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1.
Eur J Clin Invest ; 54(5): e14169, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38287209

RESUMEN

BACKGROUND: Atherosclerosis is the salient, underlying cause of cardiovascular diseases, such as arrhythmia, coronary artery disease, cardiomyopathy, pulmonary embolism and myocardial infarction. In recent years, atherosclerosis pathophysiology has evolved from a lipid-based to an inflammation-centric ideology. METHODS: This narrative review is comprised of review and original articles that were found through the PubMed search engine. The following search terms or amalgamation of terms were used: "cardiovascular disease," "atherosclerosis," "inflammation," "GRP78," "Hsp60," "oxidative low-density lipoproteins," "aldehyde dehydrogenase," "ß2-glycoprotein," "lipoprotein lipase A," "human cytomegalovirus." "SARS-CoV-2," "chlamydia pneumonia," "autophagy," "thrombosis" and "therapeutics." RESULTS: Emerging evidence supports the concept that atherosclerosis is associated with the interaction between cell surface expression of stress response chaperones, including GRP78 and Hsp60, and their respective autoantibodies. Moreover, various other autoantigens and their autoantibodies have displayed a compelling connection with the development of atherosclerosis, including oxidative low-density lipoproteins, aldehyde dehydrogenase, ß2-glycoprotein and lipoprotein lipase A. Atherosclerosis progression is also concurrent with viral and bacterial activators of various diseases. This narrative review will focus on the contributions of human cytomegalovirus as well as SARS-CoV-2 and chlamydia pneumonia in atherosclerosis development. Notably, the interaction of an autoantigen with their respective autoantibodies or the presence of a foreign antigen can enhance inflammation development, which leads to atherosclerotic lesion progression. CONCLUSION: We will highlight and discuss the complex role of the interaction between autoantigens and autoantibodies, and the presence of foreign antigens in the development of atherosclerotic lesions in relationship to pro-inflammatory responses.


Asunto(s)
Aterosclerosis , Neumonía , Humanos , Chaperón BiP del Retículo Endoplásmico , Lipoproteína Lipasa , Aterosclerosis/metabolismo , Autoanticuerpos , Inflamación , Autoantígenos , beta 2 Glicoproteína I , Lipoproteínas LDL , Aldehído Deshidrogenasa
2.
J Clin Gastroenterol ; 2023 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-37983812

RESUMEN

BACKGROUND: Acute gastric variceal bleeding (AGVB) is a potentially fatal consequence of portal hypertension, accounting for 10% to 30% of all variceal bleeding. Although endoscopic cyanoacrylate glue injection is a common treatment for acute hemostasis, it has been linked to significant side effects. In the treatment of AGVB, there is limited evidence of the efficacy and relative safety of endoscopic human thrombin injection over glue injection. MATERIALS AND METHODS: A total of 52 AGVB patients were randomized to receive either thrombin injection (25 patients) or glue injection (27 patients). The primary outcome was the incidence of any glue or thrombin injection-related post-therapy complications. Initial hemostasis, rebleeding, and mortality were all secondary end goals. RESULTS: Both groups had comparable baseline data. Hemostasis of active bleeding at endoscopy was 100.0% (10/10) in the thrombin group and 87.5% (7/8) in the glue group (P=0.44). Treatment failure after 5 days occurred in 2 patients (6.1%) in the glue group compared with none in the thrombin group (P=0.165). Between 6 and 42 days after index bleeding, rebleeding occurred in 4 patients in the thrombin group compared with 6 patients in the glue group (P=0.728). In the thrombin group, none of the patients had post-treatment ulcers on gastric varices compared with 14.81% (4/27) that occurred in the glue group (P=0.045), a statistically significant observation. Overall, complications occurred in 4 (20%) and 11 (40.7%) patients in the thrombin and glue groups, respectively (P=0.105). Two patients in the glue group died. CONCLUSION: To achieve successful AGVB hemostasis, endoscopic thrombin injection has been proven efficacious. However, glue injection may be linked to a higher rate of rebleeding and post-therapy gastric variceal ulceration compared with thrombin.

3.
Phys Chem Chem Phys ; 25(31): 20863-20870, 2023 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-37522188

RESUMEN

Thin films of double perovskite ruthenates, viz., Ba2DyRuO6 (BDRO) and Sr2DyRuO6 (SDRO), have been successfully grown on a SrTiO3 substrate using the pulsed laser deposition technique. The BDRO samples crystallizes in cubic structure, while SDRO exhibits monoclinic structure as revealed in their X-Ray diffraction examination. Temperature-dependent magnetization measurements suggest the presence of ferromagnetism in BDRO, while paramagnetism is present for the SDRO thin film. Surprisingly, both films show canted antiferromagnetism at ∼T = 5 K as revealed in their isothermal magnetization curves. The inverse susceptibility has been fitted to the Curie-Weiss law for the SDRO sample, where the Curie temperature (TC ∼ -336.6 K) has been obtained, thus suggesting the prevalence of antiferromagnetic interactions. The existence of the canted magnetism at a lower temperature may be attributed to the Dzyaloshinskii-Moriya (D-M) interactions in the monoclinic SDRO sample due to structural distortion. However, the emergence of canted antiferromagnetism at lower temperatures (5 K) in the BDRO sample with cubic symmetry having no D-M interactions may be attributed to the various modifications at the surface of the thin films. Overall, a comparison made between the magnetic properties of both the thin films i.e., BDRO & SDRO, reveals the suppression of bulk magnetic ordering when compared to their bulk counterparts. The possible reason for the absence of any magnetic ordering in these thin films may be due to any modifications in superexchange interactions, any exchange bias, stress-strain, or uncompensated spins present in these types of thin films. UV-visible measurements for both the samples reveal a direct influence of the A-site element (Sr/Ba) on their band gaps, i.e., 3.66 eV and 2.59 eV for BDRO and SDRO samples, respectively, hence suggesting their insulating nature. We have also carried out first principles calculations with DFT using the CASTEP software to gain more insights into the experimental data. These thin films with insulating-antiferromagnetic properties may be crucial for "spintronics devices".

4.
Rep Pract Oncol Radiother ; 26(4): 598-604, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34434576

RESUMEN

BACKGROUND: A purpose of the study was to investigate the dosimetric impact of contrast media on dose calculation using average 4D contrast-enhanced computed tomography (4D-CECT) and delayed 4D-CT (d4D-CT) images caused by CT simulation contrast agents for stereotactic body radiation therapy (SBRT) of liver cases. MATERIALS AND METHODS: Fifteen patients of liver SBRT treated using the volumetric modulated arc therapy (VMAT) technique were selected retrospectively. 4D-CECT, and d4D-CT were acquired with the Anzai gating system and GE CT. For all patients, gross target volume (GTV) was contoured on the ten phases after rigid registration of both the contrast and delayed scans and merged to generate internal target volume (ITV) on average CT images. Region of interest (ROI) was drawn on contrast images and then copied to the delayed images after rigid registration of two average CT datasets. The treatment plans were generated for contrast enhanced average CT, delayed average CT and contrast enhanced average CT with electron density of the heart overridden. RESULTS: No significant dosimetric difference was observed in plans parameters (mean HU value of the liver, total monitor units, total control points, degree of modulation and average segment area) except mean HU value of the aorta amongst the three arms. All the OARs were evaluated and resulted in statistically insignificant variation (p > 0.05) using one way ANOVA analysis. CONCLUSIONS: Contrast enhanced 4D-CT is advantageous in accurate delineation of tumors and assessing accurate ITV. The treatment plans generated on average 4D-CECT and average d4D-CT have a clinically insignificant effect on dosimetric parameters.

5.
J Basic Microbiol ; 58(10): 867-874, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30043998

RESUMEN

Nitrile hydrolyzing moderate halophilic bacterium Halomonas sp. IIIMB2797 was isolated from Sambhar Lake, India. Maximum cell biomass and nitrilase production were observed at 60 g L-1 NaCl in the production media which confirms its moderate halophilic nature. Nitrilase of Halomonas sp. IIIMB2797 proved to be inducible in nature as maximum activity was observed when valeronitrile was added in the production media. Whole cells of Halomonas sp. IIIMB2797 exhibited broad substrate affinity towards aromatic and aliphatic nitriles. Optimum pH and temperature for nitrilase activity was observed at 7.0 and 45 °C, respectively. Effect of salinity on nitrilase activity was also studied and maximum activity was observed in presence of 50 g L-1 NaCl in 0.1 M phosphate buffer of pH 7.0. The interesting feature of the study is that whole cells of Halomonas sp. IIIMB2797 exhibited higher nitrilase activities in presence of organic solvents which may be useful in biotransformation of nitriles to corresponding carboxylic acids for industrial applications.


Asunto(s)
Aminohidrolasas/metabolismo , Halomonas/enzimología , Lagos/microbiología , Aminohidrolasas/química , ADN Bacteriano/genética , Estabilidad de Enzimas , Genoma Bacteriano/genética , Halomonas/clasificación , Halomonas/genética , Halomonas/aislamiento & purificación , Concentración de Iones de Hidrógeno , India , Datos de Secuencia Molecular , Nitrilos/metabolismo , Filogenia , ARN Ribosómico 16S/genética , Salinidad , Análisis de Secuencia de ADN , Cloruro de Sodio , Solventes , Especificidad por Sustrato , Temperatura
6.
Bioorg Med Chem Lett ; 24(4): 1232-5, 2014 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-24440298

RESUMEN

The parasite Toxoplasma gondii can lead to toxoplasmosis in those who are immunocompromised. To combat the infection, the enzyme responsible for nucleotide synthesis thymidylate synthase-dihydrofolate reductase (TS-DHFR) is a suitable drug target. We have used virtual screening to determine novel allosteric inhibitors at the interface between the two TS domains. Selected compounds from virtual screening inhibited TS activity. Thus, these results show that allosteric inhibition by small drug-like molecules can occur in T. gondii TS-DHFR and pave the way for new and potent species-specific inhibitors.


Asunto(s)
Evaluación Preclínica de Medicamentos , Inhibidores Enzimáticos/farmacología , Complejos Multienzimáticos/antagonistas & inhibidores , Timidilato Sintasa/antagonistas & inhibidores , Toxoplasma/enzimología , Regulación Alostérica/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Modelos Moleculares , Estructura Molecular , Complejos Multienzimáticos/metabolismo , Relación Estructura-Actividad , Tetrahidrofolato Deshidrogenasa/metabolismo , Timidilato Sintasa/metabolismo
7.
Nanoscale ; 16(6): 3091-3100, 2024 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-38251395

RESUMEN

Lattice thermal conductivity (κ) in tungsten dichalcogenide Janus (WXY, where X, Y = S, Se, and Te) monolayers and heterostructures (HSs) have been investigated using ab initio DFT simulations. Tungsten-based Janus monolayers show semiconducting behavior with the bandgap in the semiconducting range for WSSe (1.70 eV), WSTe (1.26 eV), and WSeTe (1.34 eV). When Janus monolayers are stacked to form HSs with weak van der Waals (vdW) interactions, the bandgap reduces to 0.19 eV, 0.40 eV, and 0.24 eV, respectively, for WSeTe/WSTe, WSSe/WSTe, and WSSe/WSeTe HSs. Thermal vibrational characteristics of Janus monolayers are modified when these are stacked in 2D HSs with the introduction of interlayer hybrid phonon modes. Large longitudinal-transverse optical (LO-TO) splitting is noticed at the Brillouin zone-center (Γ-point): 135 cm-1, 140 cm-1, and 150 cm-1 for WSeTe/WSTe, WSSe/WSeTe and WSSe/WSTe HSs, respectively. Thermal conductivity calculations show ultra-low κ values for WSeTe/WSTe (0.01 W m-1 K-1), WSSe/WSTe (0.02 W m-1 K-1) and WSSe/WSeTe HS (0.004 W m-1 K-1) at 300 K. The results can be attributed to the hybrid phonon modes with frequencies very close to acoustic modes at the gamma point, low Debye temperature (θD) and specific heat capacity. Our results highlight the possible applications of these HSs in designing thermoelectric interfaces at the nanoscale.

8.
Biochemistry ; 52(41): 7305-7317, 2013 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-24053355

RESUMEN

Most species, such as humans, have monofunctional forms of thymidylate synthase (TS) and dihydrofolate reductase (DHFR) that are key folate metabolism enzymes making critical folate components required for DNA synthesis. In contrast, several parasitic protozoa, including Toxoplasma gondii , contain a unique bifunctional thymidylate synthase-dihydrofolate reductase (TS-DHFR) having the catalytic activities contained on a single polypeptide chain. The prevalence of T. gondii infections across the world, especially for those immunocompromised, underscores the need to understand TS-DHFR enzyme function and to find new avenues to exploit for the design of novel antiparasitic drugs. As a first step, we have solved the first three-dimensional structures of T. gondii TS-DHFR at 3.7 Å and of a loop truncated TS-DHFR, removing several flexible surface loops in the DHFR domain, improving resolution to 2.2 Å. Distinct structural features of the TS-DHFR homodimer include a junctional region containing a kinked crossover helix between the DHFR domains of the two adjacent monomers, a long linker connecting the TS and DHFR domains, and a DHFR domain that is positively charged. The roles of these unique structural features were probed by site-directed mutagenesis coupled with presteady state and steady state kinetics. Mutational analysis of the crossover helix region combined with kinetic characterization established the importance of this region not only in DHFR catalysis but also in modulating the distal TS activity, suggesting a role for TS-DHFR interdomain interactions. Additional kinetic studies revealed that substrate channeling occurs in which dihydrofolate is directly transferred from the TS to DHFR active site without entering bulk solution. The crystal structure suggests that the positively charged DHFR domain governs this electrostatically mediated movement of dihydrofolate, preventing release from the enzyme. Taken together, these structural and kinetic studies reveal unique, functional regions on the T. gondii TS-DHFR enzyme that may be targeted for inhibition, thus paving the way for designing species specific inhibitors.


Asunto(s)
Complejos Multienzimáticos/química , Proteínas Protozoarias/química , Tetrahidrofolato Deshidrogenasa/química , Timidilato Sintasa/química , Toxoplasma/enzimología , Sitios de Unión , Catálisis , Dominio Catalítico , Ácido Fólico/química , Ácido Fólico/metabolismo , Imagenología Tridimensional , Cinética , Modelos Moleculares , Complejos Multienzimáticos/genética , Complejos Multienzimáticos/metabolismo , Estructura Secundaria de Proteína , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismo , Especificidad por Sustrato , Tetrahidrofolato Deshidrogenasa/genética , Tetrahidrofolato Deshidrogenasa/metabolismo , Timidilato Sintasa/genética , Timidilato Sintasa/metabolismo , Toxoplasma/química , Toxoplasma/genética
9.
Multimed Tools Appl ; 82(12): 18117-18150, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36213342

RESUMEN

The digital image proves critical evidence in the fields like forensic investigation, criminal investigation, intelligence systems, medical imaging, insurance claims, and journalism to name a few. Images are an authentic source of information on the internet and social media. But, using easily available software or editing tools such as Photoshop, Corel Paint Shop, PhotoScape, PhotoPlus, GIMP, Pixelmator, etc. images can be altered or utilized maliciously for personal benefits. Various active, passive and other new deep learning technology like GAN approaches have made photo-realistic images difficult to distinguish from real images. Digital image tamper detection now focuses on determining the authenticity and consistency of digital photos. The major research problems use generic solutions and strategies, such as standardized data sets, benchmarks, evaluation criteria and generalized approaches.This paper overviews the evaluation of various image tamper detection methods. A brief discussion of image datasets and a comparative study of image criminological (forensic) methods are included in this paper. Furthermore, recently developed deep learning techniques along with their limitations have also been addressed. This study aims to comprehensively analyze image forgery detection methods using conventional and advanced deep learning approaches.

10.
Indian J Ophthalmol ; 71(6): 2632, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37322727

RESUMEN

Background: Many a young doctors in training find retinal laser photocoagulation a daunting task. However, if correct protocols are followed and checklists are observed, then it is not difficult to have a successful laser sitting with a happy patient. Most of the complications can be avoided with correct settings and techniques. Purpose: To enumerate the basic protocols of retinal laser photocoagulation and provide practical tips including laser settings and checklists for hassle-free laser experience. Synopsis: Laser settings for a pan-retinal photocoagulation (PRP) for proliferative diabetic retinopathy differ from those for a focal laser for macular edema. A fill in PRP is indicated when an active Proliferative diabetic retinopathy (PDR) is seen after the initial PRP is completed. The settings and protocols for laser photocoagulation for lattice degeneration are different, and various techniques of barrage laser are discussed. Practical tips and checklists are given, which will not be found in any textbooks. Highlights: Animated illustrations and fundus photos are used to explain the correct techniques of performing laser photocoagulation in different indications and scenarios. Detailed instructions and checklists are provided, which can be very useful to avoid complications and medicolegal problems. The practical tips and guidelines in an easy-to-understand manner make this video highly educational for the novice retinal surgeons who want to perfect their technique of retinal laser photocoagulation. Video Link: https://youtu.be/saQ4s49ciXI.


Asunto(s)
Retinopatía Diabética , Edema Macular , Humanos , Retinopatía Diabética/complicaciones , Coagulación con Láser/métodos , Rayos Láser , Edema Macular/etiología , Retina/cirugía
11.
3 Biotech ; 13(5): 141, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37124982

RESUMEN

Cell division cycle 20 (CDC20), a critical partner of anaphase promoting complex (APC/C), is indispensably required for metaphase-to-anaphase transition. CDC20 overexpression in TNBC breast cancer patients has been found to be correlated with poor prognosis, hence, we aimed to target CDC20 for TNBC therapeutics. In silico molecular docking of large-scale chemical libraries (phytochemicals/synthetic drugs) against CDC20 protein structure identified five synthetic drugs and four phytochemicals as potential hits interacting with CDC20 active site. The molecular selection was done based on docking scores, binding interactions, binding energies and MM/GBSA scores. Further, we analysed ADME profiles for all the hits and identified lidocaine, an aminoamide anaesthetic group of synthetic drug, with high drug-likeness properties. We explored the anti-tumorigenic effects of lidocaine on MDA-MB-231 TNBC breast cancer cells, which resulted in increased growth inhibition in dose-dependent manner. The molecular mechanism behind the cell viability defect mediated by lidocaine was found to be induction of G2/M cell cycle arrest and cellular apoptosis. Notably, lidocaine treatment of TNBC cells also resulted in downregulation of CDC20 gene expression. Thus, this study identifies lidocaine as a potential anti-neoplastic agent for TNBC cells emphasizing CDC20 as a suitable therapeutic target for breast cancer. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03554-7.

12.
Fitoterapia ; 168: 105554, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37270161

RESUMEN

Infectious diseases have remained a burgeoning cause of death and disability since long. Staphylococcus aureus (S. aureus) is a severe bacterial pathogen causing nosocomial and community infections. It exhibits widespread resistance to antibiotics posing a significant threat to their efficacy. For combating this challenge, different strategies may include modifying existing antibiotics, developing new antibacterial agents, and combining treatments with resistance mechanism inhibitors. Resistance in S. aureus occurs through horizontal gene transfer or chromosomal mutations. Acquisition mechanisms involve enzymatic modification, efflux, target bypass, and drug displacement. Mutations can impact drug targets, activate efflux pumps, or alter cell wall composition to impede drug access. Overcoming S. aureus resistance requires innovative approaches to preserve antibiotic effectiveness. The present study involves the virtual screening of phytochemicals of diverse chemical classes from Zinc database against the antibiotic resistant targets of S. aureus like ß-Lactamase, Penicillin Binding Protein 2a (PBP2a), Dihydrofolate reductase (DHFR), DNA gyrase, Multidrug ABC transporter SAV1866, Undecaprenyl diphosphate synthase (UPPS), etc. Thymol, eugenol, gallic acid, l-ascorbic acid, curcumin, berberine and quercetin were identified as potential molecules based on their docking score, binding interactions. These molecules were further analyzed for the ADMET and drug likeness properties using pkCSM, SwissADME and Qikprop tools. Further in vitro evaluation of these molecules against antibiotic-resistant strains of S. aureus, both alone and in combination with antibiotics revealed significant findings. Curcumin demonstrated the lowest MIC values (31.25-62.5 µg/ml) when tested individually. Thymol, berberine, and quercetin displayed MIC values within the range of 125-250 µg/ml, while eugenol and gallic acid exhibited MIC values ranging from 500 to 1000 µg/ml. Notably, thymol exhibited potent synergy with all four antibiotics against clinical isolates of S. aureus, with Fractional inhibitory concentration index (FICI) values consistently below 0.5, highlighting its exceptional antibacterial activity, especially in combination with amoxicillin.


Asunto(s)
Berberina , Curcumina , Staphylococcus aureus Resistente a Meticilina , Staphylococcus aureus , Timol , Eugenol/metabolismo , Curcumina/metabolismo , Quercetina/farmacología , Quercetina/metabolismo , Berberina/metabolismo , Estructura Molecular , Antibacterianos/farmacología , Antibacterianos/química , Farmacorresistencia Bacteriana , Pruebas de Sensibilidad Microbiana
13.
Chem Biol Interact ; 376: 110443, 2023 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-36893906

RESUMEN

New targeted therapy for triple negative breast cancer (TNBC) is an urgent need, as advanced disease responds poorly to conventional chemotherapy. Genomic and proteomic studies are currently investigating new genes and proteins as promising therapeutic targets. One of such therapeutic targets is a cell cycle regulatory kinase; Maternal Embryonic Leucine Zipper Kinase (MELK), overexpressed in TNBC and correlated with cancer development. We performed molecular docking for virtual screening of chemical libraries (phytochemicals/synthetic drugs) against MELK protein structure and identified 8 phytoconstituents (isoxanthorin, emodin, gamma-coniceine, quercetin, tenuazonic acid, isoliquiritigenin, kaempferol, and Nobiletin) and 8 synthetic drugs (tetrahydrofolic acid, alfuzosin, lansoprazole, ketorolac, ketoprofen, variolin B, orantinib, and firestein) as potential hits interacting with the active site residues of MELK based on bound poses, hydrogen bond, hydrophobic interactions and MM/GBSA binding free energies. ADME and drug-likeness prediction further identified few hits with high drug-likeness properties and were further tested for anti-tumorigenic potential. Two phytochemicals isoliquiritigenin and emodin demonstrated growth inhibitory effects on TNBC MDA-MB-231 cells while much lower effect was observed on non-tumorigenic MCF-10A mammary epithelial cells. Treatment with both molecules downregulated MELK expression, induced cell cycle arrest, accumulated DNA damage and enhanced apoptosis. The study identified isoliquiritigenin and emodin as potential MELK inhibitors and provides a basis for subsequent experimental validation and drug development against cancer.


Asunto(s)
Emodina , Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Proteínas Serina-Treonina Quinasas/metabolismo , Bibliotecas de Moléculas Pequeñas/farmacología , Simulación del Acoplamiento Molecular , Emodina/farmacología , Proteómica , Proliferación Celular , Detección Precoz del Cáncer , Línea Celular Tumoral
14.
ACS Omega ; 8(50): 48360-48369, 2023 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-38144151

RESUMEN

Herein, we introduce an eco-friendly electrochemical sensor based on melamine-enriched nitrogen-doped carbon nanosheets decorated with gold nanoparticles (Au-CNSm) for arsenic sensing. An extremely facile, low-toxicity, biocompatible, and affordable hydrothermal technique was adopted for the synthesis of the Au-CNSm nanocomposite. The Au-CNSm-integrated sensing platform was optimized for electrode composition by cyclic voltammetry (CV). Owing to the synergistic effects of melamine-enriched carbon nanosheets (CNSm) and gold nanoparticles (AuNPs), the anodic peak current increased in the Au-CNSm-modified sensing electrode as compared to the CNSm-decorated platform. A wide linear range of 0.0001-100 µM and a low detection limit of 0.0001 µM were obtained. The visual signals can be measured at a very minute concentration of 0.0001 µM (0.1 ppb) on a screen-printed carbon electrode (SPCE) modified with Au-CNSm. Hence, this electrode system clearly outperformed the previously reported studies in terms of linear range, limit of detection (LOD), and electrocatalytic activity for arsenic sensing. Interestingly, the fabricated biosensor can be developed as a point-of-care device for real-time environmental monitoring for public safety. Henceforth, owing to exceptional attributes such as portability, selectivity, and sensitivity, this device offers great promise in modeling a revolutionary new class of electrochemical sensing platforms for an ultrasensitive and reliable detection strategy for arsenite (As(III)).

15.
Proc Natl Acad Sci U S A ; 106(39): 16604-9, 2009 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-19805344

RESUMEN

The binding of cAMP to the Escherichia coli catabolite gene activator protein (CAP) produces a conformational change that enables it to bind specific DNA sequences and regulate transcription, which it cannot do in the absence of the nucleotide. The crystal structures of the unliganded CAP containing a D138L mutation and the unliganded WT CAP were determined at 2.3 and 3.6 A resolution, respectively, and reveal that the two DNA binding domains have dimerized into one rigid body and their two DNA recognition helices become buried. The WT structure shows multiple orientations of this rigid body relative to the nucleotide binding domain supporting earlier biochemical data suggesting that the inactive form exists in an equilibrium among different conformations. Comparison of the structures of the liganded and unliganded CAP suggests that cAMP stabilizes the active DNA binding conformation of CAP through the interactions that the N(6) of the adenosine makes with the C-helices. These interactions are associated with the reorientation and elongation of the C-helices that precludes the formation of the inactive structure.


Asunto(s)
Apoproteínas/química , Proteína Receptora de AMP Cíclico/química , ADN/metabolismo , Proteínas de Escherichia coli/química , Apoproteínas/metabolismo , Sitios de Unión , Cristalografía por Rayos X , AMP Cíclico/química , AMP Cíclico/metabolismo , Proteína Receptora de AMP Cíclico/metabolismo , ADN/química , Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , Ligandos , Modelos Moleculares , Conformación Proteica
16.
3 Biotech ; 12(2): 44, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35096501

RESUMEN

The present study entails the usefulness of thermophilic amidase-producing bacterium in the biotransformation of benzamide to benzohydroxamic acid (BHA). A bacterium Bacillus smithii IIIMB2907 was isolated from a soil sample collected from hot springs of Manikaran, Himachal Pradesh, India. The whole cells of the bacterium displayed versatile substrate specificity by exhibiting significant activity with a diverse range of amides. In addition, amidase from thermophilic bacterium was induced by adding Ɛ-caprolactam in the mineral base media. The optimum temperature and pH of acyltransferase activity of amidase enzyme were found to be 50 °C and 7.0, respectively. Interestingly, half-life (t 1/2) of this enzyme was 17.37 h at 50 °C. Bench-scale production and purification of BHA was carried out at optimized conditions which resulted in the recovery of 64% BHA with a purity of 96%. Owing to this, the reported process in the present study can be considered of immense industrial significance for the production of BHA. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-022-03109-2.

17.
Biomedicines ; 10(5)2022 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-35625836

RESUMEN

The 78 kDa glucose-regulated protein (GRP78) is considered an endoplasmic reticulum (ER)-resident molecular chaperone that plays a crucial role in protein folding homeostasis by regulating the unfolded protein response (UPR) and inducing numerous proapoptotic and autophagic pathways within the eukaryotic cell. However, in cancer cells, GRP78 has also been shown to migrate from the ER lumen to the cell surface, playing a role in several cellular pathways that promote tumor growth and cancer cell progression. There is another insidious consequence elicited by cell surface GRP78 (csGRP78) on cancer cells: the accumulation of csGRP78 represents a novel neoantigen leading to the production of anti-GRP78 autoantibodies that can bind csGRP78 and further amplify these cellular pathways to enhance cell growth and mitigate apoptotic cell death. This review examines the current body of literature that delineates the mechanisms by which ER-resident GRP78 localizes to the cell surface and its consequences, as well as potential therapeutics that target csGRP78 and block its interaction with anti-GRP78 autoantibodies, thereby inhibiting further amplification of cancer cell progression.

18.
Indian J Ophthalmol ; 68(11): 2572-2574, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33120696

RESUMEN

Thromboembolic phenomenon related to Coronavirus disease 2019 (COVID-19) has been well documented in literature; however, reported ocular manifestations of COVID-19 are limited to vision sparing ocular conditions like conjunctivitis. We report a case of a 17-year-old female who presented to us with central retinal vein occlusion with proven recent past COVID-19 infection as presumed etiology which was not known to her at the time of presentation.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/complicaciones , Neumonía Viral/complicaciones , Oclusión de la Vena Retiniana/etiología , Adolescente , COVID-19 , Prueba de COVID-19 , Técnicas de Laboratorio Clínico , Infecciones por Coronavirus/diagnóstico , Femenino , Humanos , Edema Macular/diagnóstico por imagen , Edema Macular/etiología , Pandemias , Neumonía Viral/diagnóstico , Desprendimiento de Retina/diagnóstico por imagen , Desprendimiento de Retina/etiología , Oclusión de la Vena Retiniana/diagnóstico , SARS-CoV-2 , Tomografía de Coherencia Óptica
19.
J Phys Chem A ; 113(31): 9002-13, 2009 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-19719305

RESUMEN

Ab initio investigation of structural, electronic and vibrational properties of nitrogen-doped fullerenes (C(60-n)Nn, for n = 1-12) has been performed using numerical atomic orbital density functional theory. We have obtained the ground-state structures for C(60-n)Nn for n = 1-12, which show higher stability with a single nitrogen in a pentagon and two nonadjacent nitrogen atoms in a hexagon. Nitrogen doping leads to structural deformation, with the diameter showing variation from (7.14 - 0.24) to (7.14 + 0.10) A. The average diameter of C(60-n)Nn shows a small decrease for n > or = 5, with a minimum value of 7.06 A for n = 12. The change in the average diameter signifies the volume contraction, which is also maximum for C48N12. The binding energy per atom is found to decrease as a function of the number of N atoms. The HOMO-LUMO gap is found to decrease with an increase in substitutional nitrogen atoms; however, no systematic pattern could be observed. The Mulliken charge analysis performed on all optimized geometries shows a charge transfer of -0.3 to -0.45 (or 0.3-0.45 electrons) from nitrogen to carbon atoms, resulting in nitrogen atoms behaving as electrophilic sites. The harmonic vibrational frequency analysis shows the absence of any imaginary mode. The vibrational frequencies are found to decrease with an increase in the number of nitrogen atoms in C(60-n)Nn. The results obtained are consistent with available theoretical and experimental results.


Asunto(s)
Electrones , Fulerenos/química , Vibración , Teoría Cuántica , Estereoisomerismo , Termodinámica
20.
Ocul Immunol Inflamm ; 27(2): 235-243, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-28700251

RESUMEN

PURPOSE: To assess structural changes in retina and choroid after systemic corticosteroid therapy in Vogt-Koyanagi-Harada (VKH) disease using swept-source optical coherence tomography (SS-OCT). METHODS: SS-OCT was conducted before treatment and during first-month follow-up in 16 eyes treated with systemic corticosteroids for active VKH. Retina was divided into five zones depending on pretreatment choroidal thickness (CT) of <100, >100 to <200, >200 to <300, >300 to <400 and >400µm, and changes in retinal thickness and CT after treatment in these zones were compared with baseline. RESULTS: Mean CT significantly improved from 83.1±8.75 to 156.4±62.73µm(p = 0.008) in the zone with pre-CT <100µm and significantly decreased from 336.1 ± 17.28 to 266.28 ± 81.39µm(p = 0.008) in the zone with pre-CT > 300µm. CONCLUSIONS: We have shown choroidal remodeling in VKH. SS-OCT can serve as an important noninvasive tool in assessment of treatment response in patients with VKH disease.


Asunto(s)
Coroides/patología , Metilprednisolona/uso terapéutico , Retina/patología , Tomografía de Coherencia Óptica/métodos , Síndrome Uveomeningoencefálico/diagnóstico , Agudeza Visual , Adolescente , Adulto , Coroides/efectos de los fármacos , Femenino , Estudios de Seguimiento , Glucocorticoides/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Síndrome Uveomeningoencefálico/tratamiento farmacológico , Adulto Joven
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