Piperine Modulates High Fat Diet - Induced Renal Damage by Regulating Kim-1 and Igf-1 Beta Signaling Molecules in Male Wistar Rats

Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycemia and other symptoms which ultimately cause various other complications like retinopathy , micro angioplasty and nephropathy . piperine shows antidiabetic activity by improving insulin level, signifying its usage in the management of hyperglycemia. IGF-1 is the insulin-like growth factor receptor . KIM-1 has proved to be an outstanding early indicator of kidney injury in the rats. Induction of type 2 diabetes to male wistar albino rats , they were divided into four groups , one group were treated with piperine , fasting blood glucose was analysed. Biochemical analysis and mRNA expression analysis of KIM-1 and IGF-1 by RT-PCR is done. Fasting blood glucose and the serum insulin was elevated in diabetes induced rats . piperine-treated animals exhibited a significant decrease in the level of FBG and serum insulin from the above study, it could show that piperine possesses antidiabetic activity

Effect of Piperine on an Nrf2/Keap 1 Signalling Mechanism in Adipose Tissue of High Fat Diet and Sucrose-Induced Experimental Diabetic Rats

Piperine, an alkaloid compound found in black pepper has been shown to have various health benefits such as anti-oxidants, anti-inflammatory, and anticancer activities. But mechanisms underlying the anti-diabetic activity are unclear. Keap1-Nrf2 is an anti-oxidant stress signal pathway and it is considered to be an intracellular defence mechanism to countered oxidative stress. The study was aimed at assessing antidiabetic activity of piperine against high fat diet and sucrose-induced (HFD) type-2 diabetic rats by regulating the expression of Nrf2/Keap 1 signalling. Healthy adult male albino rats of wistar strain were grouped in to 5. Considering healthy control (group-1), HFD-induced type-2 diabetes (group2), Diabetic rats treated with piperine (group 3), diabetic rats metformin (group 4) and control +Piperine treated rats ( group 5) respectively. After 30 days of treatment, fasting blood glucose (FBG) checked and adipose tissue from control and treated groups was used to determine the role of piperine on the expression of NrF2/Keap 1 mNRA in adipose by Real Time-PCR analysis. Data were analysed by one-way ANOVA and p<0.01 was considered to be statistical significance among the groups. HFD-induced T2DM showed a significant increase in the levels of FBG and altered levels of Nrf-2 and Keap-1 gene expression (2 fold) compared to normal control animals. Piperine at a dose of 40mg, fascinatingly improved the glycemic control and normalised the mRNA expression of both Nrf-2 and Keap-1 whose effects were near to that of standard drug metformin level (p<0.05) proving its potential mechanism of action. Conclusion: Our current study clearly indicates that piperine controls hyperglycemia in type-2 diabetic rats by facilitating the expression of antioxidant signalling (Nrf-2/Keap-1) in the adipose. In addition, this is the first of its kind to show the role of piperine in reducing hyperglycemia against high fat diet and sucrose –induced type-2 diabetic rats as an invivo experimental model. Hence, piperine could be considered as an important health supplement and potential drug candidate for the treatment of diabetes

Autonomous Motility of Active Filaments due to Spontaneous Flow-Symmetry Breaking

We simulate the nonlocal Stokesian hydrodynamics of an elastic filament which is active due a permanent distribution of stresslets along its contour. A bending instability of an initially straight filament spontaneously breaks flow symmetry and leads to autonomous filament motion which, depending on conformational symmetry, can be translational or rotational. At high ratios of activity to elasticity, the linear instability develops into nonlinear fluctuating states with large amplitude deformations. The dynamics of these states can be qualitatively understood as a superposition of translational and rotational motion associated with filament conformational modes of opposite symmetry. Our results can be tested in molecular-motor filament mixtures, synthetic chains of autocatalytic particles, or other linearly connected systems where chemical energy is converted to mechanical energy in a fluid environment.Comment: 7 pages, 3 figures; contains supplemental text; movies at http://proofideas.org/rjoy/gallery; published in Physical Review Letter

Sigma-2: Multiple sequence alignment of non-coding DNA via an evolutionary model

<p>Abstract</p> <p>Background</p> <p>While most multiple sequence alignment programs expect that all or most of their input is known to be homologous, and penalise insertions and deletions, this is not a reasonable assumption for non-coding DNA, which is much less strongly conserved than protein-coding genes. Arguing that the goal of sequence alignment should be the detection of <it>homology </it>and not <it>similarity</it>, we incorporate an evolutionary model into a previously published multiple sequence alignment program for non-coding DNA, Sigma, as a sensitive likelihood-based way to assess the significance of alignments. Version 1 of Sigma was successful in eliminating spurious alignments but exhibited relatively poor sensitivity on synthetic data. Sigma 1 used a <it>p</it>-value (the probability under the "null hypothesis" of non-homology) to assess the significance of alignments, and, optionally, a background model that captured short-range genomic correlations. Sigma version 2, described here, retains these features, but calculates the <it>p</it>-value using a sophisticated evolutionary model that we describe here, and also allows for a transition matrix for different substitution rates from and to different nucleotides. Our evolutionary model takes separate account of mutation and fixation, and can be extended to allow for locally differing functional constraints on sequence.</p> <p>Results</p> <p>We demonstrate that, on real and synthetic data, Sigma-2 significantly outperforms other programs in specificity to genuine homology (that is, it minimises alignment of spuriously similar regions that do not have a common ancestry) while it is now as sensitive as the best current programs.</p> <p>Conclusions</p> <p>Comparing these results with an extrapolation of the best results from other available programs, we suggest that conservation rates in intergenic DNA are often significantly over-estimated. It is increasingly important to align non-coding DNA correctly, in regulatory genomics and in the context of whole-genome alignment, and Sigma-2 is an important step in that direction.</p

Reactive thymic hyperplasia mimicking relapse in a child with post-treatment T-cell Non-Hodgkin's lymphoma: A case report and literature review

Background: Chemotherapy usually results in the premature shrinkage of thymic cells, often resulting in atrophy. However, in some children, the thymus has the potential to regenerate following the withdrawal of stimulus, resulting in an increase in thymic cells – called rebound/reactive thymic hyperplasia. This phenomenon often appears clinically and radiologically similar to lymphoma in the anterior mediastinum, leading to overtreatment. Case report: We report a 6-year-old boy with T-Lymphoblastic lymphoma (LL) who presented with mediastinal mass. He was treated with high risk ALL protocol and completed treatment uneventfully. Post-treatment PET-CT for routine assessment showed an anterior mediastinal mass with a SUVt of 4.64, highly suggestive of recurrence, however was finally diagnosed with thymic hyperplasia confirmed by biopsy. Conclusion: Pediatric hemato-oncologists and radiologists need to be aware of this phenomenon to avoid misdiagnosis and overtreatment. Relapse should always be confirmed by histopathological examination

Deciphering the Role of MicroRNAs in Neuroblastoma

Neuroblastoma (NB) is a type of peripheral sympathetic nervous system cancer that most commonly affects children. It is caused by the improper differentiation of primitive neural crest cells during embryonic development. Although NB occurs for 8% of paediatric cancers, it accounts for 15% of cancer-related deaths. Despite a considerable increase in cytotoxic chemo- and radiotherapy, patients in advanced stages remain virtually incurable. Therefore, there is a desperate necessity for new treatment strategies to be investigated. Accumulating evidence suggested that microRNAs (miRNAs) are a class of non-coding RNAs with 19&ndash;25 nucleotides lengths and play a central role in the development of NB carcinogenesis. Fascinatingly, miRNA inhibitors have an antisense property that can inhibit miRNA function and suppress the activity of mature miRNA. However, many studies have addressed miRNA inhibition in the treatment of NB, but their molecular mechanisms and signalling pathways are yet to be analysed. In this study, we impart the current state of knowledge about the role of miRNA inhibition in the aetiology of NB

Biowaste-Derived Interconnected Carbon Nanosheet-Supported Iron as a Highly Stable and Excellent Electrocatalyst for Overall Water Splitting

Water splitting needs low-cost materials that can efficiently catalyze both oxygen evolution reaction (OER) and hydrogen evolution reaction (HER). We prepared biowaste-derived self-nitrogen-doped interconnected hierarchically porous carbon nanosheet Fe@PSAC as a bifunctional and ultradurable electrocatalyst for water splitting. Fe@PSAC exhibits a low overpotential of 118 mV (84 mV/dec) for HER and 231 mV (66 mV/dec) for OER @ 10 mA/cm2 in 1.0 M KOH (without iR correction). Fe@PSAC exhibits durability for 100 h with minimum potential losses of 2.9 and 2.3% for HER and OER, respectively. The turnover frequency of Fe@PSAC (0.2297/s) and IrO2 (0.0231/s) for OER and Fe@PSAC (0.0784/s) and Pt/C (0.1806/s) for HER was nearer to Pt/C and greater than IrO2, respectively. The synergy between self-nitrogen-doped interconnected hierarchically porous carbon nanosheets and iron endows excellent bifunctional activity and stability. The Fe@PSAC//Fe@PSAC water electrolyzer exhibits excellent activity at 1.58 V to reach 10 mA/cm2 with high stability for 120 h with a 3.2% potential loss. The Fe@PSAC//Fe@PSAC electrocatalyst shows an exceptional activity of 1.58 V using solar-assisted water electrolysis. The Fe@PSAC//Fe@PSAC electrode has been strongly recommended for low-cost hydrogen fuel production on a large scale