Preventive Action of Beta-Carotene against the Indoxyl Sulfate-Induced Renal Dysfunction in Male Adult Zebrafish via Regulations of Mitochondrial Inflammatory and ß-Carotene Oxygenase-2 Actions.

Indoxyl sulfate (IS) is a metabolic byproduct of indole metabolism. IS readily interacts with the mitochondrial redox metabolism, leading to altered renal function. The ß-carotene oxygenase-2 (BCO2) enzyme converts carotenoids to intermediate products. However, the role of ß-carotene (BC) in IS-induced renal dysfunction in zebrafish and their modulatory action on BCO2 and mitochondrial inflammations have not been explored yet. Hence, the present study is designed to investigate the role of BC in the attenuation of IS-induced renal dysfunction via regulations of mitochondrial redox balance by BCO2 actions. Renal dysfunction was induced by exposure to IS (10 mg/L/hour/day) for 4 weeks. BC (50 and 100 mg/L/hour/day) and coenzyme Q10 (CoQ10; 20 mg/L/hour/day) were added before IS exposure. BC attenuated the IS-induced increase in blood urea nitrogen (BUN) and creatinine concentrations, adenosine triphosphate (ATP), and complex I activity levels, and the reduction of renal mitochondrial biomarkers, i.e., BCO2, superoxide dismutase-2 (SOD2), glutathione peroxidase-1 (GPX1), reduced and oxidized glutathione (GSH/GSSG) ratio, and carbonylated proteins. Moreover, renal histopathological changes were analyzed by the eosin and hematoxylin staining method. As a result, the administration of BC attenuated the IS-induced renal damage via the regulation of mitochondrial function.

Flexible and Transparent Circularly Polarized Patch Antenna for Reliable Unobtrusive Wearable Wireless Communications.

This paper presents a circularly polarized flexible and transparent circular patch antenna suitable for body-worn wireless-communications. Circular polarization is highly beneficial in wearable wireless communications, where antennas, as a key component of the RF front-end, operate in dynamic environments, such as the human body. The demonstrated antenna is realized with highly flexible, robust and transparent conductive-fabric-polymer composite. The performance of the explored flexible-transparent antenna is also compared with its non-transparent counterpart manufactured with non-transparent conductive fabric. This comparison further demonstrates the suitability of the proposed materials for the target unobtrusive wearable applications. Detailed numerical and experimental investigations are explored in this paper to verify the proposed design. Moreover, the compatibility of the antenna in wearable applications is evaluated by testing the performance on a forearm phantom and calculating the specific absorption rate (SAR).

Expression of proteins related to thyroid hormone function in the uterus is down-regulated at the day of implantation in hypothyroid pregnant rats.

Hypothyroidism has been linked to infertility, but the mechanisms underlying infertility-related hypothyroidism have yet to be fully elucidated. Therefore, in this study, effects of hypothyroidism on expression of the proteins related to thyroid hormone function in the uterus, which were thought to play a role implantation, including thyroid hormone receptor (TR), thyroid stimulating hormone receptor (TSHR), retinoic acid receptor (RAR) and extracellular kinase (ERK) were identified. Pregnant female rats were rendered hypothyroid by giving methimazole (MMI), orally. Following hypothyroid induction, rats were grouped into control (non-treated) and received subcutaneous thyroxine at 20, 40, and 80 µg/kg/day for five consecutive days. At Day 6, which is the day of implantation (GD 6), rats were sacrificed and the number of embryo implantation site in the uterus was calculated. Then, uterine horns were harvested and expression of the above proteins and their mRNAs were identified by Western blotting and real-time PCR, respectively. In non-treated hypothyroid pregnant rats, the number of embryo implantation sites decreased as compared to euthyroid and hypothyroid rats receiving thyroxine treatment. Similarly, expression of TRα-1, TRß-1, TSHR, ERK1/2 and RAR proteins and mRNA in the uterus of non-treated hypothyroid rats also decreased (P < 0.05 when compared to euthyroid and thyroxine-treated hypothyroid rats). In conclusion, downregulated expression of the thyroid hormone related proteins in the uterus at the day of implantation might result in infertility as reported in hypothyroid condition.

Differential expression of the receptors for thyroid hormone, thyroid stimulating hormone, vitamin D and retinoic acid and extracellular signal-regulated kinase in uterus of rats under influence of sex-steroids.

Sex-steroids play important role in modulating uterine functions. We hypothesized that these hormones affect expression of proteins in the uterus related to thyroid hormone action. Therefore, changes in expression levels of receptors for thyroid hormone (TRα-1 and TRß-1), thyroid stimulating hormone (TSHR), vitamin D (VDR) and retinoid acid (RAR) as well as extracellular signal-regulated kinase (ERK1/2) in uterus were investigated under sex-steroid influence. METHODS: Two rat models were used: (i) ovariectomised, sex-steroid replaced and (ii) intact, at different phases of oestrous cycle. A day after completion of sex-steroid treatment or following identification of oestrous cycle phases, rats were sacrificed and expression and distribution of these proteins in uterus were identified by Western blotting and immunohistochemistry, respectively. RESULTS: Expression of TRα-1, TRß-1, TSHR, VDR, RAR and ERK1/2 in uterus was higher following estradiol (E2) treatment and at estrus phase of oestrous cycle when E2 levels were high. A relatively lower expression was observed following progesterone (P) treatment and at diestrus phases of oestrous cycle when P levels were high. Under E2 influence, TRα, TRß, TSHR, VDR, RAR and ERK1/2 were distributed in luminal and glandular epithelia while under P influence, TSHR, VDR abn RAR were distributed in the stroma. CONCLUSIONS: Differential expression and distribution of TRα-1, TRß-1, TSHR, VDR, RAR and ERK1/2 in different uterine compartments could explain differential action of thyroid hormone, TSH, vitamin D, and retinoic acid in uterus under different sex-steroid conditions.

Action of Phytochemicals on Insulin Signaling Pathways Accelerating Glucose Transporter (GLUT4) Protein Translocation.

Diabetes is associated with obesity, generally accompanied by a chronic state of oxidative stress and redox imbalances which are implicated in the progression of micro- and macro-complications like heart disease, stroke, dementia, cancer, kidney failure and blindness. All these complications rise primarily due to consistent high blood glucose levels. Insulin and glucagon help to maintain the homeostasis of glucose and lipids through signaling cascades. Pancreatic hormones stimulate translocation of the glucose transporter isoform 4 (GLUT4) from an intracellular location to the cell surface and facilitate the rapid insulin-dependent storage of glucose in muscle and fat cells. Malfunction in glucose uptake mechanisms, primarily contribute to insulin resistance in type 2 diabetes. Plant secondary metabolites, commonly known as phytochemicals, are reported to have great benefits in the management of type 2 diabetes. The role of phytochemicals and their action on insulin signaling pathways through stimulation of GLUT4 translocation is crucial to understand the pathogenesis of this disease in the management process. This review will summarize the effects of phytochemicals and their action on insulin signaling pathways accelerating GLUT4 translocation based on the current literature.

Effects of thyroxine on expression of proteins related to thyroid hormone functions (TR-α, TR-ß, RXR and ERK1/2) in uterus during peri-implantation period.

INTRODUCTION: Thyroid hormone is known to play important role during embryo implantation, however mechanisms underlying its actions in uterus during peri-implantation period has not been fully identified. In this study, we hypothesized that thyroid hormone could affect expression of proteins related to its function, where these could explain mechanisms for its action in uterus during this period. METHODS: Female rats, once rendered hypothyroid via oral administration of methimazole (0.03% in drinking water) for twenty-one days were mated with fertile euthyroid male rats at 1:1 ratio. Pregnancy was confirmed by the presence of vaginal plug and this was designated as day-1. Thyroxine (20, 40 and 80 µg/kg/day) was then subcutaneously administered to pregnant, hypothyroid female rats for three days. A day after last injection (day four pregnancy), female rats were sacrificed and expression of thyroid hormone receptors (TR-α and ß), retinoid X receptor (RXR) and extracellular signal-regulated kinase (ERK1/2) in uterus were quantified by Western blotting while their distribution in endometrium was visualized by immunofluorescence. RESULTS: Expression of TRα-1, TRß-1 and ERK1/2 proteins in uterus increased with increasing doses of thyroxine however no changes in RXR expression was observed. These proteins were found in the stroma with their distribution levels were relatively higher following thyroxine treatment. CONCLUSIONS: Increased expression of TRα-1, TRß-1 and ERK1/2 at day 4 pregnancy in thyroxine-treated hypothyroid pregnant rats indicate the importance of thyroxine in up-regulating expression of these proteins that could help mediate the uterine changes prior to embryo implantation.

Rhinacanthin C ameliorates hyperglycaemia, hyperlipidemia and pancreatic destruction in streptozotocin-nicotinamide induced adult male diabetic rats.

Effect of Rhinacanthin C on hyperglycaemia, hyperlipidemia and pancreatic dysfunction in diabetes was investigated. In-vitro effect of Rhinacanthin C on glucose uptake was studied in 3T3-L1 cell line. Meanwhile, in-vivo effect of 28-days treatment with 5mg/kg/day or 20mg/kg/day Rhinacanthin C was studied in streptozotocin-nicotinamide induced male diabetic rats. Following completion of treatment, fasting blood glucose (FBG), HbA1c, insulin and lipid profile levels were measured by biochemical assays. Histopathological changes in pancreas were observed by light microscopy while levels of pancreatic oxidative stress were determined by enzymatic assays. Expression of insulin, TNFα, Ikkß and caspase-3 in pancreas were quantified by immunohistochemistry. Molecular docking was used to identify interactions between Rhinacathin C with SOD or GPx enzymes. Dose-dependent increase in glucose uptake was observed with increasing doses of Rhinacathin C. Plasma FBG, HbA1c and lipid profile except LDL levels and pancreatic malonaldehyde level were reduced but serum insulin and pancreatic anti-oxidative enzymes (SOD, CAT and GPx) levels were increased in diabetic rats receiving Rhinacanthin C treatment. Decreased pancreatic histopathological changes with higher pancreatic insulin and Glut-2 levels but lower TNFα, Ikkß and caspase-3 levels were observed in diabetic rats receiving Rhinacanthin C (P<0.05 compared to non-treated diabetic rats). In diabetic rats which received Rhinacathin C, changes in the above parameters did not achieve the value in non-diabetic rats. Docking shows Rhinacathin C possesses high degree interactions with SOD and GPx. By possessing these effects, Rhinacanthin C could be used as agent to alleviate pancreatic and other complications in diabetes.

Antinociceptive principle from Curcuma aeruginosa.

BACKGROUND: The rhizome of Curcuma aeruginosa Roxb (Zingiberaceae) has been used as a traditional folk medicine for the treatment of rheumatic disorders in Bangladesh. The aim of the current study was the bioassay-guided isolation and purification of an antinociceptive principle from the methanol extract of C. aeruginosa rhizomes. METHODS: The antinociceptive activity was determined using acetic acid induced writhing and formalin induced licking in the Swiss albino mice to investigate central and peripheral antinociceptive principle of C. aeruginosa rhizomes. Vacuum Liquid Chromatography (VLC) and open column chromatography were used for separation. Crystallization was used for the purification of the isolated compound germacrone (1). Diclofenac (10 mg/kg) and aspirin (100 mg/kg) were used as positive control and 5% carboxymethyl cellulose (CMC) in distilled water (10 ml/kg) for negative control were used in the acetic acid induced writhing and formalin induced licking methods. RESULTS: The methanol extract exhibited 37.50 and 45.31% inhibition of writhing; 33.27 and 38.13% inhibition of licking in the first phase and 69.72, 73.71% inhibition of licking in the second phase at doses of 200 and 400 mg/kg, respectively. VLC of the extract yielded five fractions (Fr. 1 to Fr. 5). Fr. 1 exhibited 33.98% inhibition that was comparably higher than other fractions (Fr. 2 to Fr. 5) at a dose of 100 mg/kg. Column chromatography of Fr. 1 generated five fractions (SF. 1 to SF. 5). Fraction SF.3 exhibited 46.88% inhibition that was most potent among the other fractions at a dose of 50 mg/kg. Crystallization of the fraction SF.3 yielded germacrone (1), a cyclic sesquiterpene. Germacrone (1) showed 22.66, 34.77 and 51.17% inhibition of writhing at doses of 10, 20 and 40 mg/kg, respectively; 30.43 and 37.53% inhibition in the initial phase and 32.27 and 60.96% inhibition in the second phase of licking at doses of 200 and 400 mg/kg, respectively. CONCLUSION: Germacrone (1) showed a potent activity in both writhing and licking methods that indicates the compound as a central and peripheral antinociceptive principle of C. aeruginosa rhizomes with possible anti-inflammatory activity.