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1.
Mol Biol Rep ; 49(8): 7541-7556, 2022 Aug.
Article de Anglais | MEDLINE | ID: mdl-35593896

RÉSUMÉ

BACKGROUND: Diagnostic and prognostic significance of epithelial-to-mesenchymal transition (EMT) associated biomarkers are evaluated in a cohort of NMIBC (non-muscle invasive bladder cancer) and MIBC (muscle invasive bladder cancer) patients. METHODS AND RESULTS: Real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemical (IHC) staining were carried out in 100 tumor specimens (59 NMIBC and 41 MIBC). The expressions of the epithelial marker, mesenchymal markers and EMT-activating transcription factors (EMT-ATFs) were determined at transcriptome and protein level followed by their statistical associations with clinicohistopathological variables of the patients. Transcriptomic expression analysis showed statistical relevance of tumor stage with increased Twist and Zeb-1; tumor type with reduced E-cadherin and increased Snail; and smoking/tobacco chewing status (S/TC) of patients with increased N-cadherin and Snail in NMIBC patients. Tumor grade with reduced message E-cadherin, gain of N-cadherin, Snail, Twist and Zeb-1; patients' age with reduced E-cadherin and Twist gain; and tumor type with increased message N-cadherin exhibited associations in MIBC patients. Protein expression analysis identified statistical relevance of tumor grade with nuclear gain of Snail and Twist; and nuclear gain of Slug with S/TC status of NMIBC patients. Novel gain of membranous Vimentin deduced association with patients' age in MIBC patients. Survival analysis identified novel Vimentin as the positive predictor of short progression free survival (PFS) and short overall survival (OS) in MIBC patients. Study established altered EMT profile as the independent negative predictor of short recurrence free survival (RFS) in NMIBC patients and positive predictor of short PFS and OS in MIBC patients. CONCLUSIONS: EMT associated biomarkers could provide diagnostic and prognostic risk stratification and hence could be of importance in the clinical management of bladder cancer patients.


Sujet(s)
Tumeurs de la vessie urinaire , Marqueurs biologiques tumoraux/métabolisme , Cadhérines/génétique , Cadhérines/métabolisme , Évolution de la maladie , Transition épithélio-mésenchymateuse/génétique , Humains , Pronostic , Facteurs de transcription de la famille Snail , Tumeurs de la vessie urinaire/métabolisme , Vimentine/génétique
2.
Fetal Pediatr Pathol ; 41(5): 837-842, 2022 Oct.
Article de Anglais | MEDLINE | ID: mdl-34587870

RÉSUMÉ

BACKGROUND: Congenital muscular dystrophies (CMD) range in phenotype from an antenatal presentation with brain and eye anomalies to isolated muscular weakness. B4GAT1 gene has recently been associated with muscular dystrophy-dystroglycanopathy, type A, 13 and two families have been reported. CASE REPORT: We report the third family with B4GAT1 associated CMD presenting as recurrent severe ventriculomegaly, cerebellar and vermian hypoplasia in fetal life, which was identified after the second affected pregnancy. The mutations identified were similar to those reported in a previously reported Indian family, homozygous, p.Asn390Asp, and p. Ala406Val, suggesting founder mutation. CONCLUSION: B4GAT1 mutations are associated with CMD and may present in fetal life as severe ventriculomegaly. The homozygous B4GAT1 mutations, p.Asn390Asp, and p. Ala406Val, described in two Indian families (including this case) might represent a founder mutation.


Sujet(s)
Hydrocéphalie , Dystrophies musculaires , Femelle , Homozygote , Humains , Hydrocéphalie/complications , Hydrocéphalie/génétique , Dystrophies musculaires/diagnostic , Dystrophies musculaires/génétique , Mutation , Phénotype , Grossesse
3.
RSC Adv ; 11(42): 26218-26227, 2021 Jul 27.
Article de Anglais | MEDLINE | ID: mdl-35479461

RÉSUMÉ

Swift heavy ion (SHI) irradiation in thin films significantly modifies the structure and related properties in a controlled manner. In the present study, the 120 MeV Ag ion irradiation on AgInSe2 nanoparticle thin films prepared by the thermal evaporation method and the induced modifications in the structure and other properties are being discussed. The ion irradiation led to the suppression of GIXRD and Raman peaks with increasing ion fluence, which indicated amorphization of the AgInSe2 structure along the path of 120 MeV Ag ions. The Poisson's fitting of the ion fluence dependence of the normalized area under the GIXRD peak of AgInSe2 gave the radius of the ion track as 5.8 nm. Microstructural analysis using FESEM revealed a broad bi-modal distribution of particles with mean particle sizes of 67.5 nm and 159 nm in the pristine film. The ion irradiation led to the development of uniform particles on the film surface with a mean size of 36 nm at high ion fluences. The composition of the film was checked by the energy dispersive X-ray fluorescence (EDXRF) spectrometer. The UV-visible spectroscopy revealed the increase of the electronic bandgap of AgInSe2 films with an increase in ion fluence due to quantum confinement. The Hall measurement and EDXRF studies showed that the unirradiated and irradiated AgInSe2 films have n-type conductivity and vary with the ion fluence. The changes in the films were tuned with different ion fluence and are favorable for both optical and electronic applications.

4.
Dalton Trans ; 49(39): 13829-13839, 2020 Oct 12.
Article de Anglais | MEDLINE | ID: mdl-33001072

RÉSUMÉ

Copper(i) complexes [Cu(L1-7)2](ClO4) (1-7) of bidentate ligands (L1-L7) have been synthesized via spontaneous reduction and characterized as catalysts for aromatic C-H activation using H2O2 as the oxidant. The single crystal X-ray structure of 1 exhibited a distorted tetrahedral geometry. All the copper(i) complexes catalyzed direct hydroxylation of benzene to form phenol with good selectivity up to 98%. The determined kinetic isotope effect (KIE) values, 1.69-1.71, support the involvement of a radical type mechanism. The isotope-labeling experiments using H218O2 showed 92% incorporation of 18O into phenol and confirm that H2O2 is the key oxygen supplier. Overall, the catalytic efficiencies of the complexes are strongly influenced by the electronic and steric factor of the ligand, which is fine-tuned by the ligand architecture. The benzene hydroxylation reaction possibly proceeded via a radical mechanism, which was confirmed by the addition of radical scavengers (TEMPO) to the catalytic reaction that showed a reduction in phenol formation.

5.
Indian J Nephrol ; 29(6): 387-392, 2019.
Article de Anglais | MEDLINE | ID: mdl-31798219

RÉSUMÉ

INTRODUCTION: The outcome of arteriovenous fistula (AVF) for hemodialysis (HD) in elderly population remains an issue. The aim of our study was to evaluate the outcomes of arteriovenous fistulas created at our institute in patients older than 65 years. METHODS: All chronic HD patients with age >65 years who had an AVF created between January 1, 2010 and January 1, 2017 were included retrospectively. Baseline demographic information including age, gender, etiology of renal failure and comorbidities were recorded. Access characteristics including access type and anatomic location were recorded. The end point of study was primary and secondary patency. Minimum follow up period of study was 1 year. RESULTS: A total of 422 AVF were created within the study period. The mean age was 69.3 years. The anatomical site of AVF creation was radiocephalic (RCF) in 74.8% (n = 316), brachiocephalic (BCF) in 18.9% (n = 80) and brachiobasilic (BBF) in 6.1% (n = 26). At one year after creation, cumulative survival of the AVF was 64.7%. At 36 months the primary and secondary patency of RCF, BCF and BBF was 43.6%, 58.6%, 42.6% and 47.3%, 62.5%, 56.9% respectively. The overall median survival did not differ between RCF and BBF fistulas. However, when both were compared with BCF (median survival 1034 days), BBF (median survival 741 days) and RCF (median survival 592 days) had significantly poorer survival (P = 0.004). The most common reason for access failure was thrombosis (28.4%) followed by failure to mature (9%) and aneurysm related complications (9%). CONCLUSIONS: Age should not be a limiting factor when choosing AVF as the preferred HD access. Brachiocephalic AVF has better primary and secondary patency with higher overall median survival. However RCF also provides reasonably good survival rates with acceptable complications in elderly population. Thrombosis and fistulas that fail to mature present as a primary concern to patients in elderly population, and demand further study.

6.
Oncogene ; 38(3): 445-453, 2019 01.
Article de Anglais | MEDLINE | ID: mdl-30104710

RÉSUMÉ

Although it has been demonstrated that transformed progenitor cell population can contribute to tumor initiation, factors contributing to this malignant transformation are poorly known. Using in vitro and xenograft-based models, previous studies demonstrated that miR-489 acts as a tumor suppressor miRNA by targeting various oncogenic pathways. It has been demonstrated that miR-489 directly targets HER2 and inhibits the HER2 signaling pathway; however, its role in mammary gland development and HER2-induced tumor initiation hasn't been studied. To dissect the role of miR-489, we sorted different populations of mammary epithelial cells and determined that miR-489 was highly expressed in mammary stem cells. MMTV-miR-489 mice that overexpressed miR-489 in mammary epithelial cells were developed and these mice exhibited an inhibition of mammary gland development in early ages with a specific impact on highly proliferative cells. Double transgenic MMTV-Her2-miR489 mice were then generated to observe how miR-489 overexpression affects HER2-induced tumorigenesis. miR-489 overexpression delayed HER2-induced tumor initiation significantly. Moreover, miR-489 overexpression inhibited tumor growth and lung metastasis. miR-489 overexpression reduced mammary progenitor cell population significantly in preneoplastic mammary glands of MMTV-Her2 mice which showed a putative transformed population in HER2-induced tumorigenesis. The miR-489 overexpression reduced CD49fhiCD61hi populations in tumors that have stem-like properties, and miR-489 overexpression altered the HER2 signaling pathway in mammary tumors. Altogether, these data indicate that the inhibition of HER2-induced tumorigenesis by miR-489 overexpression was due to altering progenitor cell populations while decreasing tumor growth and metastasis via influencing tumor promoting genes DEK and SHP2.


Sujet(s)
Transformation cellulaire néoplasique/génétique , Régulation de l'expression des gènes tumoraux , Glandes mammaires animales/métabolisme , Tumeurs expérimentales de la mamelle/anatomopathologie , microARN/physiologie , ARN tumoral/physiologie , Récepteur ErbB-2/physiologie , Animaux , Antigènes CD/analyse , Différenciation cellulaire , Protéines de liaison à l'ADN/génétique , Protéines de liaison à l'ADN/métabolisme , Cellules épithéliales/métabolisme , Femelle , Tumeurs du poumon/secondaire , Glandes mammaires animales/cytologie , Glandes mammaires animales/croissance et développement , Tumeurs expérimentales de la mamelle/génétique , Tumeurs expérimentales de la mamelle/métabolisme , Virus de la tumeur mammaire de la souris/génétique , Souris , Souris transgéniques , microARN/biosynthèse , microARN/génétique , Cellules souches tumorales/cytologie , Cellules souches tumorales/métabolisme , Protéines oncogènes/génétique , Protéines oncogènes/métabolisme , Protéines liant le poly-adp-ribose/génétique , Protéines liant le poly-adp-ribose/métabolisme , Grossesse , Protein Tyrosine Phosphatase, Non-Receptor Type 11/génétique , Protein Tyrosine Phosphatase, Non-Receptor Type 11/métabolisme , ARN tumoral/biosynthèse , ARN tumoral/génétique , Récepteur ErbB-2/génétique , Protéines de fusion recombinantes/biosynthèse , Protéines de fusion recombinantes/métabolisme , Cellules souches/métabolisme , Test clonogénique de cellules souches tumorales , Régulation positive
7.
Oncogene ; 38(3): 454, 2019 01.
Article de Anglais | MEDLINE | ID: mdl-30375491

RÉSUMÉ

In the published version of this paper the author A. Awgulewitsch's surname was incorrectly given as Awagulerwitsch instead of Awgulewitsch. This has now been corrected in the HTML version of the paper, the PDF was correct at the time of publication.

8.
Dalton Trans ; 47(18): 6421-6434, 2018 May 08.
Article de Anglais | MEDLINE | ID: mdl-29687810

RÉSUMÉ

A compartmental chemosensor probe HL has been designed and synthesized for the selective recognition of zinc ions over other transition metal ions via fluorescence "ON" strategy. The chemosensing behaviour of HL was demonstrated through fluorescence, absorption and NMR spectroscopic techniques. The molecular structure of the zinc complex derived from HL was determined by X-ray crystallography. A probable mechanism of this selective sensing behavior was described on the basis of spectroscopic results and theoretical studies by density functional theory (DFT). The biological applicability of the chemosensor HL was examined via cell imaging on HeLa cells. The HL-zinc complex served as a secondary fluorescent probe responding to the pyrophosphate anion specifically over other anions. The fluorescence enhancement of HL in association with Zn2+ ions was quenched in the presence of pyrophosphate (PPi). Thus, a dual response was established based on "OFF-ON-OFF" strategy for detection of both cation and anion. This phenomenon was utilized in the construction of a "INHIBIT" logic gate.


Sujet(s)
Colorants fluorescents/composition chimique , Imagerie optique , Théorie quantique , Cristallographie aux rayons X , Diphosphates/composition chimique , Cellules HeLa , Humains , Concentration en ions d'hydrogène , Ions/composition chimique , Modèles moléculaires , Structure moléculaire , Spectrophotométrie UV , Cellules cancéreuses en culture , Zinc/composition chimique
9.
Article de Anglais | MEDLINE | ID: mdl-28064137

RÉSUMÉ

A colorimetric and fluorometric probe (E)-2-((8-hydroxy-1,2,3,5,6,7-hexahydropyrido[3,2,1-ij]quinolin-9-yl)methylene)hydrazinecarbothioamide based on thiosemicarbazide and julolidine moieties has been synthesised in pure crystalline form and characterized by 1H NMR, UV-vis, elemental analysis and single crystal XRD. The probe functioned as multitarget ion sensor, detect biologically important metal ions Hg2+ and Mn2+ in dual channel mode. Meanwhile, in mixed solvent media DMF/H2O [8:2], probe displayed selectivity for Hg2+ over other cations by the emission spectrum. Interestingly probe has been explored to recognize F- anion in DMF through ESIPT mechanism. The 1:1 binding stoichiometry of probe with Hg2+ and Mn2+ is confirmed by Job's plot through emission titration and UV-vis titration respectively. Probe is selective and sensitive to Hg2+ and Mn2+ with detection limit as low as 15µM and 0.2µM respectively. The sensing mechanism for selective ions was also scrutinized using 1H NMR experiments and computational studies.

10.
Int J Obes (Lond) ; 40(5): 844-51, 2016 05.
Article de Anglais | MEDLINE | ID: mdl-26620890

RÉSUMÉ

BACKGROUND: Monocyte chemoattractant protein 1 (MCP-1) is known to be an important chemokine for macrophage recruitment. Thus, targeting MCP-1 may prevent the perturbations associated with macrophage-induced inflammation in adipose tissue. However, inconsistencies in the available animal literature have questioned the role of this chemokine in this process. The purpose of this study was to examine the role of MCP-1 on obesity-related pathologies. METHODS: Wild-type and MCP-1-deficient mice on an friend virus B NIH (FVB/N) background were assigned to either low-fat diet or high-fat diet (HFD) treatment for a period of 16 weeks. Body weight and body composition were measured weekly and monthly, respectively. Fasting blood glucose and insulin, and glucose tolerance were measured at 16 weeks. Macrophages, T-cell markers, inflammatory mediators and markers of fibrosis were examined in the adipose tissue at the time of killing the mice. RESULTS: As expected, HFD increased adiposity (body weight, fat mass, fat percent and adipocyte size), metabolic dysfunction (impaired glucose metabolism and insulin resistance) macrophage number (CD11b(+)F480(+) cells, and gene expression of EMR1 and CD11c), T-cell markers (gene expression of CD4 and CD8), inflammatory mediators (pNFκB and pJNK, and mRNA expression of MCP-1, CCL5, C-X-C motif chemokine-14, tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6)) and fibrosis (expression of IL-10, IL-13, TGF-ß and matrix metalloproteinase-2 (MMP2); P<0.05). However, contrary to our hypothesis, MCP-1 deficiency exacerbated many of these responses resulting in a further increase in adiposity (body weight, fat mass, fat percent and adipocyte size), metabolic dysregulation, macrophage markers (EMR1), inflammatory cell infiltration and fibrosis (formation of type I and III collagens, mRNA expression of IL-10 and MMP2; P<0.05). CONCLUSIONS: These data suggest that MCP-1 may be a necessary component of the inflammatory response required for adipose tissue protection, remodeling and healthy expansion in the FVB/N strain in response to HFD feedings.


Sujet(s)
Chimiokine CCL2/métabolisme , Alimentation riche en graisse , Inflammation/métabolisme , Inflammation/anatomopathologie , Obésité/métabolisme , Obésité/anatomopathologie , Tissu adipeux/métabolisme , Tissu adipeux/anatomopathologie , Animaux , Modèles animaux de maladie humaine , Analyse de profil d'expression de gènes , Immunohistochimie , Insulinorésistance/immunologie , Macrophages/métabolisme , Mâle , Souris , Souris de lignée C57BL , Obésité/physiopathologie , Facteur de nécrose tumorale alpha/métabolisme
11.
J Environ Biol ; 35(2): 363-7, 2014 Mar.
Article de Anglais | MEDLINE | ID: mdl-24665763

RÉSUMÉ

The bacterial infection is an important economic and limiting factor in intensive fish production. The present study focuses on investigation of the bacterial population associated with farmed common carp fingerlings, its environment and limnological quality of pond, during winter and summer season. It was found that the bacterial count in the pond sediment (6.40 cfu x 10(4)) was about 10 times higher in comparison of pond water (6.93 cfu x 10(3)). Further, the intestinal bacterial count was about 100 times higher (6.67 cfu x 10(5)) during winter and 1000 times higher (2.33 cfu x 10(6)) during summer season in comparison to the surfacial skin of fish during winter and summer (3.39 and 8.87 cfu x 10(3)), respectively. The isolated bacteria were both Gram negative and Gram positive, mostly aerobic rods. Furthermore, the temperature showed a significant relation with the bacterial counts of pond water. In the summer season, higher bacterial counts (8.72 cfu x 10(3)) were recorded as compared to winter (5.13 cfu x 10(3)). The dominant bacteria isolated from the sample of pond water, pond sediment and fish were identified as Aeromonas hydrophila, Pseudomonas fluorescens, Pseudomonas sp., Flavobacter sp., Bacillus sp., Micrococcus sp., Corynebacterium sp. Moreover, the bacterial density was dependent on C:N values, and the optimum range of C: N ratio was found between 16-23, for the carp culture ponds. Among the isolated bacterial flora, the presence of strains which were well known for their probiotic properties suggested an autochthonous source for use in aquaculture. Further, analysis of various physico-chemical parameters of pond water revealed that they were within the suitable range for the freshwater fish culture throughout farming phase.


Sujet(s)
Aquaculture , Bactéries/classification , Carpes (poisson)/microbiologie , Saisons , Microbiologie de l'eau , Animaux , Inde
12.
J Environ Biol ; 34(1): 139-45, 2013 Jan.
Article de Anglais | MEDLINE | ID: mdl-24006821

RÉSUMÉ

In cowpea, dual purpose plant types are more preferable for cultivation. Therefore, exotic and indigenous cowpea germplasm lines were evaluated in augmented design to study estimates of the correlation coefficients and path analysis of morphological as well as fodder and grain yield attributes. The present study showed a high impact of direct effects of correlation (0.9714**) and suggested that going for plant types with higher biomass per plant (0.8856**), dry weight per plant (0.4598), stem girth (0.2336) number of secondary branches (0.2788), leaves per plant (0.3251), pods per plant (0.9059) and pod clusters per plant (0.7718) would be effective for improving both fodder and seed yield in cowpea.


Sujet(s)
Fabaceae/anatomie et histologie , Fabaceae/physiologie , Graines/physiologie , Biomasse
13.
Indian J Cancer ; 49(1): 102-6, 2012.
Article de Anglais | MEDLINE | ID: mdl-22842176

RÉSUMÉ

OBJECTIVE: To assess the incidence and review the probable etiologies of port site recurrence in patients undergoing laparoscopic radical nephrectomy. MATERIALS AND METHODS: One hundred thirty-six patients undergoing laparoscopic surgeries for renal malignancy, including 133 radical nephrectomies and 3 partial nephrectomies, from December 1999 to December 2008 at our institution were followed up for a median period of 59 months (12-120 months). Of the procedures, 121 were performed by transperitoneal, 5 by retroperitoneal and 10 by combined approach (retroperitoneal renal artery clipping followed by transperitoneal nephrectomy). Formal lymphadenectomy was not performed. Postoperative surveillance after radical nephrectomy included history and physical examination with blood tests 3-6 monthly, chest X-ray yearly and abdominal contrast-enhanced computed tomography (CECT) 1-2 yearly. The development of port site recurrence was diagnosed by physical examination, CECT and pathological findings. RESULTS: Conversion to open surgery was done in 33 patients. Two (1.47% overall) port site recurrences were observed, both after radical nephrectomies done for renal masses with clinical stages T2N0M0 and TIN0M0. The pathological staging in the two were T2N1M0 Fuhrman's Grade III and T3aN1M0 Grade III, respectively. CONCLUSION: Our results report that laparoscopic approach does not necessarily increase the risk of port site recurrence, provided the cases are carefully chosen, principles of oncologic surgery are followed, and conditions that increase the risk of port site metastasis are avoided.


Sujet(s)
Néphrocarcinome , Tumeurs du rein , Récidive tumorale locale , Adolescent , Adulte , Sujet âgé , Néphrocarcinome/diagnostic , Néphrocarcinome/anatomopathologie , Néphrocarcinome/chirurgie , Femelle , Humains , Tumeurs du rein/diagnostic , Tumeurs du rein/anatomopathologie , Tumeurs du rein/chirurgie , Laparoscopie , Lymphadénectomie , Mâle , Adulte d'âge moyen , Métastase tumorale , Récidive tumorale locale/diagnostic , Récidive tumorale locale/anatomopathologie , Néphrectomie , Tomodensitométrie , Résultat thérapeutique
14.
Lett Appl Microbiol ; 54(5): 483-6, 2012 May.
Article de Anglais | MEDLINE | ID: mdl-22394198

RÉSUMÉ

AIMS: Present report describes the in vitro antimalarial activity and docking analysis of seven 4-aminoquinoline-clubbed 1,3,5-triazine derivatives on pf-DHFR-TS. METHODS AND RESULTS: The antimalarial activity was evaluated in vitro against chloroquine-sensitive 3D7 strain of Plasmodium falciparum. Compounds were docked onto the active site of pf-DHFR-TS using docking server to explicate necessary structural requirements for antimalarial activity. CONCLUSION: Title molecules demonstrated considerable bioactivity against the malaria parasite. Docking analysis revealed deep engulfment of the molecules into the inner groove of pf-DHFR-TS active site by making stable ligand-receptor posses. Hydrophobic interaction was identified as the only major interacting force playing a role between ligand-receptor interaction and minor with hydrogen bonds. SIGNIfiCANCE AND IMPACT OF THE STUDY: The study provided the novel insight into the necessary structural requirement for rationale-based antimalarial drug discovery.


Sujet(s)
Antipaludiques/pharmacologie , Complexes multienzymatiques/pharmacologie , Dihydrofolate reductase/pharmacologie , Thymidylate synthase/pharmacologie , Triazines/pharmacologie , Aminoquinoléines/composition chimique , Aminoquinoléines/pharmacologie , Antipaludiques/composition chimique , Liaison hydrogène , Complexes multienzymatiques/composition chimique , Plasmodium falciparum/effets des médicaments et des substances chimiques , Dihydrofolate reductase/composition chimique , Thymidylate synthase/composition chimique , Triazines/composition chimique
15.
Oncogene ; 31(21): 2614-26, 2012 May 24.
Article de Anglais | MEDLINE | ID: mdl-21996747

RÉSUMÉ

Human epidermal growth factor receptor 2 (HER2)/Neu is overexpressed in 20-30% of breast cancers and associated with aggressive phenotypes and poor prognosis. For deciphering the role of HER2/Neu in breast cancer, mouse mammary tumor virus (MMTV)-Her2/neu transgenic mice that develop mammary tumors resembling human HER2-subtype breast cancer have been established. Several recent studies have revealed that HER2/Neu is overexpressed in and regulates self renewal of breast tumor-initiating cells (TICs). However, in the MMTV-Her2/neu transgenic mouse model, the identity of TICs remains elusive, despite previous studies showing supportive evidence for existence of TICs in Her2/neu-induced mammary tumors. Through systematic screening and characterization, we identified that surface markers CD49f, CD61 and ESA were aberrantly overexpressed in Her2-overexpressing mammary tumor cells. Analysis of these markers and CD24 detected anomalous expansion of the luminal progenitor population in preneoplastic mammary glands of Her2/neu transgenic mice, indicating that aberrant luminal progenitors originated in Her2-induced mammary tumors. The combined markers, CD49f and CD61, further delineated the CD49f(high)CD61(high)-sorted fraction as a TIC-enriched population, which displayed increased tumorsphere formation ability, enhanced tumorigenicity both in vitro and in vivo and drug resistance to pacitaxel and doxorubicin. Moreover, the TIC-enriched population manifested increased transforming growth factor-ß (TGFß) signaling and exhibited gene expression signatures of stemness, TGFß signaling and epithelial-to-mesenchymal transition. Our findings that self-renewal and clonogenicity of TICs were suppressed by pharmacologically inhibiting the TGFß signaling further indicate that the TGFß pathway is vital for maintenance of the TIC population. Finally, we showed that the integrin-ß3 (CD61) signaling pathway was required for sustaining active TGFß signaling and self-renewal of TICs. We for the first time developed a technique to highly enrich TICs from mammary tumors of Her2/neu transgenic mice, unraveled their properties and identified the cooperative integrin-ß3-TGFß signaling axis as a potential therapeutic target for HER2-induced TICs.


Sujet(s)
Intégrine alpha6/métabolisme , Intégrine bêta3/métabolisme , Cellules souches tumorales/métabolisme , Récepteur ErbB-2/métabolisme , Facteur de croissance transformant bêta/métabolisme , Animaux , Tumeurs du sein/génétique , Transformation cellulaire néoplasique , Femelle , Humains , Tumeurs mammaires de l'animal/métabolisme , Souris , Souris transgéniques , Transduction du signal
16.
J Mycol Med ; 22(2): 134-41, 2012 Jun.
Article de Anglais | MEDLINE | ID: mdl-23518015

RÉSUMÉ

OBJECTIVE: Present research communication was towards the investigation of antifungal minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) activity of some substituted clubbed thiazole-1,3,5-triazines derivatives and effect of physicochemical properties on bioactivity. MATERIAL AND METHODS: MIC and MFC were evaluated against Candida albicans, Candida glabrata, Cryptococcus neoformans and Aspergillus niger using modified microdilution method recommended by CLSI. Cytotoxicity was determinate on the viability of marine shrimp larvaes. SAR and physicochemical correlations were studied by Molinspiration software. RESULTS: The 5 and 9 derivatives showed an excellent antifungal activity with MIC lower than fluconazole and equivalent to amphotericin B specially against C. albicans and C. glabrata. The toxicity of these two derivatives was non-existent for 5 and moderate for 9 at the used concentration. SAR study around prototype molecule suggests that presence of di-hydrophobic fragment on 1,3,5-triazine is necessary for antifungal activity than halogen substituted aromatic amine. CONCLUSION: On the basis of selectivity, potency and non-toxicity, we have obtained two molecules (5 and 9) as prospective leads for further research work on 1,3,5-triazine as antifungal drug.


Sujet(s)
Antifongiques/pharmacologie , Aspergillus niger/effets des médicaments et des substances chimiques , Candida albicans/effets des médicaments et des substances chimiques , Candida glabrata/effets des médicaments et des substances chimiques , Cryptococcus neoformans/effets des médicaments et des substances chimiques , Thiazoles/pharmacologie , Triazines/pharmacologie , Animaux , Antifongiques/composition chimique , Antifongiques/toxicité , Artemisia/effets des médicaments et des substances chimiques , Artemisia/croissance et développement , Évaluation préclinique de médicament , Larve , Tests de sensibilité microbienne , Structure moléculaire , Masse moléculaire , Relation structure-activité , Thiazoles/composition chimique , Triazines/composition chimique
17.
Interdiscip Sci ; 4(4): 239-55, 2012 Dec.
Article de Anglais | MEDLINE | ID: mdl-23354813

RÉSUMÉ

Motifs are the biologically significant fragments of nucleotide or peptide sequences in a specific pattern. Motifs are categorized as structural motifs and sequence motifs. These are discovered by phylogenetic studies of similar genes across species. Structural motifs are formed by three dimensional arrangements of amino acids consisting of two or more α helices or ß strands whereas sequence motifs are formed by the nucleotide fragments appearing in the exons of a gene. The arrangement of residues in structural motifs may not be continuous while it is continuous in sequence motifs. Sequence motifs may encode to the structural motifs. The algorithms used for motif discovery are important part of the bio-computational studies. The purpose of motif discovery is to identify patterns in biopolymer (nucleotide or protein) sequences to understand the structure and function of the molecules and their evolutionary aspects. The main aim of this paper is to provide systematic compilation of a review on different approaches, databases and tools used in motif discovery.


Sujet(s)
Motifs d'acides aminés , Biologie informatique/méthodes , Simulation numérique , Bases de données factuelles , Modèles moléculaires , Phylogenèse , Structure secondaire des protéines , Relation structure-activité
18.
Vaccine ; 29(21): 3802-10, 2011 May 12.
Article de Anglais | MEDLINE | ID: mdl-21421002

RÉSUMÉ

The need to simultaneously target infections with epidemiological overlap in the population with a single vaccine provides the basis for developing combination vaccines. Vibrio cholerae ghosts (rVCG) offer an attractive approach for developing vaccines against a number of human and animal pathogens. In this study, we constructed a multisubunit vaccine candidate co-expressing the serovar D-derived Porin B and polymorphic membrane protein-D proteins of Chlamydia trachomatis and evaluated its ability to simultaneously induce broad-based chlamydial immunity and elicit a vibriocidal antibody response to the Vibrio carrier envelope. Intramuscular (IM) immunization with the vaccine candidate elicited high levels of antigen-specific genital mucosal and systemic Th1 cell-mediated and humoral immune responses against heterologous serovars and strains, including serovars E-H and L. Also, in addition to the multisubunit vaccine, the single subunit constructs conferred significant cross protection against the heterologous mouse strain, Chlamydia muridarum. Furthermore, all mice immunized with rVCG vaccine constructs responded with a significant rise in vibriocidal antibody titer, the surrogate marker for protection in cholera. These findings demonstrate the ability of the multisubunit vaccine to induce cross protective chlamydial as well as vibriocidal immunity and establish the possibility of developing a broadly efficacious Chlamydia-cholera combination vaccine.


Sujet(s)
Anticorps antibactériens/sang , Protéines bactériennes/immunologie , Vaccins antibactériens/administration et posologie , Infections à Chlamydia/prévention et contrôle , Choléra/prévention et contrôle , Évaluation de médicament , Porines/immunologie , Animaux , Production d'anticorps , Vaccins antibactériens/immunologie , Infections à Chlamydia/immunologie , Chlamydia trachomatis/immunologie , Choléra/immunologie , Protection croisée , Cytokines/immunologie , Femelle , Vecteurs génétiques , Protéines membranaires/immunologie , Souris , Souris de lignée C57BL , Vaccins combinés/administration et posologie , Vaccins combinés/immunologie , Vaccins sous-unitaires/administration et posologie , Vaccins sous-unitaires/immunologie , Vibrio cholerae/immunologie
19.
Folia Microbiol (Praha) ; 54(3): 204-6, 2009.
Article de Anglais | MEDLINE | ID: mdl-19649736

RÉSUMÉ

The isoquinoline alkaloids hunnemanine and norsanguinarine have been isolated from methanolic extract of the whole plant of Eschscholzia californica. These two alkaloids were checked for their antifungal activity against phytopathogenic fungi Alternaria melongenae, A. brassicola, A. brassicae, Curvularia lunata, C. maculans, Helminthosporium pennisetti, H. oryzae, H. turcicum, Fusarium undum and F. lini. Hunnemanine exhibited 100 % inhibition of spore germination of A. brassicae, H. pennisetti and F. lini at 1000 ppm whereas norsanguinarine exhibited 100 % inhibition of A. brassicicola and C. maculans at this concentration.


Sujet(s)
Alcaloïdes/pharmacologie , Antifongiques/pharmacologie , Eschscholzia/composition chimique , Champignons/effets des médicaments et des substances chimiques , Isoquinoléines/pharmacologie , Dérivés de la morphine/pharmacologie , Alcaloïdes/composition chimique , Alcaloïdes/isolement et purification , Antifongiques/composition chimique , Antifongiques/isolement et purification , Isoquinoléines/composition chimique , Isoquinoléines/isolement et purification , Dérivés de la morphine/composition chimique , Dérivés de la morphine/isolement et purification , Extraits de plantes/composition chimique
20.
Acta Biol Hung ; 59(1): 1-16, 2008 Mar.
Article de Anglais | MEDLINE | ID: mdl-18401941

RÉSUMÉ

Detailed reproductive pattern and associated endocrine characteristics have been documented in only a few species of order Chiroptera. The aim of the present study was to examine the changes in body weight, serum insulin, leptin, androstenedione and luteinizing hormone (LH) concentrations during annual ovarian cycle in the sheath-tailed bat, Taphozous longimanus. Bats were sampled over three years. Leptin, a satiety hormone produced primarily by adipose tissue, provides information to feeding center of the brain about nutritional status, fat mass, appetite and energy expenditure. The circulating concentration of leptin begins to increase from October and attains a peak in December. The peak serum leptin concentration coincides with body weight in November before winter dormancy in December. The serum leptin levels dissociate from body weight during December. The other peaks of serum leptin levels coincide with late stages of the two successive pregnancies. The serum insulin concentration begins to increase from September and attains a peak during December. The insulin concentration remains low from January to August. The circulating androstenedione concentration begins to increase in October, reaching a peak in December. This increase in androstenedione concentration correlated with the period of heavy accumulation of abdominal fat and increase in body weight. There was a sharp decline in androstenedione concentration and body weight in January. The serum LH shows peaks, in November, coinciding with the peaked body weight, the other peaks in January and May, coinciding with ovulation for the two successive pregnancies. The high leptin and insulin levels might be responsible for the maintenance of reproductive response and gonadal function during adverse environmental condition in the winter, while high androstenedione, and associated body weight along with LH might be responsible for maintaining basal gonadal function. We conclude that high leptin, androstenedione and insulin serve, as signal for the reproductive functions in that sufficient body fat are available to meet the caloric demands and maintain normal function during adverse winter conditions.


Sujet(s)
Androstènedione/sang , Chiroptera/sang , Insuline/sang , Leptine/sang , Hormone lutéinisante/sang , Cycle menstruel/sang , Animaux , Poids/physiologie , Chiroptera/physiologie , Métabolisme énergétique/physiologie , Femelle , Reproduction/physiologie , Saisons
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