Status of Copper and Magnesium Levels in Diabetic Nephropathy Cases: a Case-Control Study from South India

Diabetic nephropathy is a complication of diabetes mellitus. This present study investigates the status of copper and magnesium in diabetic nephropathy cases to establish a possible relation. Forty patients of diabetic nephropathy participated in the study as cases. Forty age- and sex-matched healthy individuals served as controls. Blood samples were collected from both cases and controls for determination of FBS, PPBS, HbA1c, microalbumin, copper, and magnesium levels. The mean concentrations of FBS, PPBS, HbA1c, and microalbumin of cases were significantly higher than that of controls. The mean magnesium levels of cases (1.60 ± 0.32 meq/L) were significantly lower than controls 2.14 ± 0.16 meq/L (p < 0.05). But the mean copper levels of cases, 165.42 ± 5.71 μg/dl, shows no significant difference with controls, 166.6 ± 5.48 μg/dl, (p > 0.05).The findings in the present study suggest that hypomagnesemia may be linked with development of diabetic nephropathy.     

Regulated alterations in redox and energetic status are the key mediators of salinity tolerance in the halophyte <Emphasis Type="Italic">Sesuvium portulacastrum</Emphasis> (L.) L

The present work addresses the importance of antioxidant, redox and energetic parameters in regulating salt-tolerance in Sesuvium portulacastrum. Experiments were conducted on 45 days old plants subjected to 250 and 1,000 mM NaCl stress for 2–8 days. Plants showed no significant change in growth parameters (shoot length, dry weight, and water content) at 250 mM NaCl as compared to control. However, growth of plants was significantly affected at 1,000 mM NaCl. The differential growth behaviour could be attributed to a greater decline in the energetic parameters (in terms of ratios of NADP/NADPH and ATP/ADP) at 1,000 mM NaCl than at 250 mM NaCl. The osmotic stress imposed to plants at 250 mM NaCl was presumably balanced by the accumulation of sodium ions (Na⁺), an energetically favorable process, and did not require an increased synthesis of proline. In contrast, to counter osmotic stress at 1,000 mM NaCl, plants accumulated Na⁺ as well as proline and were, therefore, energetically stressed. Further, the response of enzymatic and molecular antioxidants at 1,000 mM was either close to or even lower than that at 250 mM, which resulted in oxidative damage at 1,000 mM, particularly on longer durations. In conclusion, it is suggested that altered redox and energetic status of the plants could play a key role in mediating the tolerance of Sesuvium under salinity stress.     

Diaphragm muscle weakness in an experimental porcine intensive care unit model

In critically ill patients, mechanisms underlying diaphragm muscle remodeling and resultant dysfunction contributing to weaning failure remain unclear. Ventilator-induced modifications as well as sepsis and administration of pharmacological agents such as corticosteroids and neuromuscular blocking agents may be involved. Thus, the objective of the present study was to examine how sepsis, systemic corticosteroid treatment (CS) and neuromuscular blocking agent administration (NMBA) aggravate ventilator-related diaphragm cell and molecular dysfunction in the intensive care unit. Piglets were exposed to different combinations of mechanical ventilation and sedation, endotoxin-induced sepsis, CS and NMBA for five days and compared with sham-operated control animals. On day 5, diaphragm muscle fibre structure (myosin heavy chain isoform proportion, cross-sectional area and contractile protein content) did not differ from controls in any of the mechanically ventilated animals. However, a decrease in single fibre maximal force normalized to cross-sectional area (specific force) was observed in all experimental piglets. Therefore, exposure to mechanical ventilation and sedation for five days has a key negative impact on diaphragm contractile function despite a preservation of muscle structure. Post-translational modifications of contractile proteins are forwarded as one probable underlying mechanism. Unexpectedly, sepsis, CS or NMBA have no significant additive effects, suggesting that mechanical ventilation and sedation are the triggering factors leading to diaphragm weakness in the intensive care unit.     

IFI16 protein mediates the anti-inflammatory actions of the type-I interferons through suppression of activation of caspase-1 by inflammasomes

Background

Type-I interferons (IFNs) are used to treat certain inflammatory diseases. Moreover, activation of type-I IFN-signaling in immune cells inhibits the production of proinflammatory cytokines and activation of inflammasomes. However, the molecular mechanisms remain largely unknown. Upon sensing cytosolic double-stranded DNA, the AIM2 protein forms the AIM2-ASC inflammasome, resulting in activation of caspase-1. Given that the IFI16 and AIM2 proteins are IFN-inducible and can heterodimerize with each other, we investigated the regulation of IFI16, AIM2, and inflammasome proteins by type-I and type-II IFNs and explored whether the IFI16 protein could negatively regulate the activation of the AIM2 (or other) inflammasome.

Methodology/ Principal Findings

We found that basal levels of the IFI16 and AIM2 proteins were relatively low in peripheral blood monocytes (CD14⁺) and in the THP-1 monocytic cell line. However, treatment of THP-1 cells with type-I (IFN-α or β) or type-II (IFN-γ) IFN induced the expression levels of IFI16, AIM2, ASC and CASP1 proteins. The induced levels of IFI16 and AIM2 proteins were detected primarily in the cytoplasm. Accordingly, relatively more IFI16 protein bound with the AIM2 protein in the cytoplasmic fraction. Notably, increased expression of IFI16 protein in transfected HEK-293 cells inhibited activation of caspase-1 by the AIM2-ASC inflammasome. Moreover, the constitutive knockdown of the IFI16 expression in THP-1 cells increased the basal and induced [induced by poly(dA:dT) or alum] activation of the caspase-1 by the AIM2 and NLRP3 inflammasomes.

Conclusions/Significance

Our observations revealed that the type-I and type-II IFNs induce the expression of IFI16, AIM2, and inflammasome proteins to various extents in THP-1 cells and the expression of IFI16 protein in THP-1 cells suppresses the activation of caspase-1 by the AIM2 and NLRP3 inflammasomes. Thus, our observations identify the IFI16 protein as a mediator of the anti-inflammatory actions of the type-I IFNs.     

Assessment of Antioxidant,Antibacterial Activities and Bioactive Compounds of the Wild Edible Mushroom Pleurotus sajor-caju

International Journal of Peptide Research and Therapeutics - The study was aimed at investigating the biologically active compounds in Pleurotus sajor-caju wild edible mushroom and its potential...     

Extra Cellular Matrix Derived Metabolite Regulates Angiogenesis by FasL Mediated Apoptosis

Object

Antiangiogenic treatments are beginning to give promising outcomes in many vascular diseases including tumor angiogenesis. In this current study the antiangiogenic and pro-apoptotic actions of α1(IV)NC1 and its N- and C- peptides α1S1(IV)NC1, α1S2(IV)NC1 were investigated in-vitro and in-vivo.

Study Method

Endothelial cells (ECs) were treated with α1(IV)NC1, α1S1(IV)NC1, α1S2(IV)NC1 and in-vitro proliferation, migration, tube formation and apoptotic assays were executed. FasL, Fas, Caspase-8, -3 and PARP activations were studied using immunoblotting analysis using specific antibodies. Also the in-vivo antiangiogenic and pro-apoptotic effects were tested using α1(IV)NC1 in a mice model.

Results

Like α1(IV)NC1, its N- and C- terminal α1S2(IV)NC1 and α1S1(IV)NC1 domains posses anti-proliferative, pro-apoptotic activity and inhibit ECs migration and tube formation in-vitro. Both α1S1(IV)NC1 and α1S2(IV)NC1 domains promote apoptosis by activating FasL and down stream apoptotic events including activation of caspase-8, -3 and PARP cleavage in a dose dependent manner in-vitro in ECs. Tumors in mice showed apoptotic TUNEL positive microvasculature upon α1(IV)NC1 treatment, indicating inhibition of tumor angiogenesis and tumor growth. Further, the antitumor activity of α1(IV)NC1 was abrogated when caspase-3 inhibitor was used. These results conform additional properties of α1(IV)NC1 as an endogenous angioinhibitor that induces apoptosis in-vitro and in-vivo by activating FasL mediated caspase-3.

Significance

α1(IV)NC1 and its N- and C- terminal α1S1(IV)NC1 and α1S2(IV)NC1 domains also posses pro-apoptotic and angioinhibitory activity in-vitro and in-vivo. α1(IV)NC1 regulates tumor angiogenesis by activating FasL mediated apoptosis in-vitro and in-vivo. These results demonstrate that α1(IV)NC1 and its peptides inhibit neo-vascular diseases.     

Emission analysis of RE3+ (RE = Sm,Dy):B2O3‐TeO2‐Li2O‐AlF3 glasses

This article reports on the optical properties of 0.5% mol of Sm³⁺, Dy³⁺ ion‐doped B₂O₃‐TeO₂‐Li₂O‐AlF₃ (LiAlFBT) glasses. The glass samples were characterized by optical absorption and emission spectra. Judd‐Ofelt theory was applied to analyze the optical absorption spectra and calculate the intensity parameters and radiative properties of the emission transitions. The emission spectra of Sm³⁺ and Dy³⁺:LiAlFBT glasses showed a bright reddish‐orange emission at 598 nm (⁴G_5/2 → ⁶H_7/2) and an intense yellow emission at 574 nm (⁴F_9/2 → ⁶H_13/2), respectively. Full width at half maximum (FWHM), stimulated emission cross section, gain bandwidth and optical gain values were also calculated to extend the applications of the Sm³⁺ and Dy³⁺:LiAlFBT glasses. Copyright © 2012 John Wiley & Sons, Ltd.     

A lipid-modified estrogen derivative that treats breast cancer independent of estrogen receptor expression through simultaneous induction of autophagy and apoptosis

It is a challenge to develop a universal single drug that can treat breast cancer at single- or multiple-stage complications, yet remains nontoxic to normal cells. The challenge is even greater when breast cancer-specific, estrogen-based drugs are being developed that cannot act against multistaged breast cancer complications owing to the cells differential estrogen receptor (ER) expression status and their possession of drug-resistant and metastatic phenotypes. We report here the development of a first cationic lipid-conjugated estrogenic derivative (ESC8) that kills breast cancer cells independent of their ER expression status. This ESC8 molecule apparently is nontoxic to normal breast epithelial cells, as well as to other noncancer cells. ESC8 induces apoptosis through an intrinsic pathway in ER-negative MDA-MB-231 cells. In addition, ESC8 treatment induces autophagy in these cells by interfering with the mTOR activity. This is the first example of an estrogen structure-based molecule that coinduces apoptosis and autophagy in breast cancer cells. Further in vivo study confirms the role of this molecule in tumor regression. Together, our results open new perspective of breast cancer chemotherapy through a single agent, which could provide the therapeutic benefit across all stages of breast cancer.     

Response of adenine and pyridine metabolism during germination and early seedling growth under arsenic stress in Brassica juncea

Adenine and pyridine nucleotides play vital roles in virtually all aspects of plant growth. This study analyzed the response of adenine and pyridine metabolism during germination and early seedling growth (ESG) of Brassica juncea exposed to two doses of arsenate (AsV), 100 and 250 μM, having non-significant or significant inhibitory effects, respectively, on germination and ESG. The ratio of NAD/NADP and NAD/NADH showed no significant change in control and 100 μM AsV, but increased significantly at 250 μM AsV during initial 24 h and also at 7th day. The activity of enzymes of NAD metabolism, viz. NAD kinase, NADP phosphatase, nicotinamidase and poly(ADP-ribose) polymerases showed significant change mostly at 250 μM AsV. Further, significant decrease was observed in the ratio of ATP/ADP and in the activities of adenylate kinase and apyrase at 250 μM AsV at 7th day. External supply of ATP (1 mM) to 100 and 250 μM AsV significantly improved germination percentage and germination strength of the seeds as compared to AsV treatments alone. The study concludes that with the increase in concentration of AsV, the balance of NAD/NADP, NAD/NADH and ATP/ADP and the activities of enzymes of adenine and pyridine metabolism were significantly altered and that these changes may be responsible for inhibitory effects of AsV on germination and ESG.