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1.
Genes Immun ; 15(5): 265-74, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24739497

RESUMO

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.


Assuntos
Teste Tuberculínico/normas , Tuberculose/diagnóstico , Adolescente , Adulto , Biomarcadores/sangue , Proteínas de Transporte/sangue , Feminino , Humanos , Índia , Lactente , Recém-Nascido , Interferon gama/sangue , Estudos Longitudinais , Masculino , Reação em Cadeia da Polimerase Multiplex/normas , Estudos Prospectivos , Receptores de Formil Peptídeo/sangue , Receptores Tipo I de Fatores de Necrose Tumoral/sangue , Sensibilidade e Especificidade , Tuberculose/imunologia , Regulação para Cima
2.
Artigo em Inglês | MEDLINE | ID: mdl-38340022

RESUMO

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.

3.
Genes Immun ; 14(6): 356-64, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23676757

RESUMO

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.


Assuntos
Antígenos CD4/metabolismo , Interleucina-13/metabolismo , Interleucina-2/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Tuberculose/diagnóstico , Proteínas rab de Ligação ao GTP/metabolismo , Vacina BCG/uso terapêutico , Biomarcadores/metabolismo , Antígenos CD4/genética , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Estudos de Casos e Controles , Quimiocina CXCL10/genética , Quimiocina CXCL10/metabolismo , Pré-Escolar , Feminino , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Humanos , Índia , Lactente , Recém-Nascido , Interleucina-13/genética , Interleucina-2/genética , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Fator de Crescimento Transformador beta1/genética , Tuberculose/metabolismo , Tuberculose/prevenção & controle , Proteínas rab de Ligação ao GTP/genética
4.
Eur Rev Med Pharmacol Sci ; 17(10): 1404-10, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23740457

RESUMO

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.


Assuntos
Culex , Encefalite Japonesa/transmissão , Gymnema sylvestre/química , Insetos Vetores , Inseticidas/farmacologia , Controle de Mosquitos , Saponinas/farmacologia , Animais , Larva/efeitos dos fármacos
5.
J Biomol Struct Dyn ; : 1-12, 2023 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-37979152

RESUMO

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.

6.
Int J Biol Macromol ; 243: 125052, 2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-37245753

RESUMO

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.


Assuntos
Quitosana , Nanopartículas Metálicas , Nanocompostos , Óxido de Zinco , Óxido de Zinco/química , Quitosana/química , Taninos Hidrolisáveis , Staphylococcus aureus , Antibacterianos/farmacologia , Antibacterianos/química , Óxidos , Corantes/química , Nanopartículas Metálicas/química , Taninos , Nanocompostos/química , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
7.
J Vector Borne Dis ; 49(2): 86-90, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22898480

RESUMO

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.


Assuntos
Adansonia/química , Anopheles/efeitos dos fármacos , Repelentes de Insetos/farmacologia , Inseticidas/farmacologia , Extratos Vegetais/farmacologia , Animais , Vetores de Doenças , Feminino , Humanos , Índia , Repelentes de Insetos/isolamento & purificação , Inseticidas/isolamento & purificação , Larva/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Análise de Sobrevida
8.
Exp Physiol ; 96(10): 1039-48, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21742753

RESUMO

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.


Assuntos
Diabetes Mellitus Experimental/fisiopatologia , Motilidade Gastrointestinal/fisiologia , Células Intersticiais de Cajal/fisiologia , Intestino Delgado/fisiologia , Plasticidade Neuronal/fisiologia , Animais , Intestino Delgado/fisiopatologia , Masculino , Ratos , Ratos Wistar
9.
Nat Med ; 6(8): 898-903, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10932227

RESUMO

The parasite Plasmodium berghei imports the enzyme delta-aminolevulinate dehydratase (ALAD), and perhaps the subsequent enzymes of the pathway from the host red blood cell to sustain heme synthesis. Here we have studied the mechanism of this import. A 65-kDa protein on the P. berghei membrane specifically bound to mouse red blood cell ALAD, and a 93-amino-acid fragment (ALAD-DeltaNC) of the host erythrocyte ALAD was able to compete with the full-length enzyme for binding to the P. berghei membrane. ALAD-DeltaNC was taken up by the infected red blood cell when added to a culture of P. falciparum and this led to a substantial decrease in ALAD protein and enzyme activity and, subsequently, heme synthesis in the parasite, resulting in its death.


Assuntos
Plasmodium berghei/enzimologia , Sintase do Porfobilinogênio/metabolismo , Animais , Antimaláricos/farmacologia , Transporte Biológico Ativo , Membrana Celular/enzimologia , Eritrócitos/enzimologia , Eritrócitos/parasitologia , Heme/biossíntese , Malária/tratamento farmacológico , Malária/enzimologia , Malária/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Plasmodium berghei/efeitos dos fármacos , Sintase do Porfobilinogênio/genética
10.
Artif Intell Med ; 102: 101766, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31980103

RESUMO

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.


Assuntos
Interfaces Cérebro-Computador , Auxiliares de Comunicação para Pessoas com Deficiência , Eletroencefalografia/métodos , Síndrome do Encarceramento/reabilitação , Redes Neurais de Computação , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Simulação por Computador , Eletrodos , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Caracteres Sexuais , Traumatismos da Medula Espinal/reabilitação , Análise de Ondaletas , Adulto Jovem
11.
Sci Rep ; 10(1): 354, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31941948

RESUMO

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.

12.
Neuropeptides ; 41(5): 293-9, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17688943

RESUMO

The distribution and relative frequency of neuroendocrine cells in the small and large intestines of one-humped camel were studied using antisera against 5-hydroxytryptamine (5-HT), cholecystokinin (CCK-8), somatostatin (SOM), peptide tyrosine tyrosine (PYY), gastric inhibitory polypeptide (GIP), neuronal nitric oxide synthase (nNOS), gastrin releasing peptide (GRP), substance P (SP), and neurokinin A (NKA). Among these cell types, CCK-8 immunoreactive (IR) cells were uniformly distributed in the mucosa, while others showed varied distribution in the villi or crypts of the small intestine. Immunoreactive cells like 5HT, CCK-8, and SOM showed peak density in the villi and crypts of the small intestine and in the colonic glands of the large intestine, while cells containing SP were discerned predominately in the crypts. 5-HT, CCK-8 and SOM cells were mainly flask-shaped and of the open-variety, while PYY and SP immunoreactive cells were mainly rounded or basket-shaped and of the closed variety. Basically the distribution pattern of the endocrine cells in the duodenum, jejunum and colon of the one-humped camel is similar to that of other mammals. Finally, the distribution of these bioactive agents may give clues as to how these agents aid in the function of the intestinal tract of this desert animal.


Assuntos
Intestino Grosso/fisiologia , Intestino Delgado/fisiologia , Serotonina/análise , Animais , Camelus , Colecistocinina/análise , Polipeptídeo Inibidor Gástrico/análise , Peptídeo Liberador de Gastrina/análise , Imuno-Histoquímica , Intestino Grosso/citologia , Intestino Delgado/citologia , Neurocinina A/análise , Óxido Nítrico Sintase Tipo III/análise , Sincalida/análise , Somatostatina/análise , Substância P/análise
13.
Int J Impot Res ; 19(5): 509-16, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17568762

RESUMO

The noradrenaline (NA) concentration in the rat corpus cavernosum (CC) increased to approximately 350% of control values after about 8 weeks of hyperglycaemia induced by the intraperitoneal injection of streptozotocin (STZ) at 10 weeks of age. These changes were maintained for at least a further 32 weeks of hyperglycaemia and occurred without any significant change in the weight in the tissue. Smaller but significant increases in NA concentration occurred in the glans penis (GP) reaching 150-175% of the control levels during the period of prolonged hyperglycaemia. In contrast, there was no significant change in the NA concentration in the penile urethra. Measurements have also been made that relate to changes in the synthesis and reuptake of NA in the CC during the period during which high NA concentration is maintained. Immunohistochemical studies for the synthetic enzyme tyrosine hydroxylase in the CC indicate that the intensity of staining in the tissue had increased after 10, 20 and 32 weeks of hyperglycaemia, relative to the tissues from control animals. Dilated nerve fibres and engorged endings were present in the CC of the diabetic animals at these times. Reuptake of tritiated NA by the terminal axonal membranes in the CC was raised to 181% of control values after 12 weeks of hyperglycaemia (P<0.05), but later declined to values that are not significantly different from the control levels (after 26 and 64 weeks of hyperglycaemia). There are few studies of the effects of prolonged diabetes on functional aspects of sympathetic postganglionic neurones in the CC, and this paper suggests that the changes described represent remodelling of noradrenergic axonal terminals starting about after 8-10 weeks of hyperglycaemia; this delay in onset of the neuropathic changes is also a feature of type I diabetes in humans.


Assuntos
Diabetes Mellitus Experimental/fisiopatologia , Terminações Nervosas/anatomia & histologia , Pênis/inervação , Sistema Nervoso Simpático/anatomia & histologia , Aminas/metabolismo , Animais , Glicemia/metabolismo , Diabetes Mellitus Experimental/metabolismo , Imuno-Histoquímica , Masculino , Terminações Nervosas/metabolismo , Pênis/metabolismo , Pênis/fisiopatologia , Ratos , Ratos Wistar , Sistema Nervoso Simpático/metabolismo , Uretra/metabolismo
14.
Ann N Y Acad Sci ; 1084: 267-79, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17151307

RESUMO

In the streptozotocin (STZ)-diabetic rat major increases in noradrenaline concentration and content of the seminal vesicles were evident as early as 7 weeks following induction of hyperglycemia and returned toward normal after 34 weeks of hyperglycemia. There were significant reductions in the concentration and content of dopamine at 19-42 weeks of diabetes, and small occasionally significant reductions in the content of serotonin and adrenaline, particularly around 19-26 weeks after STZ treatment. The uptake of tritiated noradrenaline in the diabetics was increased at 12 weeks compared to the controls, and decreased to control levels with increasing age. Release of tritiated noradrenline was increased in response to electrical field stimulation and high potassium solutions, and raising calcium concentration caused increased release at rest and during electrical stimulation. Immunohistochemical demonstration of tyrosine hydroxylase was increased during the period when the noradrenaline concentration and content were elevated. It is concluded that there are significant changes in the sympathetic innervation of the seminal vesicle during the course of STZ diabetes, and that alterations in the reuptake, release, and synthesis of the neurotransmitter noradrenaline may contribute to changes in the concentration of the amine in the tissue. It is possible that the changes observed are related to the remodeling and regrowth of sympathetic nerve endings damaged in the early stages of hyperglycemia. These changes may also contribute to disorders of ejaculation in diabetes.


Assuntos
Diabetes Mellitus Experimental/fisiopatologia , Ejaculação/fisiologia , Disfunção Erétil/etiologia , Glândulas Seminais/fisiopatologia , Animais , Glicemia/metabolismo , Diabetes Mellitus Experimental/sangue , Dopamina/sangue , Disfunção Erétil/sangue , Disfunção Erétil/fisiopatologia , Hiperglicemia/fisiopatologia , Masculino , Norepinefrina/metabolismo , Ratos , Ratos Wistar
16.
Sci Rep ; 6: 18520, 2016 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-26725873

RESUMO

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%).


Assuntos
Mycobacterium tuberculosis/imunologia , Tuberculose/diagnóstico , Biomarcadores/sangue , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Sistemas Automatizados de Assistência Junto ao Leito , Tuberculose/sangue , Tuberculose/imunologia
17.
Sci Rep ; 6: 38841, 2016 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-27941850

RESUMO

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.


Assuntos
RNA Mensageiro/sangue , Receptores CXCR5/genética , Receptores de IgG/genética , Tuberculose Pulmonar/sangue , Adolescente , Antituberculosos/uso terapêutico , Biomarcadores , Criança , Pré-Escolar , Estudos Transversais , Método Duplo-Cego , Feminino , Regulação da Expressão Gênica , Humanos , Índia , Lactente , Masculino , Desnutrição/complicações , Desnutrição/tratamento farmacológico , Manganês/uso terapêutico , Micronutrientes/uso terapêutico , Prognóstico , Estudos Prospectivos , RNA Mensageiro/genética , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/genética , Tuberculose Pulmonar/imunologia , Zinco/uso terapêutico
18.
Oncogenesis ; 4: e162, 2015 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-26258891

RESUMO

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.

19.
Gene ; 263(1-2): 171-8, 2001 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-11223255

RESUMO

Transforming Growth Factor-beta (TGF-beta) and their receptors have been characterized from many organisms. Two TGF-beta signaling receptors called Type I and II have been described for various ligands of the superfamily from organisms ranging from Drosophila to humans. In Xenopus laevis, TGF-beta2 and 5 have been reported and presumably, play important roles during early development. Several Type I and type II receptors for many ligands of the TGF-beta superfamily except TGF-beta type II receptor (TbetaIIR), have been characterized in Xenopus laevis. A chemical cross linking experiment using iodinated TGF-beta1 and -beta5, revealed four specific binding proteins on XTC cells. In order to understand the TGF-beta involvement during Xenopus development, a TGF-beta type II receptor (XTbetaIIR) has been isolated from a XTC cDNA library. XTbetaIIR was a partial cDNA lacking a portion of the signal peptide. The sequence analysis and homology comparison with the human TbetaIIR revealed 67% amino acid similarity in the extra cellular domain, 60% similarity in the transmembrane domain and 87% similarity in the cytoplasmic kinase domain, suggesting that XTbetaIIR is a putative TGF-beta type II receptor. In addition, the consensus amino acid motif for serine threonine receptor kinases was also present. Further, a dominant negative expression construct lacking the cytoplasmic kinase domain (engineered with the signal peptide from human TGF-beta type II receptor), was able to abolish TGF-beta mediated induction of a luciferase reporter plasmid, in a transient cell transfection assay. This substantiates the notion that XTbetaIIR cDNA can act as a receptor for TGF-beta. RT-PCR analysis using RNA isolated from various developmental stages of Xenopus laevis revealed expression of this gene in all the early stages of development and in the adult organs, except in stages 46/48.


Assuntos
DNA Complementar/isolamento & purificação , Receptores de Fatores de Crescimento Transformadores beta/genética , Xenopus laevis/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Reagentes de Ligações Cruzadas , DNA Complementar/química , DNA Complementar/genética , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Luciferases/genética , Luciferases/metabolismo , Dados de Sequência Molecular , Proteínas Quinases/genética , Proteínas Serina-Treonina Quinases , Estrutura Terciária de Proteína , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo II , Receptores de Fatores de Crescimento Transformadores beta/química , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Alinhamento de Sequência , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Fator de Crescimento Transformador beta/química , Células Tumorais Cultivadas , Xenopus laevis/embriologia , Xenopus laevis/crescimento & desenvolvimento
20.
Am J Trop Med Hyg ; 70(3): 256-9, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15031513

RESUMO

The Plasmodium falciparum chloroquine resistance transporter (Pfcrt) K76T mutation and haplotype (amino acids 72-76) and the P. falciparum multidrug resistance 1 (Pfmdr1) mutation (N86Y) were analyzed as markers of chloroquine resistance in the DNAs of 73 blood samples from patients with P. falciparum malaria in India. Seventy of the 73 DNAs had the Pfcrt K76T mutation. Of these, 66 had the SVMNT haplotype and four had CVIET, the African/Southeast Asian haplotype. Only 20 of 69 DNAs had the Pfmdr1 N86Y mutation. It is surprising that the Pfcrt haplotype in India is predominantly SVMNT, rather than that seen in Southeast Asia. The widespread prevalence of the Pfcrt K76T mutation is a cause for concern.


Assuntos
Cloroquina/farmacologia , Haplótipos , Malária Falciparum/tratamento farmacológico , Proteínas de Membrana/genética , Plasmodium falciparum/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Animais , Resistência a Medicamentos/genética , Humanos , Proteínas de Membrana Transportadoras , Plasmodium falciparum/efeitos dos fármacos , Proteínas de Protozoários
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