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2.
J Chem Inf Model ; 64(13): 4980-4990, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38888163

RESUMEN

Drug-target affinity (DTA) prediction is an important task in the early stages of drug discovery. Traditional biological approaches are time-consuming, effort-consuming, and resource-consuming due to the large size of genomic and chemical spaces. Computational approaches using machine learning have emerged to narrow down the drug candidate search space. However, most of these prediction models focus on single feature encoding of drugs and targets, ignoring the importance of integrating different dimensions of these features. We propose a deep learning-based approach called Multi-Dimensional Fusion for Drug Target Affinity Prediction (MDF-DTA) incorporating different dimensional features. Our model fuses 1D, 2D, and 3D representations obtained from different pretrained models for both drugs and targets. We evaluated MDF-DTA on two standard benchmark data sets: DAVIS and KIBA. Experimental results show that MDF-DTA outperforms many state-of-the-art techniques in the DTA task across both data sets. Through ablation studies and performance evaluation metrics, we evaluate the importance of individual representations and the impact of each representation on MDF-DTA.


Asunto(s)
Descubrimiento de Drogas , Descubrimiento de Drogas/métodos , Aprendizaje Profundo , Preparaciones Farmacéuticas/metabolismo , Preparaciones Farmacéuticas/química , Unión Proteica , Aprendizaje Automático , Proteínas/metabolismo , Proteínas/química
3.
J Fluoresc ; 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38502407

RESUMEN

A series of chelated metal complexes, [Co(LI)2] (1), [Ni(LI)2] (2), [Cu(LI)2] (3) [Co(LII)2] (4), [Ni(LII)2] (5) and [Cu(LII)2] (6) were designed and synthesized from newly synthesized Schiff bases, LI = 2-((E)-(5-(4-fluorophenyl)isoxazol-3-ylimino)methyl)-5-methylphenol and LII = 2-((E)-(5-(4-fluorophenyl)isoxazol-3-ylimino)methyl)-4-chlorophenol. The synthesized compounds were characterized by elemental analysis, nuclear magnetic resonance spectroscopy (NMR), electronic spectroscopy (UV-Vis), infrared spectroscopy (FT-IR), magnetic susceptibility (µeff), electron spin resonance spectroscopy (ESR), Thermogravimetric analysis (TGA), scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX), and powder X-ray diffraction analysis (P-XRD). The spectral investigations have been clearly suggested 1:2 (metal: ligand) stoichiometric complexes with square planar geometrical arrangement around the metal ion. The thermal gravimmetric analysis (TGA) of these complexes indicates greater thermal stability and various steps involved in thermal decomposition of metal complexes. The binding ability between these metal complexes and calf thymus DNA (CT-DNA) was investigated by UV-Vis, fluorescence spectroscopy and viscometric experiments, which disclosed that, the complexes interacted to CT-DNA via an intercalation binding mode. The cleavage property of metal complexes against pBR322 DNA has been explored by gel electrophoresis technique mediated by UV-illumination and H2O2, showed momentous cleavage activity. Antioxidant activity of all complexes was determined by DPPH free radical scavenging experiment and showed prominent antioxidant activity. Further, the antibacterial and antifungal activities of all compounds were screened against bacterial and fungal strains via in-vitro disc diffusion method. These studies revealed that the complexes showed comparatively more antimicrobial activity than free ligands against tested microbial strains.

4.
Anim Biotechnol ; 34(8): 3609-3616, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36866847

RESUMEN

A 60-day feeding trial was conducted to study the hematology, liver, and intestinal histoarchitecture of Labeo rohita fed with a combination of exogenous enzymes, essential amino acids, and essential fatty acids to DORB (De-oiled rice bran) based diets. Three treatments viz., T1 [DORB + phytase and xylanase (0.01% each)], T2 [DORB + phytase (0.01%) + xylanase (0.01%) + L-lysine(1.4%) + L-methionine (0.4%) + EPA and DHA (0.5%)] and T3 [DORB + phytase (0.01%), xylanase and cellulase (0.075%) + L-lysine (1.4%) +L-methionine (0.4%) + EPA and DHA (0.5%)] were used in the present study. Serum total protein, albumin content and A/G ratio varied significantly (p < 0.05) among groups. Globulin content did not vary significantly among groups (p ≥ 0.05). The Hb content, RBC and MCV count varied significantly (p < 0.05) whereas MCH, MCHC content, WBC and lymphocyte count did not vary significantly among groups (p > 0.05). The liver and intestine examination revealed no visible alteration and showed normal histo-architecture. Based on the finding it is concluded that DORB supplemented with exogenous enzymes, essential amino acids and essential fatty acids with phytase (0.01%), xylanase and cellulase (0.075%), L-lysine (1.4%), DL-methionine (0.4%) and EPA and DHA (0.5%) improves the health of L. rohita.


Asunto(s)
6-Fitasa , Celulasas , Cyprinidae , Hematología , Oryza , Animales , Oryza/metabolismo , Aminoácidos Esenciales , Lisina , 6-Fitasa/metabolismo , Alimentación Animal/análisis , Dieta/veterinaria , Ácidos Grasos Esenciales , Hígado/metabolismo , Intestinos , Metionina/farmacología
5.
MAGMA ; 35(3): 449-457, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34741702

RESUMEN

OBJECTIVE: In medical domain, cross-modality image synthesis suffers from multiple issues , such as context-misalignment, image distortion, image blurriness, and loss of details. The fundamental objective behind this study is to address these issues in estimating synthetic Computed tomography (sCT) scans from T2-weighted Magnetic Resonance Imaging (MRI) scans to achieve MRI-guided Radiation Treatment (RT). MATERIALS AND METHODS: We proposed a conditional generative adversarial network (cGAN) with multiple residual blocks to estimate sCT from T2-weighted MRI scans using 367 paired brain MR-CT images dataset. Few state-of-the-art deep learning models were implemented to generate sCT including Pix2Pix model, U-Net model, autoencoder model and their results were compared, respectively. RESULTS: Results with paired MR-CT image dataset demonstrate that the proposed model with nine residual blocks in generator architecture results in the smallest mean absolute error (MAE) value of [Formula: see text], and mean squared error (MSE) value of [Formula: see text], and produces the largest Pearson correlation coefficient (PCC) value of [Formula: see text], SSIM value of [Formula: see text] and peak signal-to-noise ratio (PSNR) value of [Formula: see text], respectively. We qualitatively evaluated our result by visual comparisons of generated sCT to original CT of respective MRI input. DISCUSSION: The quantitative and qualitative comparison of this work demonstrates that deep learning-based cGAN model can be used to estimate sCT scan from a reference T2 weighted MRI scan. The overall accuracy of our proposed model outperforms different state-of-the-art deep learning-based models.


Asunto(s)
Retraso en el Despertar Posanestésico , Radioterapia Guiada por Imagen , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Tomografía Computarizada por Rayos X/métodos
6.
J Neurosci Res ; 99(7): 1815-1834, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33819353

RESUMEN

Rapid eye movement sleep (REMS) favors brain development and memory, while it is decreased in neurodegenerative diseases. REMS deprivation (REMSD) affects several physiological processes including memory consolidation; however, its detailed mechanism(s) of action was unknown. REMS reduces, while REMSD elevates noradrenaline (NA) level in the brain; the latter induces several deficiencies and disorders, including changes in neuronal cytomorphology and apoptosis. Therefore, we proposed that REMS- and REMSD-associated modulation of NA level might affect neuronal plasticity and affect brain functions. Male albino rats were REMS deprived by flower-pot method for 6 days, and its effects were compared with home cage and large platform controls as well as post-REMSD recovered and REMS-deprived prazosin (α1-adrenoceptor antagonist)-treated rats. We observed that REMSD reduced CA1 and CA3 neuronal dendritic length, branching, arborization, and spine density, while length of active zone and expressions of pre- as well as post-synaptic proteins were increased as compared to controls; interestingly, prazosin prevented most of the effects in vivo. Studies on primary culture of neurons from chick embryo brain confirmed that NA at lower concentration(s) induced neuronal branching and arborization, while higher doses were destructive. The findings support our contention that REMSD adversely affects neuronal plasticity, branching, and synaptic scaffold, which explain the underlying cytoarchitectural basis of REMSD-associated patho-physio-behavioral changes. Consolidation of findings of this study along with that of our previous reports suggest that the neuronal disintegration could be due to either withdrawal of direct protective and proliferative role of low dose of NA or indirect effect of high dose of NA or both.


Asunto(s)
Hipocampo/fisiopatología , Plasticidad Neuronal/fisiología , Norepinefrina/metabolismo , Privación de Sueño/fisiopatología , Animales , Embrión de Pollo , Masculino , Plasticidad Neuronal/efectos de los fármacos , Norepinefrina/farmacología , Ratas , Ratas Wistar
7.
PLoS Pathog ; 15(4): e1007717, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-31009520

RESUMEN

Infectious complications are a common cause of morbidity and mortality in cancer patients undergoing chemotherapy due to increased risk of oral and gastrointestinal candidiasis, candidemia and septicemia. Interactions between C. albicans and endogenous mucosal bacteria are important in understanding the mechanisms of invasive infection. We published a mouse intravenous chemotherapy model that recapitulates oral and intestinal mucositis, and myelosuppression in patients receiving 5-fluorouracil. We used this model to study the influence of C. albicans on the mucosal bacterial microbiome and compared global community changes in the oral and intestinal mucosa of the same mice. We validated 16S rRNA gene sequencing data by qPCR, in situ hybridization and culture approaches. Mice receiving both 5Fu and C. albicans had an endogenous bacterial overgrowth on the oral but not the small intestinal mucosa. C. albicans infection was associated with loss of mucosal bacterial diversity in both sites with indigenous Stenotrophomonas, Alphaproteobacteria and Enterococcus species dominating the small intestinal, and Enterococcus species dominating the oral mucosa. Both immunosuppression and Candida infection contributed to changes in the oral microbiota. Enterococci isolated from mice with oropharyngeal candidiasis were implicated in degrading the epithelial junction protein E-cadherin and increasing the permeability of the oral epithelial barrier in vitro. Importantly, depletion of these organisms with antibiotics in vivo attenuated oral mucosal E-cadherin degradation and C. albicans invasion without affecting fungal burdens, indicating that bacterial community changes represent overt dysbiosis. Our studies demonstrate a complex interaction between C. albicans, the resident mucosal bacterial microbiota and the host environment in pathogenesis. We shed significant new light on the role of C. albicans in shaping resident bacterial communities and driving mucosal dysbiosis.


Asunto(s)
Candida albicans/patogenicidad , Candidiasis Bucal/etiología , Disbiosis/inducido químicamente , Fluorouracilo/efectos adversos , Mucosa Intestinal/microbiología , Mucosa Bucal/microbiología , Animales , Antimetabolitos/efectos adversos , Candida albicans/efectos de los fármacos , Candida albicans/genética , Candidiasis Bucal/patología , Modelos Animales de Enfermedad , Femenino , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/patología , Ratones , Ratones Endogámicos C57BL , Mucosa Bucal/efectos de los fármacos , Mucosa Bucal/patología
8.
Fish Physiol Biochem ; 47(1): 49-58, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33099718

RESUMEN

The present study aims to delineate the effect of exogenous enzyme supplementation of fermented or non-fermented de-oiled rice bran (DORB) on haematology, histology and expression of IGF I gene expression of Labeo rohita. Four test diets, namely, T1 (DORB), T2 (fermented DORB), T3 (DORB+exogenous enzyme) and T4 (fermented DORB+exogenous enzyme) were formulated and fed to the L. rohita for a period of 60 days. The test diets T3 and T4 were supplemented with 0.1 g kg-1 xylanase (16,000 U kg-1) and 0.1 g kg-1 phytase (500 U kg-1) enzymes. A total of 120 juveniles of L. rohita (average weight 5.01 ± 0.02 g) were stocked in 12 rectangular tanks with 10 fish per tank in triplicates. At the end of the experiment, haematology, histology and IGF I gene expression of the different groups were analysed. The haemoglobin (Hb) content, RBC count and WBC count of L. rohita varied significantly (p < 0.05) among different groups. T3 diet-fed group had the highest Hb content, RBC count and WBC count as compared to the other groups. The MCV content was significantly (p < 0.05) lower in T3 group. The DORB type, exogenous enzyme supplementation and their interaction have no significant (p > 0.05) effect on MCH, MCHC and lymphocyte content of the cultured fish. The group which were fed T3 diet had significantly (p < 0.05) higher IGF-I gene expression as compared to other groups. The histological examination of liver revealed no pathological alteration of this organ. Similarly, there were no pathological changes observed in intestinal tissue in any dietary treatment group. Based on the findings of the present study, it is concluded that exogenous enzyme supplementation of DORB-based diets improves the physiological status and growth performances of Labeo rohita.


Asunto(s)
6-Fitasa/farmacología , Cyprinidae , Suplementos Dietéticos , Endo-1,4-beta Xilanasas/farmacología , Alimentación Animal , Animales , Cyprinidae/sangre , Cyprinidae/genética , Dieta/veterinaria , Proteínas de Peces/genética , Expresión Génica , Pruebas Hematológicas , Hemoglobinas/análisis , Factor I del Crecimiento Similar a la Insulina/genética , Intestinos/anatomía & histología , Hígado/anatomía & histología
9.
Fish Physiol Biochem ; 46(1): 265-275, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31656978

RESUMEN

A 60-day feeding trial was conducted with six experimental diets containing 260 g/kg crude protein and 70 g/kg lipid with varying level of de-oiled rice bran (DORB), viz., 33 (T33), 38 (T38), 43 (T43), 48 (T48), 53 (T53) and 58% (T58) to assess the digestive, metabolic and haematological responses in Labeo rohita. One hundred and eighty (180) fingerlings with ten fish per tank having an average weight of 9.8 ± 0.5 g were randomly distributed within six treatments in triplicates following a completely randomised design. The amylase and lipase activities in the whole intestine did not vary significantly (P > 0.05), but protease activity varied significantly with respect to DORB level in the diet. At higher (53 and 58%) inclusion level of DORB, the protease activities were lower. T33, T38 and T43 groups showed significantly (P < 0.05) higher aspartate aminotransferase (AST) activity compared to the other groups, whereas lowest activity was recorded in the group fed with highest inclusion level (58%). The oxidative stress enzyme like superoxide dismutase (SOD), catalase and glutathione-S-transferase exhibited significantly higher activities in liver of T58 group of L. rohita. However, the activity of catalase and SOD showed no significant variation in gill tissue. The haematological parameter values such as red blood cell (RBC), white blood cell (WBC), haemoglobin (Hb) and packed cell volume (PCV) were lower in the highest DORB fed group (T58) as compared to their lower DORB inclusion counterparts. No change in NBT value was recorded irrespective of DORB inclusion level in the diet. Hence, from these results, it can be concluded that the dietary inclusion of DORB up to 43% in the diet of L. rohita at 26% crude protein and 7% lipid level is best for the optimal activity of digestive, metabolic and haematological parameters.


Asunto(s)
Alimentación Animal , Cyprinidae/fisiología , Proteínas en la Dieta , Aceite de Salvado de Arroz , Animales , Aspartato Aminotransferasas , Dieta , Hematócrito , Oryza , Estrés Oxidativo
10.
Fish Physiol Biochem ; 44(4): 1037-1049, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29594890

RESUMEN

A 60-day feeding trial was conducted to study the effect of exogenous enzymes (xylanase and phytase) supplementation in the non-fermented and fermented de-oiled rice bran (DORB)-based diet of Labeo rohita. Four test diets (T1-DORB-based diet, T2-fermented DORB-based diet, T3-phytase and xylanase supplemented DORB-based diet, and T4-phytase and xylanase supplemented fermented DORB-based diet) were formulated and fed to the respective groups. Test diets T3 and T4 were supplemented with 0.01% xylanase (16,000 U kg-1) and 0.01% phytase (500 U kg-1) enzymes. One hundred twenty juveniles of L. rohita, with an average weight 5.01 ± 0.02 g, were stocked in 12 uniform size plastic rectangular tanks in triplicate with 10 fishes per tank following a completely randomized design (CRD). Exogenous enzyme supplementation to the T3 group significantly improved the growth performance of L. rohita (p < 0.05). Fermented DORB fed groups registered significantly lower growth irrespective of the supplementation of exogenous enzymes. The carcass composition (except CP %), enzyme activities (except amylase activity), globulin, and A/G ratio did not vary significantly (p > 0.05). Based on the results of the present study, it is concluded that exogenous enzyme supplementation significantly increases the growth of fish fed with DORB-based diet.


Asunto(s)
Cyprinidae/fisiología , Dieta/veterinaria , Suplementos Dietéticos , Enzimas/metabolismo , Alimentos Fermentados/análisis , Oryza/química , Alimentación Animal , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Aceite de Salvado de Arroz/administración & dosificación
11.
Antimicrob Agents Chemother ; 60(11): 6795-6805, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27600040

RESUMEN

The global dissemination and increasing incidence of carbapenem-resistant, Gram-negative organisms have resulted in acute public health concerns. Here, we present a retrospective multicenter study on molecular characterization of metallo-ß-lactamase (MBL)-producing clinical Escherichia coli isolates recovered from extraintestinal infections in two hospitals in Pune, India. We screened a large sample size of 510 E. coli isolates for MBL production wherein we profiled their molecular determinants, antimicrobial resistance phenotypes, functional virulence properties, genomic features, and transmission dynamics. Approximately 8% of these isolates were MBL producers, the majority of which were of the NDM-1 (69%) type, followed by NDM-5 (19%), NDM-4 (5.5%), and NDM-7 (5.5%). MBL producers were resistant to all antibiotics tested except for colistin, fosfomycin, and chloramphenicol, which were effective to various extents. Plasmids were found to be an effective means of dissemination of NDM genes and other resistance traits. All MBL producers adhered to and invaded bladder epithelial (T24) cells and demonstrated significant serum resistance. Genomic analysis of MBL-producing E. coli isolates revealed higher resistance but a moderate virulence gene repertoire. A subset of NDM-1-positive E. coli isolates was identified as dominant sequence type 101 (ST101) while two strains belonging to ST167 and ST405 harbored NDM-5. A majority of MBL-producing E. coli strains revealed unique genotypes, suggesting that they were clonally unrelated. Overall, the coexistence of virulence and carbapenem resistance in clinical E. coli isolates is of serious concern. Moreover, the emergence of NDM-1 among the globally dominant E. coli ST101 isolates warrants stringent surveillance and control measures.


Asunto(s)
Farmacorresistencia Bacteriana Múltiple/genética , Escherichia coli Patógena Extraintestinal/genética , Escherichia coli Patógena Extraintestinal/metabolismo , beta-Lactamasas/metabolismo , Infecciones por Escherichia coli/microbiología , Escherichia coli Patógena Extraintestinal/patogenicidad , Variación Genética , Genoma Bacteriano , Humanos , India , Pruebas de Sensibilidad Microbiana , Epidemiología Molecular , Plásmidos/genética , beta-Lactamasas/genética
12.
Antimicrob Agents Chemother ; 59(10): 6087-95, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26195517

RESUMEN

Escherichia coli sequence type 131 (ST131) is a pandemic clone associated with multidrug-resistant, extraintestinal infections, attributable to the presence of the CTX-M-15 extended-spectrum ß-lactamase gene and mutations entailing fluoroquinolone resistance. Studies on subclones within E. coli ST131 are critically required for targeting and implementation of successful control efforts. Our study comprehensively analyzed the genomic and functional attributes of the H30-Rx subclonal strains NA097 and NA114, belonging to the ST131 lineage. We carried out whole-genome sequencing, comparative analysis, phenotypic virulence assays, and profiling of the antibacterial responses of THP1 cells infected with these subclones. Phylogenomic analysis suggested that the strains were clonal in nature and confined entirely to a single clade. Comparative genomic analysis revealed that the virulence and resistance repertoires were comparable among the H30-Rx ST131 strains except for the commensal ST131 strain SE15. Similarly, seven phage-specific regions were found to be strongly associated with the H30-Rx strains but were largely absent in the genome of SE15. Phenotypic analysis confirmed the virulence and resistance similarities between the two strains. However, NA097 was found to be more robust than NA114 in terms of virulence gene carriage (dra operon), invasion ability (P < 0.05), and antimicrobial resistance (streptomycin resistance). RT(2) gene expression profiling revealed generic upregulation of key proinflammatory responses in THP1 cells, irrespective of ST131 lineage status. In conclusion, our study provides comprehensive, genome-inferred insights into the biology and immunological properties of ST131 strains and suggests clonal diversification of genomic and phenotypic features within the H30-Rx subclone of E. coli ST131.


Asunto(s)
Escherichia coli/enzimología , beta-Lactamasas/metabolismo , Línea Celular , Farmacorresistencia Bacteriana Múltiple/genética , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Humanos , Virulencia/genética , beta-Lactamasas/genética
13.
Exp Cell Res ; 322(2): 249-64, 2014 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-24530578

RESUMEN

Invasion is the key requirement for cancer metastasis. Expression of ß1,6 branched N-oligosaccharides associated with invasiveness, has been shown to promote adhesion to most Extra Cellular Matrix (ECM) and basement membrane (BM) components and haptotactic motility on ECM (fibronectin) but attenuate it on BM (laminin/matrigel) components. To explore the mechanism and to evaluate the significance of these observations in terms of invasion, highly invasive B16BL6 cells were compared with the parent (B16F10) cells or B16BL6 cells in which glycosylation was inhibited. We demonstrate that increased adhesion to matrix components induced secretion of MMP-9, important for invasion. Further, both the subunits of integrin receptors for fibronectin (α5ß1) and laminin (α3ß1) on B16BL6 cells were shown to carry these oligosaccharides. Although, glycosylation of receptors had no effect on their surface expression, it had same differential effect on cell spreading as haptotactic motility. Absence of correlation between invasiveness and expression of most tetraspanins (major regulators of integrin function) hints at an alternate mechanism. Here we show that glycosylation on α3ß1 impedes its association with CD151 and modulates spreading and motility of cells apparently to reach an optimum required for invasion of BM. These studies demonstrate the complex mechanisms used by cancer cells to be invasive.


Asunto(s)
Membrana Basal/patología , Movimiento Celular , Colágeno/metabolismo , Integrina alfa3beta1/metabolismo , Laminina/metabolismo , Melanoma Experimental/patología , Proteoglicanos/metabolismo , Receptores de Laminina/metabolismo , Tetraspanina 24/metabolismo , Animales , Membrana Basal/metabolismo , Western Blotting , Adhesión Celular , Colágeno/genética , Combinación de Medicamentos , Fibronectinas/genética , Fibronectinas/metabolismo , Citometría de Flujo , Regulación Neoplásica de la Expresión Génica , Glicosilación , Integrina alfa3beta1/genética , Integrina alfa5beta1/genética , Integrina alfa5beta1/metabolismo , Laminina/genética , Metaloproteinasa 9 de la Matriz/metabolismo , Melanoma Experimental/metabolismo , Ratones , Invasividad Neoplásica , Proteoglicanos/genética , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores de Laminina/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tetraspanina 24/genética , Células Tumorales Cultivadas
14.
Antimicrob Agents Chemother ; 58(12): 7240-9, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25246402

RESUMEN

In view of the epidemiological success of CTX-M-15-producing lineages of Escherichia coli and particularly of sequence type 131 (ST131), it is of significant interest to explore its prevalence in countries such as India and to determine if antibiotic resistance, virulence, metabolic potential, and/or the genetic architecture of the ST131 isolates differ from those of non-ST131 isolates. A collection of 126 E. coli isolates comprising 43 ST131 E. coli, 40 non-ST131 E. coli, and 43 fecal E. coli isolates collected from a tertiary care hospital in India was analyzed. These isolates were subjected to enterobacterial repetitive intergenic consensus (ERIC)-based fingerprinting, O typing, phylogenetic grouping, antibiotic sensitivity testing, and virulence and antimicrobial resistance gene (VAG) detection. Representative isolates from this collection were also analyzed by multilocus sequence typing (MLST), conjugation, metabolic profiling, biofilm production assay, and zebra fish lethality assay. All of the 43 ST131 E. coli isolates were exclusively associated with phylogenetic group B2 (100%), while most of the clinical non-ST131 and stool non-ST131 E. coli isolates were affiliated with the B2 (38%) and A (58%) phylogenetic groups, respectively. Significantly greater proportions of ST131 isolates (58%) than non-ST131 isolates (clinical and stool E. coli isolates, 5% each) were technically identified to be extraintestinal pathogenic E. coli (ExPEC). The clinical ST131, clinical non-ST131, and stool non-ST131 E. coli isolates exhibited high rates of multidrug resistance (95%, 91%, and 91%, respectively), extended-spectrum-ß-lactamase (ESBL) production (86%, 83%, and 91%, respectively), and metallo-ß-lactamase (MBL) production (28%, 33%, and 0%, respectively). CTX-M-15 was strongly linked with ESBL production in ST131 isolates (93%), whereas CTX-M-15 plus TEM were present in clinical and stool non-ST131 E. coli isolates. Using MLST, we confirmed the presence of two NDM-1-positive ST131 E. coli isolates. The aggregate bioscores (metabolite utilization) for ST131, clinical non-ST131, and stool non-ST131 E. coli isolates were 53%, 52%, and 49%, respectively. The ST131 isolates were moderate biofilm producers and were more highly virulent in zebra fish than non-ST131 isolates. According to ERIC-based fingerprinting, the ST131 strains were more genetically similar, and this was subsequently followed by the genetic similarity of clinical non-ST131 and stool non-ST131 E. coli strains. In conclusion, our data provide novel insights into aspects of the fitness advantage of E. coli lineage ST131 and suggest that a number of factors are likely involved in the worldwide dissemination of and infections due to ST131 E. coli isolates.


Asunto(s)
Biopelículas/efectos de los fármacos , Infecciones por Escherichia coli/veterinaria , Escherichia coli/genética , Enfermedades de los Peces/microbiología , beta-Lactamasas/genética , Animales , Antibacterianos/farmacología , Biopelículas/crecimiento & desarrollo , Bioensayo , Dermatoglifia del ADN , Farmacorresistencia Bacteriana Múltiple/genética , Escherichia coli/clasificación , Escherichia coli/efectos de los fármacos , Escherichia coli/aislamiento & purificación , Infecciones por Escherichia coli/microbiología , Infecciones por Escherichia coli/mortalidad , Heces/microbiología , Enfermedades de los Peces/mortalidad , Expresión Génica , Genotipo , Hospitales , Humanos , India , Tipificación de Secuencias Multilocus , Fenotipo , Filogenia , Análisis de Supervivencia , Atención Terciaria de Salud , Pez Cebra , beta-Lactamasas/metabolismo
15.
Int J Med Microbiol ; 304(8): 1066-76, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25172221

RESUMEN

The Helicobacter pylori gene JHP0940 has been shown to encode a serine/threonine kinase which can induce cytokines in gastric epithelial cells relevant to chronic gastric inflammation. Here we demonstrate that JHP0940 can be secreted by the bacteria, triggers apoptosis in cultured mouse macrophages and acts as an auto-phosphorylating tyrosine kinase. Recombinant JHP0940 protein was found to decrease the viability of RAW264.7 cells (a mouse macrophage cell line) up to 55% within 24h of co-incubation. The decreased cellular viability was due to apoptosis, which was confirmed by TUNEL assay and Fas expression analysis by flow-cytometry. Further, we found that caspase-1 and IL-1beta were activated upon treatment with JHP0940. These results point towards possible action through the host inflammasome. Our in vitro studies using tyrosine kinase assays further demonstrated that JHP0940 acts as auto-phosphorylating tyrosine kinase and induces pro-inflammatory cytokines in RAW264.7 cells. Upon exposure with JHP0940, these cells secreted IL-1beta, TNF-alpha and IL-6, in a dose- and time-dependent manner, as detected by ELISA and transcript profiling by q-RT-PCR. The pro-inflammatory, pro-apoptotic and other regulatory responses triggered by JHP0940 lead to the assumption of its possible role in inducing chronic inflammation for enhanced bacterial persistence and escape from host innate immune responses by apoptosis of macrophages.


Asunto(s)
Apoptosis , Proteínas Bacterianas/metabolismo , Helicobacter pylori/enzimología , Interacciones Huésped-Patógeno , Macrófagos/microbiología , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Tirosina Quinasas/metabolismo , Factores de Virulencia/metabolismo , Animales , Línea Celular , Supervivencia Celular , Citocinas/metabolismo , Ensayo de Inmunoadsorción Enzimática , Macrófagos/fisiología , Ratones , Fosforilación , Procesamiento Proteico-Postraduccional
16.
Cureus ; 16(2): e53878, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38465194

RESUMEN

Background and objective The Medical Council of India [now replaced by the National Medical Commission (NMC)] has implemented a new competency-based curriculum for medical education. Eight competencies in the curriculum are related to the principles of disability-inclusive compassionate care. This study aimed to evaluate the knowledge, perceptions, and attitudes among undergraduate medical students about people with disability after attending learning sessions on disability competency. Materials and methods After they attended the learning session during the foundation course, participants were evaluated by using a questionnaire involving 26 questions, of which 17 were based on the Likert scale to assess general perceptions towards the person with a disability, while three questions aimed to assess attitudes, and six closed-ended questions tried to assess knowledge about disability. Results In the present study, 79.7% (n=157) of the students thought that people with disabilities faced problems getting involved in society, and 81.2% (n=160) felt that it was harder for them to make friends than others. The majority of the students disagreed with the idea that people with disabilities are a burden on society (n=149, 75.6%) or their families (n=119, 60.4%); 65% (n=128) of the students thought that people with disabilities are more determined than others to reach their goals and achieve more owing to their disability (n=104, 52.85%). A total of 161 (81.7%) students disagreed with the statement that people with disabilities should not be optimistic about their future. A comparison of the pre- and post-test data revealed that students' knowledge regarding disability increased and they gained a more positive attitude towards people with a disability after attending teaching and learning sessions (p<0.0001). Conclusion Our findings showed a significant improvement in the undergraduate medical students' understanding and empathy toward individuals with disabilities following sessions on disability competency. Teaching and learning sessions on disability competencies for newly admitted students in medical school can sensitize, orient, increase knowledge, and develop positive attitudes toward people with disabilities. Further studies on the topic are needed involving different phases of clinical teaching.

17.
J Family Med Prim Care ; 13(3): 841-844, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38736799

RESUMEN

Introduction: Acute myeloid leukaemia (AML) is a tumour of hematopoietic progenitors caused by acquired oncogenic mutations that impede differentiation, leading to the accumulation of immature myeloid blasts in the marrow. Aberrant phenotype is a phenomenon in which lymphoid-associated and other myeloid lineage markers are expressed in myeloblasts or myeloid-associated markers are expressed in lymphoblasts. Materials and Methods: Diagnosed cases of AML were included in this study to study the aberrant expression using multiparametric flow cytometry. Results: Out of a sample size of 50, 30 cases expressed aberrant CD markers. Male: Female ratio was 0.76. Majority of cases belonged to the age group >60 years of age. CD 7 was overall the most common aberrant CD marker. Conclusion: Immunophenotyping has a significant role in diagnosis and predicting prognosis of hematopoietic malignancies in the absence of more advanced diagnostic tools like cytogenetics.

18.
Cureus ; 16(1): e53017, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38410303

RESUMEN

INTRODUCTION: Diabetic peripheral neuropathy (DPN) presents a formidable health challenge in type 2 diabetes mellitus (T2DM) patients. This study in eastern Uttar Pradesh aims to assess the roles of vascular endothelial growth factor (VEGF) and adiponectin in DPN, recognizing the crucial need for understanding its molecular underpinnings for enhanced diagnosis and management. METHODS: In a cross-sectional study analyzing clinical and biochemical data, 86 individuals aged 35 to 65 years were examined, including 43 with neuropathy and 43 without. Neuropathy assessment included the neuropathy symptom score (NSS), diabetes neuropathy examination (DNE) score, and nerve conduction studies. Levels of VEGF and adiponectin were correlated with motor nerve amplitude, NSS, and DNE scores. Receiver operating characteristic (ROC) curve analysis gauged diagnostic potential, and logistic regression assessed predictors for DPN. RESULTS: Patients with neuropathy exhibited significantly elevated VEGF levels compared to those without, while adiponectin showed no significant difference. VEGF demonstrated a negative correlation with motor nerve amplitude and a positive correlation with NSS and DNE scores. ROC analysis revealed strong diagnostic capability for VEGF (area under the curve: 0.807). NSS and DNE scores indicated good and moderate diagnostic accuracy, respectively. In logistic regression analysis, VEGF emerged as the sole significant predictor (odds ratio: 1.11, 95% CI (1.03, 1.20), p = 0.0092). CONCLUSION: Findings suggest VEGF's potential as a biomarker for diagnosing DPN in T2DM, associated with neuropathy severity. Adiponectin showed no significant association. The study underscores NSS and DNE scores' therapeutic relevance as valid neuropathy assessment tools.

19.
Nat Prod Res ; 38(6): 1080-1084, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37157823

RESUMEN

Semecarpus anacardium L.f. has been commonly used in various traditional medicines from ancient times. The nuts have been described in Ayurveda medication systems to treat numerous clinical ailments. However, isolating phytochemical constituents from nuts remain challenging and exhibits cytotoxic effects on other cells. In this study, we have standardized procedures for isolating phytochemicals from the leaf extract. The ethyl acetate leaf extract selectively affects cancer cells in a dose-dependent manner (IC50: 0.57 µg/ml in MCF-7 cells) in various cancer cell lines and induces apoptosis in cancer cells. However, the non-malignant cells were relatively insensitive to the extract. Next, the incubation of the leaf extract induces cell cycle arrest and suppresses cancer cell migration in the cell culture model. Moreover, oral administration of extract significantly restored tumor growth in mice. Together, these observations suggest the anti-cancer activities of S. anacardium L.f. leaf potential for both in vitro and in vivo models.


Asunto(s)
Antineoplásicos , Neoplasias , Semecarpus , Ratones , Animales , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Neoplasias/tratamiento farmacológico , Nueces
20.
Nat Prod Res ; : 1-9, 2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38333925

RESUMEN

The compound 2,3-dehydrosilychristin, a flavonolignan linked to silychristin and silymarin, remains intriguing due to its challenging isolation from silymarin. While silymarin has been the exclusive source of flavonolignans - silybin, silychristin and silydianin - 2,3-dehydrosilychristin is reported in this study from Vitex negundo Linn. leaves. 2,3-Dehydrosilychristin (7) and 14 other compounds were isolated through focused extraction. Its subsequent pharmacological evaluation demonstrated potent antioxidant and in-vitro anti-inflammatory effects, notably inhibiting cytokines TNF-α, IL-6, IL-8 and VEGF. In in-vivo assessments, 2,3-dehydrosilychristin (7) revealed remarkable hepatoprotective potential by reducing liver enzyme levels AST and ALT. These findings expand the potential of 2,3-dehydrosilychristin and suggest bioprospecting Vitex species as alternate sources of bioactive flavonolignans.

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