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1.
Clin Sci (Lond) ; 137(10): 785-805, 2023 05 31.
Artículo en Inglés | MEDLINE | ID: mdl-36951146

RESUMEN

Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a life-threatening condition caused due to significant pulmonary and systemic inflammation. Chlorogenic acid (CGA) has been shown to possess potent antioxidant, anti-inflammatory, and immunoprotective properties. However, the protective effect of CGA on viral and bacterial-induced ALI/ARDS is not yet explored. Hence, the current study is aimed to evaluate the preclinical efficacy of CGA in lipopolysaccharide (LPS) and polyinosinic:polycytidylic acid (POLY I:C)-induced ALI/ARDS models in vitro and in vivo. Human airway epithelial (BEAS-2B) cells exposed to LPS+POLY I:C significantly elevated oxidative stress and inflammatory signaling. Co-treatment with CGA (10 and 50 µM) prevented inflammation and oxidative stress mediated by TLR4/TLR3 and NLRP3 inflammasome axis. BALB/c mice, when chronically challenged with LPS+POLY I:C showed a significant influx of immune cells, up-regulation of pro-inflammatory cytokines, namely: IL-6, IL-1ß, and TNF-α, and treatment with intranasal CGA (1 and 5 mg/kg) normalized the elevated levels of immune cell infiltration as well as pro-inflammatory cytokines. D-Dimer, the serum marker for intravascular coagulation, was significantly increased in LPS+ POLY I:C challenged animals which was reduced with CGA treatment. Further, CGA treatment also has a beneficial effect on the lung and heart, as shown by improving lung physiological and cardiac functional parameters accompanied by the elevated antioxidant response and simultaneous reduction in tissue damage caused by LPS+POLY I:C co-infection. In summary, these comprehensive, in vitro and in vivo studies suggest that CGA may be a viable therapeutic option for bacterial and viral-induced ALI-ARDS-like pathology.


Asunto(s)
FN-kappa B , Síndrome de Dificultad Respiratoria , Ratones , Animales , Humanos , FN-kappa B/metabolismo , Lipopolisacáridos/farmacología , Proteína con Dominio Pirina 3 de la Familia NLR , Ácido Clorogénico/farmacología , Ácido Clorogénico/uso terapéutico , Receptor Toll-Like 4/metabolismo , Antioxidantes/farmacología , Estrés Oxidativo , Citocinas/metabolismo , Inflamación/tratamiento farmacológico , Poli I/farmacología
2.
Nonlinear Dyn ; 111(7): 6873-6893, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36644569

RESUMEN

During the COVID-19 pandemic, one of the major concerns was a medical emergency in human society. Therefore it was necessary to control or restrict the disease spreading among populations in any fruitful way at that time. To frame out a proper policy for controlling COVID-19 spreading with limited medical facilities, here we propose an SEQAIHR model having saturated treatment. We check biological feasibility of model solutions and compute the basic reproduction number ( R 0 ). Moreover, the model exhibits transcritical, backward bifurcation and forward bifurcation with hysteresis with respect to different parameters under some restrictions. Further to validate the model, we fit it with real COVID-19 infected data of Hong Kong from 19th December, 2021 to 3rd April, 2022 and estimate model parameters. Applying sensitivity analysis, we find out the most sensitive parameters that have an effect on R 0 . We estimate R 0 using actual initial growth data of COVID-19 and calculate effective reproduction number for same period. Finally, an optimal control problem has been proposed considering effective vaccination and saturated treatment for hospitalized class to decrease density of the infected class and to minimize implemented cost.

3.
Int J Mol Sci ; 23(23)2022 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-36499047

RESUMEN

Piperine (PIP) is a major phytoconstituent in black pepper which is responsible for various pharmacological actions such as anti-inflammatory, antioxidant, and antitumor activity. To investigate the effects and mechanisms of PIP on cigarette smoke (CS)-induced lung pathology using both in-vitro and in-vivo models. BEAS-2B and A549 cells were exposed to CS extract (CSE) for 48 h; BALB/c mice were exposed to CS (9 cigarettes/day, 4 days) to induce features of airway disease. PIP at doses of (0.25, 1.25, and 6.25 µM, in vitro; 1 and 10 mg/kg, in vivo, i.n) and DEX (1 µM, in vitro; 1 mg/kg, in vivo, i.n) were used to assess cytotoxicity, oxidative stress, epithelial−mesenchymal transition (EMT), Sirtuin1 (SIRT1), inflammation-related cellular signaling, and lung function. PIP treatment protects cells from CSE-induced lung epithelial cell death. PIP treatment restores the epithelial marker (p < 0.05) and decreases the mesenchymal, inflammatory markers (p < 0.05) in both in vitro and in vivo models. The PIP treatment improves the altered lung function (p < 0.05) in mice induced by CS exposure. Mechanistically, PIP treatment modulates SIRT1 thereby reducing the inflammatory markers such as IL-1ß, IL-6 and TNF-α (p < 0.05) and enhancing the epigenetic marker HDAC2 (p < 0.05) and antioxidant marker Nrf2 (p < 0.05) expressions. Thus, PIP alleviates pulmonary inflammation by modulating the SIRT1-mediated inflammatory cascade, inhibits EMT, and activates Nrf2 signaling.


Asunto(s)
Transición Epitelial-Mesenquimal , Piperidinas , Neumonía , Humo , Animales , Ratones , Antioxidantes/farmacología , Pulmón/patología , Ratones Endogámicos BALB C , Factor 2 Relacionado con NF-E2/genética , Estrés Oxidativo , Neumonía/tratamiento farmacológico , Neumonía/patología , Sirtuina 1/genética , Nicotiana/efectos adversos , Humo/efectos adversos , Piperidinas/farmacología
4.
Nonlinear Dyn ; 105(1): 971-996, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34177118

RESUMEN

In this paper, we have considered a deterministic epidemic model with logistic growth rate of the susceptible population, non-monotone incidence rate, nonlinear treatment function with impact of limited hospital beds and performed control strategies. The existence and stability of equilibria as well as persistence and extinction of the infection have been studied here. We have investigated different types of bifurcations, namely Transcritical bifurcation, Backward bifurcation, Saddle-node bifurcation and Hopf bifurcation, at different equilibrium points under some parametric restrictions. Numerical simulation for each of the above-defined bifurcations shows the complex dynamical phenomenon of the infectious disease. Furthermore, optimal control strategies are performed using Pontryagin's maximum principle and strategies of controls are studied for two infectious diseases. Lastly using efficiency analysis we have found the effective control strategies for both cases.

5.
Financ Res Lett ; 43: 101977, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33613130

RESUMEN

This study analyzes the relationship between COVID-19 related fear and short-term IPO performance. Though the average market-adjusted initial return of IPOs in the year 2020 is higher than that of the last four decades, it decreases if fear of pandemic increases. The evidence is robust when we use matching firm-adjusted initial returns. Next, we analyze the persistence of performance after the IPO date. The results show that the performance of IPO firms is more sensitive to the fear of the pandemic than the performance of similar existing firms.

6.
Microb Pathog ; 111: 307-315, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28867635

RESUMEN

Management of infectious wounds, particularly chronic wounds and burn injuries, is a matter of global concern. Worldwide estimates reveal that, billions of dollars are being spent annually for the management of such chronic ailments. Evidently, bacterial biofilms pose a greater problem in the effective management of infection in chronic wounds, since most of the currently available antibiotics are unable to act on the microorganisms residing inside the protected environment of the biofilms. Accordingly, in the present study, we have attempted to evaluate the anti-biofilm properties of human placental extract (PLX) and also other virulence factors that are mediated via the quorum sensing (QS) signalling system. PLX is well known for its anti inflammatory action and it has been shown earlier some anti microbial and enzymatic activity also. PLX was found to produce significant inhibition of biofilm formation and also decreased the levels of pyoverdin and pyocyanin. The microscopic analysis (both light microscopy and atomic force microscopy) of biofilms was also used for substantiating the findings from spectrophotometric (crystal violet estimation) and fluorescence analysis (resazurin uptake). PLX pre-treatment decreased the hydrophobicity of gram-positive and gram negative cells, indicating the effect of placental extract on adherence property of planktonic cell, serving as an indicator for its antibiofilm effect on microorganisms. The reduced extracellular DNA (eDNA) content in biofilm matrix following treatment with PLX also indicates the effectiveness of placenta extract on bacterial adherence, which in turn serves as evidence substantiating the antibiofilm effects of the PLX. Furthermore, PLX was also found to be significantly effective in the in vitro wound biofilm model. Thus the present study, the first of its kind with PLX, establishes the therapeutic benefit of the same particularly in infected wounds, opening up newer avenue for further exploration.


Asunto(s)
Biopelículas/efectos de los fármacos , Extractos Placentarios/farmacología , Pseudomonas aeruginosa/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Infección de Heridas/microbiología , Humanos , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/crecimiento & desarrollo , Pseudomonas aeruginosa/fisiología , Percepción de Quorum/efectos de los fármacos , Staphylococcus aureus/genética , Staphylococcus aureus/crecimiento & desarrollo , Staphylococcus aureus/fisiología
7.
Curr Res Food Sci ; 8: 100709, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38450094

RESUMEN

The unobservable use of hormones in fish production is becoming an alarming issue worldwide. To reveal the fact in Bangladesh, 144 fish samples (rui (Labeo rohita), catla (Catla catla), and monosex tilapia (Oreochromis niloticus)) were collected from different fish farms and markets of Mymensingh district. The market samples had two sources (Mymensingh and Rajshahi district). The steroid hormonal (testosterone, estrogen, and progesterone) residue was analyzed by HPLC-UV detection. A standard questionnaire survey was conducted where most farmers (80%) denied using the hormone in fish production. Among the analyzed samples of all three fishes, hormonal residues were detected in approximately 98% of samples, and around 92% contained residues above the ADI. Among the contaminated samples, 70% of samples had a single residue and 30% had multiple residues. The testosterone and progesterone hormonal residue was detected in all three fishes in both farm and market samples and ranged (above ADI) from 2.1 to 16.96 µg/kg and 31.47-731.57 µg/kg (p < 0.05) respectively. The estrogen hormone residue was only detected in market samples (Rajshahi district) of rui and catla and no residue was detected in tilapia fish and the hormone level (above ADI) ranged from 8.23 to 40.13 µg/kg. This study revealed that the use of hormones varies on the attitude of farmers based on the local culture pattern as estrogen hormone residue was only detected in market samples. The consumption of contaminated fish at such concentrations may cause many health hazards in humans, especially in children. Thus, this study reveals a new alarming fact to focus on, and an effective monitoring system should be implemented as soon as possible for public health concerns.

8.
Int J Dyn Control ; 11(1): 301-323, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35637768

RESUMEN

In this manuscript, we consider an epidemic model having constant recruitment of susceptible individuals with non-monotone disease transmission rate and saturated-type treatment rate. Two types of disease control strategies are taken here, namely vaccination for susceptible individuals and treatment for infected individuals to minimize the impact of the disease. We study local as well as global stability analysis of the disease-free equilibrium point and also endemic equilibrium point based on the values of basic reproduction number R 0 . Therefore, disease eradicates from the population if basic reproduction number less than unity and disease persists in the population if basic reproduction number greater than unity. We use center manifold theorem to study the dynamical behavior of the disease-free equilibrium point for R 0 = 1 . We investigate different bifurcations such as transcritical bifurcation, backward bifurcation, saddle-node bifurcation, Hopf bifurcation and Bogdanov-Takens bifurcation of co-dimension 2. The biological significance of all types of bifurcations are described. Some numerical simulations are performed to check the reliability of our theoretical approach. Sensitivity analysis is performed to identify the influential model parameters which have most impact on the basic reproduction number of the proposed model. To control or eradicate the influence of the emerging disease, we need to control the most sensitive model parameters using necessary preventive measures. We study optimal control problem using Pontryagin's maximum principle. Finally using efficiency analysis, we determine most effective control strategy among applied controls.

9.
Heliyon ; 9(5): e16186, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37234665

RESUMEN

Predicting landslides is becoming a crucial global challenge for sustainable development in mountainous areas. This research compares the landslide susceptibility maps (LSMs) prepared from five GIS-based data-driven bivariate statistical models, namely, (a) Frequency Ratio (FR), (b) Index of Entropy (IOE), (c) Statistical Index (SI), (d) Modified Information Value Model (MIV) and (e) Evidential Belief Function (EBF). These five models were tested in the high landslides-prone humid sub-tropical type Upper Tista basin of the Darjeeling-Sikkim Himalaya by integrating the GIS and remote sensing. The landslide inventory map consisting of 477 landslide locations was prepared, and about 70% of all landslide data was utilized for training the model, and 30% was used to validate it after training. A total of fourteen landslide triggering parameters (elevation, slope, aspect, curvature, roughness, stream power index, TWI, distance to stream, distance to road, NDVI, LULC, rainfall, modified fournier index, and lithology) were taken into consideration for preparing the LSMs. The multicollinearity statistics revealed no collinearity problem among the fourteen causative factors used in this study. Based on the FR, MIV, IOE, SI, and EBF approaches, 12.00%, 21.46%, 28.53%, 31.42%, and 14.17% areas, respectively, identified in the high and very high landslide-prone zones. The research also revealed that the IOE model has the highest training accuracy of 95.80%, followed by SI (92.60%), MIV (92.20%), FR (91.50%), and EBF (89.90%) models. Consistent with the actual distribution of landslides, the very high, high, and medium hazardous zones stretch along the Tista River and major roads. The suggested landslide susceptibility models have enough accuracy for usage in landslide mitigation and long-term land use planning in the study area. Decision-makers and local planners may utilise the study's findings. The techniques for determining landslide susceptibility can also be employed in other Himalayan regions to manage and evaluate landslide hazards.

10.
J Adv Vet Anim Res ; 10(4): 794-800, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38370881

RESUMEN

Objectives: Lead (Pb), a toxic heavy metal, is a serious concern for poultry that negatively affects their productivity and health. To combat those issues efficiently, it is necessary to include feed supplements that have rich antioxidant properties for satisfactory health and productivity. Spirulina platensis (Sp), a microalgae, is a compound that provides several health benefits for humans and animals. This study explores that supplementation of Sp in diet as well as in water reduces the burden of Pb in different tissues, improves hematology, and improves the productive performance of advanced-age laying hens. Materials and methods: Forty birds were separated into four groups: the control (C), Spirulina (Sp), Pb, and (Pb + Sp) groups. The Pb group was given Pb acetate at a dose of 2 gm/l in water ad libitum for 4 weeks. Sp group was fed Sp at a dose of 4 gm/kg feed. The Pb + Sp group was given Pb and Sp as in the previous groups. Results: Productive performance and hematology such as hemoglobin (Hb), packed cell volume, red blood cell, mean corpuscular volume, mean corpuscular Hb (MCH) concentration, and MCH were significantly (p < 0.05) decreased in Pb-treated groups compared to controls. The distribution of Pb concentration was highest in the bones and lowest in the gizzard. However, Sp treatment significantly (p < 0.05) increased the productive performance and the hematological parameters. Moreover, Pb concentration in different organs significantly decreased in the group treated with Sp. Conclusion: This study indicates that Sp can possibly be used as a natural and powerful dietary additive to mitigate heavy metal intoxication in chickens, thereby being efficient and effective for production.

11.
ERJ Open Res ; 9(3)2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37260462

RESUMEN

Background: Cigarette smoking remains a primary cause of chronic lung diseases. After a steady decline, smoking rates have recently increased especially with the introduction of newer electronic nicotine delivery devices, and it is also emerging that dual- or poly-product usage is on the rise. Additionally, with the introduction of IQOS (a heated tobacco product) globally, its impact on human health needs to be investigated. In this study we tested if dual exposure (cigarette smoke (CS)+IQOS) is detrimental to lung epithelial cells when compared with CS or IQOS exposure alone. Methods: Human airway epithelial cells (BEAS-2B) were exposed to either CS, IQOS or their dual combination (CS+IQOS) at concentrations of 0.1%, 1.0%, 2.5% and 5.0%. Cytotoxicity, oxidative stress, mitochondrial homeostasis, mitophagy and effects on epithelial-mesenchymal transition (EMT) signalling were assessed. Results: Both CS and IQOS alone significantly induced loss of cell viability in a concentration-dependent manner which was further enhanced by dual exposure compared with IQOS alone (p<0.01). Dual exposure significantly increased oxidative stress and perturbed mitochondrial homeostasis when compared with CS or IQOS alone (p<0.05). Additionally, dual exposure induced EMT signalling as shown by increased mesenchymal (α-smooth muscle actin and N-cadherin) and decreased epithelial (E-cadherin) markers when compared with CS or IQOS alone (p<0.05). Conclusion: Collectively, our study demonstrates that dual CS+IQOS exposure enhances pathogenic signalling mediated by oxidative stress and mitochondrial dysfunction leading to EMT activation, which is an important regulator of small airway fibrosis in obstructive lung diseases.

12.
Int Ophthalmol ; 32(6): 599-601, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22752649

RESUMEN

Scurvy is one of the oldest diseases known to mankind, caused by vitamin C deficiency. Nowadays it exists primarily in certain vulnerable populations such as patients with neurodevelopmental disabilities. Proptosis due to orbital haemorrhage is a rare complication of scurvy. Here we describe a case of diaplegic cerebral palsy presented with sudden onset of bilateral proptosis and swollen and tender knee joints. Subsequent computed tomography of the orbit revealed hematoma in the superior aspect of both orbits in the extraconal position. X-ray of the knee joints revealed bony changes consistent with scurvy. After 6 weeks of treatment with vitamin C orally, the proptosis and the bony changes returned to normal. Although scurvy is a rare disease in the general pediatric population, it still exists in certain vulnerable populations like neurologically disabled ones, and this uncommon cause for proptosis should be considered in such children.


Asunto(s)
Deficiencia de Ácido Ascórbico/complicaciones , Exoftalmia/etiología , Hematoma/complicaciones , Órbita/irrigación sanguínea , Preescolar , Diagnóstico Diferencial , Exoftalmia/diagnóstico , Exoftalmia/fisiopatología , Movimientos Oculares , Hematoma/diagnóstico , Humanos , Masculino , Tomografía Computarizada por Rayos X
13.
Sci Rep ; 12(1): 9141, 2022 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-35650252

RESUMEN

In the recent past, deep learning-based models have achieved tremendous success in computer vision-related tasks with the help of large-scale annotated datasets. An interesting application of deep learning is synthetic data generation, especially in the domain of medical image analysis. The need for such a task arises due to the scarcity of original data. Class imbalance is another reason for applying data augmentation techniques. Generative Adversarial Networks (GANs) are beneficial for synthetic image generation in various fields. However, stand-alone GANs may only fetch the localized features in the latent representation of an image, whereas combining different GANs might understand the distributed features. To this end, we have proposed AGGrGAN, an aggregation of three base GAN models-two variants of Deep Convolutional Generative Adversarial Network (DCGAN) and a Wasserstein GAN (WGAN) to generate synthetic MRI scans of brain tumors. Further, we have applied the style transfer technique to enhance the image resemblance. Our proposed model efficiently overcomes the limitation of data unavailability and can understand the information variance in multiple representations of the raw images. We have conducted all the experiments on the two publicly available datasets - the brain tumor dataset and the Multimodal Brain Tumor Segmentation Challenge (BraTS) 2020 dataset. Results show that the proposed model can generate fine-quality images with maximum Structural Similarity Index Measure (SSIM) scores of 0.57 and 0.83 on the said two datasets.


Asunto(s)
Neoplasias Encefálicas , Procesamiento de Imagen Asistido por Computador , Neoplasias Encefálicas/diagnóstico por imagen , Biología Computacional , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Redes Neurales de la Computación
14.
Eur J Pharmacol ; 915: 174467, 2022 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-34478690

RESUMEN

Airflow limitation in chronic obstructive pulmonary disease (COPD) is the result of exaggerated airway fibrosis and obliteration of the small airways due to persistent inflammation, and an impaired anti-oxidant response. EMT has been implicated as an active signalling process in cigarette smoke (CS)-induced lung pathology, and macrolide Azithromycin (AZT) use has gained interest in treating COPD. Here, we tested effectiveness of intra-nasal AZT alone and in combination with dexamethasone (DEX) on CS-induced acute lung inflammation. Human alveolar epithelial cells (A549) were treated with CS extract (CSE) for 48 h, and male Balb/c mice were exposed to CS (3 cigarettes-3 times/day) for 4 days. The effects of AZT alone (0.25 and 1.25 µM, in vitro; 0.5 and 5 mg/kg, in vivo) or in combination with DEX (1 µM, in vitro; 1 mg/kg, in vivo) on CS-induced cellular cytotoxicity, oxidative stress, inflammation, and lung function were assessed. AZT alone and in combination with DEX significantly inhibited the CS (E)-induced expression of mesenchymal protein markers and the regulatory protein ß-catenin. Furthermore, AZT by itself or in combination with DEX significantly suppressed CS-induced expression of the proinflammtory cytokines TNFα, IL1ß and IL6 and prevented pNFkB. Mechanistically, AZT restored the CS-induced reduction in anti-oxidant transcription factor NRF2 and upregulated HDAC2 levels, thereby repressing inflammatory gene expression. Beneficial effects of AZT functionally translated in improved lung mechanics in vivo. Further preclinical and clinical studies are warranted to fully establish and validate the therapeutic efficacy of AZT as a mono- or combination therapy for the treatment of COPD.


Asunto(s)
Azitromicina
15.
N Biotechnol ; 68: 77-86, 2022 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-35150929

RESUMEN

Paper-based nucleic acid detection and diagnosis are currently gaining much interest in point-of-care (POC) applications. The major steps involved in any nucleic acid amplification testing (NAAT) based diagnostics are nucleic acid isolation, reverse transcription (RT) (in the case of RNA), amplification and detection. RT is an important step in quantifying the viral load in case of disease diagnosis as well as quantifying gene expression levels in other molecular studies. cDNA synthesis is routinely carried out using a thermal cycler, with the process requiring temperatures between 40ºC to 65ºC. Here we report for the first time an instrument-free RT, performed at room temperature on cellulose-based paper devices. cDNA synthesis on paper was confirmed by RT-PCR and Sanger sequencing of the PCR products. Purified RNA from varied sources such as cell lysate, tissue and blood were used to test the methodology. Synthetic hepatitis C virus (HCV) RNA and human blood RNA were used as proof-of-concept to demonstrate the use of these devices in diagnostic applications. Further, ready-to-use paper-based reverse transcription (PRT) devices have been developed, wherein only the RNA sample is added on the device and the cDNA can be eluted after 30 min of incubation at room temperature. The devices were found to be stable for 30 days at - 20ºC storage. The cellulose-based PRT devices are simple, time saving and user-friendly for a complete instrument-free cDNA synthesis at room temperature.


Asunto(s)
Técnicas de Amplificación de Ácido Nucleico , Transcripción Reversa , Humanos , Técnicas de Amplificación de Ácido Nucleico/métodos , ARN , Temperatura
16.
Phytomedicine ; 97: 153926, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35030388

RESUMEN

BACKGROUND: Rheumatoid arthritis is a chronic and idiopathic autoimmune disorder. Perillyl alcohol (POH) is a monoterpene which can be extracted from widely available essential oils and is known for its strong anti-inflammatory and anti-oxidant properties. HYPOTHESIS/PURPOSE: Recent studies have been proven that inhibitors of farnesyltransferase enzyme showed significant anti-arthritic activity. POH is one such natural molecule having anti-inflammatory and anti-oxidant properties by inhibiting farnesyltransferase enzyme which further down regulates NF-κB and Nrf2 via Ras/Raf/MAPK pathway. Also, the effect of POH against rheumatoid arthritis is not known yet. Hence, the present research was intended to assess the anti-arthritic potential of POH in-vitro and in-vivo. METHODS: The in-vitro effects of POH on RAW 264.7 cells stimulated with LPS 1 µg/ml were investigated to its potential therapeutic effects. CFA 100 µl was intradermally administered to rats for the induction of arthritis. POH 100 mg/kg and 200 mg/kg administered topically from day 1 to day 28. Paw volumes measured, radiography analysis, anti-oxidant status, Gene expression studies, western blot analysis and histological analysis were performed to check the effects of POH. RESULTS: Our in-vitro findings suggested that POH inhibits inflammation by suppressing reactive oxygen species (ROS), NF-кB and Nrf2 signaling axis. Besides this, POH also rescinded the nitrate levels, pro-inflammatory cytokine levels like IL-1ß, IL-6 and TNF-α also PGE2 and COX-2 levels induced by LPS in murine macrophages. Additionally, our in-vivo results revealed that POH conscientiously alleviated CFA induced inflammation by restoring arthritis index, body weight, nitrosative, lipid peroxidation assays. Macroscopically through measuring paw volumes and X-ray, it was evidenced that POH has decreased inflammation and bone erosion. Not only in-vitro but also in-vivo, POH has abridged cytokine levels IL-1ß, IL-6, and TNF-α. Histopathological evaluation presented POH treatment alleviated joint inflammation, pannus formation, and bone erosion significantly. Moreover, POH suppressed the protein expression of NF-кB, COX-2, iNOS and improved Nrf2, and SOD2 levels in paw tissues estimated by western blotting. CONCLUSION: POH was effective in ameliorating LPS stimulation mediated oxidative stress and pro-inflammatory cytokines in RAW 264.7 cells in-vitro and FCA induced arthritis in rats in-vivo through its anti-inflammatory effects via regulating TLR4/NF-κB and Keap1/Nrf2 signaling pathways..


Asunto(s)
Artritis Experimental , Artritis Reumatoide , Animales , Artritis Experimental/tratamiento farmacológico , Artritis Reumatoide/tratamiento farmacológico , Citocinas/metabolismo , Inflamación , Proteína 1 Asociada A ECH Tipo Kelch , Lipopolisacáridos , Ratones , Modelos Teóricos , Monoterpenos/farmacología , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/metabolismo , Ratas , Transducción de Señal , Receptor Toll-Like 4
17.
Int Immunopharmacol ; 103: 108436, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34929480

RESUMEN

Psoriasis is a chronic inflammatory and proliferative skin disease characterized by pathological skin lesions which significantly impact the quality of life. Recent studies have been proven that inhibitors of farnesyltransferase enzyme showed significant anti-psoriatic activity. Perillyl alcohol (POH) is one such natural molecule having anti proliferative, anti-inflammatory and anti-oxidant properties by inhibiting farnesyltransferase enzyme which further down regulates NF-κB and STAT3 via Ras/Raf/MAPK pathway. Hence, in the current study we aimed to find the effect of POH on human keratinocytes (HaCat) cells in in-vitro and IMQ induced psoriatic like skin inflammation model in mice. POH significantly decreased the intracellular ROS levels and inhibited the phosphorylation of NF-κB and STAT3 in in-vitro. It was found that POH (200 mg/kg, topical application) has reduced the epidermal hyperplasia, psoriasis area and severity index (PASI) scoring; splenomegaly in imiquimod (IMQ) induced psoriatic mice. Further, POH treatment has decreased the pro-inflammatory serum cytokine levels such as IL-6, IL-12/23, TNF-α and IL-1ß and also reduced the expression levels of various inflammatory proteins, COX-2, iNOS, IL-17A, IL-22, NF-кB and STAT3 evidenced by Immunoblotting studies from skin samples. The levels of endogenous antioxidants like glutathione GSH, SOD, Nrf2 were restored to normal levels upon POH treatment. POH downregulated the proteins levels of TLR7, TLR8, CyclinD1 and mRNA expression of Bcl-2 in the skin samples when compared to the IMQ group. POH has ameliorated the hyper-keratosis and acanthosis which was evidenced by histopathology. Collectively, our results suggest that POH has a promising therapeutic application for ameliorating psoriasis-like skin inflammation.


Asunto(s)
Antiinflamatorios/uso terapéutico , Inflamación/tratamiento farmacológico , Queratinocitos/fisiología , Monoterpenos/uso terapéutico , Psoriasis/tratamiento farmacológico , Piel/patología , Animales , Proliferación Celular , Células Cultivadas , Humanos , Queratinocitos/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos ICR , FN-kappa B/metabolismo , Factor de Transcripción STAT3/metabolismo , Transducción de Señal
18.
Acta Paediatr ; 100(9): e132-4, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21342254

RESUMEN

AIM: We report a case of fulminant hepatitis and glomerulonephritis by Hepatitis A virus infection. METHODS: We observed the patient's clinical course and analyzed his data retrospectively. RESULTS: The three-year-old boy presented with features of acute renal failure and stage 2 hepatic encephalopathy. Renal biopsy showed diffuse mesangioproliferative glomerulonephritis with immunoglobulin M and complement 3 deposition. After receiving supportive treatment for over 6 weeks, the hepatic and renal function became normal. Renal biopsy after 3 months was normal. CONCLUSION: Acute renal failure is a rare complication of Hepatitis A virus infection. Physicians should be aware of the potential renal involvement of Hepatitis A virus infection as the prognosis is not always favourable.


Asunto(s)
Glomerulonefritis Membranoproliferativa/etiología , Encefalopatía Hepática/etiología , Hepatitis A/complicaciones , Hígado/patología , Preescolar , Complemento C3/metabolismo , Glomerulonefritis Membranoproliferativa/diagnóstico , Glomerulonefritis Membranoproliferativa/terapia , Encefalopatía Hepática/diagnóstico , Encefalopatía Hepática/terapia , Hepatitis A/diagnóstico , Hepatitis A/terapia , Virus de la Hepatitis A Humana/aislamiento & purificación , Humanos , Inmunoglobulina M/inmunología , Masculino , Estudios Retrospectivos
19.
Heliyon ; 7(9): e08035, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34622048

RESUMEN

With a huge amount of information being stored as structured data, there is an increasing need for retrieving exact answers to questions from tables. Answering natural language questions on structured data usually involves semantic parsing of query to a machine understandable format which is then used to retrieve information from the database. Training semantic parsers for domain specific tasks is a tedious job and does not guarantee accurate results. In this paper, we used conversational analytics tool to create the user interface and to get the required entities and intents from the query thus avoiding the traditional semantic parsing approach. We then make use of Knowledge Graph for querying in structured data domain. Knowledge graphs can be easily leveraged for question answering systems, to use them as the database. We extract appropriate answers for different types of queries which have been illustrated in the Results section.

20.
Sci Rep ; 11(1): 8304, 2021 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-33859222

RESUMEN

COVID-19, a viral infection originated from Wuhan, China has spread across the world and it has currently affected over 115 million people. Although vaccination process has already started, reaching sufficient availability will take time. Considering the impact of this widespread disease, many research attempts have been made by the computer scientists to screen the COVID-19 from Chest X-Rays (CXRs) or Computed Tomography (CT) scans. To this end, we have proposed GraphCovidNet, a Graph Isomorphic Network (GIN) based model which is used to detect COVID-19 from CT-scans and CXRs of the affected patients. Our proposed model only accepts input data in the form of graph as we follow a GIN based architecture. Initially, pre-processing is performed to convert an image data into an undirected graph to consider only the edges instead of the whole image. Our proposed GraphCovidNet model is evaluated on four standard datasets: SARS-COV-2 Ct-Scan dataset, COVID-CT dataset, combination of covid-chestxray-dataset, Chest X-Ray Images (Pneumonia) dataset and CMSC-678-ML-Project dataset. The model shows an impressive accuracy of 99% for all the datasets and its prediction capability becomes 100% accurate for the binary classification problem of detecting COVID-19 scans. Source code of this work can be found at GitHub-link .


Asunto(s)
COVID-19/diagnóstico por imagen , Redes Neurales de la Computación , Radiografía Torácica/métodos , Tomografía Computarizada por Rayos X/métodos , COVID-19/virología , Conjuntos de Datos como Asunto , Humanos , SARS-CoV-2/aislamiento & purificación
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