PROAPOPTOTIC, ANTI-CELL PROLIFERATIVE, ANTI-INFLAMMATORY AND ANTI-ANGIOGENIC POTENTIAL OF CARNOSIC ACID DURING 7,12 DIMETHYLBENZ[A]ANTHRACENE-INDUCED HAMSTER BUCCAL POUCH CARCINOGENESIS.

The present study has investigated the modulating effect of carnosic acid on the expression pattern of cell proliferative (proliferating cell nuclear antigen (PCNA) cyclin D1 and a transcription factor c-fos), apoptotic (p53, Bcl-2, Bax caspase -3 and 9), inflammatory (Nuclear factor kappa B (NFκB) and cyclooxygenase-2 (COX- 2) and angiogenic (vascular endothelial growth factor (VEGF) markers during 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. Oral tumors were developed in the hamsters buccal pouches by painting with 0.5% DMBA in liquid paraffin three times a week for 14 weeks. Hundred per cent tumour formation (well-differentiated squamous cell carcinoma) accompanied by deregulation in the above mentioned molecular markers was noticed in hamsters treated with DMBA alone (tumour bearing hamsters). Oral administration of carnosic acid at dose of 10mg/kg bw to hamsters treated with DMBA not only completely prevented the tumour formation, but also corrected the abnormalities in the expression pattern of molecular markers. The present study suggests that carnosic acid might have inhibited the tumour formation by exerting anti-cell-proliferative, anti-inflammatory, anti-angiogenic and apoptotic potential during DMBA-induced hamster buccal pouch carcinogenesis

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Not AvailableBackground: There is renewed interest towards understanding the host-pathogen interaction in the light of epigenetic modifications. Although epithelial tissue is the major site for host-pathogen interactions, there is handful of studies to show how epithelial cells respond to pathogens. Bacterial infection in the mammary gland parenchyma induces local and subsequently systemic inflammation that results in a complex disease called mastitis. Globally Staphylococcus aureus is the single largest mastitis pathogen and the infection can ultimately result in either subclinical or chronic and sometimes lifelong infection. Results: In the present report we have addressed the differential inflammatory response in mice mammary tissue during intramammary infection and the altered epigenetic context induced by two closely related strains of S. aureus, isolated from field samples. Immunohistochemical and immunoblotting analysis showed strain specific hyperacetylation at histone H3K9 and H3K14 residues. Global gene expression analysis in S. aureus infected mice mammary tissue revealed a selective set of upregulated genes that significantly correlated with the promoter specific, histone H3K14 acetylation. Furthermore, we have identified several differentially expressed known miRNAs and 3 novel miRNAs in S. aureus infected mice mammary tissue by small RNA sequencing. By employing these gene expression data, an attempt has been made to delineate the gene regulatory networks in the strain specific inflammatory response. Apparently, one of the isolates of S. aureus activated the NF-κB signaling leading to drastic inflammatory response and induction of immune surveillance, which could possibly lead to rapid clearance of the pathogen. The other strain repressed most of the inflammatory response, which might help in its sustenance in the host tissue. Conclusion: Taken together, our studies shed substantial lights to understand the mechanisms of strain specific differential inflammatory response to S. aureus infection during mastitis. In a broader perspective this study also paves the way to understand how certain bacteria can evade the immune surveillance and cause sustained infection while others are rapidly cleared from the host body.Not Availabl

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Not AvailableBackground There is renewed interest towards understanding the host-pathogen interaction in the light of epigenetic modifications. Although epithelial tissue is the major site for host-pathogen interactions, there is handful of studies to show how epithelial cells respond to pathogens. Bacterial infection in the mammary gland parenchyma induces local and subsequently systemic inflammation that results in a complex disease called mastitis. Globally Staphylococcus aureus is the single largest mastitis pathogen and the infection can ultimately result in either subclinical or chronic and sometimes lifelong infection. Results In the present report we have addressed the differential inflammatory response in mice mammary tissue during intramammary infection and the altered epigenetic context induced by two closely related strains of S. aureus, isolated from field samples. Immunohistochemical and immunoblotting analysis showed strain specific hyperacetylation at histone H3K9 and H3K14 residues. Global gene expression analysis in S. aureus infected mice mammary tissue revealed a selective set of upregulated genes that significantly correlated with the promoter specific, histone H3K14 acetylation. Furthermore, we have identified several differentially expressed known miRNAs and 3 novel miRNAs in S. aureus infected mice mammary tissue by small RNA sequencing. By employing these gene expression data, an attempt has been made to delineate the gene regulatory networks in the strain specific inflammatory response. Apparently, one of the isolates of S. aureus activated the NF-κB signaling leading to drastic inflammatory response and induction of immune surveillance, which could possibly lead to rapid clearance of the pathogen. The other strain repressed most of the inflammatory response, which might help in its sustenance in the host tissue. Conclusion Taken together, our studies shed substantial lights to understand the mechanisms of strain specific differential inflammatory response to S. aureus infection during mastitis. In a broader perspective this study also paves the way to understand how certain bacteria can evade the immune surveillance and cause sustained infection while others are rapidly cleared from the host body.Not Availabl

Impact response and damage tolerance of hybrid glass/kevlar-fibre epoxy structural composites

The present study is aimed at investigating the effect of hybridisation on Kevlar/E-Glass based epoxy composite laminate structures. Composites with 3 mm thickness and 16 layers of fibre (14 layers of E-glass centred and 2 outer layers of Kevlar) were fabricated using compression moulding technique. The fibre orientation of the Kevlar layers had 3 variations (0, 45 and 60°), whereas the E-glass fibre layers were maintained at 0° orientation. Tensile, flexural, impact (Charpy and Izod), interlaminar shear strength and ballistic impact tests were conducted. The ballistic test was performed using a gas gun with spherical hard body projectiles at the projectile velocity of 170 m/s. The pre- and post-impact velocities of the projectiles were measured using a high-speed camera. The energy absorbed by the composite laminates was further reported during the ballistic test, and a computerised tomographic scan was used to analyse the impact damage. The composites with 45° fibre orientation of Kevlar fibres showed better tensile strength, flexural strength, Charpy impact strength, and energy absorption. The energy absorbed by the composites with 45° fibre orientation was 58.68 J, which was 14% and 22% higher than the 0° and 60° oriented composites

­­Eleven tips for operational researchers working with health programmes: our experience based on implementing differentiated tuberculosis care in south India

Due to the workload and lack of a critical mass of trained operational researchers within their ranks, health systems and programmes may not be able to dedicate sufficient time to conducting operational research (OR). Hence, they may need the technical support of operational researchers from research/academic organisations. Additionally, there is a knowledge gap regarding implementing differentiated tuberculosis (TB) care in programme settings. In this ‘how we did it’ paper, we share our experience of implementing a differentiated TB care model along with an inbuilt OR component in Tamil Nadu, a southern state in India. This was a health system initiative through a collaboration of the State TB cell with the Indian Council of Medical Research institutes and the World Health Organisation country office in India. The learnings are in the form of eleven tips: four broad principles (OR on priority areas and make it a health system initiative, implement simple and holistic ideas, embed OR within routine programme settings, aim for long-term engagement), four related to strategic planning (big team of investigators, joint leadership, decentralised decision-making, working in advance) and three about implementation planning (conducting pilots, smart use of e-tools and operational research publications at frequent intervals). These may act as a guide for other Indian states, high TB burden countries that want to implement differentiated care, and for operational researchers in providing technical assistance for strengthening implementation and conducting OR in health systems and programmes (TB or other health programmes). Following these tips may increase the chances of i) an enriching engagement, ii) policy/practice change, and iii) sustainable implementation

Nanoscience-Based Strategies to Engineer Antimicrobial Surfaces

Microbial contamination and biofilm formation of medical devices is a major issue associated with medical complications and increased costs. Consequently, there is a growing need for novel strategies and exploitation of nanoscience-based technologies to reduce the interaction of bacteria and microbes with synthetic surfaces. This article focuses on surfaces that are nanostructured, have functional coatings, and generate or release antimicrobial compounds, including ``smart surfaces`` producing antibiotics on demand. Key requirements for successful antimicrobial surfaces including biocompatibility, mechanical stability, durability, and efficiency are discussed and illustrated with examples of the recent literature. Various nanoscience-based technologies are described along with new concepts, their advantages, and remaining open questions. Although at an early stage of research, nanoscience-based strategies for creating antimicrobial surfaces have the advantage of acting at the molecular level, potentially making them more efficient under specific conditions. Moreover, the interface can be fine tuned and specific interactions that depend on the location of the device can be addressed. Finally, remaining important challenges are identified: improvement of the efficacy for long-term use, extension of the application range to a large spectrum of bacteria, standardized evaluation assays, and combination of passive and active approaches in a single surface to produce multifunctional surfaces