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Machine Learning and Data Mining Methods in Diabetes Research

The remarkable advances in biotechnology and health sciences have led to a significant production of data, such as high throughput genetic data and clinical information, generated from large Electronic Health Records (EHRs). To this end, application of machine learning and data mining methods in biosciences is presently, more than ever before, vital and indispensable in efforts to transform intelligently all available information into valuable knowledge. Diabetes mellitus (DM) is defined as a group of metabolic disorders exerting significant pressure on human health worldwide. Extensive research in all aspects of diabetes (diagnosis, etiopathophysiology, therapy, etc.) has led to the generation of huge amounts of data. The aim of the present study is to conduct a systematic review of the applications of machine learning, data mining techniques and tools in the field of diabetes research with respect to a) Prediction and Diagnosis, b) Diabetic Complications, c) Genetic Background and Environment, and e) Health Care and Management with the first category appearing to be the most popular. A wide range of machine learning algorithms were employed. In general, 85% of those used were characterized by supervised learning approaches and 15% by unsupervised ones, and more specifically, association rules. Support vector machines (SVM) arise as the most successful and widely used algorithm. Concerning the type of data, clinical datasets were mainly used. The title applications in the selected articles project the usefulness of extracting valuable knowledge leading to new hypotheses targeting deeper understanding and further investigation in DM.

Mechanisms and Αpplications of Ιnterleukins in Cancer Immunotherapy

Over the past years, advances in cancer immunotherapy have resulted in innovative and novel approaches in molecular cancer diagnostics and cancer therapeutic procedures. However, due to tumor heterogeneity and inter-tumoral discrepancy in tumor immunity, the clinical benefits are quite restricted. The goal of this review is to evaluate the major cytokines-interleukins involved in cancer immunotherapy and project their basic biochemical and clinical applications. Emphasis will be given to new cytokines in pre-clinical development, and potential directions for future investigation using cytokines. Furthermore, current interleukin-based approaches and clinical trial data from combination cancer immunotherapies will also be discussed. It appears that continuously increasing comprehension of cytokine-induced effects, cancer stemness, immunoediting, immune-surveillance as well as understanding of molecular interactions emerging in the tumor microenvironment and involving microRNAs, autophagy, epithelial-mesenchymal transition (EMT), inflammation, and DNA methylation processes may hold much promise in improving anti-tumor immunity. To this end, the emerging in-depth knowledge supports further studies on optimal synergistic combinations and additional adjuvant therapies to realize the full potential of cytokines as immunotherapeutic agents.

Design, synthesis and characterization of novel binary V(V)-Schiff base materials linked with insulin-mimetic vanadium-induced differentiation of 3T3-L1 fibroblasts to adipocytes. Structure-function correlations at the molecular level.

Among the various roles of vanadium in the regulation of intracellular signaling, energy metabolism and insulin mimesis, its exogenous activity stands as a contemporary challenge currently under investigation and a goal to pursue as a metallodrug against Diabetes mellitus II. In this regard, the lipogenic activity of vanadium linked to the development of well-defined anti-diabetic vanadodrugs has been investigated through: a) specifically designing and synthesizing Schiff base organic ligands L, bearing a variable number of terminal alcohols, b) a series of well-defined soluble binary V(V)-L compounds synthesized and physicochemically characterized, c) a study of their cytotoxic effect and establishment of adipogenic activity in 3T3-L1 fibroblasts toward mature adipocytes, and d) biomarker examination of a closely-linked molecular target involving or influenced by the specific V(V) forms, cumulatively delineating factors involved in potential pathways linked to V(V)-induced insulin-like activity. Collectively, the results a) project the importance of specific structural features in Schiff ligands bound to V(V), thereby influencing the emergence of its (a)toxicity and for the first time its insulin-like activity in pre-adipocyte differentiation, b) contribute to the discovery of molecular targets influenced by the specific vanadoforms seeking to induce glucose uptake, and c) indicate an interplay of V(V) structural speciation and cell-differentiation biological activity, thereby gaining insight into vanadiums potential as a future metallodrug in Diabetes mellitus.

Structure-specific adipogenic capacity of novel, well-defined ternary Zn(II)-Schiff base materials. Biomolecular correlations in zinc-induced differentiation of 3T3-L1 pre-adipocytes to adipocytes.

Among the various roles of zinc discovered to date, its exogenous activity as an insulin mimetic agent stands as a contemporary challenge currently under investigation and a goal to pursue in the form of a metallodrug against type 2 Diabetes Mellitus. Poised to investigate the adipogenic potential of Zn(II) and appropriately configure its coordination sphere into well-defined anti-diabetic forms, (a) a series of new well-defined ternary dinuclear Zn(II)-L (L=Schiff base ligands with a variable number of alcoholic moieties) compounds were synthesized and physicochemically characterized, (b) their cytotoxicity and migration effect(s) in both pre- and mature adipocytes were assessed, (c) their ability to effectively induce cell differentiation of 3T3-L1 pre-adipocytes into mature adipocytes was established, and (d) closely linked molecular targets involving or influenced by the specific Zn(II) forms were perused through molecular biological techniques, cumulatively delineating factors involved in Zn(II)-induced adipogenesis. Collectively, the results (a) reveal the significance of key structural features of Schiff ligands coordinated to Zn(II), thereby influencing its (a)toxicity behavior and insulin-like activity, (b) project molecular targets influenced by the specific forms of Zn(II) formulating its adipogenic potential, and (c) exemplify the interwoven relationship between Zn(II)-L structural speciation and insulin mimetic biological activity, thereby suggesting ways of fine tuning structure-specific zinc-induced adipogenicity in future efficient antidiabetic drugs.

The adipogenic potential of Cr(III). A molecular approach exemplifying metal-induced enhancement of insulin mimesis in diabetes mellitus II

Insulin resistance is identified through numerous pathophysiological conditions, such as Diabetes mellitus II, obesity, hypertension and other metabolic syndromes. Enhancement of insulin action and\or its complete replacement by insulin-enhancing or insulin-mimetic agents seems to improve treatment of metabolic diseases. Over the last decades, intensive research has targeted the investigation of such agents, with chromium emerging as an important inorganic cofactor involved in the requisite metabolic chemistry. Chromium in its trivalent state has been shown to play a central role in carbohydrate metabolism by enhancing insulin signaling, action, and thus the sensitivity of insulin-sensitive tissues. A very likely link between diabetes and obesity is the adipose tissue, which stores energy in the form of triglycerides and releases free fatty acids. To date, there is paucity of information on the exact mechanism of the chromium effect concerning insulin-activated molecular paths, such as adipogenesis. The aim of the present study is to delve into such an effect by employing a well-defined form of chromium (Cr(III)-citrate) on the a) survival of pre- and mature adipocytes (3T3-L1), b) endogenous cell motility, and c) insulin-enhancing adipogenic capacity. The emerging results suggest that Cr(III)-citrate a) is (a)toxic in a concentration- and time-dependent manner, b) has no influence on cell motility, c) can induce 3T3-L1 pre-adipocyte differentiation into mature adipocytes through elevation of tissue specific biomarker levels (PPAR-γ, GLUT 4 and GCK), and d) exemplifies structurally-based metal-induced adipogenesis as a key process contributing to the development of future antidiabetic metallodrugs.

Role of Vanadium in Cellular and Molecular Immunology: Association with Immune-Related Inflammation and Pharmacotoxicology Mechanisms.

Over the last decade, a diverse spectrum of vanadium compounds has arisen as anti-inflammatory therapeutic metallodrugs targeting various diseases. Recent studies have demonstrated that select well-defined vanadium species are involved in many immune-driven molecular mechanisms that regulate and influence immune responses. In addition, advances in cell immunotherapy have relied on the use of metallodrugs to create a “safe,” highly regulated, environment for optimal control of immune response. Emerging findings include optimal regulation of B/T cell signaling and expression of immune suppressive or anti-inflammatory cytokines, critical for immune cell effector functions. Furthermore, in-depth perusals have explored NF-κB and Toll-like receptor signaling mechanisms in order to enhance adaptive immune responses and promote recruitment or conversion of inflammatory cells to immunodeficient tissues. Consequently, well-defined vanadium metallodrugs, poised to access and resensitize the immune microenvironment, interact with various biomolecular targets, such as B cells, T cells, interleukin markers, and transcription factors, thereby influencing and affecting immune signaling. A synthetically formulated and structure-based (bio)chemical reactivity account of vanadoforms emerges as a plausible strategy for designing drugs characterized by selectivity and specificity, with respect to the cellular molecular targets intimately linked to immune responses, thereby giving rise to a challenging field linked to the development of immune system vanadodrugs.

Changes of circulating micro-RNAs in response to treatment with teriparatide or denosumab in postmenopausal osteoporosis

Context Expression of microRNAs (miRs) related to bone metabolism in the serum may be affected by antiosteoporotic treatment. Objective To investigate the effect of two antiosteoporotic agents with opposite effects on bone metabolism on miR expression profile in the serum. Design Observational, open label, nonrandomized clinical trial. Setting The outpatient clinics for Metabolic Bone Diseases of 424 General Military Hospital, Thessaloniki, Greece. Patients and Interventions Postmenopausal women with low bone mass were treated with either teriparatide (TPTD; n = 30) or denosumab (n = 30) for 12 months. Main Outcome Measures Changes in the serum expression of selected miRs linked to bone metabolism at 3 and 12 months of treatment. Secondary measurements: associations of measured miRs with changes in bone mineral density (BMD) at 12 months and the bone turnover markers (BTMs) C-terminal cross-linking telopeptide of type I collagen and procollagen type I N-terminal propeptide at 3 and 12 months. Results We found significantly decreased relative expression of miR-33-3p at 3 months (P = 0.03) and of miR-133a at 12 months (P = 0.042) of TPTD treatment. BMD values at 12 months of TPTD treatment were significantly and inversely correlated with miR-124-3p expression at 3 months (P = 0.008). Relative expression of miR-24-3p and miR-27a was correlated with changes in BTMs during TPTD treatment and of miR-21-5p, miR-23a-3p, miR-26a-5p, miR-27a, miR-222-5p, and miR-335-5p with changes in BTMs during denosumab treatment. Conclusions Circulating miRs are differentially affected by treatment with TPTD and denosumab. TPTD affects the relative expression of miRs related to the expression of RUNX-2 (miR-33) and DKK-1 gene (miR-133).

A Novel Bacteria-Based Broadcast System Exploiting Chemotaxis

Bacterial and molecular-based communication has recently emerged as one of the paradigms for establishing communication environments in the nanoscale. This paper presents a novel bacteria-based communication system exploiting the phenomenon of chemotaxis. Such a system could provide solutions in applications with the requirement for biocompatibility or low power consumption. In order to demonstrate and investigate the properties of this system, a simulator was employed and experiments were performed, where bits were transmitted using bacteria release pulses and successfully received at a sensor node. The experiments highlight the value of the chemotaxis phenomenon for augmenting information transfer as well as the influence of the parameters of distance and number of bacteria per pulse on the received signal strength and achievable bit error rate.

In vitro structure-specific Zn(II)-induced adipogenesis and structure-function bioreactivity correlations

The advent of Zn(II) metallodrugs in metabolic syndrome pathologies generates a strong challenge toward synthetic endeavors targeting well-defined, atoxic and biologically active binary/ternary species of Zn(II). Proper formulation of that metal ions coordination sphere sets the stage for construction of appropriately configured Schiff ligands based on tromethamine and variably modified vanillin core components. The arising Schiff ligands react with Zn(II) in a defined stoichiometry, thereby delivering new binary Zn(II)-L species with defined physicochemical properties. Analytical (elemental), spectroscopic (FT-IR, Thermogravimetric Analysis) and crystallographic techniques attest to the distinct nature of the derived binary-ternary materials, bearing defined Zn(II):L molecular stoichiometry, variable nuclearity, charge, bulk and balance mix of hydrophilicity-hydrophobicity, thereby providing the physicochemical profile based on which biological studies could ensue. The structurally based selection of species was applied onto in vitro 3T3-L1 cultures, essentially exploring toxicity, migration, morphology, cell differentiation and maturation. The systematic effort toward comparative work on appropriately defined Zn(II) species and insulin in inducing adipogenesis reveals the salient structural features in the Schiff family of ligands configuring Zn(II) so as to promote complex formation sufficient to engage biomolecular targets during the process of initiation and maturation. Molecular targets of importance in adipogenesis were examined under the influence of Zn(II) and their expression levels suggest the structural composition that a Zn(II) ion might have to optimally pursue cell differentiation. Thus, a well-defined selection of binary Zn(II)-L species is tightly associated with the incurred bioactivity, thereby setting the stage for the development of efficient Zn(II) metallodrugs to combat Diabetes mellitus II.

Fick’s Law Model Revisited: A New Approach to Modeling Multiple Sources Message Dissemination in Bacterial Communication Nanosystems

As advances in nanotechnology continue their ascending course, new areas of application for nanoscale communication open up, involving biological systems. Such systems have peculiarities that must be taken into consideration, when trying to study new communication paradigms based on micro-biological communication systems. In this paper, an innovative mathematical model is employed, in an effort to study message dissemination through bacterial communication in the form of delivery of information within a simple, biologically inspired, communication system consisting of bacteria, yet representative of the characteristics of biological nanocommunication environments. Stimulus spreading is being investigated within the realm of message dissemination in electromagnetic networks, for single and multiple infection sources using macro scale simulation techniques, with the help of a simulation tool, which was developed based on a commercial simulation suite. The observed results indicate that the mathematical model predictions are in strong agreement with the simulations described by Fick’s laws of diffusion and well-approximated through the Fisher–Kolmogorov–Petrovsky–Piscunov (FKPP) equation, enabling use of conventional simulation systems for fast biological nanosystem property investigation.