Effect of Tea Polyphenol on Oxidative Injury in S180 Cells Induced Hepatocarcinoma Mice

The purpose of this study was to evaluate the antioxidant nature of tea polyphenol on S180 cells induced liver cancer in mice. In the present study, hepatocellular carcinoma was induced by tumor transplantation of liver in situ. The antitumor activity of tea polyphenol has been determined in vivo in hepatocellular carcinoma mice after treatment of drug (50, 100, 150 mg/kg body weight) by gavage for 20 days. Results showed that a significant increase in serum aspartate transaminase (AST), alkaline phosphatase (ALP), alanine aminotransfere (ALT), malondialdehyde (MDA) level, decrease in serum white blood cells (WBC), serum total protein (TP), albumin (ALB), A/G, tumor necrosis factor-α (TNF-α) and interferon-gamma (IFN-γ), liver reduced glutathione (GSH) levels were observed. In addition, the levels of enzymic and non-enzymic antioxidants were decreased when subjected to S180 cells induction. These altered enzyme levels were ameliorated significantly by administration of tea polyphenol at the concentration of 50, 100, 150 mg/kg body weight in drug-treated animals. These results indicate that the protective effect of tea polyphenol was associated with inhibition of MDA induced by S180 cells and to maintain the antioxidant enzyme levels

Sphingosine-1-phosphate lyase mutations cause primary adrenal insufficiency and steroid-resistant nephrotic syndrome

Primary adrenal insufficiency is life threatening and can present alone or in combination with other comorbidities. Here, we have described a primary adrenal insufficiency syndrome and steroid-resistant nephrotic syndrome caused by loss-of-function mutations in sphingosine-1-phosphate lyase (SGPL1). SGPL1 executes the final decisive step of the sphingolipid breakdown pathway, mediating the irreversible cleavage of the lipid-signaling molecule sphingosine-1-phosphate (S1P). Mutations in other upstream components of the pathway lead to harmful accumulation of lysosomal sphingolipid species, which are associated with a series of conditions known as the sphingolipidoses. In this work, we have identified 4 different homozygous mutations, c.665G>A (p.R222Q), c.1633_1635delTTC (p.F545del), c.261+1G>A (p.S65Rfs*6), and c.7dupA (p.S3Kfs*11), in 5 families with the condition. In total, 8 patients were investigated, some of whom also manifested other features, including ichthyosis, primary hypothyroidism, neurological symptoms, and cryptorchidism. Sgpl1-/- mice recapitulated the main characteristics of the human disease with abnormal adrenal and renal morphology. Sgpl1-/- mice displayed disrupted adrenocortical zonation and defective expression of steroidogenic enzymes as well as renal histology in keeping with a glomerular phenotype. In summary, we have identified SGPL1 mutations in humans that perhaps represent a distinct multisystemic disorder of sphingolipid metabolism

A Protective Role of Arecoline Hydrobromide in Experimentally Induced Male Diabetic Rats

Objectives. Arecoline, the most potent and abundant alkaloid of betel nut, causes elevation of serum testosterone and androgen receptor expression in rat prostate, in addition to increase in serum insulin levels in rats, leading to insulin resistance and type 2 diabetes-like conditions. This study investigated the role of arecoline on the reproductive status of experimentally induced type 1 diabetic rats. Methods. Changes in the cellular architecture were analyzed by transmission electron microscopy. Blood glucose, serum insulin, testosterone, FSH, and LH were assayed. Fructose content of the coagulating gland and sialic acid content of the seminal vesicles were also analyzed. Results. Arecoline treatment for 10 days at a dose of 10 mg/kg of body weight markedly facilitated β-cell regeneration and reversed testicular and sex accessory dysfunctions by increasing the levels of serum insulin and gonadotropins in type 1 diabetic rats. Critical genes related to β-cell regeneration, such as pancreatic and duodenal homeobox 1 (pdx-1) and glucose transporter 2 (GLUT-2), were found to be activated by arecoline at the protein level. Conclusion. It can thus be suggested that arecoline is effective in ameliorating the detrimental effects caused by insulin deficiency on gonadal and male sex accessories in rats with type 1 diabetes

Transcriptome-Wide Detection of Intron/Exon Definition in the Endogenous Pre-mRNA Transcripts of Mammalian Cells and Its Regulation by Depolarization

Pairing of splice sites across an intron or exon is the central point of intron or exon definition in pre-mRNA splicing with the latter mode proposed for most mammalian exons. However, transcriptome-wide pairing within endogenous transcripts has not been examined for the prevalence of each mode in mammalian cells. Here we report such pairings in rat GH3 pituitary cells by measuring the relative abundance of nuclear RNA-Seq reads at the intron start or end (RISE). Interestingly, RISE indexes are positively correlated between 5′ and 3′ splice sites specifically across introns or exons but inversely correlated with the usage of adjacent exons. Moreover, the ratios between the paired indexes were globally modulated by depolarization, which was disruptible by 5-aza-Cytidine. The nucleotide matrices of the RISE-positive splice sites deviate significantly from the rat consensus, and short introns or exons are enriched with the cross-intron or -exon RISE pairs, respectively. Functionally, the RISE-positive genes cluster for basic cellular processes including RNA binding/splicing, or more specifically, hormone production if regulated by depolarization. Together, the RISE analysis identified the transcriptome-wide regulation of either intron or exon definition between weak splice sites of short introns/exons in mammalian cells. The analysis also provides a way to further track the splicing intermediates and intron/exon definition during the dynamic regulation of alternative splicing by extracellular factors

Reduction of cadmium toxicity in wheat through plasma technology.

Cadmium (Cd) contamination in plant-derived food is a big concern. This study examines whether and how Ar/O2 and Ar/Air plasma techniques lead to Cd detoxification in wheat. Treatment with Ar/O2 and Ar/Air changed the seed surface and decreased the pH of seeds as well as the cultivation media. Generally, plants subjected to Cd treatment from seeds treated with Ar/O2and Ar/Air plasma showed considerable progress in morphology and total chlorophyll synthesis compared to Cd-treated wheat, suggesting that plasma technology is effective for Cd detoxification. Furthermore, Ar/O2 and Ar/Air plasma treated plants showed a significant decrease in root and shoot Cd concentration, which is consistent with the reduced expression of Cd transporters in the root (TaLCT1 and TaHMA2) compared with the plants not treated with plasma in response to Cd stress. This Cd inhibition is possibly accomplished by the decrease of pH reducing the bioavailability of Cd in the rhizosphere. These observations are in line with maintenance of total soluble protein along with reduced electrolyte leakage and cell death (%) in root and shoot due to Ar/O2 and Ar/Air treatments. Further, Cd-induced elevated H2O2 or oxidative damage in tissues was mainly diminished through the upregulation of antioxidant enzymes (SOD and CAT) and their corresponding genes (TaSOD and TaCAT) induced by Ar/O2 and Ar/Air plasma. Grafting results suggest that root originating nitric oxide signal possibly drives the mechanisms of Cd detoxification due to plasma treatment in wheat. These findings provide a novel and eco-friendly use of plasma technology for the mitigation of Cd toxicity in wheat plants

Impact of pre-hospital care on the outcome of children arriving with agonal breathing to a pediatric emergency service in South India

Background: Data on the prehospital interventions received by critically ill children at arrival to Paediatric Emergency Services (PES) is limited in developing countries. This study aims to describe the pre-hospital care scenario, transport and their impact on outcome in non-traumatic, acutely ill children presenting in PES with agonal breathing. Methods: Prospective observational study done on children aged below 15 years arriving in PES with agonal breathing due to non-trauma related causes. Results: Out of 75 children studied, 69% were infants. The duration of illness among 65% of them (75) was less than 3 days. Majority of them (81%) had received treatment prior to arrival. Government sector physicians (72%), half of them (51%) being pediatricians were the major treating doctors. 37% of the children had arrived to the Emergency in an ambulance. Cardiopulmonary Resuscitation (CPR) was given to 27% on arrival in PES. Other interventions included fluid boluses to correct shock (92%) and inotrope infusion (56%). Sepsis (24%) and pneumonia (24%) were the most common diagnoses. Out of 75, 57 (76%) children who were stabilized and shifted to PICU and among them 27 (47%) survived to discharge. Normal blood pressure (p=0.0410) and non-requirement of CPR (0.0047) and inotropic infusion (0.0459) in PES were associated with a higher chance of survival. Conclusion: 36% (27/75) of children who arrived to our PES with agonal breathing survived to hospital discharge. Survival was significantly better among those who did not need CPR