A Nutrient Network Regulating Cellular Cholesterol and Glucose Metabolism

Indiana University-Purdue University Indianapolis (IUPUI)Insulin resistance, a hallmark of type 2 diabetes (T2D), is associated with accompanying derangements such as hyperinsulinemia that promote the progression of insulin resistance, yet a mechanism(s) is imperfectly understood. Data have demonstrated that hyperinsulinemia promotes insulin resistance as evidenced by diminished ability of insulin to mobilize glucose transporter GLUT4 to the plasma membrane (PM). We found that loss of PM phosphatidylinositol 4,5-bisphosphate (PIP2)-regulated filamentous actin (F-actin) structure contributes to hyperinsulinemia-induced insulin resistance. We tested if increased glucose flux through hexosamine biosynthesis pathway (HBP) causes dysregulation of PM components necessary for GLUT4 translocation. Increased HBP activity was detected in 3T3-L1 adipocytes cultured in hyperinsulinemia (5 nM Ins; 12 h) and also 2 mM glucosamine (GlcN), a distal HBP activator, inducing losses of PM PIP2 and F-actin. In accordance with HBP flux directly weakening PIP2/F-actin structure, inhibition of the rate-limiting HBP enzyme (glutamine:fructose-6-phosphate amidotransferase) restored F-actin and insulin responsiveness. Furthermore, less invasive challenges with glucose led to PIP2/F-actin dysregulation. New findings support a negative correlation between PM cholesterol accrual, PIP2/F-actin structure and GLUT4 regulation. These data stemmed from parallel study aimed at understanding the antidiabetic mechanism of the nutrient chromium (Cr3+). We found that chromium picolinate (CrPic) enhanced insulin-stimulated GLUT4 trafficking via reduction in PM cholesterol. In line with glucose/cholesterol toxicity findings, we demonstrated that therapeutic effects of CrPic occurred solely in adipocytes with increased HBP activity and a concomitant elevation in PM cholesterol. Mechanistically, data are consistent with a role of AMP-activated protein kinase (AMPK) in CrPic action. These data show that CrPic increases AMPK activity and perhaps suppresses cholesterol synthesis via distal phosphorylation and inactivation of 3-hydroxy-3-methylglutaryl CoA reductase (HMGR), a rate-limiting enzyme in cholesterol synthesis. Continued study of the consequence of increased HBP activity revealed alterations in cholesterogenic transcription factors – Sp1, SREBP-1, and NFY – with Sp1 showing a significant increase in O-linked glycosylation. Consistent with Sp1 modification eliciting maximal transcriptional activation of SREBP-1, Hmgr mRNA was significantly enhanced. In conclusion, these data are consistent with a central role of PM cholesterol in glucose transport and suggest perturbations in this lipid have a contributory role in developing insulin resistance

Effect of Partial Replacement of Slag and Nano Silica Infused Slag on Properties of Concrete

Investigations were carried out on the changes in properties of concrete when steel slag is used in concrete in its normal form and after modifying its properties by infusing it with nano-silica. The sand is replaced by steel slag and modified steel slag by 10%, 20% and 30% in M30 grade concrete. Tests results on compressive strength and workability of concrete revealed that compressive strength of concrete cubes after 28 days increased by 25.4%, 26.4% and 45.2% for 10%, 20% and 30% respectively after replacing sand by steel slag. After modification of steel slag properties by infusing it with nano silica, the 28 days compressive strength was observed to be increased by 38.19%, 35.80% and 27.89% for 10%, 20% and 30% as compared to traditional concrete mix respectively after replacement. Infusing steel slag with nano silica increased the compressive strength of concrete mix by 20.17%, 25.74% and 49.64% for 10%, 20% and 30% respectively when compared to normal steel slag concrete mix. It was also observed that using steel slag in concrete mix also influences on water consumption in concrete mix. Workability tests conducted using 0.45 and 0.5 w/c ratio and the inference was that the workability increased with the increase in percentage of steel slag but workability decreases with the increase in percentage of modified steel slag

Posterior sub-Tenon capsule anesthesia for photocoagulation treatment of diabetic retinopathy performed in an inner-city county hospital clinic setting

poster abstractProliferative diabetic retinopathy (PDR) is a blinding eye disease demanding prompt therapy. However, treatment with panretinal photocoagulation (PRP) can be painful thereby limiting its extent. In addition, compliance to diabetic eye visits remains poor particularly in inner cities. Therefore, it is imperative to optimize treatment during clinic visits. The purpose of this study is to present the effect of sub-Tenon (Sub-T) capsule lidocaine anesthesia on PRP treatment extent for PDR performed during the eye clinic visit. This is an IRB-approved retrospective review of initial 12 eyes (9 subjects) with PDR undergoing PRP treatment involving Sub-T anesthesia in the eye clinic. Sub-T capsule lidocaine anesthesia was delivered and PRP was immediately performed. Primary end point was extent of treatment (number of PRP laser spots) delivered. Comparison was made to PRP in prior sessions without Sub-T anesthesia. All subjects had active PDR and sometimes vitreous hemorrhage (VH) at time of treatment. Decision was made to offer Sub-T anesthesia due to intolerable pain from prior PRP treatments in all subjects. We observed all subjects were able to tolerate a significantly greater extent of PRP with Sub-T anesthesia even with presence of VH, oftentimes undergoing thousands of laser spots and capable to complete treatment in same clinic visit. By comparison, prior PRP treatments (without Sub-T anesthesia) were much less extensive sometimes involving only a few laser spots. We conclude that Sub-T anesthesia allows a tier of pain control for those not able to tolerate traditional PRP without anesthesia performed in the eye clinic. This new information suggests that certain patients undergoing PRP can be offered Sub-T anesthesia, and it will be important to define algorithm for selection of such individuals

Micropropagation and conservation of selected endangered anticancer medicinal plants from the Western Ghats of India

Globally, cancer is a constant battle which severely affects the human population. The major limitations of the anticancer drugs are the deleterious side effects on the quality of life. Plants play a vital role in curing many diseases with minimal or no side effects. Phytocompounds derived from various medicinal plants serve as the best source of drugs to treat cancer. The global demand for phytomedicines is mostly reached by the medicinal herbs from the tropical nations of the world even though many plant species are threatened with extinction. India is one of the mega diverse countries of the world due to its ecological habitats, latitudinal variation, and diverse climatic range. Western Ghats of India is one of the most important depositories of endemic herbs. It is found along the stretch of south western part of India and constitutes rain forest with more than 4000 diverse medicinal plant species. In recent times, many of these therapeutically valued herbs have become endangered and are being included under the red-listed plant category in this region. Due to a sharp rise in the demand for plant-based products, this rich collection is diminishing at an alarming rate that eventually triggered dangerous to biodiversity. Thus, conservation of the endangered medicinal plants has become a matter of importance. The conservation by using only in situ approaches may not be sufficient enough to safeguard such a huge bio-resource of endangered medicinal plants. Hence, the use of biotechnological methods would be vital to complement the ex vitro protection programs and help to reestablish endangered plant species. In this backdrop, the key tools of biotechnology that could assist plant conservation were developed in terms of in vitro regeneration, seed banking, DNA storage, pollen storage, germplasm storage, gene bank (field gene banking), tissue bank, and cryopreservation. In this chapter, an attempt has been made to critically review major endangered medicinal plants that possess anticancer compounds and their conservation aspects by integrating various biotechnological tool

Trace elements in glucometabolic disorders: an update

Many trace elements, among which metals, are indispensable for proper functioning of a myriad of biochemical reactions, more particularly as enzyme cofactors. This is particularly true for the vast set of processes involved in regulation of glucose homeostasis, being it in glucose metabolism itself or in hormonal control, especially insulin. The role and importance of trace elements such as chromium, zinc, selenium, lithium and vanadium are much less evident and subjected to chronic debate. This review updates our actual knowledge concerning these five trace elements. A careful survey of the literature shows that while theoretical postulates from some key roles of these elements had led to real hopes for therapy of insulin resistance and diabetes, the limited experience based on available data indicates that beneficial effects and use of most of them are subjected to caution, given the narrow window between safe and unsafe doses. Clear therapeutic benefit in these pathologies is presently doubtful but some data indicate that these metals may have a clinical interest in patients presenting deficiencies in individual metal levels. The same holds true for an association of some trace elements such as chromium or zinc with oral antidiabetics. However, this area is essentially unexplored in adequate clinical trials, which are worth being performed

Botany, chemistry, and pharmaceutical significance of Sida cordifolia: a traditional medicinal plant

Sida cordifolia Linn. belonging to the family, Malvaceae has been widely employed in traditional medications in many parts of the world including India, Brazil, and other Asian and African countries. The plant is extensively used in the Ayurvedic medicine preparation. There are more than 200 plant species within the genus Sida, which are distributed predominantly in the tropical regions. The correct taxonomic identification is a major concern due to the fact that S. cordifolia looks morphologically similar with its related species. It possesses activity against various human ailments, including cancer, asthma, cough, diarrhea, malaria, gonorrhea, tuberculosis, obesity, ulcer, Parkinson’s disease, urinary infections, and many others. The medical importance of this plant is mainly correlated to the occurrence of diverse biologically active phytochemical compounds such as alkaloids, flavonoids, and steroids. The major compounds include β-phenylamines, 2-carboxylated tryptamines, quinazoline, quinoline, indole, ephedrine, vasicinone, 5-3-isoprenyl flavone, 5,7-dihydroxy-3-isoprenyl flavone, and 6-(isoprenyl)- 3-methoxy- 8-C-β-D-glucosyl-kaempferol 3-O-β-D-glucosyl[1–4]-α-D-glucoside. The literature survey reveals that most of the pharmacological investigations on S. cordifolia are limited to crude plant extracts and few isolated pure compounds. Therefore, there is a need to evaluate many other unexplored bioactive phytoconstituents with evidences so as to justify the traditional usages of S. cordifolia. Furthermore, detailed studies on the action of mechanisms of these isolated compounds supported by clinical research are necessary for validating their application in contemporary medicines. The aim of the present chapter is to provide a detailed information on the ethnobotanical, phytochemical, and pharmacological aspects of S. cordifolia

The Heat Shock Protein 27 Immune Complex Enhances Exosomal Cholesterol Efflux

Previously, we demonstrated that Heat Shock Protein 27 (HSP27) reduces the inflammatory stages of experimental atherogenesis, is released by macrophage (MΦ) exosomes and lowers cholesterol levels in atherosclerotic plaques. Recently, we discovered that natural autoantibodies directed against HSP27 enhance its signaling effects, as HSP27 immune complexes (IC) interact at the cell membrane to modulate signaling. We now seek to evaluate the potential role of the HSP27 IC on MΦ exosomal release and cholesterol export. First, in human blood samples, we show that healthy control subjects have 86% more exosomes compared to patients with coronary artery disease (p < 0.0001). Treating human THP-1 MΦ with rHSP27 plus a validated anti-HPS27 IgG antibody increased the abundance of exosomes in the culture media (+98%; p < 0.0001) as well as expression of Flotillin-2, a marker reflective of exosomal release. Exosome cholesterol efflux was independent of Apo-A1. THP-1 MΦ loaded with NBD-labeled cholesterol and treated with the HSP27 IC showed a 22% increase in extracellular vesicles labeled with NBD and a 95% increase in mean fluorescent intensity. In conclusion, exosomal abundance and secretion of cholesterol content increases in response to HSP27 IC treatment, which may represent an important therapeutic option for diseases characterized by cholesterol accumulation

Searching for the IoT Resources: Fundamentals, Requirements, Comprehensive Review, and Future Directions

Internet of Things (IoT) paradigm links physical objects in the real world to cyber world and enables the creation of smart environments and applications. A physical object is the fundamental building block of the IoT, known as a Smart Device, that can monitor the environment. These devices can communicate with each other and have data processing abilities. When deployed, smart devices collect real-time data and publish the gathered data on the Web. The functionality of smart devices can be abstracted as a service and an IoT application can be built by combining the smart devices with these services that help to address challenges of day-to-day activities. The IoT comprises billions of these intelligent communicating devices that generate enormous amount of data, and hence performing analysis on this data is a significant task. Using search techniques, the size and extent of data can be reduced and limited, so that an application can choose just the most important and valuable data items as per its necessities. It is, however, a tedious task to effectively seek and select a proper device and/or its data among a large number of available devices for a specific application. Search techniques are fundamental to IoT and poses various challenges like a large number of devices, dynamic availability, restrictions on resource utilization, real time data in various types and formats, past and historical monitoring. In the recent past, various methods and techniques have been developed by the research community to address these issues. In this paper, we present a review of the state-of-the-art search methods for the IoT, classifying them according to their design principle and search approaches as: IoT data and IoT object-based techniques. Under each classification, we describe the method adopted, their advantages and disadvantages. Finally, we identify and discuss key challenges and future research directions that will allow the next generation search techniques to recognize and respond to user queries and satisfy the information needs of users