Dietary inclusion of Withania somnifera and Asparagus racemosus induces growth, activities of digestive enzymes, and transcriptional modulation of MyoD, MyoG, Myf5, and MRF4 genes in fish, Channa punctatus.

The present study explores growth potential of two medicinal herbs, Withania somnifera (Ashwagandha or 'A') and Asparagus racemosus (Shatavari or 'S') after their dietary inclusion in fish, Channa punctatus (13.5 ± 2 g; 11.5 ± 1 cm).

Sinus Node Sparing Hybrid Thoracoscopic Ablation Outcomes in Patients with Inappropriate Sinus Tachycardia (SUSRUTA-IST) Registry.

Background: Medical treatment of inappropriate sinus tachycardia (IST) remains suboptimal. Radiofrequency sinus node (RF-SN) ablation has poor success and higher complication rates.

Objective: We aimed to compare clinical outcomes of the novel SN sparing hybrid ablation technique with those of RF-SN modification for IST management.

In vivo assessment of dichlorvos induced histological and biochemical impairments coupled with expression of p53 responsive apoptotic genes in the liver and kidney of fish, Channa punctatus (Bloch, 1793).

Sub-lethal exposure of dichlorvos induces oxidative stress, consequent genetic instability and apoptosis coupled with impairments in biochemical, histopathological and transcription of genes in Channa punctatus. Exposure of 5% (0.041 mg/L; E2) and 10% (0.

Convergence of Epicardial and Endocardial RF Ablation for the Treatment of Symptomatic Persistent AF (CONVERGE Trial): Rationale and design.

Atrial fibrillation is the most common sustained arrhythmia affecting over 33 million people worldwide. Approximately 70% of AF patients have non-paroxysmal AF. As AF progresses from paroxysmal to non-paroxysmal forms, the prevalence of comorbidities increases.

A protective study of curcumin associated with Cr induced oxidative stress, genetic damage, transcription of genes related to apoptosis and histopathology of fish, Channa punctatus (Bloch, 1793).

Ameliorative potential of curcumin against Cr-induced eco-toxicological manifestations was assessed in liver of exposed Channa punctatus (Actinopterygii) in six groups for 45 d; Group I as control. Group II with 3 mg/L of curcumin; group III with 7.89 mg/L of Cr.

Biomonitoring of Heavy Metals in River Ganga Water, Sediments, Plant, and Fishes of Different Trophic Levels.

In this study, the pattern of metals concentration in water, sediment, plants, and three edible fish species (Channa striata, Labeo rohita, and Catla catla) of different trophic levels, captured from Jajmau (Kanpur), an important fishery area of river Ganga in Uttar Pradesh, India was examined. The heavy metals, Ni, Pb, Fe, Cu, Zn, Cd, Cr, and Co, were estimated in the liver, kidney, muscles, and gill tissues of abovesaid species of fish. The highest metal concentration was reported in the bottom feeder fish as compared with the column and surface feeders.

Anticancer activity of 2'-hydroxyflavanone towards lung cancer.

In previous studies, we found that 2'-hydroxyflavonone (2HF), a citrus flavonoid, inhibits the growth of renal cell carcinoma in a VHL-dependent manner. This was associated with the inhibition of glutathione S-transferases (GSTs), the first step enzyme of the mercapturic acid pathway that catalyzes formation of glutathione-electrophile conjugates (GS-E). We studied 2HF in small cell (SCLC) and non-small cell (NSCLC) lung cancer cell lines for sensitivity to 2HF antineoplastic activity and to determine the role of the GS-E transporter Rlip (Ral-interacting protein; RLIP76; RALBP1) in the mechanism of action of 2HF.

An in vivo analysis of Cr induced biochemical, genotoxicological and transcriptional profiling of genes related to oxidative stress, DNA damage and apoptosis in liver of fish, Channa punctatus (Bloch, 1793).

Present study was designed to assess the hexavalent chromium (Cr) mediated oxidative stress that induces DNA damage and apoptosis in adult fish, Channa punctatus (35 ± 3.0 g; 14.5 ± 1.

Rlip depletion prevents spontaneous neoplasia in TP53 null mice.

TP53 (p53) is a tumor suppressor whose functions are lost or altered in most malignancies. p53 homozygous knockout (p53) mice uniformly die of spontaneous malignancy, typically T-cell lymphoma. RALBP1 (RLIP76, Rlip) is a stress-protective, mercapturic acid pathway transporter protein that also functions as a Ral effector involved in clathrin-dependent endocytosis.

Zn induced molecular responses associated with oxidative stress, DNA damage and histopathological lesions in liver and kidney of the fish, Channa punctatus (Bloch, 1793).

Zn is essential for normal physiological functioning of all organisms in small quantities, but when its concentration enhances in surrounding environment it acts as a toxicant to organisms. Common sources of Zn pollution are electroplating, alloying, mining, and allied industrial operations. The present study aims to assess the biochemical, histopathological and genotoxicological implications under Zn intoxication along with its accumulation patterns in prime biotransformation sites-liver and kidney, of a bottom feeder fish, Channa punctatus.

Phorate induced oxidative stress, DNA damage and differential expression of p53, apaf-1 and cat genes in fish, Channa punctatus (Bloch, 1793).

The present study was conducted to assess the in-vivo activities of certain molecular biomarkers under the impact of phorate exposure. Fish, Channa punctatus (35 ± 3.0 g; 14.

Regulatory roles of glutathione-S-transferases and 4-hydroxynonenal in stress-mediated signaling and toxicity.

Glutathione-S-Transferases (GSTs) have primarily been thought to be xenobiotic metabolizing enzymes that protect cells from toxic drugs and environmental electrophiles. However, in last three decades, these enzymes have emerged as the regulators of oxidative stress-induced signaling and toxicity. 4-Hydroxy-trans 2-nonenal (HNE) an end-product of lipid peroxidation, has been shown to be a major determinant of oxidative stress-induced signaling and toxicity.

4 Null Mouse Embryonic Fibroblasts Exhibit Enhanced Sensitivity to Oxidants: Role of 4-Hydroxynonenal in Oxidant Toxicity.

The alpha class glutathione s-transferase (GST) isozyme GSTA4-4 (EC2.5.1.

Lens specific RLIP76 transgenic mice show a phenotype similar to microphthalmia.

RALBP1/RLIP76 is a ubiquitously expressed protein, involved in promotion and regulation of functions initiated by Ral and R-Ras small GTPases. Presence of multiple domains in its structure enables RLIP76 to be involved in a number of physiological processes such as endocytosis, exocytosis, mitochondrial fission, actin cytoskeleton remodeling, and transport of exogenous and endogenous toxicants. Previously, we have established that RLIP76 provides protection to ocular tissues against oxidative stress by transporting the glutathione-conjugates of the toxic, electrophilic products of lipid peroxidation generated during oxidative stress.

4-Hydroxynonenal induces G2/M phase cell cycle arrest by activation of the ataxia telangiectasia mutated and Rad3-related protein (ATR)/checkpoint kinase 1 (Chk1) signaling pathway.

4-Hydroxynonenal (HNE) has been widely implicated in the mechanisms of oxidant-induced toxicity, but the detrimental effects of HNE associated with DNA damage or cell cycle arrest have not been thoroughly studied. Here we demonstrate for the first time that HNE caused G2/M cell cycle arrest of hepatocellular carcinoma HepG2 (p53 wild type) and Hep3B (p53 null) cells that was accompanied with decreased expression of CDK1 and cyclin B1 and activation of p21 in a p53-independent manner. HNE treatment suppressed the Cdc25C level, which led to inactivation of CDK1.

Role of SMC1 in overcoming drug resistance in triple negative breast cancer.

Triple-negative breast cancer (TNBC) is one of the hardest subtypes of breast cancer to treat due to the heterogeneity of the disease and absence of well-defined molecular targets. Emerging evidence has shown the role of cohesin in the formation and progression of various cancers including colon and lung cancer but the role of cohesin in breast cancer remains elusive. Our data showed that structural maintenance of chromosome 1 (SMC1), a subunit of the cohesin protein complex, is differentially overexpressed both at RNA and protein level in a panel of TNBC cell lines as compared to normal epithelial or luminal breast cancer cells, suggesting that the amplified product of this normal gene may play role in tumorigenesis in TNBC.

P300 regulates the human RLIP76 promoter activity and gene expression.

A 76-kDa Ral-interacting protein (RLIP76) has been implicated in the pathogenesis of cancer and diabetes. It is often over expressed in human malignant cell lines and human tumor samples and has been associated with metastasis and chemoresistance. RLIP76 homozygous knockout mice exhibit increased insulin sensitivity, hypoglycemia, and hypolipidemia, and resist cancer development.

Clinical evaluation of a novel 12-hole irrigated tip catheter ablation system for the treatment of typical atrial flutter-results from the Duo FLAIR clinical study.

Introduction: Higher current density at the proximal end of a six-hole catheter is not irrigated and thus could lead to uneven heating and possibly coagulum and charring. This study tested a novel 12-hole irrigated catheter with six additional holes at the proximal end that provides more uniform cooling during atrial flutter (AFL) ablation.

Methods: A total of 188 patients (28 females, 66 ± 11 years) were treated for typical AFL at 22 sites in the USA and Canada using Cool Path Duo at 50 W and 45 °C at an irrigation rate of 13 ml/min.

Loss of glutathione S-transferase A4 accelerates obstruction-induced tubule damage and renal fibrosis.

Glutathione transferase isozyme A4 (GSTA4) exhibits high catalytic efficiency to metabolize 4-hydroxynonenal (4-HNE), a highly reactive lipid peroxidation product that has been implicated in the pathogenesis of various chronic diseases. We investigated the role of 4-HNE in the mechanisms of unilateral ureteral obstruction (UUO)-induced fibrosis and its modulation by GSTA4-4 in a mouse model. Our data indicate that after UUO, accumulation of 4-HNE and its adducts were increased in renal tissues, with a concomitant decrease in the expression of GSTA4-4 in mice.

Role of 4-hydroxynonenal in chemopreventive activities of sulforaphane.

Chemoprevention of cancer via herbal and dietary supplements is a logical approach to combating cancer and currently it is an attractive area of research investigation. Over the years, isothiocyanates, such as sulforaphane (SFN) found in cruciferous vegetables, have been advocated as chemopreventive agents, and their efficacy has been demonstrated in cell lines and animal models. In vivo studies with SFN suggest that in addition to protecting normal healthy cells from environmental carcinogens, it also exhibits cytotoxicity and apoptotic effects against various cancer cell types.

The expression and function of vascular endothelial growth factor in retinal pigment epithelial (RPE) cells is regulated by 4-hydroxynonenal (HNE) and glutathione S-transferaseA4-4.

It is well established that 4-hydroxynonenal (HNE) plays a major role in oxidative stress-induced signaling and the toxicity of oxidants. Surprisingly our recent studies also demonstrate that low levels of HNE generated during oxidative stress promote cell survival mechanisms and proliferation. Since the expression and secretion of VEGF is known to be affected by Oxidative stress, during present studies, we have examined dose dependent effect of HNE on VEGF expression and secretion in a model of retinal pigment epithelial (RPE) cells in culture.

Inhibition of mercapturic acid pathway-mediated disposal of 4-hydroxynonenal causes complete and sustained remission of human cancer xenografts in nude mice.

Environmental electrophilic chemical carcinogens are detoxified via mercapturic acid pathway to be excreted as mercapturic acid derivatives. Mercapturic acid pathway is also involved in the metabolism of pro-apoptotic and toxic endogenous electrophiles such as 4-hydroxynonenal (HNE). HNE is a common denominator in stress induced signaling and is a pro-apoptotic second messenger that affects cell cycle signaling in a concentration dependent manner.

Glutathione-conjugate transport by RLIP76 is required for clathrin-dependent endocytosis and chemical carcinogenesis.

Targeted depletion of the RALBP1-encoded 76-kDa splice variant, RLIP76, causes marked and sustained regression of human xenografts of lung, colon, prostate, and kidney cancers without toxicity in nude mouse models. We proposed that the remarkable efficacy and broad spectrum of RLIP76-targeted therapy is because its glutathione-conjugate (GS-E) transport activity is required for clathrin-dependent endocytosis (CDE), which regulates all ligand-receptor signaling, and that RLIP76 is required not only for survival of cancer cells but also for their very existence. We studied RLIP76 mutant proteins and the functional consequences of their expression into RLIP76(-/-) MEFs, identified key residues for GS-E binding in RLIP76, established the requirement of RLIP76-mediated GS-E transport for CDE, and showed a direct correlation between GS-E transport activities with CDE.

Role of 4-hydroxynonenal in epidermal growth factor receptor-mediated signaling in retinal pigment epithelial cells.

Lipid peroxidation (LPO) end-product 4-hydroxynonenal (4-HNE) has been implicated in the mechanism of retinopathy. Lately it has been shown that besides being cytotoxic, 4-HNE plays an important role in oxidative stress-induced signaling. In this study, we have investigated the effect of 4-HNE on epidermal growth factor receptor (EGFR)-mediated signaling, its potential functional consequences, and the regulatory role of the 4-HNE metabolizing isozymes, glutathione S-transferase A4-4 (GSTA4-4) on this signaling in retinal pigment epithelial (RPE) cells.

Evidence that Gsta4 modifies susceptibility to skin tumor development in mice and humans.

Background: The incidence of nonmelanoma skin cancer (NMSC) is equivalent to that of all other cancers combined. Previously, we mapped the 12-O-tetradecanoylphorbol-13-acetate (TPA) skin tumor promotion susceptibility locus, Psl1, to distal chromosome 9 in crosses of sensitive DBA/2 mice with relatively resistant C57BL/6 mice. Here, we used the mouse two-stage skin carcinogenesis model to identify the gene(s) responsible for the effects of Psl1.