RESUMEN
Multimodal sentiment analysis, an increasingly vital task in the realms of natural language processing and machine learning, addresses the nuanced understanding of emotions and sentiments expressed across diverse data sources. This study presents the Hybrid LXGB (Long short-term memory Extreme Gradient Boosting) Model, a novel approach for multimodal sentiment analysis that merges the strengths of long short-term memory (LSTM) and XGBoost classifiers. The primary objective is to address the intricate task of understanding emotions across diverse data sources, such as textual data, images, and audio cues. By leveraging the capabilities of deep learning and gradient boosting, the Hybrid LXGB Model achieves an exceptional accuracy of 97.18% on the CMU-MOSEI dataset, surpassing alternative classifiers, including LSTM, CNN, DNN, and XGBoost. This study not only introduces an innovative model but also contributes to the field by showcasing its effectiveness and balance in capturing the nuanced spectrum of sentiments within multimodal datasets. The comparison with equivalent studies highlights the model's remarkable success, emphasizing its potential for practical applications in real-world scenarios. The Hybrid LXGB Model offers a unique and promising perspective in the realm of multimodal sentiment analysis, demonstrating the significance of integrating LSTM and XGBoost for enhanced performance.
RESUMEN
There has been an abrupt increase in brain tumor (BT) related medical cases during the past ten years. The tenth most typical type of tumor affecting millions of people is the BT. The cure rate can, however, rise if it is found early. When evaluating BT diagnosis and treatment options, MRI is a crucial tool. However, segmenting the tumors from magnetic resonance (MR) images is complex. The advancement of deep learning (DL) has led to the development of numerous automatic segmentation and classification approaches. However, most need improvement since they are limited to 2D images. So, this article proposes a novel and optimal DL system for segmenting and classifying the BTs from 3D brain MR images. Preprocessing, segmentation, feature extraction, feature selection, and tumor classification are the main phases of the proposed work. Preprocessing, such as noise removal, is performed on the collected brain MR images using bilateral filtering. The tumor segmentation uses spatial and channel attention-based three-dimensional u-shaped network (SC3DUNet) to segment the tumor lesions from the preprocessed data. After that, the feature extraction is done based on dilated convolution-based visual geometry group-19 (DCVGG-19), making the classification task more manageable. The optimal features are selected from the extracted feature sets using diagonal linear uniform and tangent flight included butterfly optimization algorithm. Finally, the proposed system applies an optimal hyperparameters-based deep neural network to classify the tumor classes. The experiments conducted on the BraTS2020 dataset show that the suggested method can segment tumors and categorize them more accurately than the existing state-of-the-art mechanisms.Communicated by Ramaswamy H. Sarma.
RESUMEN
Chitosan functionalization is a growing field of interest to enhance the unique characteristics of metal oxide nanoparticles. In this study, a facile synthesis method has been used to develop a gallotannin loaded chitosan/zinc oxide (CS/ZnO) nanocomposite. Initially, white color formation confirmed the formation, and physico-chemical natures of the prepared nanocomposite were examined using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) coupled with energy dispersive spectroscopy (EDS), and transmission electron microscopy (TEM). Crystalline of CS amorphous phase and ZnO patterns were demonstrated by XRD. FTIR revealed the presence of CS and gallotannin bio-active groups in the formed nanocomposite. Electron microscopy study exhibited that the produced nanocomposite had an agglomerated sheets like morphology with an average size of 50-130 nm. Further, the produced nanocomposite was evaluated for methylene blue (MB) degradation activity from aqueous solution. After 30 min of irradiation, the efficiency of nanocomposite degradation was found to be 96.64 %. Moreover, prepared nanocomposite showed a potential and concentration-dependent antibacterial activity against S. aureus. In conclusion, our findings demonstrated that prepared nanocomposite can be used as an excellent photocatalyst as well as a bactericidal agent in industrial and clinical sectors.
Asunto(s)
Quitosano , Nanopartículas del Metal , Nanocompuestos , Óxido de Zinc , Óxido de Zinc/química , Quitosano/química , Taninos Hidrolizables , Staphylococcus aureus , Antibacterianos/farmacología , Antibacterianos/química , Óxidos , Colorantes/química , Nanopartículas del Metal/química , Taninos , Nanocompuestos/química , Espectroscopía Infrarroja por Transformada de Fourier , Difracción de Rayos XRESUMEN
Austenitic stainless steels are prominent materials for their superior corrosion resistance and a combination of strength and ductility. However, the relatively low yield strength limits its application in high strength structural applications. Cryorolling is one of the promising methods of enhancing the mechanical properties of sheet metals. In the present work, Cryorolling of UNS S31000 stainless steel resulted in five-fold enhancement in yield strength with a significant loss in ductility. However, flash annealing at 800 °C for 120 s could restore its ductility up to 50% of its original ductility. The enhancement in strength is attributed to the formation of deformation nano-twins during flash annealing along with a bimodal grain structure.
RESUMEN
Due to growth in population, Individual persons with disabilities are increasing daily. To overcome the disability especially in Locked in State (LIS) due to Spinal Cord Injury (SCI), we planned to design four states moving robot from four imagery tasks signals acquired from three electrode systems by placing the electrodes in three positions namely T1, T3 and FP1. At the time of the study we extract the features from Continuous Wavelet Transform (CWT) and trained with Optimized Neural Network model to analyze the features. The proposed network model showed the highest performances with an accuracy of 93.86 % then that of conventional network model. To confirm the performances we conduct offline test. The offline test also proved that new network model recognizing accuracy was higher than the conventional network model with recognizing accuracy of 97.50 %. To verify our result we conducted Information Transfer Rate (ITR), from this analysis we concluded that optimized network model outperforms the other network models like conventional ordinary Feed Forward Neural Network, Time Delay Neural Network and Elman Neural Networks with an accuracy of 21.67 bits per sec. By analyzing classification performances, recognizing accuracy and Information Transformation Rate (ITR), we concluded that CWT features with optimized neural network model performances were comparably greater than that of normal or conventional neural network model and also the study proved that performances of male subjects was appreciated compared to female subjects.
Asunto(s)
Interfaces Cerebro-Computador , Equipos de Comunicación para Personas con Discapacidad , Electroencefalografía/métodos , Síndrome de Enclaustramiento/rehabilitación , Redes Neurales de la Computación , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Simulación por Computador , Electrodos , Femenino , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Caracteres Sexuales , Traumatismos de la Médula Espinal/rehabilitación , Análisis de Ondículas , Adulto JovenRESUMEN
Biomarkers reflecting the extent of Mycobacterium tuberculosis-induced pathology and normalization during anti-tuberculosis treatment (ATT) would considerably facilitate trials of new treatment regimens and the identification of patients with treatment failure. Therefore, in a cohort of 99 Indian children with intrathoracic tuberculosis (TB), we performed blood transcriptome kinetic analysis during ATT to explore 1) the association between transcriptional biomarkers in whole blood (WB) and the extent of TB disease at diagnosis and treatment outcomes at 2 and 6 months, and 2) the potential of the biomarkers to predict treatment response at 2 and 6 months. We present the first data on the association between transcriptional biomarkers and the extent of TB disease as well as outcome of ATT in children: Expression of three genes down-regulated on ATT (FCGR1A, FPR1 and MMP9) exhibited a positive correlation with the extent of TB disease, whereas expression of eight up-regulated genes (BCL, BLR1, CASP8, CD3E, CD4, CD19, IL7R and TGFBR2) exhibited a negative correlation with the extent of disease. Baseline levels of these transcripts displayed an individual capacity >70% to predict the six-month treatment outcome. In particular, BLR1 and FCGR1A seem to have a potential in monitoring and perhaps tailoring future antituberculosis therapy.
Asunto(s)
ARN Mensajero/sangre , Receptores CXCR5/genética , Receptores de IgG/genética , Tuberculosis Pulmonar/sangre , Adolescente , Antituberculosos/uso terapéutico , Biomarcadores , Niño , Preescolar , Estudios Transversales , Método Doble Ciego , Femenino , Regulación de la Expresión Génica , Humanos , India , Lactante , Masculino , Desnutrición/complicaciones , Desnutrición/tratamiento farmacológico , Manganeso/uso terapéutico , Micronutrientes/uso terapéutico , Pronóstico , Estudios Prospectivos , ARN Mensajero/genética , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/genética , Tuberculosis Pulmonar/inmunología , Zinc/uso terapéuticoRESUMEN
The World Health Organization (WHO) calls for an accurate, rapid, and simple point-of-care (POC) test for the diagnosis of pediatric tuberculosis (TB) in order to make progress "Towards Zero Deaths". Whereas the sensitivity of a POC test based on detection of Mycobacterium tuberculosis (MTB) is likely to have poor sensitivity (70-80% of children have culture-negative disease), host biomarkers reflecting the on-going pathological processes across the spectrum of MTB infection and disease may hold greater promise for this purpose. We analyzed transcriptional immune biomarkers direct ex-vivo and translational biomarkers in MTB-antigen stimulated whole blood in 88 Indian children with intra-thoracic TB aged 6 months to 15 years, and 39 asymptomatic siblings. We identified 12 biomarkers consistently associated with either clinical groups "upstream" towards culture-positive TB on the TB disease spectrum (CD14, FCGR1A, FPR1, MMP9, RAB24, SEC14L1, and TIMP2) or "downstream" towards a decreased likelihood of TB disease (BLR1, CD3E, CD8A, IL7R, and TGFBR2), suggesting a correlation with MTB-related pathology and high relevance to a future POC test for pediatric TB. A biomarker signature consisting of BPI, CD3E, CD14, FPR1, IL4, TGFBR2, TIMP2 and TNFRSF1B separated children with TB from asymptomatic siblings (AUC of 88%).
Asunto(s)
Mycobacterium tuberculosis/inmunología , Tuberculosis/diagnóstico , Biomarcadores/sangre , Niño , Estudios Transversales , Femenino , Humanos , Masculino , Sistemas de Atención de Punto , Tuberculosis/sangre , Tuberculosis/inmunologíaRESUMEN
Colorectal cancer (CRC) is the third most common cancer in the world, and second leading cause of cancer deaths in the US. Although, anti-EGFR therapy is commonly prescribed for CRC, patients harboring mutations in KRAS or BRAF show poor treatment response, indicating an ardent demand for new therapeutic targets discovery. SPINK1 (serine peptidase inhibitor, Kazal type 1) overexpression has been identified in many cancers including the colon, lung, breast and prostate. Our study demonstrates the functional significance of SPINK1 in CRC progression and metastases. Stable knockdown of SPINK1 significantly decreases cell proliferation, invasion and soft agar colony formation in the colon adenocarcinoma WiDr cells. Conversely, an increase in these oncogenic phenotypes was observed on stimulation with SPINK1-enriched conditioned media (CM) in multiple benign models such as murine colonic epithelial cell lines, MSIE and YAMC (SPINK3-negative). Mechanistically, SPINK1 promotes tumorigenic phenotype by activating phosphatidylinositol 3-kinase (PI3K/AKT) and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathways, and the SPINK1-positive WiDr cells are sensitive to AKT and MEK inhibitors. Importantly, SPINK1 silencing mediated upregulation of various Metallothionein isoforms, considered as tumor suppressors in CRC, confer sensitivity to doxorubicin, which strengthens the rationale for using the combinatorial treatment approach for the SPINK1-positive CRC patients. Furthermore, in vivo studies using chicken chorioallantoic membrane assay, murine xenograft studies and metastasis models further suggest a pivotal role of SPINK1 in CRC progression and metastasis. Taken together, our study demonstrates an important role for the overexpressed SPINK1 in CRC disease progression, a phenomenon that needs careful evaluation towards effective therapeutic target development.
RESUMEN
BACKGROUND: Non-tuberculous mycobacteria (NTM) are different from Mycobacterium tuberculosis (MTB) both in their ubiquitous environmental distribution and in their reduced capacity to cause disease. While often neglected in favour of other infectious diseases, NTM may interfere with important aspects of TB control and management, namely the efficacy of new anti-tuberculosis (TB) vaccines; the immuno-diagnostic Tuberculin skin test (TST) and QuantiFERON TB Gold In Tube assay (QFTGIT); and immune biomarkers explored for their diagnostic and/or predictive potential. Our objective was therefore to explore host immune biomarkers in children who had NTM isolated from respiratory and/or gastric specimens. METHODOLOGY AND PRINCIPLE FINDINGS: The present study was nested within a prospective cohort study of BCG-vaccinated neonates in Southern India. In this setting, immune biomarkers from peripheral blood were analyzed in 210 children aged <3 years evaluated for TB using dual-colour-Reverse-Transcriptase-Multiple-Ligation-dependent-Probe-Amplification (dcRT-MLPA) and Bio-Plex assays. The children were classified based on clinical examination, chest X-rays and mycobacterial culture reports as either: 1) TB disease, 2) NTM present and 3) controls. The study shows a down-regulation of RAB33A (p<0.001) and up-regulation of TGFß1, IL-2 and IL-6 (all p<0.05) in children with TB disease, and that RAB33A, TGFBR2 and IL-10 (all p<0.05) were differentially expressed in children with NTM present when compared to children that were culture negative for MTB and NTM (controls). CONCLUSIONS AND SIGNIFICANCE: Carriage of NTM may reduce the specificity of future diagnostic and predictive immune biomarkers relevant to TB management.
Asunto(s)
Vacuna BCG/inmunología , Biomarcadores/sangre , Micobacterias no Tuberculosas/inmunología , Prueba de Tuberculina , Tuberculosis/diagnóstico , Preescolar , Estudios de Cohortes , Regulación hacia Abajo , Femenino , Humanos , India , Lactante , Recién Nacido , Interleucina-10/biosíntesis , Interleucina-2/biosíntesis , Interleucina-6/biosíntesis , Masculino , Mycobacterium tuberculosis/inmunología , Micobacterias no Tuberculosas/aislamiento & purificación , Estudios Prospectivos , Sensibilidad y Especificidad , Factor de Crecimiento Transformador beta1/biosíntesis , Tuberculosis/microbiología , Tuberculosis/terapia , Regulación hacia Arriba , Proteínas de Unión al GTP rab/biosíntesisRESUMEN
The tuberculin skin test (TST) and QuantiFERON-TB-Gold-In-tube (QFTGIT) are adjunctive tests used in the diagnosis of pediatric tuberculosis (TB). Neither test can rule out TB; however, a positive test usually triggers preventive treatment in TB contacts aged <5 years. TST and QFTGIT can give divergent results and it is unclear how discordant results should be interpreted in terms of TB risk and preventive treatment. To understand the immune processes underlying concordant or discordant TST and QFTGIT results, we analyzed immune responses in children from Palamaner Taluk in India (a TB-endemic region with routine neonatal BCG vaccination) who were referred to a TB case verification ward on suspicion of TB. Two hundred and ten children aged <3 years were classified according to their TST and QFTGIT results, and their immune responses analyzed by dual-colour-Reverse-Transcriptase-Multiple-Ligation-dependent-Probe-Amplification, using a panel of 45 genes and a 10-plex antigen-specific enzyme-linked immunosorbent assay. We show that immune biomarkers FPR1, TNFRSF1A and interferon (IFN)-γ are upregulated (all P<0.05) in concordant test-positive children, whereas BPI is downregulated (P<0.05). In contrast, SEC14L1 (P=0.034) and Interferon gamma-induced protein 10 (IP-10) (P=0.001) are differentially expressed between the TST+QFTGIT- /TST-QFTGIT+ groups. Known TB exposure was more frequent in concordant positive children and results were consistent with elevated expression of genes associated with inflammatory responses. Children with discordant test results displayed a mixed profile with activation of both pro- and anti-inflammatory markers. TST and/or QFTGIT positivity appears to reflect distinct but overlapping aspects of host immunity.
Asunto(s)
Prueba de Tuberculina/normas , Tuberculosis/diagnóstico , Adolescente , Adulto , Biomarcadores/sangre , Proteínas Portadoras/sangre , Femenino , Humanos , India , Lactante , Recién Nacido , Interferón gamma/sangre , Estudios Longitudinales , Masculino , Reacción en Cadena de la Polimerasa Multiplex/normas , Estudios Prospectivos , Receptores de Formil Péptido/sangre , Receptores Tipo I de Factores de Necrosis Tumoral/sangre , Sensibilidad y Especificidad , Tuberculosis/inmunología , Regulación hacia ArribaRESUMEN
Bluetongue is an infectious disease caused by bluetongue virus (BTV), which affects sheep, goat, cattle and certain wild ruminants. However severe clinical signs are usually seen with significant mortality in sheep than cattle and goat. To date, comparative studies on innate immune responses of sheep and goat infected with BTV is lacking. In this study, we compared the innate immune response of sheep and goat by infecting the peripheral blood mononuclear cells (PBMCs) with BTV serotype 23. In our study, we observed that sheep PBMCs supports higher virus replication than goat PBMCs. To delineate the role of innate immune response in differential viral replication observed in this study, we examined TLR3 (Receptor for dsRNA virus) mRNA expression and cytokine profiles (IL-1ß, Il-6, IL-8, Il-10, IL-12p40, TNF-α, IFN-γ and IFN-α) following Poly I:C (TLR3 ligand) stimulation and BTV 23 infection. In our present study, sheep PBMCs had significantly higher TLR3 mRNA levels, TLR3 specific ligand (Poly I:C) stimulation resulted in increased levels of IFN-γ at transcriptional and translational levels along with IL-8 and IL-10 at transcriptional levels. Whereas, the levels of TNF-α was higher in goat PBMCs at transcriptional levels. BTV infected sheep PBMCs expressed significantly higher levels of IFN-γ at transcriptional and translational levels along with IL-6, IL-8 and IL-10 at transcriptional levels. Whereas the expression levels of TNF-α and IFN-α at transcriptional and translational levels were significantly high in goat PBMCs. To examine the potential factor for consistent increase in the expression of TNF-α, we sequenced the promoter region of TNF-α and identified a total of five single nucleotide polymorphisms (SNP) and one indel in goat TNF-α promoter region. Luciferase assay for transcriptional activity of the promoter showed that goat TNF-α has significantly enhanced transcriptional activity in comparison with sheep TNF-α promoter. Altogether, our data suggests that the expression levels of TNF-α and IFN-α and/or IL-10 plays crucial role in replication of BTV 23.
Asunto(s)
Virus de la Lengua Azul/inmunología , Enfermedades de las Cabras/inmunología , Inmunidad Innata/inmunología , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/virología , Adyuvantes Inmunológicos/farmacología , Animales , Lengua Azul/inmunología , Citocinas/sangre , Regulación de la Expresión Génica/efectos de los fármacos , Enfermedades de las Cabras/virología , Cabras/inmunología , Inmunidad Innata/efectos de los fármacos , Poli I-C/farmacología , Polimorfismo Genético/genética , Regiones Promotoras Genéticas/genética , Ovinos/inmunología , Carga ViralRESUMEN
AIM: To determine the larvicidal activity of various extracts of Gymnema (G.) sylvestre against the Japanese Encephalitis vector, Culex tritaeniorynchus in Tamilnadu, India. To identify the active principle present in the promising fraction obtained in Chlorofom:Methanol extract of Fraction 2. MATERIALS AND METHODS: The G. Sylvestre leaf extracts were tested, employing WHO procedure against fourth instar larvae of C. tritaeniorhynchus and the larval mortalities were recorded at various concentrations (6.25 microg/ml); the 24h LC(50) values of the G. Sylvestre leaf extracts were determined following Probit analysis. It was noteworthy, that treatment level 100 ppm exhibited highest mortality rates for the three different crude extracts and was significantly different from the mean mortalities recorded for the other concentrations. RESULTS: The LC(50) values of 34.756 microg/ml (24.475-51.41), 31.351 microg/ml (20.634-47.043) and 28.577 microg/ml (25.159-32.308) were calculated in acetone, chloroform and methanol extract with the chi-square values of 10.301, 31.351 and 4.093 respectively. CONCLUSIONS: The present investigation proved that G. Sylvestre could be possibly utilized as an important component in the Vector control Programme.
Asunto(s)
Culex , Encefalitis Japonesa/transmisión , Gymnema sylvestre/química , Insectos Vectores , Insecticidas/farmacología , Control de Mosquitos , Saponinas/farmacología , Animales , Larva/efectos de los fármacosRESUMEN
Pediatric tuberculosis (TB) often goes undiagnosed because of the lack of reliable diagnostic methods. With the aim of assessing biomarker(s) that can aid in the diagnosis of TB infection and disease, we investigated 746 Indian children with suspected TB. Whole-blood mRNA from 210 children was examined by dual-color Reverse-Transcriptase Multiple Ligation-dependent Probe-Amplification for the expression of 45 genes and a Bio-Plex assay for the expression of cytokines/chemokines in QuantiFERON supernatants. The study shows that transcription of SEC14L1, GUSB, BPI, CCR7 and TGFß-1 (all P ≤ 0.05) was downregulated in TB disease compared with uninfected controls, while transcription of RAB33A was downregulated in TB disease compared with both latent TB (P < 0.05) and controls (P < 0.01). The transcription of CD4, TGFß-1 (P < 0.01) and the expression of IL-2 (P < 0.01) and IL-13 (P < 0.05) was upregulated in latent TB compared with that in controls. Using the Least Absolute Shrinkage and Selection Operator (lasso) model, RAB33A alone discriminated between TB disease and latent TB (area under the curve (AUC) 77.5%), whereas a combination of RAB33A, CXCL10, SEC14L1, FOXP3 and TNFRSF1A was effective in discriminating between TB disease and controls (AUC 91.7%). A combination of 11 biomarkers predicted latent TB with moderate discriminatory power (AUC 72.2%). In conclusion, RAB33A is a potential biomarker for TB disease, whereas CD4, TGFß-1 and IL-2, IL-13 may identify latent TB in children.
Asunto(s)
Antígenos CD4/metabolismo , Interleucina-13/metabolismo , Interleucina-2/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Tuberculosis/diagnóstico , Proteínas de Unión al GTP rab/metabolismo , Vacuna BCG/uso terapéutico , Biomarcadores/metabolismo , Antígenos CD4/genética , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Estudios de Casos y Controles , Quimiocina CXCL10/genética , Quimiocina CXCL10/metabolismo , Preescolar , Femenino , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/metabolismo , Humanos , India , Lactante , Recién Nacido , Interleucina-13/genética , Interleucina-2/genética , Masculino , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores Tipo I de Factores de Necrosis Tumoral/genética , Receptores Tipo I de Factores de Necrosis Tumoral/metabolismo , Factor de Crecimiento Transformador beta1/genética , Tuberculosis/metabolismo , Tuberculosis/prevención & control , Proteínas de Unión al GTP rab/genéticaRESUMEN
The use of the herbicide paraquat (1,1'-dimethyl-4,4'-bipyridylium dichloride; PQ) which is widely used in agriculture is known to cause dopaminergic neurotoxicity. However, the mechanisms underlying this effect are not fully understood. This present study investigated the behavioral manifestations, motor coordination, and dopaminergic neurodegeneration following exposure to PQ. Male rats were injected with PQ (10 mg/kg i.p.) daily for three weeks. Rotarod systems were used for measuring locomotor activity and motor coordination. The effects of PQ on dorsiflexor, electrophysiologically-induced muscle contraction were studied. Dopamine concentrations in the ventral mesencephalon were measured by high performance liquid chromatography and the number of dopaminergic neurons in substantia nigra pars compacta was estimated by tyrosine hydroxylase immunohistochemistry. PQ induced difficulty in movement and significant reduction in motor activity and twitch tension at the dorsiflexor skeletal muscle. The number of tyrosine hydroxylase positive neurons was significantly less in the substantia nigra pars compacta and nigral dopamine level was significantly reduced in PQ treated animals (20.4+/-3.4 pg/mg) when compared with control animals (55.0+/-2.4 pg/mg wet tissue). Daily treatment of PQ for three weeks induces selective dopaminergic neuronal loss in the substantia nigra and significant behavioral and peripheral motor deficit effects.
Asunto(s)
Dopamina/metabolismo , Actividad Motora/efectos de los fármacos , Fuerza Muscular/efectos de los fármacos , Músculo Esquelético/fisiopatología , Paraquat/envenenamiento , Sustancia Negra/metabolismo , Animales , Ataxia/inducido químicamente , Ataxia/fisiopatología , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo/efectos de los fármacos , Herbicidas/envenenamiento , Masculino , Músculo Esquelético/efectos de los fármacos , Enfermedades Musculares/inducido químicamente , Enfermedades Musculares/fisiopatología , Neurotoxinas/envenenamiento , Ratas , Ratas Wistar , Sustancia Negra/efectos de los fármacosRESUMEN
The objective of this study was to assess cytokine production upon activation of pattern recognition receptors responsible for sensing bacterial and viral pathogen associated molecular patterns in two genetically diverse buffalo breeds, Toda and Murrah. A very limited molecular-epidemiological analysis showed a higher prevalence of Anaplasma and Theileria in Murrah than Toda buffaloes. Toda buffalo peripheral blood mononuclear cells (PBMC) produced significantly higher levels of IFN γ and/or TNF α mRNAs in response to peptidoglycan, poly I:C, lipopolysaccharide, imiquimod and CpG. Flagellin stimulation did not result in any significant differences in the expression levels of the cytokines tested between these breeds. The levels of ligand induced IFN γ and TNF α mRNA and proteins also correlated except when induced with CpG. The proximal promoter region of TNF α across these two breeds were also sequenced to detect SNPs and promoter assay performed to determine their role in altering the transcriptional activity. Two polymorphisms were identified at -737 (T/A) and -1092 (G/T) positions in Toda buffalo TNF α promoter and promoter assay revealed higher transcription activity in Toda buffalos than in Murrah. This suggests that disease tolerance of these buffalo breeds could be due to the differences in their cytokine transcription levels in response to the respective PAMPs that may be at least in part determined by polymorphisms in the cytokine promoter regions.
Asunto(s)
Búfalos/genética , Citocinas/metabolismo , Regulación de la Expresión Génica/inmunología , Regiones Promotoras Genéticas/genética , Receptores Toll-Like/agonistas , Factor de Necrosis Tumoral alfa/metabolismo , Adyuvantes Inmunológicos/farmacología , Aminoquinolinas/farmacología , Anaplasma/aislamiento & purificación , Anaplasmosis/sangre , Anaplasmosis/diagnóstico , Anaplasmosis/inmunología , Animales , Bacterias/metabolismo , Búfalos/metabolismo , Citocinas/genética , Imiquimod , Leucocitos Mononucleares/metabolismo , Ligandos , Lipopolisacáridos/farmacología , Peptidoglicano/farmacología , Polimorfismo Genético , ARN Mensajero/genética , ARN Mensajero/metabolismo , Theileria/aislamiento & purificación , Theileriosis/sangre , Theileriosis/diagnóstico , Theileriosis/inmunología , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
BACKGROUND & OBJECTIVES: Development of plant-based alternative compounds for mosquito control has gained importance now-a-days, in view of increasing resistance in mosquito vectors to existing insecticides. The larvicidal and repellent activities of benzene, chloroform, hexane and methanol leaf extracts of Indian medicinal plant, Adansonia digitata were investigated against malarial vector, Anopheles stephensi. METHODS: In all, 25 III instar larvae of An. stephensi were exposed to various concentrations (30-180 mg/l) in the laboratory by using the standard protocol described by WHO (2005). The larvae were exposed for 24 h and mortalities were subjected to log-probit analysis. Repellent activity of crude leaf extract at the dosages of 2, 4 and 6 mg/cm2 was evaluated in a net cage (45 × 30 × 45 cm) containing 100 blood starved female mosquitoes of An. stephensi using the protocol of WHO (1996). RESULTS: Preliminary phytochemical analysis of A. digitata showed the presence of triterpenoids and saponins. The LC50 and LC90 values of hexane, benzene, chloroform, and methanol extracts of A. digitata against An. stephensi larvae in 24 h were 111.32, 97.13, 88.55, 78.18 and 178.63, 176.19, 168.14, 155.42 mg/l, respectively. The repellent activity of methanol extract was found to be most effective and at higher concentration of 6 mg/cm2 benzene, chloroform hexane and methanol extracts provided 100% protection up to 150, 180, 120 and 210 min against An. stephensi, respectively. CONCLUSION: The preliminary study indicated that A. digitata showed larvicidal and repellent activities against An. stephensi and could be used for controlling mosquitoes. Further studies are indicated to purify the active compounds from these plants for developing larvicide and repellents.
Asunto(s)
Adansonia/química , Anopheles/efectos de los fármacos , Repelentes de Insectos/farmacología , Insecticidas/farmacología , Extractos Vegetales/farmacología , Animales , Vectores de Enfermedades , Femenino , Humanos , India , Repelentes de Insectos/aislamiento & purificación , Insecticidas/aislamiento & purificación , Larva/efectos de los fármacos , Extractos Vegetales/aislamiento & purificación , Hojas de la Planta/química , Análisis de SupervivenciaRESUMEN
The primary objective of this study was to assess the expression profile and levels of toll-like receptor (TLR) mRNAs in the spleen, lung, mediastinal lymph node (MLN), jejunum, rectum, skin and peripheral blood mononuclear cells (PBMC) of Toda and Murrah buffalos. Spleen and PBMC had increased expression of TLR mRNAs 2, 4, 5, 6, 8, 9 and 10; lung had increased expression of TLR mRNAs 2, 4, 5, 6 and 8, MLN TLR mRNA 6, 9, 10 and decrease in TLR 3 and 7 mRNAs in skin. No significant differences were observed in the expression levels of any of the TLR mRNA in jejunum and rectum. Toda buffaloes showed significantly higher expression levels of TLR 9 mRNA in MLN, TLR mRNAs 1, 5, 6, 9 and 10 in skin and TLR mRNAs 2, 4, 7 and 9 in PBMC than Murrah buffaloes living in the vicinity. Toda and Murrah buffaloes were inoculated with TLR5 (flagellin) and TLR9 (CpG ODN) ligands in vivo and expression levels of the respective TLRs analyzed 12h later. Following CpG inoculation, Toda buffaloes had significantly higher levels of TLR 9 mRNA expression but not in Murrah. However, flagellin induction did not increase TLR 5 mRNA expression in both these breeds. Histological sections of the skin were made and infiltrating cell clusters were graded and quantified. Following CpG inoculation, Toda buffaloes showed higher numbers of infiltrating grade 1 and grade 3 cell clusters while Murrah showed lower numbers of infiltrating grade 1 cells as compared to mock-inoculated skin sections. Flagellin treatment revealed no significant differences in infiltrating cell clusters in both the breeds. The results have shown differential expression of TLR mRNAs in various tissues between two divergent buffalo breeds with the highest difference in TLR expression profile seen in the skin, the largest portal of entry of pathogens, of Toda.
Asunto(s)
Búfalos/inmunología , Perfilación de la Expresión Génica , Receptores Toll-Like/genética , Animales , Biopsia , Cruzamiento , India , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Piel/inmunología , Piel/patologíaRESUMEN
Cadmium (Cd), an environmental and industrial pollutant, poses a potential threat and affects many systems in human and animals. Although several reports on Cd toxicity were presented, the acute effect of Cd on systemic and thrombotic events was not reported so far. Cd (2.284 mg/kg) or saline (control) was injected intraperitoneally (ip), and the systemic parameters were assessed in mice. Compared to control group, acute intraperitoneal injection of Cd, in mice showed significant quickening of platelet aggregation (P<0.001) leading to pial cerebral thrombosis. Likewise, Cd exposure caused a significant increase in white blood cell numbers (P<0.05) indicating the occurrence of systemic inflammation. Also, alanine aminotransferase (ALT) (P<0.05) and creatinine (P<0.01) levels were both significantly increased. Interestingly, the superoxide dismutase activity was significantly decreased in Cd treated group compared to control group (P<0.001), suggesting the occurrence of oxidative stress. We conclude that the Cd exposure in mice causes acute thromboembolic events, oxidative stress and alter liver and kidney functions.
Asunto(s)
Cadmio/toxicidad , Inflamación/metabolismo , Tromboembolia/metabolismo , Alanina Transaminasa/metabolismo , Animales , Creatinina/metabolismo , Inflamación/inducido químicamente , Riñón/efectos de los fármacos , Riñón/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos , Estrés Oxidativo/efectos de los fármacos , Tromboembolia/inducido químicamenteRESUMEN
The number of myenteric interstitial cells of Cajal (ICC-MY), responsible for the generation and propagation of the slow wave in the small intestine, has been shown to decrease in diabetes, suggesting impairment of slow-wave (SW) propagation and related motility. To date, however, this expected decrease in SW propagation has neither been recorded nor analysed. Eleven rats were treated with streptozotocin and housed in pairs with 11 age-matched control animals. After 3 or 7 months, segments of duodenum, jejunum and ileum were isolated and divided into two parts. One part was processed for immediate freezing, cryosectioning and immunoprobing using anti-c-Kit antibody to quantify ICC-MY. The second part was superfused in a tissue bath, and SW propagation was recorded with 121 extracellular electrodes. In addition, a cellular automaton was developed to study the effects of increasing the number of inactive cells on overall propagation. The number of ICC-MY was significantly reduced after 3 months of diabetes, but rebounded to control levels after 7 months of diabetes. Slow-wave frequencies, velocities and extracellular amplitudes were unchanged at any stage of diabetes. The cellular automaton showed that SW velocity was not linearly related to the number of inactive cells. The depletion of ICC-MY is not as severe as is often assumed and in fact may rebound after some time. In addition, at least in the streptozotocin model, the initial reduction in ICC-MY is not enough to affect SW propagation. Diabetic intestinal dysfunction may therefore be more affected by impairments of other systems, such as the enteric system or the muscle cells.