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In absence of frank purulence, wound cultures represent 'gold-standard' for diagnosis of fracture related infection (FRI). However, these are time-intensive, and may be falsely negative, necessitating the need for accurate and rapid biomarker-based diagnosis. We conducted this study to determine the accuracy of 3 wound-based biomarkers for the diagnosis of FRI.This was a prospective cohort study on adult patients who underwent an operative procedure for an upper or lower limb fracture. Wound fluid levels of alpha-defensin (AD), neutrophil elastase (NE) and IL-6 were evaluated on post-operative day 2, and patients were followed up for one month. Patients were categorized as cases (FRI) or controls (no FRI), on the basis of the consensus definition of FRI. Univariate analysis, along with receiver operating characteristic (ROC) analysis was performed.48 patients were included. AD levels showed a 2.6-fold elevation in cases (n = 26, Median = 23.74 µg/ml) as compared to controls (n = 22, Median = 8.78 µg/ml). The area under the curve for this variable was 0.71 (95% Confidence Intervals = 0.56 - 0.86). The levels of NE and IL-6 were not significantly different between cases and controls.Wound AD levels are significantly elevated in patients with FRI. However, these results need to be validated in a larger cohort of patients before it can be used as a biomarker of FRI.

BackgroundHypertrophic cardiomyopathy (HCM) is a genetic heart muscle disease with preserved or increased ejection fraction in the absence of secondary causes. Mutations in the sarcomeric protein-encoding genes predominantly cause HCM. However, relatively little is known about the genetic impact of signalling proteins on HCM.Methods and resultsHere, using exome and targeted sequencing methods, we analysed two independent cohorts comprising 401 Indian patients with HCM and 3521 Indian controls. We identified novel variants in ribosomal protein S6 kinase beta-1 (RPS6KB1 or S6K1) gene in two unrelated Indian families as a potential candidate gene for HCM. The two unrelated HCM families had the same heterozygous missense S6K1 variant (p.G47W). In a replication association study, we identified two S6K1 heterozygotes variants (p.Q49K and p.Y62H) in the UK Biobank cardiomyopathy cohort (n=190) compared with matched controls (n=16 479). These variants are neither detected in region-specific controls nor in the human population genome data. Additionally, we observed an S6K1 variant (p.P445S) in an Arab patient with HCM. Functional consequences were evaluated using representative S6K1 mutated proteins compared with wild type in cellular models. The mutated proteins activated the S6K1 and hyperphosphorylated the rpS6 and ERK1/2 signalling cascades, suggesting a gain-of-function effect.ConclusionsOur study demonstrates for the first time that the variants in the S6K1 gene are associated with HCM, and early detection of the S6K1 variant carriers can help to identify family members at risk and subsequent preventive measures. Further screening in patients with HCM with different ethnic populations will establish the specificity and frequency of S6K1 gene variants.

Endothelial dysfunction and vascular remodeling are the hallmarks of pulmonary arterial hypertension (PAH). For PAH treatment, there is a rising demand of Stem cell therapy. Interestingly, research reveals that stem/progenitor cells may have an impact in disease progression and therapy in PAH patients. Clinical trials for stem cell therapy in cardiac cell regeneration for heart repair in PAH patients are now underway. The clinical potential of stem/progenitor cell treatment that offers to PAH patients helps in lesion formation which occurs through regaining of vascular cell activities. Majorly the stem cells which are specifically derived from bone marrow such as mesenchymal stem cells (MSCs), endothelial progenitor cells (EPCs) and induced pluripotent cells (iPSCs), adipose-derived stem cells (ADSCs), and cardiac stromal cells (CSCs) are among the subtypes that are proved to play a pivotal role in the repair of the heart. But with only MSCs and EPCs, have shown positive outcomes and act as therapeutically efficient in regaining cure for PAH in clinical trials. This chapter also seeks to explain the potential limitations and challenges with most recent achievements in stem/progenitor cell research in PAH.

Landslide is one of the major hazards in hilly regions especially when we talk about Indian Himalayan mountain ranges. Colluvial soil obtained at base of hill slope is generally week and unconsolidated which need improvement to reuse. Here work is done to improve shear strength of weak Colluvial soil of Kotropi landslide, Himachal Pradesh. This colluvial soil can be used again in various engineering work after adding certain material in it. Although various additives are available but rice husk ash and micro silica powder is selected for partial replacement of soil due to its economic, social and environmental benefits. Soil tests are conducted to get different Geotechnical properties of soil. Various samples of soil are made by adding different percentage of additives. Shear strength of different sample is compared to find optimum proportion of additives. It is observed that 15% of rice husk ash and 4% of micro silica powder provide maximum strength.

Diverse internal and external pathologic stimuli can trigger cellular stress response pathways (CSRPs) that are usually counteracted by intrinsic homeostatic machinery, which responds to stress by initiating complex signaling mechanisms to eliminate either the stressor or the damaged cells. There is growing evidence that CSRPs can have context-dependent homeostatic or pathologic functions that may result in tissue fibrosis under persistence of stress. CSRPs can drive intercellular communications through exosomes (trafficking and secretory pathway determinants) secreted in response to stress-induced proteostasis rebalancing. The injured tissue environment upon sensing the stress turns on a precisely orchestrated network of immune responses by regulating cytokine-chemokine production, recruitment of immune cells, and modulating fibrogenic niche and extracellular matrix (ECM) cross-talk during fibrotic pathologies like cardiac fibrosis, liver fibrosis, laryngotracheal stenosis, systemic scleroderma, interstitial lung disease and inflammatory bowel disease. Immunostimulatory RNAs (like double stranded RNAs) generated through deregulated RNA processing pathways along with RNA binding proteins (RBPs) of RNA helicase (RNA sensors) family are emerging as important components of immune response pathways during sterile inflammation. The paradigm-shift in RNA metabolism associated interactome has begun to offer new therapeutic windows by unravelling the novel RBPs and splicing factors in context of developmental and fibrotic pathways. We would like to review emerging regulatory nodes and their interaction with CSRPs, and tissue remodeling with major focus on cardiac fibrosis, and inflammatory responses underlying upper airway fibrosis.

Objectives To identify epigenetic and transcriptional factors controlling osteoclastogenesis (OCG), that have been shown to play a role in the pathogenesis of skeletal diseases. Methods A systematic review was conducted in accordance with the PRISMA guidelines. The PubMed and EMBASE databases were searched up to 30th April 2020; references of included articles and pertinent review articles were also screened to identify eligible studies. Studies were included if they described epigenetic and/or transcriptional regulation of OCG in a specific skeletal disorder, and quantified alterations in OCG by any well-described experimental method. Risk of bias was assessed by a previously described modification of the CAMARADES tool. Results The combined searches yielded 2265 records. Out of these, 24 studies investigating 12 different skeletal disorders were included in the review. Osteoporosis, followed by osteopetrosis, was the most commonly evaluated disorder. A total of 22 different epigenetic and transcriptional regulators of OCG were identified; key epigenetic regulators included DNA methylation, histone methylation, histone acetylation, miRNAs and lncRNAs. In majority of the disorders, dysregulated OCG was noted to occur at the stage of formation of committed osteoclast from preosteoclast. Dysregulation the stage of formation of the preosteoclast from late monocyte was noted in rheumatoid arthritis and fracture, whereas dysregulation at stage of formation of late monocyte from early monocyte was noted in osteopetrosis and spondyloarthritis. Quality assessment revealed a high risk of bias in domains pertaining to randomization, allocation concealment, blinding of outcome assessors and determination of sample size. Conclusions A variety of epigenetic and transcriptional factors can result in dysregulated osteoclastogenesis in different skeletal disorders. Dysregulation can occur at any stage; however, the formation of committed osteoclasts from preosteoclasts is the most common target. Although the published literature on this subject seems promising, the overall strength of evidence is limited by the small number of studies evaluating individual skeletal disorders, and also by deficiencies in key aspects of study design.

Soil stabilization means modification of the soils properties to meet the specified engineering requirements. There are several methods for the stabilization of soil like compaction and use of admixtures. Lime and cement were commonly used materials as stabilizer for modifying the properties of soils. From the study, it had been observed that solid waste materials such as fly ash, rice husk ash with or without lime or cement can be used for improving the properties of soil. MSW is a type of the solid waste material available in environment. They are increasing exponentially day by day. Disposal of these waste materials is essential as they are causing hazardous effects on the environment. Disposal requires too much land. In this paper, MSW (municipal solid waste) ash was undertaken for the stabilization of soils and its different proportion was mixed with cohesive soil. Laboratory tests such as pycnometer, compaction, and unconfined compressive strength test were performed to measure the engineering characteristics of the stabilized material and influence of MSW ash on various parameters and unconfined compressive strength of cohesive soil evaluated. The MSW ash was added in percentages of 0, 5, 10, 15, and 20%, by dry weight of soil.

Permeability of soil is one of the most significant property. It controls the hydraulic stability of soil mass. It is dependent on various index properties like particle size of soil, percentage of impurities, void ratio, etc. However, permeability of soil is difficult to find out and it consumes time, especially in the case of fine grained soils. In this paper, change in permeability of soil due to mixing of additive (Fly ash) is investigated. Experiments were conducted in the National Institute of Technology, Kurukshetra soil laboratory. Various samples were collected for laboratory investigations to determine various soil parameters such as specific gravity, grain size distribution (particle mean size), and coefficient of permeability. Collected soil for the experiment is locally available sand. Additives are added in collected soil samples at different replacement ratios. Permeability of sample is checked and it is observed that permeability of sand firstly decreases up to a certain limit, then it increases.

Stabilisation of a fine-grained soil using plastic waste is experimentally investigation in this study. Samples are prepared by mixing with four different plastic waste contents (0, 0.5, 1, and 1.5% of weight of dry soil). Variations in compaction characteristics and Unconfined compressive strength are investigated as per Indian standard experimental procedures. Percentage decrease/increase in the stated parameters is computed with respect to their untreated value. Study shows that plastic waste additive increases maximum dry density, optimum moisture content, and unconfined compressive strength to some extent. The plastic waste cut into strips form of size 5 mm × 3 mm

This paper describes the concept of routing in wireless sensor networks. Routing algorithm provides reliable path from source to destination. Energy efficiency is main constraint in Wireless Sensor Networks. For improving life time and energy consumption various routing algorithms have been proposed. In this paper describe the hierarchical routing techniques. Hierarchical routing includes tree based routing, cluster based routing, chain based protocol, and grid based routing. And also compare the hierarchical routing techniques.

Today breakthroughs in wireless technologies have greatly spurred the emergence of industrial wireless sensor networks (IWSNs).To facilitate the adaptation of IWSNs to industrial applications, concerns about networks full coverage and connectivity must be addressed to fulfill reliability and real time requirements. Although connected target coverage algorithms have been studied notice both limitations and applicability of various coverage areas from an industry viewpoint. In this paper is discuss the two energy efficiency connected target coverage (CTC) algorithms CWGC(Communication Weighted Greedy Cover) and OTTC(Overlapped Target and Connected Coverage) algorithm based on dynamic node to resolve the problem of Coverage improvement. This paper uses the simulation in MATLAB represent the performance of two CTC algorithms with Dynamic node to improve network lifetime and low energy consumption and quality of service. Compare the dynamic nodes results with static nodes results

Dilated cardiomyopathy (DCM) is an important cause of heart failure and sudden cardiac death worldwide. Transcription factor TBX20 has been shown to play a crucial role in cardiac development and maintenance of adult mouse heart. Recent studies suggest that TBX20 may have a role in pathophysiology of DCM. In the present study, we examined TBX20 expression in idiopathic DCM patients and in an animal model of cardiomyopathy, and studied its correlation with echocardiographic indices of LV function. Endomyocardial biopsies (EMBs) from intraventricular septal from the right ventricle region were obtained from idiopathic DCM patients (IDCM, n = 30) and from patients with ventricular septal defect (VSD, n = 14) with normal LVEF who served as controls. An animal model of DCM was developed by right renal artery ligation in Wistar rats. Cardiac TBX20 mRNA levels were measured by real-time PCR in IDCM, controls, and in rats. The role of DNA promoter methylation and copy number variation (CNVs) in regulating TBX20 gene expression was also investigated. Cardiac TBX20 mRNA levels were significantly increased (8.9 fold, p < 0.001) in IDCM patients and in RAL rats as compared to the control group. Cardiac TBX20 expression showed a negative correlation with LVEF (r = -0.71, p < 0.001) and a positive correlation with left ventricular end-systolic volume (r = 0.39, p = 0.038). No significant difference in TBX20 CNVs and promoter methylation was observed between IDCM patients and control group. Our results suggest a potential role of TBX20 in pathophysiology of DCM.

Wireless Sensor Networks WSNs deliver smart communication paradigm which can set up intelligent networks handling all the applications as per the user requirements. The WSNs offer several advantages like flexibility, fault tolerance, low cost and easy deployment. Typically, a WSN consists of spatially distributed autonomous sensors to monitor physical or environmental conditions. These sensors generate report over the network on the occurrence of any event. For a WSN to provide better reliability and improved lifetime, an efficient Medium Access Control MAC protocol design holds a paramount importance. Several multichannel MAC protocols exist which performs better than the single channel protocols. The MAC layer coordinates transmission between the users sharing a spectrum and improves the throughput and energy efficiency. Cognitive Radio CR is an adaptive, intelligent radio and network technology that can automatically detect available channels in a wireless spectrum and make those channels available for concurrent transmissions. Dynamic spectrum access in the form of cognitive radio provides spectrum efficient communication for all WSNs which led to the development of Cognitive Radio Sensor Networks CRSNs . This paper highlights an intensive survey of MAC protocols defined for WSNs and the design of Cognitive Radio based WSNs. Anupam Mittal | Geetika Sharma "MAC: Protocols for Cognitive Radio Sensor Networks and their Comparision" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-2 | Issue-5 , August 2018, URL: https://www.ijtsrd.com/papers/ijtsrd17060.pdf

Swarm Intelligence is an artificial intelligence discipline which is concerned with the design of intelligent multi agent systems by taking inspiration from the collective behaviours of social insects and other animal societies. PSO is a population based optimization technique use for finding optimum solution. PSO technique is originated from social behavior bird flocking. The purpose of the research is to compare particle swarm optimization based routing algorithms used in MANET and VANET. Swarm intelligence based routing algorithm will more promising for specific nature of ad hoc networks scenarios constraints environmental conditions and will tune and simulate to get an efficient and effective routing protocol for MANET and VANET. Geetika Sharma | Anupam Mittal "Comparative Analysis of Particle Swarm Optimization Based Routing Protocols for MANET and VANET" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-2 | Issue-5 , August 2018, URL: https://www.ijtsrd.com/papers/ijtsrd15874.pdf

Cardiorenal syndrome is defined by primary heart failure conditions influencing or leading to renal injury or dysfunction. Dilated cardiomyopathy (DCM) is a major co-existing form of heart failure (HF) with renal diseases. Myocardin (MYOCD), a cardiac-specific co-activator of serum response factor (SRF), is increased in DCM mice and patient cardiac tissues and plays a crucial role in the pathophysiology of DCM. Inhibiting the increased MYOCD has shown to be partially rescuing the DCM mice phenotype. However, expression levels of MYOCD in the cardiac tissues of the cardiorenal syndromic patients and the beneficial effect of inhibiting MYOCD in a cardiorenal syndrome model remains to be explored.Here, we analyzed the expression levels of MYOCD in the DCM patients with and without renal diseases. We also explored, whether cardiac specific silencing of MYOCD expression could ameliorate the cardiac remodeling and improve cardiac function in a renal artery ligated rat model (RAL). We observed an increase in MYOCD levels in the endomyocardial biopsies of DCM patients associated with renal failure compared to DCM alone. Silencing of MYOCD in RAL rats by a cardiac homing peptide conjugated MYOCD siRNA resulted in attenuation of cardiac hypertrophy, fibrosis and restoration of the left ventricular functions.Our data suggest hyper-activation of MYOCD in the pathogenesis of the cardiorenal failure cases. Also, MYOCD silencing showed beneficial effects by rescuing cardiac hypertrophy, fibrosis, size and function in a cardiorenal rat model.

Myocardin (MYOCD), a cardiac specific transcriptional co-activator is up-regulated in heart failure (HF). Up-regulation of MYOCD expression has been proposed to be an important adaptive response in cardiac remodelling. However, molecular mechanisms contributing to increased cardiac MYOCD expression in HF are not known. The goal of this study was to identify microRNA(s) regulating cardiac MYOCD expression and to study the effect of cardiac modulation of MYOCD specific miRNA in an animal model of HF. miRNA(s) targeting MYOCD were identified using in silico approach and validated by 3’-UTR luciferase reporter assay. Cardiac expression of miRNA was measured in endomyocardial biopsies from idiopathic DCM (IDCM) patients, renal artery ligation rat model of HF (RAL) and in Ang II treated cardiomyocytes by real-time PCR. miRNA-33a, miRNA-33b, miRNA-139 and miRNA-542 were identified with MYOCD as putative target. Cardiac expression of miRNA-33a and miRNA-33b was significantly decreased, whereas expression of miRNA-139 and miRNA-542 was not altered in IDCM. miRNA-33a expression was also decreased in RAL and in Ang II treated cardiomyocytes. Luciferase assay confirmed MYOCD as target gene for miRNA-33a. miRNA-33a overexpression significantly decreased expression of MYOCD, ANP and fibrotic genes in Ang II treated cardiomyocytes. Cardiac specific delivery of miRNA-33a, using a homing peptide conjugated siRNA, attenuated cardiac hypertrophy and fibrosis, decreased expression of ANP, β-MHC and fibrotic genes and ameliorated the impaired diastolic dysfunction in RAL. Our results provide the first evidence that miRNA-33a regulates MYOCD expression and cardiac specific augmentation of miRNA-33a attenuated cardiac remodelling and partially restored left ventricular function. Our results suggest miR-33a as a potential therapeutic target in reversal of cardiac remodelling and improvement in heart function in HF.

Hypertrophic cardiomyopathy (HCM) is a heterogenous disease predominantly caused by sarcomeric genes. However, 40-50% cases etiology are not known. RAF1 mutations cause syndromic and isolated childhood cardiomyopathies. Functional mutations in untranslated regions (UTRs) of RAF-1 gene are rare, and their role in cardiomyopathy is unexplored. UTRs are important sites for interaction of epigenetic regulators such as microRNAs (miR). miRs have exhibited as crucial regulators of the cardiac remodeling process. We identified a novel mutation in RAF-1 3’-UTR (an important site for binding of miR-19a-3p/19b-3p) in large family members associated with HCM. Whole exome sequencing revealed that these family members are negative for mutations in known cardiomyopathy associated genes. miR-19a/b are known to play a crucial role in cardiac hypertrophy. The aim of this study is to determine the role of miR-19a-3p/19b-3p in regulating RAF-1 expression and delineating the molecular and functional consequences of identified RAF-1 3’-UTR mutation. Our results show that the overexpression of miR-19b-3p, leads to downregulation of RAF-1 expression and regulation. Notably, miR-19b-3p was found to be pro-hypertrophic as its overexpression resulted in increasing hypertrophic markers including ANP and β-MHC expression. Moreover, findings from experiments using RAF1 +/+ and RAF1 -/- mouse embryo fibroblasts (MEFs) confirms the role of miR-19b-3p interaction and regulation of RAF-1 signaling axis. Interestingly, we also observed many autophagy markers (Atg3, Atg 12-5 complex, and LC3 II) are dysregulated by miR-19-b-3p overexpression. Our study uncovers a novel mechanism through which miR-19b-3p regulates autophagy by targeting RAF-1.

Objectives: Wireless Mesh Network is a promising technology in delivering the last mile broadband access. The smart routing technique has been defined during this paper for mesh networks with path selection along the connectivity hole avoidance using pushback mechanism. This paper also deploys a load balancing algorithm among the best paths available. The new design also incorporates the multi-channel triangulation method for the purpose of the optimal path selection among the multiple options. Energy aware routing mechanism is also deployed for evaluating the energy consumed during this network. Methods: The mesh network topology with 120 mesh network nodes deployed randomly over the given area of 100 x 100 meters in order to simulate the multiple networks zones. The network has been majorly divided into the three major zones in order to depict the mesh network zones, which are signified with the different colors in the given topology. The initial connectivity is entirely based upon the transmission radius of the nodes, which keeps the initial connectivity module in to the one-hop connections formation. Findings: The planned methodology compares with the existing routing scheme of Delaunay Triangulation. The performance parameters which compared with existing technique are average distance stretch and packet drop ratio. In this paper, other evaluation metrics are determined which are throughput, latency, number of aggregators and energy consumption. Novelty of the Study: The experimental observations have shown that planned routing mechanism outperforms to other existing scheme in terms of average distance stretch and packet drop ratio.

Paper is regarding the use of coverage algorithms on the static and dynamic node to resolve the problem of Coverage. Objectives: Main objective of this research is to minimize energy consumption. Its objective is to provide full connectivity and coverage with dynamic nodes in industrial WSN. Methods: Initially, deploy a number of nodes in an industrial area with the usage of MATLAB environment. Then apply two algorithms Communication Weighted Greedy Cover andOverlapped Target and Connected Coverage algorithms. Communication weighted greedy cover algorithm is used to separate movement of nodes. OTTC algorithm is used to reduce overlapped target problem. Findings: In Industrial Wireless Sensor Network the problem of Network coverage occursdue to large area coverage and heterogeneity of the network. CWCG and OTTC algorithms consume more energy while covering all the nodes. A solution is needed to develop an energy efficient network coverage algorithm which provides full coverage and connectivity. This research paper shows coverage with dynamic nodes in industrial area. Dynamic nodes reduce coverage and overlapped target problem.

This paper regarding the use of the natural phenomenon’s based optimization techniques to resolve the problem of nonclustered nodes. Objectives: This research minimizes energy consumption. Its objective is to provide efficient clustering for avoidance of residual nodes and prevents occurrence of dead nodes with usage of mobile nodes. Methods: In this research paper firstly deploy number of mobile nodes in specified region with usage of MATLAB environment. For grouping of these nodes LEACH protocol uses for clustering. During clustering with LEACH some nodes residual and not become part of any cluster. Firefly Optimization used for prevention of residual nodes and efficient clustering. It uses distance and light intensity parameters for clustering. GSA algorithm used for finding best path for data transmission with less energy consumption. Findings: In this research paper shows efficient clustering of nodes with prevention of residual nodes. In existing LEACH protocol some static nodes are residual and not become part of any cluster. These nodes send data directly to base station and consume large amount of energy. These individual nodes die early due to maximum energy consumption. But in this research mobile nodes are used and occurrence of dead nodes prevented on basis of distance and light intensity parameters. Nodes which are at minimum distance are brighter than farthest nodes. Minimum distance nodes join nearest cluster and prevent formation of remaining nodes. Improvements: In this paper results shown that it performs better in terms of network lifetime, energy consumption, end to end delay and throughput and number of dead nodes.

p53-p21 pathway mediates cardiomyocyte hypertrophy and apoptosis and is upregulated in diabetic cardiomyopathy (DbCM). We investigated role of microRNAs in regulating p53-p21 pathway in high glucose (HG)-induced cardiomyocyte hypertrophy and apoptosis. miR-30c and miR-181a were identified to target p53. Cardiac expression of microRNAs was measured in diabetic patients, diabetic rats, and in HG-treated cardiomyocytes. Effect of microRNAs over-expression and inhibition on HG-induced cardiomyocyte hypertrophy and apoptosis was examined. Myocardial expression of p53 and p21 genes was increased and expression of miR-30c and miR-181a was significantly decreased in diabetic patients, DbCM rats, and in HG-treated cardiomyocytes. Luciferase assay confirmed p53 as target of miR-30c and miR-181a. Over-expression of miR-30c or miR-181a decreased expression of p53, p21, ANP, cardiomyocyte cell size, and apoptosis in HG-treated cardiomyocytes. Concurrent over-expression of these microRNAs resulted in greater decrease in cardiomyocyte hypertrophy and apoptosis, suggesting a synergistic effect of these microRNAs. Our results suggest that dysregulation of miR-30c and miR-181a may be involved in upregulation of p53-p21 pathway in DbCM.

Chronic underlying inflammation is involved in the pathophysiology of coronary artery disease (CAD). Polyalthia longifolia var. pendula bark extract (PLE) is known to exhibit anti-inflammatory activity and has high content of phytosteroids. Since phytosteroids mimic estrogen structurally, we postulated that PLE may provide protection in postmenopausal women against CAD. Thus the effect of PLE has been explored on expression of estrogen receptors (ERalpha and ERbeta) and inflammatory inducible nitric oxide synthase (iNOS) genes in vitro in peripheral blood mononuclear cells (PBMCs) obtained from postmenopausal women. A total of 20 postmenopausal women were included in the present study. Group I (N = 10) included women with angiographically proven CAD, and group II (N = 10) is composed of equal number of age-matched healthy postmenopausal females as controls. Significantly low levels of serum 17-beta estradiol were observed in subjects of group I as compared to group II (p0.01). A marked increase in L: -citrulline levels (p0.05) and significantly augmented levels of reactive nitrogen intermediates (p0.05) were observed in group I subjects. PLE significantly attenuated PMA-induced expression of both ERalpha and ERbeta receptors and inflammatory iNOS gene in vitro in a dose- and time-dependent manner and had an additive effect on these genes when compared with tamoxifen. Ours is the first report to demonstrate that PLE contains certain bioactive principles, which possess anti-inflammatory and estrogenic properties, and thereby hold the promise to be screened for their anti-atherogenic potential in experimental animals to favorably alter several other markers of cardiovascular risk.

Summary Aim Cardiac hypertrophy and myocardial fibrosis significantly contribute to the pathogenesis of diabetic cardiomyopathy (DCM). Altered expression of several genes and their regulation by microRNAs has been reported in hypertrophied failing hearts. This study aims to examine the role of Cdc42, Pak1, and miR-30c in the pathogenesis of cardiac hypertrophy in DCM. Methods DCM was induced in Wistar rats by low-dose streptozotocin-high-fat diet for 12 weeks. Cardiac expression of Cdc42, Pak1 and miR-30c, and hypertrophy markers (ANP and β-MHC) was studied in DCM vs control rats and in high-glucose (HG)-treated H9c2 cardiomyocytes. Results Diabetic rats showed cardiomyocyte hypertrophy, increased heart-to-body weight ratio, and an increased expression of ANP and β-MHC. Cardiac expression of Cdc42 and Pak1 genes was increased in diabetic hearts and in HG-treated cardiomyocytes. miR-30c was identified to target Cdc42 and Pak1 genes, and cardiac miR-30c expression was found to be decreased in DCM rats, patients with DCM, and in HG-treated cardiomyocytes. miR-30c overexpression decreased Cdc42 and Pak1 genes and attenuated HG-induced cardiomyocyte hypertrophy, whereas miR-30c inhibition increased Cdc42 and Pak1 gene expression and myocyte hypertrophy in HG-treated cardiomyocytes. Conclusion Downregulation of miR-30c mediates prohypertrophic effects of hyperglycemia in DCM by upregulation of Cdc42 and Pak1 genes.