nano-architecture assembly with OTA. Further, we demonstrated the sensing ability of developed CQDs@DNA-based nanoarchitecture assembly towards the quantification of OTA in real food monitoring analysis for real-time applications, which makes this developed nanoarchitecture assembly the potential candidate to conveniently monitor food safety and quality for human health.


Asunto(s)
Micotoxinas , Ocratoxinas , Humanos , Colorantes/análisis , ADN/química , Inocuidad de los Alimentos , Micotoxinas/análisis , Ocratoxinas/análisis , Carbono , Puntos Cuánticos
9.
ACS Omega ; 7(37): 33349-33357, 2022 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-36157789

RESUMEN

This work reports on the potential of polymer brushes (PBs) grown on GaAs substrates (PB-GaAs) as a promising platform for the detection of Legionella pneumophila (Lp). Three functionalization approaches of the GaAs surface were used, and their compatibility with antibodies against Lp was evaluated using Fourier transform infrared spectroscopy and fluorescence microscopy. The incorporation of PBs on GaAs has allowed a significant improvement of the antibody immobilization by increased surface coverage. Bacterial capture experiments demonstrated the promising potential for enhanced immobilization of Lp in comparison with the conventional alkanethiol self-assembled monolayer-based biosensing architectures. Consistent with an eightfold improved capture of bacteria on the surface of a PB-functionalized GaAs/AlGaAs digital photocorrosion biosensor, we report the attractive detection of Lp at 500 CFU/mL.

10.
Science ; 374(6572): 1252-1258, 2021 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-34855483

RESUMEN

How cells with DNA replication defects acquire mutations that allow them to escape apoptosis under environmental stress is a long-standing question. Here, we report that an error-prone Okazaki fragment maturation (OFM) pathway is activated at restrictive temperatures in rad27Δ yeast cells. Restrictive temperature stress activated Dun1, facilitating transformation of unprocessed 5' flaps into 3' flaps, which were removed by 3' nucleases, including DNA polymerase δ (Polδ). However, at certain regions, 3' flaps formed secondary structures that facilitated 3' end extension rather than degradation, producing alternative duplications with short spacer sequences, such as pol3 internal tandem duplications. Consequently, little 5' flap was formed, suppressing rad27Δ-induced lethality at restrictive temperatures. We define a stress-induced, error-prone OFM pathway that generates mutations that counteract replication defects and drive cellular evolution and survival.


Asunto(s)
Supervivencia Celular , Replicación del ADN , ADN de Hongos/genética , ADN , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/fisiología , Estrés Fisiológico , Proteínas de Ciclo Celular/metabolismo , ADN Polimerasa III/genética , ADN Polimerasa III/metabolismo , ADN de Hongos/química , ADN de Hongos/metabolismo , Endonucleasas de ADN Solapado/genética , Conformación de Ácido Nucleico , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Transducción de Señal , Temperatura
11.
J Indian Soc Pedod Prev Dent ; 39(1): 61-66, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33885389

RESUMEN

BACKGROUND: Lead accumulations have been found in teeth and related to behavior deficits in children, but there is a dearth of studies in exploring the role of zinc and manganese dysregulations in autism spectrum disorders (ASD) using the primary tooth as biomarker. AIMS: The objectives of the study were to evaluate and compare the concentrations of zinc and manganese in the primary teeth serving as biomarker, in typically developing children and children with ASD. SETTINGS AND DESIGN: Twelve primary incisors indicated for extraction were collected from children between the age group 6 and 9 years, for the study. Six primary incisors were obtained from children who had been diagnosed with ASD (study group). The other six teeth were obtained from typically developing children, in the similar age group. METHODS: The primary incisors obtained were analyzed for metal concentrations using the technique Inductively Coupled Plasma Optical Emission Spectrometry. STATISTICAL ANALYSIS: This study was statistically analyzed by student's t-test. RESULTS: It was observed that there are significant differences in metal concentrations found between tooth samples of ASD children and typically developing children. Zinc concentrations were double and manganese concentrations were three times, in teeth of ASD children group as compared to the children in the control group. CONCLUSIONS: Results of the current study indicate that there are considerable differences in concentrations of zinc and manganese between the two groups and support the contention that there might be an association between metal exposures of a pregnant mother and child during early years of childhood and incidence of ASD.


Asunto(s)
Trastorno del Espectro Autista , Niño , Femenino , Humanos , Embarazo , Trastorno del Espectro Autista/diagnóstico , Biomarcadores , Manganeso , Diente Primario
12.
J Control Release ; 333: 188-245, 2021 05 10.
Artículo en Inglés | MEDLINE | ID: mdl-33766690

RESUMEN

Cancer being one of the most precarious and second most fatal diseases evokes opportunities for multimodal delivery platforms which will act synergistically for efficient cancer treatment. Multifunctional iron oxide magnetic nanoparticles (IONPs) are being studied for few decades and still attracting increasing attention for several biomedical applications owing to their multifunctional design and intrinsic magnetic properties that provide a multimodal theranostic platform for cancer therapy, monitoring and diagnosis. The review article aims to provide brief information on various surface chemistries involved in modulating IONPs properties to exhibit potential therapy in cancer treatment. The review addresses structural, magnetic, thermal and optical properties of IONPs which aids in the fabrication of efficient multimodal nanoplatform in cancer therapy. The review discussed the pharmacokinetics of IONPs and attributes influencing them. This review inculcates recent advancements in therapies, focused on tumor-microenvironment-responsive and targeted therapy along with their eminent role in cancer diagnosis. The concept of stimuli-responsive including endogenous, exogenous and dual/multi stimuli-based delivery platform demonstrated significantly enhanced anticancer therapy. Several therapeutic approaches viz. chemotherapy, radiotherapy, immunotherapy, hyperthermia, gene therapy, sonodynamic therapy, photothermal, photodynamic-based therapy along with biosensing and several toxicity aspects of IONPs have been addressed in this review for effective cancer treatment.


Asunto(s)
Hipertermia Inducida , Neoplasias , Terapia Combinada , Compuestos Férricos , Humanos , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Fototerapia , Nanomedicina Teranóstica , Microambiente Tumoral
13.
Front Genome Ed ; 3: 799722, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35098210

RESUMEN

The replication-defective, non-pathogenic, nearly ubiquitous single-stranded adeno-associated viruses (AAVs) have gained importance since their discovery about 50 years ago. Their unique life cycle and virus-cell interactions have led to the development of recombinant AAVs as ideal genetic medicine tools that have evolved into effective commercialized gene therapies. A distinctive property of AAVs is their ability to edit the genome precisely. In contrast to all current genome editing platforms, AAV exclusively utilizes the high-fidelity homologous recombination (HR) pathway and does not require exogenous nucleases for prior cleavage of genomic DNA. Together, this leads to a highly precise editing outcome that preserves genomic integrity without incorporation of indel mutations or viral sequences at the target site while also obviating the possibility of off-target genotoxicity. The stem cell-derived AAV (AAVHSCs) were found to mediate precise and efficient HR with high on-target accuracy and at high efficiencies. AAVHSC editing occurs efficiently in post-mitotic cells and tissues in vivo. Additionally, AAV also has the advantage of an intrinsic delivery mechanism. Thus, this distinctive genome editing platform holds tremendous promise for the correction of disease-associated mutations without adding to the mutational burden. This review will focus on the unique properties of direct AAV-mediated genome editing and their potential mechanisms of action.

14.
Chemistry ; 27(18): 5737-5744, 2021 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-33350530

RESUMEN

An anion-mediated preorganization approach was used to design and synthesize the benzimidazolium-based calix compound R1⋅2 ClO4 - . X-ray crystallography analysis revealed that the hydrogen-bonding interactions between the benzimidazolium cations and N,N-dimethylformamide (DMF) helped R1⋅2 ClO4 - encapsulate DMF molecule(s). A nanoreactor, with R1⋅2 ClO4 - and l-histidine (l-His) as the components, was fabricated by using a neutralization method. The nanoreactor could detoxify paraoxon in 30 min. l-His played a vital role in this process. Paraoxonase is a well-known enzyme used for pesticide degradation. The Ellman's reagent was used to determine the percentage inhibition of the acetylcholinesterase (AChE) activity in the presence of the nanoreactor. The results indicated that the nanoreactor inhibited AChE inhibition.


Asunto(s)
Acetilcolina , Arildialquilfosfatasa , Acetilcolinesterasa , Inhibidores de la Colinesterasa , Histidina , Nanotecnología
15.
J Mater Chem B ; 8(36): 8405-8413, 2020 09 23.
Artículo en Inglés | MEDLINE | ID: mdl-32966537

RESUMEN

Okadaic acid (OA) is one of the known marine biotoxins produced by various dinoflagellates and exists in seafood such as shellfish. The consumption of contaminated shellfish with OA leads to diarrheic shellfish poisoning (DSP), which results in the inhibition of protein phosphatase enzymes in humans. This poisoning can cause immunotoxicity and tumor promotion due to the accumulation of okadaic acid in more than the allowed limit in bivalve molluscs. The reported methods for the detection of okadaic acid include mouse bioassays, immunoassays, chromatography coupled with spectroscopic techniques, electrochemical sensors and immunosensors. We have developed a naphthalimide-gold-based nanocomposite for the detection of okadaic acid. Individually, the organic nanoparticles (ONPs) of synthesized naphthalimide-based receptors and gold-coated ONPs are less sensitive for detection. However, fabrication of the composite of Au@ONPs and ONPs enhance the sensing properties and selectivity. The composite shows a ratiometric response in the UV-Vis absorption spectrum and quenching in the fluorescence profile with a detection limit of 20 nM for OA in aqueous medium. In cyclic voltammetry, a shift was observed in the cathodic peak (-0.532 V to -0.618 V) as well as in the anodic peak (-0.815 V to -0.847 V) with the addition of okadaic acid. To study the quick binding of the composite with OA, a time response experiment was performed. Also, the developed sensor retains its sensing ability in the pH range of 5-9 and in high salt conditions. Our developed composite can be used for the detection of OA in real applications.


Asunto(s)
Nanocompuestos/química , Naftalimidas/química , Ácido Ocadaico/análisis , Contaminantes Químicos del Agua/análisis , Agua Potable/análisis , Oro/química , Oro/toxicidad , Células HeLa , Humanos , Límite de Detección , Nanopartículas del Metal/química , Nanopartículas del Metal/toxicidad , Nanocompuestos/toxicidad , Naftalimidas/toxicidad , Ácido Ocadaico/química , Ríos/química , Espectrometría de Fluorescencia , Espectrofotometría Ultravioleta , Contaminantes Químicos del Agua/química
16.
Chem Asian J ; 15(14): 2160-2165, 2020 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-32472609

RESUMEN

The exponential growth in the research field of water pollution control demands the evolution of novel sensing materials for regulation and quantification of metals ions. Within this context, the current work reports a new strategy for the synthesis of carbon dots from the hydrothermal treatment of organic nanoparticles. The organic nanoparticles are found to be selective towards Cs(I) ions with a detection limit of 5.3 nM, whereas the highly fluorescent carbon dots are found to be selective towards Ag(I) ions with a detection limit of 4.8 nM. Both sensing systems illustrate rapid sensing with a working pH range from 4-9. The interfacial molecular restructuring of the sensing systems in the aqueous phase has been investigated in the absence and presence of targeted metal ions using a sum frequency generation vibrational spectroscopic tool. The practical applicability of the sensors was checked in environmental samples. This work opens new avenues for the exploration of temperature-guided sensing modulation in nanomaterials.

17.
ACS Appl Bio Mater ; 3(1): 477-485, 2020 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-35019464

RESUMEN

The spontaneous electron transfer between GaAs and ionic gold through the galvanic displacement reaction results in the formation of gold nanoparticles and a Au9Ga4 alloy. We investigated this process for decorating Legionella pneumophila and Escherichia coli, aiming at enhanced imaging of these bacteria. The surface of bacteria was modified with gold ions through the electrostatic linkage of ionic liquids with phosphate units of the bacterial cell wall. The modified bacteria were further incubated with an antibody-functionalized GaAs substrate. Due to a large gap in the reduction potential of gold and gallium ions, the induced reaction involving bacteria resulted in a reduction of the gold ions to gold nanoparticles and oxidation of GaAs to Ga2O3 and a Au9Ga4 alloy. The bacteria covered with a Au/AuGa nanoshell, if excited at 377 nm, show a bright emission at 447 nm originating from Au/Au9Ga4. This approach offers a simple and potentially less expensive method for high-contrast imaging of bacteria in comparison to the conventional methods of staining with different dyes or by conjugating green fluorescent proteins.

18.
Mol Cell Biol ; 39(20)2019 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-31332096

RESUMEN

In response to perturbed DNA replication, ATR (ataxia telangiectasia and Rad3-related) kinase is activated to initiate the checkpoint signaling necessary for maintaining genome integrity and cell survival. To better understand the signaling mechanism, we carried out a large-scale genetic screen in fission yeast looking for mutants with enhanced sensitivity to hydroxyurea. From a collection of ∼370 primary mutants, we found a few mutants in which Rad3 (ATR ortholog)-mediated phospho-signaling was significantly compromised. One such mutant carried an uncharacterized mutation in tel2, a gene encoding an essential and highly conserved eukaryotic protein. Previous studies in various biological models have shown that Tel2 mainly functions in Tel2-Tti1-Tti2 (TTT) complex that regulates the steady-state levels of all phosphatidylinositol 3-kinase-like protein kinases, including ATR. We show here that although the levels of Rad3 and Rad3-mediated phospho-signaling in DNA damage checkpoint were moderately reduced in the tel2 mutant, the phospho-signaling in the DNA replication checkpoint was almost completely eliminated. In addition, the tel2 mutation caused telomere shortening. Since the interactions of Tel2 with Tti1 and Tti2 were significantly weakened by the mutation, destabilization of the TTT complex likely contributes to the observed checkpoint and telomere defects.


Asunto(s)
Quinasa de Punto de Control 2/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Proteínas de Schizosaccharomyces pombe/genética , Proteínas de Schizosaccharomyces pombe/metabolismo , Schizosaccharomyces/genética , Acortamiento del Telómero , Proteínas de Unión a Telómeros/genética , Quinasa de Punto de Control 2/genética , Daño del ADN/efectos de los fármacos , Replicación del ADN , Hidroxiurea/farmacología , Complejos Multiproteicos , Mutación Missense , Schizosaccharomyces/metabolismo , Transducción de Señal , Proteínas de Unión a Telómeros/metabolismo
19.
Inorg Chem ; 58(15): 9773-9784, 2019 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-31318533

RESUMEN

In recent years, transition metal complexes have been developed for catalytical degradation of a phosphate ester bond, particularly in RNA and DNA; however, less consideration has been given for development of complexes for the degradation of a phosphorothioate bond, as they are the foremost used pesticides in the environment and are toxic to human beings. In this context, we have developed copper complexes of benzimidazolium based ligands for catalytical degradation of a series of organophosphates (parathion, paraoxon, methyl-parathion) at ambient conditions. The copper complexes (assigned as N1-N3) were characterized using single X-ray crystallography which revealed that all three complexes are mononuclear and distorted square planner in geometry. Further, the solution state studies of the prepared complexes were carried out using UV-visible absorption, fluorescence spectroscopy, and cyclic voltametry. The complexes N1 and N2 have benzimidazolium ionic liquid as base attached with two 2-mercapto-benzimidazole pods, whereas complex N3 contains a nonionic ligand. The synthesized copper complexes were evaluated for their catalytic activity for degradation of organophosphates. It is interesting that the complex containing the ionic ligand efficiently degrades phosphorothioate pesticides, whereas complex N3 was not found to be appropriate for degradation due to a weaker conversion rate. The organophosphate degradation studies were monitored by recording absorbance spectra of parathion in the presence of catalyst, i.e., copper complexes with respect to time. The parathion was hydrolyzed into para-nitrophenol and diethyl thiophosphate. Moreover, to analyze the inhibition activity of the pesticides toward acetylcholine esterase enzyme in the presence of prepared metal complexes, Ellman's assay was performed and revealed that, within 20 min, the inhibition of acetylcholine esterase enzyme decreases by up to 13%.


Asunto(s)
Acetilcolina/metabolismo , Esterasas/metabolismo , Estructuras Metalorgánicas/química , Plaguicidas/química , Plaguicidas/toxicidad , Fosfatos/química , Acetilcolina/análisis , Bencimidazoles/química , Catálisis , Cobre/química , Cristalografía por Rayos X , Esterasas/análisis , Estructuras Metalorgánicas/síntesis química , Modelos Moleculares , Estructura Molecular , Fosfatos/toxicidad
20.
Mater Sci Eng C Mater Biol Appl ; 97: 467-478, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30678934

RESUMEN

Organic nanoparticles (ONPs) possess great research interests for their promising effects in the enhancement of bioactivity including anticancer activity with less toxicity. The present study describes the preparation, characterization and biological evaluation of aqueous phase ONPs of potent 1,2-disubstituted benzimidazole derivative (BZ6) for anticancer activity. BZ6-ONPs were characterized through UV-absorption and fluorescence spectroscopic analysis for their photo-physical properties. DLS, TEM and SEM studies were carried out for morphological and structural analysis. Cytotoxicity determination on a panel of four different cancer cell lines (MCF-7, MiaPaca-2, HT-29 and HCT-116) revealed that the BZ6-ONPs show highest activity in human breast cancer MCF-7 cells. Surprisingly, the BZ6-ONPs were found to be non-toxic towards normal breast epithelial fR2 cells. Additionally, the FITC-ONPs showed enhanced uptake in 3D tumor spheroids of MCF-7 cells compared to the free FITC. BZ6-ONPs strongly halted cell proliferation and induced apoptosis, possibly through oxidative stress-mediated reactive oxygen species (ROS) generation and loss of mitochondrial membrane potential (MMP) in MCF-7 cells. Moreover, molecular mechanism-based studies revealed that BZ6-ONPs downregulated AKT/NF-κB/vimentin/survivin-mediated oncogenic signaling pathway promoting cell proliferation and malignancy. In a nutshell, BZ6-ONPs are therapeutically efficacious, which needs further development as a treatment option in human mammary gland carcinomas.


Asunto(s)
Bencimidazoles/química , Nanopartículas/química , Estrés Oxidativo , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Femenino , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , FN-kappa B/metabolismo , Nanopartículas/toxicidad , Estrés Oxidativo/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Esferoides Celulares/citología , Esferoides Celulares/efectos de los fármacos , Esferoides Celulares/metabolismo
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