Evaluation of the expression of genes associated with iron metabolism in peripheral blood mononuclear cells from Type 2 diabetes mellitus patients.

AIMS: Type 2 Diabetes (T2DM) has been linked to ferroptosis. This study aimed to assess expression levels of genes linked with iron metabolism in peripheral blood mononuclear cells (PBMCs) from T2DM patients and to investigate the association of these expression levels with anthropometric and clinical parameters. METHODS: Gene expression of iron metabolism genes (Ferritin Light Chain, FTL; Ferritin Heavy Chain, FTH1; Transferrin Receptor, TFRC; Divalent Metal Transporter 1, SLC11A2; Ferroportin, SLC40A1) in archival PBMCs was assessed using quantitative real-time PCR assays. Correlations of gene expression with anthropometric/biochemical patient data were evaluated. RESULTS: The study included 36 (18 male/18 female) T2DM patients and 45 (28 male/17 female) normoglycemic (NGT) subjects with a mean age of 38.1 ± 6.8 years and 47.6 ± 8.6 years respectively. Relative expression of FTL was significantly lower in T2DM females compared to that in NGT females (P = 0.027). Relative expression of SLC40A1 was significantly lower in the T2DM group (P = 0.043) and in the T2DM females (P = 0.021). Relative expression of SLC11A2 was negatively correlated with systolic blood pressure in T2DM male patients. Relative expression of SLC40A1 was negatively associated with serum phosphorous and positively associated with serum thyroid stimulating hormone in male T2DM patients. CONCLUSIONS: Our findings indicate a reduction in the expression of FTL in perimenopausal T2DM females. Also, in male T2DM patients and NGT subjects, biochemical markers are significantly correlated with the expression of FTL, FTH1, SLC11A2, and SLC40A1 in PBMCs.

Identification of stable reference genes in peripheral blood mononuclear cells from type 2 diabetes mellitus patients.

Reference genes are obligatory for accurate normalization of mRNA transcript levels across samples and experimental conditions in Real Time-polymerase chain reaction (qRT-PCR) based quantitative gene expression assays. Selection of stably expressed reference genes is therefore crucial for ensuring reproducibility of such assays. However, there is a complete dearth of data on stability of commonly used reference genes in Peripheral Blood Mononuclear Cells (PBMCs) from Type 2 diabetes mellitus (T2DM) patients. We have evaluated the gene expression stability of 4 widely used reference genes (Beta-actin, ACTB; Peptidylprolyl Isomerase B, PPIB; Tyrosine 3 Monooxygenase/Tryptophan 5-Monooxygenase Activation Protein Zeta, YWHAZ; and Glyceraldehyde-3-Phosphate Dehydrogenase, GAPDH); in PBMCs from 39 T2DM patients and 47 normoglycemic (NGT) subjects. ACTB and YWHAZ were found to be the most stable genes in PBMCs from T2DM patients and therefore, can be recommended as suitable reference genes in similar contexts. GAPDH and PPIB expressions were not stable in PBMCs from T2DM patients. On using ACTB and YWHAZ as reference genes for measuring relative expression of GAPDH and PPIB in these subjects, relative GAPDH expression was found to be significantly lower in female T2DM patients, compared to female NGT subjects [GAPDH relative normalization unit (RNU): female T2DM (n = 19), median (Q1, Q3): 9.0 (8.1, 9.9); female NGT (n = 18): median (Q1, Q3): 10.1 (9.1, 11.0); P = 0.034]. Dysregulation of GAPDH in PBMCs from female T2DM patients could be associated with sex-specific differences in pathogenesis and outcomes of T2DM.

Withdrawal of High-Carbohydrate, High-Fat Diet Alters Status of Trace Elements to Ameliorate Metabolic Syndrome in Rats With Type 2 Diabetes Mellitus.

OBJECTIVES: Inadequate nutrient supply and insulin resistance contribute to the pathogenesis of metabolic syndrome (MetS) and increase the risk of developing cardiovascular disease. MetS can be induced by prolonged feeding of a high-carbohydrate, high-fat (HCHF) diet. The present study was designed using Wistar albino rats as an experimental model to investigate the effect of subchronic withdrawal of an HCHF diet during MetS on distribution of copper (Cu), iron (Fe), magnesium (Mg), manganese (Mn), zinc (Zn) and chromium (Cr) in different biological media. METHODS: The experimental animals were fed an HCHF diet for up to 16 weeks for induction of MetS. After inducing MetS, some animals were shifted to a basal diet for the next 4 weeks. Distribution of trace elements (TE) in serum, liver and faeces at the different time intervals and their relationship with dietary TE were analyzed. RESULTS: On withdrawal of the HCHF diet, concentrations of Zn, Mg, Mn (serum, p<0.05; liver, p<0.001) and Cr were increased, and Cu and Fe were decreased in serum and liver at week 16. Furthermore, levels of Cu and Fe were reduced significantly (p<0.05) in faeces on feeding the HCHF diet and increased on withdrawal of the diet, which also reflects the metabolic fate of TE during MetS. CONCLUSIONS: Consumption of an HCHF diet over a long time period leads to alteration of the TE profile in serum, liver and feces during MetS, which is reversed upon dietary intervention. This can be correlated with their concentrations in HCHF and basal diets, and hence can contribute to proper dietary control of this global issue.

Woven Kevlar Fiber/Polydimethylsiloxane/Reduced Graphene Oxide Composite-Based Personal Thermal Management with Freestanding Cu-Ni Core-Shell Nanowires.

Thermotherapy is a widespread technique that provides relief for muscle spasms and joint injuries. A great deal of energy is used to heat the surrounding environment, and heat emitted by the human body is wasted on our surroundings. Herein, a woven Kevlar fiber (WKF)-based personal thermal management device was fabricated by directly growing vertical copper-nickel (Cu-Ni) nanowires (NWs) on the WKF surface using a hydrothermal method. The treated WKF was combined with reduced graphene oxide (rGO) dispersed in polydimethylsiloxane (PDMS) to form composites using vacuum-assisted resin transfer molding (VARTM). This WKF-based personal thermal management system contained a conductive network of metallic NWs and rGO that promoted effective Joule heating and reflected back the infrared (IR) radiation emitted by the human body. It thus behaved as a type of thermal insulation. The Cu-Ni NWs were synthesized with a tunable Ni layer on Cu core NWs to enhance the oxidation resistance of the Cu NWs. The combined effect of the NW networks and rGO enabled a surface temperature of 70 °C to be attained on application of 1.5 V to the composites. The Cu3Ni1-WKF/PDMS provided 43% more thermal insulation and higher IR reflectance than bare WKF/PDMS. The absorbed impact energy and tensile strength was highest for the Cu1Ni3- and rGO-integrated WKF/PDMS samples. Those Cu-Ni NWs having higher Ni contents displayed better mechanical properties and those with higher Cu contents showed higher Joule heating performance and IR reflectivity at a given rGO loading. The composite shows sufficient breathability and very high durability. The high flexibility of the composites and their ability to generate sufficient heat during various human motions ensures their suitability for wearable applications.

Development of banana (Musa balbisiana) pseudo stem fiber as a surgical bio-tool to avert post-operative wound infections.

The search to develop an ideal suture material encourages us to explore novel suture biomaterials with superior characteristics to the current commercially available products. Surgical sutures play a crucial role in the development of post-operative wound infection by acting as a substrate for biofilm formation which leads to dehisced wounds. In this context, the present invention meets this need by fabricating banana (Musa balbisiana) fibre into an advanced antimicrobials releasing suture biomaterial (BSc) for the prevention of post-operative wound infection. Suture material developed from banana pseudo stem fiber was impregnated with chloramphenicol, clotrimazole and growth factors with the aid of a hydro-gel system. The fabricated suture material was found to be biocompatible towards human erythrocytes and L929 mouse fibroblast cells. BSc exhibited promising physico-chemical characteristics which were comparable to the commercially available Bombyx mori silk fibroin (BMSF) suture. BSc displayed a biphasic release pattern with sustained release of chloramphenicol for up to 140 h. Apart from being environment friendly and having a facile fabrication method, this advanced suture biomaterial showed broad spectrum in vitro antimicrobial activity against bacterial and fungal pathogens. BSc successfully impeded biofilm formation on its surface, as is evident from the confocal microscopy analysis. This contributes to superior wound healing efficacy in terms of reduced microbial burden and a subsequent decrease in the inflammatory cytokine levels. Histopathological observations further supported the pronounced healing efficacy of BSc sutured wounds. The findings of this study establish the banana pseudo stem fiber as a novel advanced suture biomaterial to prevent post-operative wound infections.

Fabrication and Synthesis of Highly Ordered Nickel Cobalt Sulfide Nanowire-Grown Woven Kevlar Fiber/Reduced Graphene Oxide/Polyester Composites.

Well-aligned NiCo2S4 nanowires, synthesized hydrothermally on the surface of woven Kevlar fiber (WKF), were used to fabricate composites with reduced graphene oxide (rGO) dispersed in polyester resin (PES) by means of vacuum-assisted resin transfer molding. The NiCo2S4 nanowires were synthesized with three precursor concentrations. Nanowire growth was characterized using scanning electron microscopy, transmission electron microscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. Hierarchical and high growth density of the nanowires led to exceptional mechanical properties of the composites. Compared with bare WKF/PES, the tensile strength and absorbed impact energy were enhanced by 96.2% and 92.3%, respectively, for WKF/NiCo2S4/rGO (1.5%)/PES. The synergistic effect of NiCo2S4 nanowires and rGO in the fabricated composites improved the electrical conductivity of insulating WKF/PES composites, reducing the resistance to ∼103 Ω. Joule heating performance depended strongly on the precursor concentration of the nanowires and the presence of rGO in the composite. A maximum surface temperature of 163 °C was obtained under low-voltage (5 V) application. The Joule heating performance of the composites was demonstrated in a surface deicing experiment; we observed that 17 g of ice melted from the surface of the composite in 14 min under an applied voltage of 5 V at -28 °C. The excellent performance of WKF/NiCo2S4/rGO/PES composites shows great potential for aerospace structural applications requiring outstanding mechanical properties and Joule heating capability for deicing of surfaces.

Withdrawal from high-carbohydrate, high-saturated-fat diet changes saturated fat distribution and improves hepatic low-density-lipoprotein receptor expression to ameliorate metabolic syndrome in rats.

OBJECTIVE: The "lipid hypothesis" determined that saturated fatty acid (SFA) raises low-density lipoprotein cholesterol, thereby increasing the risk for metabolic syndrome (MetS). The aim of this study was to investigate the effect of subchronic withdrawal from a high-carbohydrate, high-saturated fat (HCHF) diet during MetS with reference to changes in deleterious SFA (C12:0, lauric acid; C14:0, myristic acid; C16:0, palmitic acid; C18:0, stearic acid) distribution in liver, white adipose tissue (WAT), and feces. METHODS: MetS induced by prolonged feeding of an HCHF diet in Wistar albino rat is used as a model of human MetS. The MetS-induced rats were withdrawn from the HCHF diet and changed to a basal diet for final 4 wk of the total experimental duration of 16 wk. SFA distribution in target tissues and hepatic low-density lipoprotein receptor (LDLr) expression were analyzed. RESULTS: Analyses of changes in SFA concentration of target tissues indicate that C16:0 and C18:0 reduced in WAT and liver after withdrawal of the HCHF diet. There was a significant (P < 0.001) decrease in fecal C12:0 with HCHF feeding, which significantly (P < 0.01) increased after withdrawal of this diet. Also, an improvement in expression of hepatic LDLr was observed after withdrawal of HCHF diet. CONCLUSION: The prolonged consumption of an HCHF diet leads to increased SFA accumulation in liver and WAT, decreased SFA excretion, and reduced hepatic LDLr expression during MetS, which is prominently reversed after subchronic withdrawal of the HCHF diet. This can contribute to better understanding of the metabolic fate of dietary SFA during MetS and may apply to the potential reversal of complications by the simple approach of nutritional modification.

Microwave-synthesized freestanding iron-carbon nanotubes on polyester composites of woven Kevlar fibre and silver nanoparticle-decorated graphene.

We synthesized Ag nanoparticle-decorated multilayered graphene nanosheets (Ag-graphene) from graphite nanoplatelets and silver nitrate through 90-100 s of microwave exposure, without the use of any mineral acids or harsh reducing agents. Fe nanoparticle-decorated carbon nanotubes (Fe-CNTs) were grown on polypyrrole (PPy) deposited on woven Kevlar fibre (WKF), using ferrocene as a catalyst, under microwave irradiation. Fe-CNTs grown on WKF and Ag-graphene dispersed in polyester resin (PES) were combined to fabricate Ag-graphene/Fe-CNT/PPy-coated WKF/PES composites by vacuum-assisted resin transfer moulding. The combined effect of Fe-CNTs and Ag-graphene in the resulting composites resulted in a remarkable enhancement of tensile properties (a 192.56% increase in strength and 100.64% increase in modulus) as well as impact resistance (a 116.33% increase). The electrical conductivity significantly increased for Ag-graphene/Fe-CNT/PPy-coated WKF/PES composites. The effectiveness of electromagnetic interference shielding, which relies strongly on the Ag-graphene content in the composites, was 25 times higher in Ag-graphene/Fe-CNT/PPy-coated WKF/PES than in neat WKF/PES composites. The current work offers a novel route for fabricating highly promising, cost effective WKF/PES composites through microwave-assisted synthesis of Fe-CNTs and Ag-graphene.

Antioxidant Effect of Sericin in Brain and Peripheral Tissues of Oxidative Stress Induced Hypercholesterolemic Rats.

This study evaluated the antioxidant effect of crude sericin extract (CSE) from Antheraea assamensis in high cholesterol fed rats. Investigation was conducted by administering graded oral dose of 0.25 and 0.5 gm/kg body weight (b.w.)/day of CSE for a period of 28 days. Experiments were conducted in 30 rats and were divided into five groups: normal control, high cholesterol fed (HCF), HCF + 0.065 gm/kg b.w./day fenofibrate (FF), HCF + sericin 0.25 gm/kg b.w./day (LSD), and HCF + sericin 0.5 gm/kg b.w./day (HSD). In brain, heart, liver, serum, and kidney homogenates nitric oxide (NO), thiobarbituric acid reactive substances (TBARS), protein carbonyl content (PCC), superoxide dismutase, reduced glutathione (GSH) was measured. LSD treatment prevented the alterations in GSH and PCC levels in hypercholesterolemic (HyC) brain tissue homogenates of rats. CSE lowers the serum total cholesterol level in HyC rats by promoting fecal cholesterol (FC) excretion. CSE increases FC level by promoting inhibition of cholesterol absorption in intestine. The endogenous antioxidant reduced significantly and the oxidative stress marker TBARS level increases significantly in the peripheral tissue of HCF rats. However, the administration of LSD and HSD exhibited a good antioxidant activity by reducing the TBARS level and increasing the endogenous antioxidant in peripheral tissue. In addition, a histological examination revealed loss of normal liver and kidney architecture in cholesterol fed rats which were retained in sericin treated groups. The findings of this study suggested that CSE improves hypercholesterolemia in rats fed a HyC diet. Clinical relevance of this effect of CSE seems worthy of further studies.

Antidiabetic and Antilipidemic Effect of Musa balbisiana Root Extract: A Potent Agent for Glucose Homeostasis in Streptozotocin-Induced Diabetic Rat.

Folklore studies have revealed that Musa balbisiana Colla (MB; Family: Musaceae) has high medicinal properties. The purpose of the present study is to evaluate antihyperglycemic, and antioxidant activity of MB extracts in streptozotocin (STZ) induced diabetic rats. In vitro antioxidant and antidiabetic activity of MB extracts, i.e., root extract (RE), shoot extract and inflorescence extract were determined by using various methods viz 1,-1-diphenyl-2-picrylhydrazyl (DPPH) and a method to assess their possible effect on glucose diffusion across gastrointestinal tract and identify bioactive compound of potent extract. In vivo antilipidemic and antidiabetic activity was evaluated by administrating oral dose of RE for 15 days on STZ- induced diabetic rat. RE showed highest antioxidant activity by scavenging DPPH radical (IC50 32.96 µg/ml) and inhibit 30% glucose movement in vitro. The methanol extract of root showed the presence of calyx [4] arene category of the compound. Furthermore, RE treated rat revealed a reduction in fasting blood glucose (62.5%), serum total cholesterol (36.2%), triglyceride (54.5%), and low-density lipoprotein (50.94%) after 15 days as compared to STZ treated animal. There was an initiation of regenerative structures of the affected organs after 15 days of RE treatment. Histopathological observations clearly differentiate the structural changes in pancreas, liver, and kidney of STZ and RE treated group. The presence of calyx [4] arene class of compound may be responsible for its antioxidant and antidiabetic properties by absorbing glucose in vivo.

Pathophysiology of metabolic syndrome: The onset of natural recovery on withdrawal of a high-carbohydrate, high-fat diet.

OBJECTIVES: Chronic consumption of high-carbohydrate, high-fat (HCHF) diet induces metabolic syndrome (MetS) and markedly impairs the ultra-structure of organs. To our knowledge, no scientific study has yet to report the effect of withdrawal of an HCHF diet on MetS-associated ultra-structural abnormalities in affected organs and tissues. Therefore, the aim of this study was to investigate the effects of subchronic withdrawal of the HCHF diet, specifically with a pathophysiological approach. METHODS: Wister albino rats (N = 72) were divided into three groups: Groups A and B were fed a standard basal diet and an HCHF diet, respectively, for 16 wk. Group C was on an HCHF diet for the initial 12 wk and then returned to basal diet for 4 wk. Histopathological changes in the heart, lungs, liver, spleen, pancreas, small intestine, kidney, white adipose tissue (WAT), skeletal muscle, and hippocampus of the brain were monitored at 4, 8, 12, and 16 wk. RESULTS: Lipid droplets (LDs) in liver, fibrosis in the pancreas, abnormalities in the glomerulus of the kidney, and an increase in the size of adipocytes were observed in groups B and C at week 12. Withdrawal of the HCHF diet in group C showed the onset of regenerative features at the ultra-structural level. HCHF diet-fed rats in group B had higher body weights; raised lipid profiles, blood glucose levels, and insulin resistance than basal diet-fed rats in group A and HCHF to basal diet-fed rats in group C at week 16. CONCLUSION: An HCHF diet induces ultra-structural abnormalities, which are significantly reversed by subchronic withdrawal of a MetS-inducing HCHF diet, indicating the onset of natural recovery at the ultra-structural level of affected organs.