Synthesis, characterization and anti-tumor activity of novel thymoquinone analogs against pancreatic cancer.

Thymoquinone (TQ), isolated from the seeds of Nigella sativa, show moderate efficacy against pancreatic cancer. In the present work we report synthesis and characterization of novel TQ analogs appended with gallate and fluorogallate pharmacophores and evaluation of their effects against pancreatic cancer cell lines for cell viability and induction of apoptosis. The efficacy of the analogs alone or in combination with Gemcitabine was assessed in vitro.

Biotransformation of clerodane diterpenoids by Rhizopus stolonifer and antibacterial activity of resulting metabolites.

Microbial transformation of clerodane lactone (1) by a plant pathogen fungus, Rhizopus stolonifer, resulted in the production of metabolites 3 and 4. While incubation of clerodane methyl ester (2) by R. stolonifer yielded metabolites 5-8.

SML resist processing for high-aspect-ratio and high-sensitivity electron beam lithography.

A detailed process characterization of SML electron beam resist for high-aspect-ratio nanopatterning at high sensitivity is presented. SML contrast curves were generated for methyl isobutyl ketone (MIBK), MIBK/isopropyl alcohol (IPA) (1:3), IPA/water (7:3), n-amyl acetate, xylene, and xylene/methanol (3:1) developers. Using IPA/water developer, the sensitivity of SML was improved considerably and found to be comparable to benchmark polymethylmethacrylate (PMMA) resist without affecting the aspect ratio performance.

The effect of optotype size and velocity parameters on the performance of healthy young adult subjects on the gaze stabilization test.

Hypothesis: The purpose of the current study was to examine the influence of the optotype (the letter E) size, presentation time, and head velocity on gaze stabilization test (GST) performance.

Background: The gaze stabilization test is a functional measure of the vestibulo-ocular reflex.

Methods: Twenty-one healthy young subjects (mean age, 26 ± 4; range, 21-34, 10 male subjects) performed the computerized GST.

Copious urinary excretion of a male Syrian hamster (Mesocricetus auratus) salivary gland protein after its endocrine-like release upon β-adrenergic stimulation.

Salivary glands, although widely considered as typically exocrine, may also release specific proteins in an endocrine manner. However, endocrine release of salivary gland proteins is not generally acknowledged since the evidences are not easily demonstrable. Submandibular salivary glands (SMG) of male Syrian hamsters express male-specific secretory proteins (MSP; which are lipocalins) visible in SDS-PAGE of SMG extracts, as major bands and also detectable in immunoblots of whole-saliva and urine as low MSP crossreactions.

Transcriptome profiling of microRNA by Next-Gen deep sequencing reveals known and novel miRNA species in the lipid fraction of human breast milk.

While breast milk has unique health advantages for infants, the mechanisms by which it regulates the physiology of newborns are incompletely understood. miRNAs have been described as functioning transcellularly, and have been previously isolated in cell-free and exosomal form from bodily liquids (serum, saliva, urine) and tissues, including mammary tissue. We hypothesized that breast milk in general, and milk fat globules in particular, contain significant numbers of known and limited novel miRNA species detectable with massively parallel sequencing.

Glutathione redox potential is low and glutathionylated and cysteinylated hemoglobin levels are elevated in maintenance hemodialysis patients.

Glutathione (GSH), the most abundant intracellular low molecular mass thiol, protects cells from oxidative damage and regulates their function. Available information is inconsistent regarding levels of GSH and its disulfide (GSSG) in maintenance hemodialysis patients (HD). In addition, very limited data are available in HD about the relationship of GSH and GSSG with other measures of thiol metabolism and with the clinical profile.

Dendritic cells and multiple sclerosis: disease, tolerance and therapy.

Multiple sclerosis (MS) is a devastating neurological disease that predominantly affects young adults resulting in severe personal and economic impact. The majority of therapies for this disease were developed in, or are beneficial in experimental autoimmune encephalomyelitis (EAE), the animal model of MS. While known to target adaptive anti-CNS immune responses, they also target, the innate immune arm.

Anti-cancer, anti-inflammatory and anti-microbial activities of plant extracts used against hematological tumors in traditional medicine of Jordan.

Ethnopharmacological Relevance: Mercurialis annua L., Bongardia chrysogonum L., and Viscum cruciatum Sieb have been traditionally used by local herbalists in Jordan for the treatment of hematopoietic neoplasms.

Does the lipid environment impact the open-state conductance of an engineered β-barrel protein nanopore?

Using rational membrane protein design, we were recently able to obtain a β-barrel protein nanopore that was robust under an unusually broad range of experimental circumstances. This protein nanopore was based upon the native scaffold of the bacterial ferric hydroxamate uptake component A (FhuA) of Escherichia coli. In this work, we expanded the examinations of the open-state current of this engineered protein nanopore, also called FhuA ΔC/Δ4L, employing an array of lipid bilayer systems that contained charged and uncharged as well as conical and cylindrical lipids.

Intermittent fasting during Ramadan attenuates proinflammatory cytokines and immune cells in healthy subjects.

Intermittent fasting and caloric restriction have been shown to extend life expectancy and reduce inflammation and cancer promotion in animal models. It was hypothesized that intermittent prolonged fasting practiced during the month of Ramadan (RIF) could positively affect the inflammatory state. To investigate this hypothesis, a cross-sectional study was designed to investigate the impact of RIF on selected inflammatory cytokines and immune biomarkers in healthy subjects.

Network pharmacology: reigning in drug attrition?

In the process of drug development, there has been an exceptionally high attrition rate in oncological compounds entering late phases of testing. This has seen a concurrent reduction in approved NCEs (new chemical entities) reaching patients. Network pharmacology has become a valuable tool in understanding the fine details of drug-target interactions as well as painting a more practical picture of phenotype relationships to patients and drugs.

Determination of the quaternary structure of a bacterial ATP-binding cassette (ABC) transporter in living cells.

Pseudomonas aeruginosa is a pathogenic Gram-negative bacterium that affects patients with cystic fibrosis and immunocompromised individuals. This bacterium coexpresses two unique forms of lipopolysaccharides (LPSs) on its surface, the A- and B-band LPS, which are among the main virulence factors that contribute to its pathogenicity. The polysaccharides in A-band LPSs are synthesized in the cytoplasm and translocated into the periplasm via an ATP-binding cassette (ABC) transporter consisting of a transmembrane protein, Wzm, and a cytoplasmic nucleotide-binding protein, Wzt.

Lymphoepithelial cyst of the pancreas in female children--report of two cases.

Lymphoepithelial cyst (LEC) of the pancreas is almost always reported as a case report or in small series mostly in male adult patients with vague clinical manifestations and difficult pre-operative diagnosis. Between the years 2007 and 2012, two female children with LEC of the pancreas were operated on at the Children's Surgical Unit of Murtala Mohammad Specialist Hospital, Kano in northern Nigeria. Satisfactory outcomes were achieved after distal pancreatectomy and splenectomy in one and a Whipple procedure in the other.

Inspection of the engineered FhuA ΔC/Δ4L protein nanopore by polymer exclusion.

Extensive engineering of protein nanopores for biotechnological applications using native scaffolds requires further inspection of their internal geometry and size. Recently, we redesigned ferric hydroxamate uptake component A (FhuA), a 22-β-stranded protein containing an N-terminal 160-residue cork domain (C). The cork domain and four large extracellular loops (4L) were deleted to obtain an unusually stiff engineered FhuA ΔC/Δ4L nanopore.

Impact of ramadan intermittent fasting on oxidative stress measured by urinary 15-f(2t)-isoprostane.

Fasting and caloric restriction have been associated with reduced incidence of chronic diseases and cancers. These effects have been attributed to reduced oxidative stress. Since Ramadan intermittent fasting (RIF) has been associated with reduced caloric intake, it was hypothesized that RIF would alleviate oxidative stress in healthy volunteers.

Acrolein cytotoxicity in hepatocytes involves endoplasmic reticulum stress, mitochondrial dysfunction and oxidative stress.

Acrolein is a common environmental, food and water pollutant and a major component of cigarette smoke. Also, it is produced endogenously via lipid peroxidation and cellular metabolism of certain amino acids and drugs. Acrolein is cytotoxic to many cell types including hepatocytes; however the mechanisms are not fully understood.

The ability of phosphodiesterase-5 inhibitors sildenafil and ordonafil to reverse L-NAME induced cardiac hypertrophy in the rabbit: possible role of calcineurin and p38.

Phosphodiesterase 5 inhibitors (PDE-5Is) can suppress and (or) reverse pressure overload induced myocardial hypertrophy. This study investigated the suppressive effect of 2 PDE-5Is (sildenafil and ordonafil) on N-nitro-l-arginine methyl ester (L-NAME)-induced cardiac hypertrophy in rabbit heart, and examined their possible mechanism of action. L-NAME increased left ventricular thickness to 6.

Gene regulation of UDP-galactose synthesis and transport: potential rate-limiting processes in initiation of milk production in humans.

Lactose synthesis is believed to be rate limiting for milk production. However, understanding the molecular events controlling lactose synthesis in humans is still rudimentary. We have utilized our established model of the RNA isolated from breast milk fat globule from seven healthy, exclusively breastfeeding women from 6 h to 42 days following delivery to determine the temporal coordination of changes in gene expression in the carbohydrate metabolic processes emphasizing the lactose synthesis pathway in human mammary epithelial cell.

Engineering a rigid protein tunnel for biomolecular detection.

One intimidating challenge in protein nanopore-based technologies is designing robust protein scaffolds that remain functionally intact under a broad spectrum of detection conditions. Here, we show that an extensively engineered bacterial ferric hydroxamate uptake component A (FhuA), a β-barrel membrane protein, functions as a robust protein tunnel for the sampling of biomolecular events. The key implementation in this work was the coupling of direct genetic engineering with a refolding approach to produce an unusually stable protein nanopore.

Protein sensing with engineered protein nanopores.

The use of nanopores is a powerful new frontier in single-molecule sciences. Nanopores have been used effectively in exploring various biophysical features of small polypeptides and proteins, such as their folding state and structure, ligand interactions, and enzymatic activity. In particular, the α-hemolysin (αHL) protein pore has been used extensively for the detection, characterization, and analysis of polypeptides because this protein nanopore is highly robust, versatile, and tractable under various experimental conditions.

Clinical relevance of cyclooxygenase-2 and matrix metalloproteinases (MMP-2 and MT1-MMP) in human breast cancer tissue.

Breast cancer (BC) is the most common neoplasm among women in most developed countries, including Egypt. Elevated levels of certain proteins in human BC are associated with unfavorable prognosis and progressive stages of the disease. The aim of our study was to evaluate the protein expression profile and prognostic significance of cyclooxygenase-2 (COX-2), matrix metalloproteinase-2 (MMP-2), MMP-9 and membrane type 1-MMP (MT1-MMP) and their interaction in operable BC patients.

Famotidine inhibits glycogen synthase kinase-3β: an investigation by docking simulation and experimental validation.

Famotidine was investigated as an inhibitor of glycogen synthase kinase-3β (GSK-3β) in an attempt to explain the molecular mechanism of its hypoglycemic side effects. The investigation included simulated docking experiments, in vitro enzyme inhibition assay, glycogen sparing studies using animal models and single dose oral glucose tolerance test (OGTT). Docking studies showed how famotidine is optimally fit within the binding pocket of GSK-3β via numerous attractive interactions with some specific amino acids.

Zinc and liver disease.

Zinc is an essential trace element required for normal cell growth, development, and differentiation. It is involved in DNA synthesis, RNA transcription, and cell division and activation. It is a critical component in many zinc protein/enzymes, including critical zinc transcription factors.