Kadukkai maathirai (a polyherbal traditional siddha formulation) prevents D-galactosamine induced hepatic necrosis in rats

708-713This study evaluated the prophylactic effect of Kadukkai maathirai in D-galactosamine (D-gal) induced hepatotoxicity in rats. D-galactosamine (D-gal) 400 mg/kg intraperitoneally was used to induce liver damage in rats. To assess the hepatoprotective effect of KM, three different doses of KM (36, 72 and 144 mg/kg body weight) were used. The hepatoprotective effect of KM was compared with standard drug silymarin (50 mg/kg). The biochemical parameters such as AST, ALT, ALP and total bilirubin were estimated. The livers were dissected out to look for histological changes. KM 144 mg/kg and silymarin showed a significant decrease in AST, ALP and total bilirubin. Both KM and silymarin significantly prevented decrease in liver weight. In KM treated groups, the liver did not show necrosis of hepatocytes, and apoptotic bodies with mild to moderate inflammatory infiltrate in the lobules and portal tracts. Hence, the results of this study confirms the hepatoprotective effect KM in rats

Kadukkai maathirai (a polyherbal traditional siddha formulation) prevents D-galactosamine induced hepatic necrosis in rats

This study evaluated the prophylactic effect of Kadukkai maathirai in D-galactosamine (D-gal) induced hepatotoxicity in rats. D-galactosamine (D-gal) 400 mg/kg intraperitoneally was used to induce liver damage in rats. To assess the hepatoprotective effect of KM, three different doses of KM (36, 72 and 144 mg/kg body weight) were used. The hepatoprotective effect of KM was compared with standard drug silymarin (50 mg/kg). The biochemical parameters such as AST, ALT, ALP and total bilirubin were estimated. The livers were dissected out to look for histological changes. KM 144 mg/kg and silymarin showed a significant decrease in AST, ALP and total bilirubin. Both KM and silymarin significantly prevented decrease in liver weight. In KM treated groups, the liver did not show necrosis of hepatocytes, and apoptotic bodies with mild to moderate inflammatory infiltrate in the lobules and portal tracts. Hence, the results of this study confirms the hepatoprotective effect KM in rats

Salivary exRNA biomarkers to detect gingivitis and monitor disease regression

AimThis study tests the hypothesis that salivary extracellular RNA (exRNA) biomarkers can be developed for gingivitis detection and monitoring disease regression.Materials and MethodsSalivary exRNA biomarker candidates were developed from a total of 100 gingivitis and nonâ gingivitis individuals using Affymetrix’s expression microarrays. The top 10 differentially expressed exRNAs were tested in a clinical cohort to determine whether the discovered salivary exRNA markers for gingivitis were associated with clinical gingivitis and disease regression. For this purpose, unstimulated saliva was collected from 30 randomly selected gingivitis subjects, the gingival and plaque indexes scores were taken at baseline, 3 and 6 weeks and salivary exRNAs were assayed by means of reverse transcription quantitative polymerase chain reaction.ResultsEight salivary exRNA biomarkers developed for gingivitis were statistically significantly changed over time, consistent with disease regression. A panel of four salivary exRNAs [SPRR1A, lncâ TET3â 2:1, FAM25A, CRCT1] can detect gingivitis with a clinical performance of 0.91 area under the curve, with 71% sensitivity and 100% specificity.ConclusionsThe clinical values of the developed salivary exRNA biomarkers are associated with gingivitis regression. They offer strong potential to be advanced for definitive validation and clinical laboratory development test.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144647/1/jcpe12930.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144647/2/jcpe12930_am.pd

Activation of Akt Is Essential for the Propagation of Mitochondrial Respiratory Stress Signaling and Activation of the Transcriptional Coactivator Heterogeneous Ribonucleoprotein A2

This article shows that mitochondrial respiratory dysfunction activates a stress signaling that induces Akt1 activation. Akt1 activation occurs through calcineurin-mediated IGF1R/PI3-K pathway. Akt1-mediated phosphorylation of hnRNPA2 is a key requirement for the propagation of stress signaling and activation of nuclear target genes

A Novel Intracellular Isoform of Matrix Metalloproteinase-2 Induced by Oxidative Stress Activates Innate Immunity

Experimental and clinical evidence has pinpointed a critical role for matrix metalloproteinase-2 (MMP-2) in ischemic ventricular remodeling and systolic heart failure. Prior studies have demonstrated that transgenic expression of the full-length, 68 kDa, secreted form of MMP-2 induces severe systolic failure. These mice also had unexpected and severe mitochondrial structural abnormalities and dysfunction. We hypothesized that an additional intracellular isoform of MMP-2, which affects mitochondrial function is induced under conditions of systolic failure-associated oxidative stress.Western blots of cardiac mitochondria from the full length MMP-2 transgenics, ageing mice and a model of accelerated atherogenesis revealed a smaller 65 kDa MMP-2 isoform. Cultured cardiomyoblasts subjected to transient oxidative stress generated the 65 kDa MMP-2 isoform. The 65 kDa MMP-2 isoform was also induced by hypoxic culture of cardiomyoblasts. Genomic database analysis of the MMP-2 gene mapped transcriptional start sites and RNA transcripts induced by hypoxia or epigenetic modifiers within the first intron of the MMP-2 gene. Translation of these transcripts yields a 65 kDa N-terminal truncated isoform beginning at M(77), thereby deleting the signal sequence and inhibitory prodomain. Cellular trafficking studies demonstrated that the 65 kDa MMP-2 isoform is not secreted and is present in cytosolic and mitochondrial fractions, while the full length 68 kDa isoform was found only in the extracellular space. Expression of the 65 kDa MMP-2 isoform induced mitochondrial-nuclear stress signaling with activation of the pro-inflammatory NF-κB, NFAT and IRF transcriptional pathways. By microarray, the 65 kDa MMP-2 induces an innate immunity transcriptome, including viral stress response genes, innate immunity transcription factor IRF7, chemokines and pro-apoptosis genes.A novel N-terminal truncated intracellular isoform of MMP-2 is induced by oxidative stress. This isoform initiates a primary innate immune response that may contribute to progressive cardiac dysfunction in the setting of ischemia and systolic failure

Identification and Classification of Conserved RNA Secondary Structures in the Human Genome

The discoveries of microRNAs and riboswitches, among others, have shown functional RNAs to be biologically more important and genomically more prevalent than previously anticipated. We have developed a general comparative genomics method based on phylogenetic stochastic context-free grammars for identifying functional RNAs encoded in the human genome and used it to survey an eight-way genome-wide alignment of the human, chimpanzee, mouse, rat, dog, chicken, zebra-fish, and puffer-fish genomes for deeply conserved functional RNAs. At a loose threshold for acceptance, this search resulted in a set of 48,479 candidate RNA structures. This screen finds a large number of known functional RNAs, including 195 miRNAs, 62 histone 3′UTR stem loops, and various types of known genetic recoding elements. Among the highest-scoring new predictions are 169 new miRNA candidates, as well as new candidate selenocysteine insertion sites, RNA editing hairpins, RNAs involved in transcript auto regulation, and many folds that form singletons or small functional RNA families of completely unknown function. While the rate of false positives in the overall set is difficult to estimate and is likely to be substantial, the results nevertheless provide evidence for many new human functional RNAs and present specific predictions to facilitate their further characterization

Correction: Physiochemical characterization and cytotoxicity evaluation of mercury-based formulation for the development of anticancer therapeuticals.

[This corrects the article DOI: 10.1371/journal.pone.0195800.]