Targeting of nucleotide-binding proteins by HAMLET--a conserved tumor cell death mechanism.

HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) kills tumor cells broadly suggesting that conserved survival pathways are perturbed. We now identify nucleotide-binding proteins as HAMLET binding partners, accounting for about 35% of all HAMLET targets in a protein microarray comprising 8000 human proteins. Target kinases were present in all branches of the Kinome tree, including 26 tyrosine kinases, 10 tyrosine kinase-like kinases, 13 homologs of yeast sterile kinases, 4 casein kinase 1 kinases, 15 containing PKA, PKG, PKC family kinases, 15 calcium/calmodulin-dependent protein kinase kinases and 13 kinases from CDK, MAPK, GSK3, CLK families.

Gene-gene, gene-environment, gene-nutrient interactions and single nucleotide polymorphisms of inflammatory cytokines.

Inflammation plays a significant role in the etiology of type 2 diabetes mellitus (T2DM). The rise in the pro-inflammatory cytokines is the essential step in glucotoxicity and lipotoxicity induced mitochondrial injury, oxidative stress and beta cell apoptosis in T2DM. Among the recognized markers are interleukin (IL)-6, IL-1, IL-10, IL-18, tissue necrosis factor-alpha (TNF-α), C-reactive protein, resistin, adiponectin, tissue plasminogen activator, fibrinogen and heptoglobins.

An approach to model based testing of multiagent systems.

Autonomous agents perform on behalf of the user to achieve defined goals or objectives. They are situated in dynamic environment and are able to operate autonomously to achieve their goals. In a multiagent system, agents cooperate with each other to achieve a common goal.

IVisTMSA: Interactive Visual Tools for Multiple Sequence Alignments.

IVisTMSA is a software package of seven graphical tools for multiple sequence alignments. MSApad is an editing and analysis tool. It can load 409% more data than Jalview, STRAP, CINEMA, and Base-by-Base.

Oxidative airway inflammation leads to systemic and vascular oxidative stress in a murine model of allergic asthma.

Oxidant-antioxidant imbalance plays an important role in repeated cycles of airway inflammation observed in asthma. It is when reactive oxygen species (ROS) overwhelm antioxidant defenses that a severe inflammatory state becomes apparent and may impact vasculature. Several studies have shown an association between airway inflammation and cardiovascular complications; however so far none has investigated the link between airway oxidative stress and systemic/vascular oxidative stress in a murine model of asthma.

Mutational spectrum of the TYR and SLC45A2 genes in Pakistani families with oculocutaneous albinism, and potential founder effect of missense substitution (p.Arg77Gln) of tyrosinase.

Background: Oculocutaneous albinism (OCA) is an autosomal recessive disorder of abnormal melanin formation, which results in hypopigmentation of skin, hair and eyes. OCA is classified into four types based on clinical and genetic findings. OCA1 is the most severe form of albinism, and is caused by mutations in the tyrosinase (TYR) gene, while OCA4 is caused due to mutations in SLC45A2.

Proteinase activated receptor-2-mediated dual oxidase-2 up-regulation is involved in enhanced airway reactivity and inflammation in a mouse model of allergic asthma.

Airway epithelial cells (AECs) express a variety of receptors, which sense danger signals from various aeroallergens/pathogens being inhaled constantly. Proteinase-activated receptor 2 (PAR-2) is one such receptor and is activated by cockroach allergens, which have intrinsic serine proteinase activity. Recently, dual oxidases (DUOX), especially DUOX-2, have been shown to be involved in airway inflammation in response to Toll-like receptor activation.

The molecular motor F-ATP synthase is targeted by the tumoricidal protein HAMLET.

HAMLET (human alpha-lactalbumin made lethal to tumor cells) interacts with multiple tumor cell compartments, affecting cell morphology, metabolism, proteasome function, chromatin structure and viability. This study investigated if these diverse effects of HAMLET might be caused, in part, by a direct effect on the ATP synthase and a resulting reduction in cellular ATP levels. A dose-dependent reduction in cellular ATP levels was detected in A549 lung carcinoma cells, and by confocal microscopy, co-localization of HAMLET with the nucleotide-binding subunits α (non-catalytic) and β (catalytic) of the energy converting F1F0 ATP synthase was detected.

Regulation of TNF-α and NF-κB activation through the JAK/STAT signaling pathway downstream of histamine 4 receptor in a rat model of LPS-induced joint inflammation.

Histamine 4 receptor (H4R) is a novel target for the pharmacological modulation of histamine-mediated immune signals during inflammatory diseases. The purpose of this study was to assess the effects of the H4R agonist 4-methylhistamine dihydrochloride (4-MeH) and antagonist JNJ7777120 (JNJ) in the inflamed rat knee. Animals were fasted for 18h before a single dose of 4-MeH or JNJ (30mg/kg) was administered intraperitoneally (i.

Evaluating the accuracy and efficiency of multiple sequence alignment methods.

A comparison of 10 most popular Multiple Sequence Alignment (MSA) tools, namely, MUSCLE, MAFFT(L-INS-i), MAFFT (FFT-NS-2), T-Coffee, ProbCons, SATe, Clustal Omega, Kalign, Multalin, and Dialign-TX is presented. We also focused on the significance of some implementations embedded in algorithm of each tool. Based on 10 simulated trees of different number of taxa generated by R, 400 known alignments and sequence files were constructed using indel-Seq-Gen.

Sympatric species distribution, genetic diversity and population structure of Haemonchus isolates from domestic ruminants in Pakistan.

Haemonchus species are major gastro-intestinal parasites affecting ruminants across the world. The present study aimed to assess the sympatric species distribution, genetic diversity, population structure and frequency of β-tubulin isotype 1 alleles associated with benzimidazole resistance. Internal transcribed spacer 2 (ITS2) sequences revealed three sympatric species of Haemonchus, H.

Chloride-liberal fluids are associated with acute kidney injury after liver transplantation.

Introduction: Acute kidney injury (AKI) occurs frequently after liver transplantation and is associated with significant morbidity and mortality. Recent evidence has linked the predominant usage of 'chloride-liberal' intravenous fluids, such as 0.9% saline to the development of renal dysfunction in general critically ill patients.

Impact of laccase enzyme inducers on solid waste compost maturity and stability.

The influence of inducers of laccase produced by Pleurotus ostreatus-P1 on the physicochemical properties of solid waste compost was investigated. In order to examine the degree of humification and time period for maturity and stability of compost, three different treatments (T: laccase; T1: laccase+CuSO4; and T2: laccase+CuSO4+CaCl2) were inoculated on solid waste in the initial stage of the composting process. During the composting process, the carbon nitrogen ratio (C/N), nitrate ([Formula: see text]), ammonium nitrogen ([Formula: see text]), cation exchange capacity (CEC), humic acid (HA) and fulvic acid (FA) humification rate (HR), Humification Index (HI), and degree of polymerization (DP) were assessed for the evaluation of compost maturity and stability, and it was found that T2 treatment C/N, CEC, and HI was greater, 46.

Protection against tacrolimus-induced cardiotoxicity in rats by olmesartan and aliskiren.

Context: Tacrolimus (TAC), a calcineurin inhibitor, is commonly used as an immunosuppressive agent in organ transplantation, but its clinical use may be limited due to cardiotoxicity. Olmesartan (OLM; angiotensin receptor blocker) and aliskiren (ALK; renin inhibitor) may attenuate cardiotoxicity induced by TAC by inhibition of renin-angiotensin aldosterone system.

Objective: The aim of this study was to evaluate the effect of OLM and ALK on TAC-induced cardiotoxicity.

The incidence of cisplatin nephrotoxicity post hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgery.

Background: Cisplatin is commonly used in hyperthermic intraperitoneal chemotherapy (HIPEC) for the management of peritoneal carcinomatosis. Little is known about the nephrotoxic effects of cisplatin use in HIPEC.

Objectives: To report the incidence of nephrotoxicity post-HIPEC using cisplatin 50 mg/m(2) plus doxorubicin 15 mg/m(2).

Olmesartan attenuates tacrolimus-induced biochemical and ultrastructural changes in rat kidney tissue.

Tacrolimus, a calcineurin inhibitor, is clinically used as an immunosuppressive agent in organ transplantation, but its use is limited due to its marked nephrotoxicity. The present study investigated the effect of olmesartan (angiotensin receptor blocker) on tacrolimus-induced nephrotoxicity in rats. A total of 24 rats were divided into four groups, which included control, tacrolimus, tacrolimus + olmesartan, and olmesartan groups.

Acute glutathione depletion leads to enhancement of airway reactivity and inflammation via p38MAPK-iNOS pathway in allergic mice.

Glutathione (GSH) plays a major role in allergic airway responses through a variety of mechanism which include direct scavenging of oxidative species, being a reducing equivalent and regulation of cellular signaling through redox sensitive mechanisms. Therefore, the aim of the present study was to evaluate the role of acute GSH depletion on airway reactivity, inflammation and NO signaling in a mouse model of allergic asthma. Buthionine sulfoximine (BSO), an inhibitor of gamma-glutamylcysteine synthetase was used for depletion of GSH levels.

Identification of a novel mutation (p.Ile198Thr) in gene TYR in a Pakistani family with nonsyndromic oculocutaneous albinism.

The TYR gene (MIM #6069333) is located at position 11q14.3 on the human chromosome, and encodes tyrosinase, which is expressed in melanocytes and controls the biosynthesis of melanin. Most TYR mutations eliminate the activity of tyrosinase, preventing melanocytes from producing any melanin throughout life.

Airway and systemic oxidant-antioxidant dysregulation in asthma: a possible scenario of oxidants spill over from lung into blood.

Asthma is characterized by repeated episodes of airway obstruction and an ongoing cycle of airway inflammation. Reactive oxygen species (ROS) produced by inflammatory cells in the lung play a key role in the pathogenesis as well as amplification of inflammation in asthmatic airways. Several enzymatic and non-enzymatic antioxidants are available in the lung and systemic circulation to counteract ROS-mediated damage on various biomolecules such as lipid membranes, proteins, and DNA; however during asthmatic inflammation these defenses are overwhelmed due to excessive production of ROS thereby leading to inflammatory events in the airways/systemic circulation.

Escheriosome-mediated cytosolic delivery of PLK1-specific siRNA: potential in treatment of liver cancer in BALB/c mice.

Aim: In the present study, the anticancer efficacy of a novel escheriosome-based formulation of PLK1-specific siRNA was evaluated against liver cancer in BALB/c mice.

Materials & Methods: The escheriosome-based siRNA nanoparticles were prepared using lipids isolated from Escherichia coli. The escheriosomes were characterized for size, surface charge and stability.

Carbon tetrachloride-induced hepatotoxicity in rat is reversed by treatment with riboflavin.

Liver is a vital organ for the detoxification of toxic substances present in the body and hepatic injury is associated with excessive exposure to toxicants. The present study was designed to evaluate the possible hepatoprotective effects of riboflavin against carbon tetrachloride (CCl4) induced hepatic injury in rats. Rats were divided into six groups.

Glutathione modulation during sensitization as well as challenge phase regulates airway reactivity and inflammation in mouse model of allergic asthma.

Glutathione, being a major intracellular redox regulator has been shown to be implicated in regulation of airway reactivity and inflammation. However, no study so far has investigated the effect of glutathione depletion/repletion during sensitization and challenge phases separately, which could provide an important insight into the pathophysiology of allergic asthma. The aim of the present study was to evaluate the role of glutathione depletion/repletion during sensitization and challenge phases separately in a mouse model of allergic asthma.

Treatment with aliskiren ameliorates tacrolimus-induced nephrotoxicity in rats.

Introduction: Tacrolimus is frequently used as immunosuppressive agent in organ transplantation but its clinical use is limited due to its marked nephrotoxicity.

Materials And Methods: Male Wistar albino rats weighing 150-200 g (10-12 weeks old) were used. Animals were divided into four groups.

Survival pattern in patients with acute organophosphate poisoning on mechanical ventilation: A retrospective intensive care unit-based study in a tertiary care teaching hospital.

Background And Aims: Organophosphorus (OP) compound poisoning is one of the most common poisonings in India. The aim of the study was to study the outcomes and predictors of mortality in patients with acute OP poisoning requiring mechanical ventilation.

Methods: A retrospective study was conducted in the intensive care unit and 117 patients were included.