Postprandial Hypertriglyceridemia Predicts Development of Insulin Resistance Glucose Intolerance and Type 2 Diabetes

Insulin resistance (IR) and type 2 diabetes mellitus (T2DM) have been found to be associated with postprandial hypertriglyceridemia (PPHTg). However, whether PPHTg can cause IR and diabetes is not clear. We therefore investigated the role of PPHTg in development of T2DM in rat model of T2DM. 96 male Wistar rats were randomized into four groups (24 rats each). Control Group A, high sucrose diet (HSD) Group B, HSD+Pioglitazone (10mg/kg/day) Group C and HSD+Atorvastatin (20mg/kg/day) Group D. Fat and glucose tolerance tests were done at regular intervals in all groups besides insulin and body weight measurement. At 26 weeks, low dose streptozotocin (15mg/kg,i.p.) was given to half of the rats. All rats were followed up till 48 weeks. PPHTg developed as early as week 2 in Group B and stabilized by week 14. Group B displayed highest PPHTg compared to other groups. Atorvastatin treatment (Group D) abolished PPHTg which became comparable to controls, pioglitazone treatment partially blunted PPHTg resulting in intermediate PPHTg. Group B with highest PPHTg showed highest subsequent IR, glucose intolerance (GI) and highest incidence of prediabetes at week 26 and diabetes at week 34 and 46 compared to other groups. Group D rats displayed lower IR, GI, low incidence of prediabetes and diabetes at these time points compared to Groups B and C. ROC analysis showed that triglyceride area under the curve of each time point significantly predicts the risk of diabetes. Present study provides the evidence that PPHTg predicts the development of IR, GI and T2DM in rat model of diet induced T2DM.     

Blue excitable green emitting Ce3+ doped CaS phosphor for w‐LEDs

CaS:Ce³⁺ is an efficient green‐emitting (535 nm) phosphor, excitable with blue light (450–470 nm) and was synthesized via a solid‐state reaction method by heating under a reducing atmosphere. The luminescent properties, photoluminescent (PL) excitation and emission of the phosphor were analyzed by spectrofluorophotometry. The excitation and emission peaks of the CaS:Ce³⁺ phosphor lay in the visible region, which made them relevant for light‐emitting diode (LED) application for the generation of white light. Judd‐Oflet parameters were calculated and revealed that green light emitted upon blue illumination. The prepared phosphor had strong blue absorption at 470 nm and a broad green emission band range from 490–590 nm with the peak at 537 nm. The characteristics of the CaS:Ce³⁺ phosphor make it suitable for use as a wavelength tunable green emitting phosphor for three band white LEDs pumped by a blue LED (470 nm). The Commission International de l'Eclairage co‐ordinates were calculated by a spectrophotometric method using the spectral energy distribution (0.304, 0.526) and confirm the green emission. The potential application of this phosphor is as a phosphor‐converted white light‐emitting diode. Copyright © 2015 John Wiley & Sons, Ltd.     

Hyaluronic acid modified pH-sensitive liposomes for targeted intracellular delivery of doxorubicin

Context: Surface-modified pH-sensitive liposomal system may be useful for intracellular delivery of chemotherapeutics.

Objective: Achieving site-specific targeting with over-expressed hyaluronic acid (HA) receptors along with using pH sensitive liposome carrier for intracellular drug delivery was the aim of this study.

Materials and methods: Stealth HA-targeted pH-sensitive liposomes (SL-pH-HA) were developed and evaluated to achieve effective intracellular delivery of doxorubicin (DOX) vis–a-vis enhanced antitumor activity.

Results: The in vitro release studies demonstrated that the release of DOX from SL-pH-HA was pH-dependent, i.e. faster at mildly acidic pH ～5, compared to physiological pH ～7.4. SLpH-HA was evaluated for their cytotoxicity potential on CD44 receptor expressing MCF-7 cells. The half maximal inhibitory concentration (IC50) of SL-pH-HA and SL-HA were about 1.9 and 2.5?μM, respectively, after 48?h of incubation. The quantitative uptake study revealed higher localization of targeted liposomes in the receptor positive cells, which was further confirmed by fluorescent microscopy. The antitumor efficacy of the DOX-loaded HA-targeted pH-sensitive liposomes was also verified in a tumor xenograft mouse model.

Discussion: DOX was efficiently delivered to the tumor site by active targeting via HA and CD44 receptor interaction. The major side-effect of conventional DOX formulation, i.e. cardiotoxicity was also estimated by measuring serum enzyme levels of LDH and CPK and found to be minimized with developed formulation. Overall, HA targeted pH-sensitive liposomes were significantly more potent than the non-targeted liposomes in cells expressing high levels of CD44.

Conclusion: Results strongly implies the promise of such liposomal system as an intracellular drug delivery carrier developed for potential anticancer treatment.     

Altered endocrine,cytokine signaling and oxidative stress: A plausible reason for differential changes in testicular cells in diet-induced and genetically-inherited – obesity in adult rats

Obesity is emerging as a potential risk factor for male infertility. It is a multifactorial disorder with primarily genetic and/or environmental factors. Our earlier studies have shown differential effects of genetically inherited-and high fat diet induced-obesity on hormones, fertility and spermatogenesis in adult male rats. In the present study, we assessed the effect of high fat diet induced – and genetically inherited – obesity on the underlying molecular mechanisms affecting spermatogenesis. The expression of hormone receptors, cytokines and markers of oxidative stress as well as cell cycle mediators were affected in both the obese groups, however, the changes were different in the two groups. This could be due to difference in fat distribution between the two types of obese groups. Altered expression of hormone receptors, cytokines, cell cycle mediators and differential effects on oxidative stress could be the plausible reason for differential changes in germ cell population in both the groups.     

Late‐onset retinal degeneration pathology due to mutations in CTRP5 is mediated through HTRA1

Late‐onset retinal degeneration (L‐ORD) is an autosomal dominant macular degeneration characterized by the formation of sub‐retinal pigment epithelium (RPE) deposits and neuroretinal atrophy. L‐ORD results from mutations in the C1q‐tumor necrosis factor‐5 protein (CTRP5), encoded by the CTRP5/C1QTNF5 gene. To understand the mechanism underlying L‐ORD pathology, we used a human cDNA library yeast two‐hybrid screen to identify interacting partners of CTRP5. Additionally, we analyzed the Bruch's membrane/choroid (BM‐Ch) from wild‐type (Wt), heterozygous S163R Ctrp5 mutation knock‐in (Ctrp5^S163R/wt), and homozygous knock‐in (Ctrp5^S163R/S163R) mice using mass spectrometry. Both approaches showed an association between CTRP5 and HTRA1 via its C‐terminal PDZ‐binding motif, stimulation of the HTRA1 protease activity by CTRP5, and CTRP5 serving as an HTRA1 substrate. The S163R‐CTRP5 protein also binds to HTRA1 but is resistant to HTRA1‐mediated cleavage. Immunohistochemistry and proteomic analysis showed significant accumulation of CTRP5 and HTRA1 in BM‐Ch of Ctrp5^S163R/S163R and Ctrp5^S163R/wt mice compared with Wt. Additional extracellular matrix (ECM) components that are HTRA1 substrates also accumulated in these mice. These results implicate HTRA1 and its interaction with CTRP5 in L‐ORD pathology.     

Driving Precision Medicine through Proteomics and Metabolomics - 12th Central and Eastern European Proteomic Conference (CEEPC), Bucharest,Romania

As Romanians prepared to celebrate 100 years of the '‘Great Unification of 1918?' which united all provinces into one Romania, the 12^th Central and Eastern European Proteomic Conference (CEEPC) jointly with the 39^th Anniversary of the Institute of Cellular Biology and Pathology '‘N. Simionescu’' (ICBP-NS), held their inaugural meeting at the Romanian Academy in Bucharest – a national forum of highest scientific recognition. With an exciting theme entitled, ‘Advances in Proteomics and Progress in Precision Medicine’, delegates gathered to debate Precision medicine’s revolution in diagnosis and treatment, which now accounts for predictive, preventative, and targeted treatment strategies with informed decisions according to individual’s unique clinical, molecular and genetic profile. Proteomics has a pivotal role to play in furthering precision health and medicine for the benefit of mankind. To this end, CEEPC continues to drive advances in proteomics, metabolomics, and diseases as well as raising awareness of pressing global humanitarian and health-care issues including mental health diseases, aging, chronic diseases, global epidemics and environmental issues. Today, CEEPC is a well-recognized major annual conference with a focused vision and a highly valued ideology as it continues to propagate scientific, medical and proteomic collaborations whilst expanding as more Eastern European countries prepare to join.     

Cardiac resynchronization therapy pacemakers versus defibrillators in older non-ischemic cardiomyopathy patients

Introduction

With the recent publication of the negative DANISH trial, the mortality benefit of the implantable cardioverter-defibrillator (ICD) has been put in question in patients with non-ischemic cardiomyopathy (NICM). Because a majority of patients in DANISH receive cardiac resynchronization therapy (CRT) devices, we investigated in the present study the survival of recipients of CRT pacemakers (CRT-P) versus CRT ICDs (CRT-D) in a cohort of older (≥75 years) NICM patients at our institution.