ASSESSMENT OF DENTAL FLUOROSIS IN CHILDREN OF JAIPUR DISTRICT, RAJASTHAN, INDIA

Objective: The objective of the present study was carried out to explore the potential association between fluoride concentration in drinking water and severity of dental fluorosis (DF) in the children.Methods: The study of dental fluorosis (DF) in the children (6-14 years old) was conducted in the two blocks (a) Jamwaramgarh block ;Heerawala, Palera ,Nayabas, Saipur and Birasana, (b) Amber block; Jugalpura, Chitanukalan, Sunder ka bas, Peelwa and Sirsali of Jaipur district, Rajasthan, India of the study villages. Total 150, children were surveyed. The role of fluoride (F) levels in drinking water in the etiology of dental fluorosis (DF) and the cases of dental fluorosis (DF) in both dentitions and teeth were also assessed using DEAN'S classification. The fluoride (F) concentration in source of drinking water was estimated by fluoride (F) ion specific electrode (Thermo Scientific Orion Star A329, USA).Results: The F concentration in (Tube well and Hand pump) water ranges from 0.7 to 15.0 parts per million (ppm) in Jamwaramgarh block and 1.40 to 5. 10 parts per million (ppm) in Amber block. Prevalence of dental fluorosis (DF) 27 (36%) in Jamwaramgar block and 26 (34.66%) in Amber block out of 75 children were examined in each block. Significantly increase in levels of F in drinking water is positively correlated with dental fluorosis.Conclusion: This study finding has shown the relation of dental fluorosis (DF) to high fluoride (F) levels in drinking water sources. A higher fluoride (F) levels in source of drinking water is a major risk factor for dental fluorosis. In view of the severity of the problem the intake of calcium rich foods and defluoridation techniques may help reducing risk of dental fluorosis (DF) in the children.Â

Role of positron emission tomography-computed tomography in bronchial mucoepidermoid carcinomas: a case series and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Mucoepidermoid carcinoma of the tracheobronchial tree is rare. Such tumors usually present with signs and symptoms of bronchial obstruction. Histologically, they can be classified as high-grade or low-grade tumors. Experience of imaging these tumors with ¹⁸fluorodeoxyglucose positron emission tomography-computed tomography (¹⁸F-FDG PET-CT) is limited. We present three cases of this rare tumor, describe the functional imaging results, and review the available literature.</p> <p>Case presentation</p> <p>Three Caucasian patients, two men (21 and 24 years of age) and one woman (14 years of age), with bronchial masses were evaluated by us. All three patients were symptomatic, and underwent a thorough clinical examination, bronchoscopy and biopsy, plain computed tomography, ¹⁸F-FDG PET-CT and ⁶⁸Gallium 1,4,7,10-Tetraazacyclododecane-N^I,N^II,N^III,N^IIII,- tetra acetic acid (D) - Phel¹-Tyr³-octreotide positron emission tomography-computed tomography (⁶⁸Ga-DOTATOC PET-CT). ¹⁸F-FDG PET-CT revealed mild uptake in all three patients, whereas ⁶⁸Ga-DOTATOC PET-CT revealed no significant uptake in any patient, making carcinoid tumor unlikely. Results of histopathological examination were consistent with low-grade mucoepidermoid carcinoma in all patients.</p> <p>Conclusion</p> <p>Our study reveals that functional imaging may be helpful in the initial investigation of patients with mucoepidermoid carcinoma. ¹⁸F-FDG PET-CT may have a prognostic relevance by predicting the histopathologic differentiation of the tumor.</p

Genetic determinants of co-accessible chromatin regions in activated T cells across humans.

Over 90% of genetic variants associated with complex human traits map to non-coding regions, but little is understood about how they modulate gene regulation in health and disease. One possible mechanism is that genetic variants affect the activity of one or more cis-regulatory elements leading to gene expression variation in specific cell types. To identify such cases, we analyzed ATAC-seq and RNA-seq profiles from stimulated primary CD4+ T cells in up to 105 healthy donors. We found that regions of accessible chromatin (ATAC-peaks) are co-accessible at kilobase and megabase resolution, consistent with the three-dimensional chromatin organization measured by in situ Hi-C in T cells. Fifteen percent of genetic variants located within ATAC-peaks affected the accessibility of the corresponding peak (local-ATAC-QTLs). Local-ATAC-QTLs have the largest effects on co-accessible peaks, are associated with gene expression and are enriched for autoimmune disease variants. Our results provide insights into how natural genetic variants modulate cis-regulatory elements, in isolation or in concert, to influence gene expression

MMP-9, uPAR and Cathepsin B Silencing Downregulate Integrins in Human Glioma Xenograft Cells In Vitro and In Vivo in Nude Mice

Involvement of MMP-9, uPAR and cathepsin B in adhesion, migration, invasion, proliferation, metastasis and tumor growth has been well established. In the present study, MMP-9, uPAR and cathepsin B genes were downregulated in glioma xenograft cells using shRNA plasmid constructs and we evaluated the involvement of integrins and changes in their adhesion, migration and invasive potential.MMP-9, uPAR and cathepsin B single shRNA plasmid constructs were used to downregulate these molecules in xenograft cells. We also used MMP-9/uPAR and MMP-9/cathepsin B bicistronic constructs to evaluate the cumulative effects. MMP-9, uPAR and cathepsin B downregulation significantly inhibits xenograft cell adhesion to several extracellular matrix proteins. Treatment with MMP-9, uPAR and cathepsin B shRNA of xenografts led to the downregulation of several alpha and beta integrins. In all the assays, we noticed more prominent effects with the bicistronic plasmid constructs when compared to the single plasmid shRNA constructs. FACS analysis demonstrated the expression of alphaVbeta3, alpha6beta1 and alpha9beta1 integrins in xenograft cells. Treatment with bicistronic constructs reduced alphaVbeta3, alpha6beta1 and alpha9beta1 integrin expressions in xenograft injected nude mice. Migration and invasion were also inhibited by MMP-9, uPAR and cathepsin B shRNA treatments as assessed by spheroid migration, wound healing, and Matrigel invasion assays. As expected, bicistronic constructs further inhibited the adhesion, migration and invasive potential of the xenograft cells as compared to individual treatments.Downregulation of MMP-9, uPAR and cathespin B alone and in combination inhibits adhesion, migration and invasive potential of glioma xenografts by downregulating integrins and associated signaling molecules. Considering the existence of integrin inhibitor-resistant cancer cells, our study provides a novel and effective approach to inhibiting integrins by downregulating MMP-9, uPAR and cathepsin B in the treatment of glioma

Prospect and potential of Burkholderia sp. against Phytophthora capsici Leonian: a causative agent for foot rot disease of black pepper

Foot rot disease is a very destructive disease in black pepper in Malaysia. It is caused by Phytophthora capsici Leonian, which is a soilborne pathogenic protist (phylum, Oomycota) that infects aerial and subterranean structures of many host plants. This pathogen is a polycyclic, such that multiple cycles of infection and inoculum production occur in a single growing season. It is more prevalent in the tropics because of the favourable environmental conditions. The utilization of plant growth-promoting rhizobacteria (PGPR) as a biological control agent has been successfully implemented in controlling many plant pathogens. Many studies on the exploration of beneficial organisms have been carried out such as Pseudomonas fluorescens, which is one of the best examples used for the control of Fusarium wilt in tomato. Similarly, P. fluorescens is found to be an effective biocontrol agent against the foot rot disease in black pepper. Nowadays there is tremendous novel increase in the species of Burkholderia with either mutualistic or antagonistic interactions in the environment. Burkholderia sp. is an indigenous PGPR capable of producing a large number of commercially important hydrolytic enzymes and bioactive substances that promote plant growth and health; are eco-friendly, biodegradable and specific in their actions; and have a broad spectrum of antimicrobial activity in keeping down the population of phytopathogens, thus playing a great role in promoting sustainable agriculture today. Hence, in this book chapter, the potential applications of Burkholderia sp. to control foot rot disease of black pepper in Malaysia, their control mechanisms, plant growth promotion, commercial potentials and the future prospects as indigenous PGPR were discussed in relation to sustainable agriculture

Co-Depletion of Cathepsin B and uPAR Induces G0/G1 Arrest in Glioma via FOXO3a Mediated p27Kip1 Upregulation

Cathepsin B and urokinase plasminogen activator receptor (uPAR) are both known to be overexpressed in gliomas. Our previous work and that of others strongly suggest a relationship between the infiltrative phenotype of glioma and the expression of cathepsin B and uPAR. Though their role in migration and adhesion are well studied the effect of these molecules on cell cycle progression has not been thoroughly examined.Cathepsin B and uPAR single and bicistronic siRNA plasmids were used to downregulate these molecules in SNB19 and U251 glioma cells. FACS analysis and BrdU incorporation assay demonstrated G0/G1 arrest and decreased proliferation with the treatments, respectively. Immunoblot and immunocyto analysis demonstrated increased expression of p27(Kip1) and its nuclear localization with the knockdown of cathepsin B and uPAR. These effects could be mediated by alphaVbeta3/PI3K/AKT/FOXO pathway as observed by the decreased alphaVbeta3 expression, PI3K and AKT phosphorylation accompanied by elevated FOXO3a levels. These results were further confirmed with the increased expression of p27(Kip1) and FOXO3a when treated with Ly294002 (10 microM) and increased luciferase expression with the siRNA and Ly294002 treatments when the FOXO binding promoter region of p27(Kip1) was used. Our treatment also reduced the expression of cyclin D1, cyclin D2, p-Rb and cyclin E while the expression of Cdk2 was unaffected. Of note, the Cdk2-cyclin E complex formation was reduced significantly.Our study indicates that cathepsin B and uPAR knockdown induces G0/G1 arrest by modulating the PI3K/AKT signaling pathway and further increases expression of p27(Kip1) accompanied by the binding of FOXO3a to its promoter. Taken together, our findings provide molecular mechanism for the G0/G1 arrest induced by the downregulation of cathepsin B and uPAR in SNB19 and U251 glioma cells

Crosstalk between Medulloblastoma Cells and Endothelium Triggers a Strong Chemotactic Signal Recruiting T Lymphocytes to the Tumor Microenvironment

Cancer cells can live and grow if they succeed in creating a favorable niche that often includes elements from the immune system. While T lymphocytes play an important role in the host response to tumor growth, the mechanism of their trafficking to the tumor remains poorly understood. We show here that T lymphocytes consistently infiltrate the primary brain cancer, medulloblastoma. We demonstrate, both in vitro and in vivo, that these T lymphocytes are attracted to tumor deposits only after the tumor cells have interacted with tumor vascular endothelium. Macrophage Migration Inhibitory Factor (MIF)” is the key chemokine molecule secreted by tumor cells which induces the tumor vascular endothelial cells to secrete the potent T lymphocyte attractant “Regulated upon Activation, Normal T-cell Expressed, and Secreted (RANTES).” This in turn creates a chemotactic gradient for RANTES-receptor bearing T lymphocytes. Manipulation of this pathway could have important therapeutic implications

MMP-2 siRNA Inhibits Radiation-Enhanced Invasiveness in Glioma Cells

Our previous work and that of others strongly suggests a relationship between the infiltrative phenotype of gliomas and the expression of MMP-2. Radiation therapy, which represents one of the mainstays of glioma treatment, is known to increase cell invasion by inducing MMP-2. Thus, inhibition of MMP-2 provides a potential means for improving the efficacy of radiotherapy for malignant glioma.We have tested the ability of a plasmid vector-mediated MMP-2 siRNA (p-MMP-2) to modulate ionizing radiation-induced invasive phenotype in the human glioma cell lines U251 and U87. Cells that were transfected with p-MMP-2 with and without radiation showed a marked reduction of MMP-2 compared to controls and pSV-transfected cells. A significant reduction of proliferation, migration, invasion and angiogenesis of cells transfected with p-MMP-2 and in combination with radiation was observed compared to controls. Western blot analysis revealed that radiation-enhanced levels of VEGF, VEGFR-2, pVEGFR-2, p-FAK, and p-p38 were inhibited with p-MMP-2-transfected cells. TUNEL staining showed that radiation did not induce apoptosis in U87 and U251 cells while a significant increase in TUNEL-positive cells was observed when irradiated cells were simultaneously transfected with p-MMP-2 as compared to controls. Intracranial tumor growth was predominantly inhibited in the animals treated with p-MMP-2 alone or in combination with radiation compared to controls.MMP-2 inhibition, mediated by p-MMP-2 and in combination with radiation, significantly reduced tumor cell migration, invasion, angiogenesis and tumor growth by modulating several important downstream signaling molecules and directing cells towards apoptosis. Taken together, our results demonstrate the efficacy of p-MMP-2 in inhibiting radiation-enhanced tumor invasion and progression and suggest that it may act as a potent adjuvant for radiotherapy in glioma patients

Downregulation of uPAR and Cathepsin B Induces Apoptosis via Regulation of Bcl-2 and Bax and Inhibition of the PI3K/Akt Pathway in Gliomas

Glioma is the most commonly diagnosed primary brain tumor and is characterized by invasive and infiltrative behavior. uPAR and cathepsin B are known to be overexpressed in high-grade gliomas and are strongly correlated with invasive cancer phenotypes.In the present study, we observed that simultaneous downregulation of uPAR and cathepsin B induces upregulation of some pro-apoptotic genes and suppression of anti-apoptotic genes in human glioma cells. uPAR and cathepsin B (pCU)-downregulated cells exhibited decreases in the Bcl-2/Bax ratio and initiated the collapse of mitochondrial membrane potential. We also observed that the broad caspase inhibitor, Z-Asp-2, 6-dichlorobenzoylmethylketone rescued pCU-induced apoptosis in U251 cells but not in 5310 cells. Immunoblot analysis of caspase-9 immunoprecipitates for Apaf-1 showed that uPAR and cathepsin B knockdown activated apoptosome complex formation in U251 cells. Downregulation of uPAR and cathepsin B also retarded nuclear translocation and interfered with DNA binding activity of CREB in both U251 and 5310 cells. Further western blotting analysis demonstrated that downregulation of uPAR and cathepsin B significantly decreased expression of the signaling molecules p-PDGFR-β, p-PI3K and p-Akt. An increase in the number of TUNEL-positive cells, increased Bax expression, and decreased Bcl-2 expression in nude mice brain tumor sections and brain tissue lysates confirm our in vitro results.In conclusion, RNAi-mediated downregulation of uPAR and cathepsin B initiates caspase-dependent mitochondrial apoptosis in U251 cells and caspase-independent mitochondrial apoptosis in 5310 cells. Thus, targeting uPAR and cathepsin B-mediated signaling using siRNA may serve as a novel therapeutic strategy for the treatment of gliomas

Design of agile supply chains including analysing the trade-off between number of partners and reliability

The reliability of supply partners is particularly vital in agile supply chains as it is vulnerable to the inability of a supply partner to meet its high responsiveness and flexibility requirements resulting in the disruption of the whole network. Disruption can have expensive and extensive results for the entire agile supply chain. To mitigate the risk of disruption and improve the reliability of the whole agile supply chain, decision-makers need to pay more attention to supply chain design and construction, whilst simultaneously taking into account the sourcing strategy decisions. This paper proposes a series of models for the design of agile supply chains using dynamic programming modelling. These provide decision-makers with a systematic way of analysing one of the key decisions of sourcing strategy, namely the trade-off between the number of supply partners and reliability. The efficacy of the models is demonstrated through their application to a Chinese bus and coach manufacturer by way of an empirical illustration. The results show that this approach is effective for this application and it can be applied in other related decision-making scenarios. The methods offered in this paper provide managers with a practical tool to design their agile supply chains while considering the trade-offs between the number of partners and the reliability of the entire agile supply chain