Putative therapeutic impacts of cardiac CTRP9 in ischaemia/reperfusion injury

Recently, cytokines belonging to C1q/tumour necrosis factor‐related proteins (CTRPs) superfamily have attracted increasing attention due to multiple metabolic functions and desirable anti‐inflammatory effects. These various molecular effectors exhibit key roles upon the onset of cardiovascular diseases, making them novel adipo/cardiokines. This review article aimed to highlight recent findings correlated with therapeutic effects and additional mechanisms specific to the CTRP9, particularly in cardiac ischaemia/reperfusion injury (IRI). Besides, the network of the CTPR9 signalling pathway and its possible relationship with IRI were discussed. Together, the discovery of all involved underlying mechanisms could shed light to alleviate the pathological sequelae after the occurrence of IRI.     

Construction of a dual-tag system for gene expression, protein affinity purification and fusion protein processing

An E. coli vector system was constructed which allows the expression of fusion genes via a l-rhamnose-inducible promotor. The corresponding fusion proteins consist of the maltose-binding protein and a His-tag sequence for affinity purification, the Saccharomyces cerevisiae Smt3 protein for protein processing by proteolytic cleavage and the protein of interest. The Smt3 gene was codon-optimized for expression in E. coli. In a second rhamnose-inducible vector, the S. cerevisiae Ulp1 protease gene for processing Smt3 fusion proteins was fused in the same way to maltose-binding protein and His-tag sequence but without the Smt3 gene. The enhanced green fluorescent protein (eGFP) was used as reporter and protein of interest. Both fusion proteins (MalE-6xHis-Smt3-eGFP and MalE-6xHis-Ulp1) were efficiently produced in E. coli and separately purified by amylose resin. After proteolytic cleavage the products were applied to a Ni-NTA column to remove protease and tags. Pure eGFP protein was obtained in the flow-through of the column in a yield of around 35% of the crude cell extract.     

Nanoemulsion as a Potential Ophthalmic Delivery System for Dorzolamide Hydrochloride

Dilutable nanoemulsions are potent drug delivery vehicles for ophthalmic use due to their numerous advantages as sustained effect and high ability of drug penetration into the deeper layers of the ocular structure and the aqueous humor. The aim of this article was to formulate the antiglaucoma drug dorzolamide hydrochloride as ocular nanoemulsion of high therapeutic efficacy and prolonged effect. Thirty-six systems consisting of different oils, surfactants, and cosurfactants were prepared and their pseudoternary-phase diagrams were constructed by water titration method. Seventeen dorzolamide hydrochloride nanoemulsions were prepared and evaluated for their physicochemical and drug release properties. These nanoemulsions showed acceptable physicochemical properties and exhibited slow drug release. Draize rabbit eye irritation test and histological examination were carried out for those preparations exhibiting superior properties and revealed that they were nonirritant. Biological evaluation of dorzolamide hydrochloride nanoemulsions on normotensive albino rabbits indicated that these products had higher therapeutic efficacy, faster onset of action, and prolonged effect relative to either drug solution or the market product. Formulation of dorzolamide hydrochloride in a nanoemulsion form offers, thus, a more intensive treatment of glaucoma, a decrease in the number of applications per day, and a better patient compliance compared to conventional eye drops.     

FDTD analysis of a noninvasive hyperthermia system for brain tumors

ABSTRACT: BACKGROUND: Hyperthermia is considered one of the new therapeutic modalities for cancer treatment and is based on the difference in thermal sensitivity between healthy tissues and tumors. During hyperthermia treatment, the temperature of the tumor is raised to 40--4[DEGREE SIGN]C for a definite period resulting in the destruction of cancer cells. This paper investigates design, modeling and simulation of a new non-invasive hyperthermia applicator system capable of effectively heating deep seated as well as superficial brain tumors using inexpensive, simple, and easy to fabricate components without harming surrounding healthy brain tissues. METHODS: The proposed hyperthermia applicator system is composed of an air filled partial half ellipsoidal chamber, a patch antenna, and a head model with an embedded tumor at an arbitrary location. The irradiating antenna is placed at one of the foci of the hyperthermia chamber while the center of the brain tumor is placed at the other focus. The finite difference time domain (FDTD) method is used to compute both the SAR patterns and the temperature distribution in three different head models due to two different patch antennas at a frequency of 915 MHz. RESULTS: The obtained results suggest that by using the proposed noninvasive hyperthermia system it is feasible to achieve sufficient and focused energy deposition and temperature rise to therapeutic values in deep seated as well as superficial brain tumors without harming surrounding healthy tissue. CONCLUSIONS: The proposed noninvasive hyperthermia system proved suitable for raising the temperature in tumors embedded in the brain to therapeutic values by carefully selecting the systems components. The operator of the system only needs to place the center of the brain tumor at a pre-specified location and excite the antenna at a single frequency of 915 MHz. Our study may provide a basis for a clinical applicator prototype capable of heating brain tumors.     

Ethanol-Induced Oxidative Stress: The Role of Binaphthyl Diselenide as a Potent Antioxidant

It is widely accepted that oxidative stress plays a central role in alcohol-induced pathogenesis. The protective effect of binaphthyl diselenide (NapSe)2 was investigated in ethanol (Etoh)-induced brain injury. Thirty male adult Wistar rats were divided randomly into five groups of six animals each and treated as follows: (1) The control group received the vehicle (soy bean oil, 1 mL/kg, p.o.). (2) Ethanol group of animals was administered with ethanol (70% v/v, 2 mL/kg, p.o.). (3) (NapSe)2 1 mg/kg, 1 mL/kg plus ethanol 70% (v/v, 2 mL/kg, p.o. (5) (NapSe)2 10 mg/kg, 1 mL/kg) plus ethanol 70% (v/v, 2 mL/kg, p.o). After acute treatment, all rats were sacrificed by decapitation. Evidence for oxidative stress in rat brain was obtained from the observed levels of thiobarbituric acid reactive species, of non-protein thiol (NPSH) groups, and of ascorbic acid, as well as from the activities of catalase (CAT) and of superoxide dismutase (SOD). (NapSe)2 compensated the deficits in the antioxidant defense mechanisms (CAT, SOD, NPSH, and ascorbic acid), and suppressed lipid peroxidation in rat brain resulting from Etoh administration. It was concluded that ethanol exposure causes alterations in the antioxidant defense system and induces oxidative stress in rat brain. (NaPSe)2 at 5 mg/kg restored the antioxidant defenses in rat brain and mitigated the toxic effects of alcohol, suggesting that could be used as a potential therapeutic agent for alcohol-induced oxidative damage in rat brain.     

Amplified immunohistochemical detection of PrPsc in animal transmissible spongiform encephalopathies using streptomycin.

Due to its sensitivity, immunohistochemistry (IHC) of abnormal prion protein (PrPsc) is used to study experimental and natural cases of transmissible spongiform encephalopathies (TSEs) such as Creutzfeldt-Jakob disease in humans or scrapie and bovine spongiform encephalopathy (BSE) in animals. The limits of detection are particularly critical when PrPsc IHC is used for diagnostic purposes. In this article, we describe for the first time the use of streptomycin sulfate in IHC, providing a novel original and easy way to amplify specifically PrPsc immunohistochemical detection in natural cases of BSE and scrapie, as well as in experimental TSEs in mice models using two different PrP antibodies.     

N-terminally fusion of Her2/neu to HSP70 decreases efficiency of Her2/neu DNA vaccine

DNA vaccines consisted of tumor-associated antigen (TAA) are well suited for immunotherapy against tumor. The construct can contain TAA fused to an appropriate molecule (biologic adjuvant) to improve the efficacy of anti-tumor immune response. Heat shock protein 70 (HSP70) has been shown to be an excellent candidate, capable of cross-priming TAA by antigen presenting cells leading to a robust T-cell response. However, the relationship between strong T-cell responses and tumor rejection is not always mutually exclusive, for which TAA loss or activation of suppressive mechanisms may occur. HSP70 fused to downstream of Her2/neu as DNA vaccine has been shown to be efficient against Her2-expressing tumors. In this study, we examined if N-terminally fusion of Her2/neu to HSP70 could also improve efficiency of Her2/neu DNA vaccine. Therefore, mice with an established Her2/neu expressing tumor were immunized with DNA vaccine consisting of extracellular and trans-membrane domain (EC+TM) of rat Her2/neu alone or N-terminally fused to HSP70 and immune response was evaluated. Administration of rat Her2/neu led to partial control of tumor progression. Surprisingly, fusion of HSP70 to N-terminal of rat Her2/neu led to tumor progression. Our result proposes that fusion direction of biologic adjuvant is an important consideration when Her2/neu is used.     

Protective effects of cinnamon powder against hyperlipidemia and hepatotoxicity in butter fed female albino mice

A butter-enriched high-fat diet changes lipid metabolism, resulting in fat storage, hyperlipidemia and obesity. Effects of cinnamon powder were investigated in butter-fed mice. 40 Swiss Albino mice, aged 28 to 30 days, were randomly assigned into two groups. Group A was an untreated control group (n = 8) and another group (n = 32) was a butter-treated group fed 10% butter. In the fifth week, mice of the butter-fed group were further divided into four equal groups: B, C, D, and E (n = 8), fed 10% butter with cinnamon 200 mg, 400 mg, and 600 mg powder per liter drinking water, respectively for 10 weeks. The butter-fed group was gained the most weight. Cinnamon supplementation significantly normalized weight gain and had no harmful effects on hematological parameters. Butter supplementation significantly increased total cholesterol (TC), triglycerides, and LDL cholesterol (LDL-c) whereas, cinnamon powder significantly reduced TC, LDL-c and glucose levels. In butter-fed mice, a significant increase was observed in the liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels with subsequent fat deposition in the liver. Excitingly, these enzymes were decreased and no fat depositions were observed in the liver of cinnamon-treated mice. Applying different concentrations of cinnamon powder improved the lipid profile in butter-fed female albino mice.     

Prevalence,antimicrobial resistance profile,and characterization of multi-drug resistant bacteria from various infected wounds in North Egypt

Multi-drug resistant (MDR) bacteria associated with wounds are extremely escalating. This study aims to survey different wounds in Alexandria hospitals, North Egypt, to explore the prevalence and characteristics of MDR bacteria for future utilization in antibacterial wound dressing designs. Among various bacterial isolates, we determined 22 MDR bacteria could resist different classes of antibiotics. The collected samples exhibited the prevalence of mono-bacterial infections (60%), while 40% included poly-bacterial species due to previous antibiotic administration. Moreover, Gram-negative bacteria showed dominance with a ratio of 63.6%, while Gram-positive bacteria reported 36.4%. Subsequently, the five most virulent bacteria were identified following the molecular approach by 16S rRNA and physiological properties using the VITEK 2 automated system. They were deposited in GenBank as Staphylococcus haemolyticus MST1 ({"type":"entrez-nucleotide","attrs":{"text":"KY550377","term_id":"1304487819","term_text":"KY550377"}}KY550377), Pseudomonas aeruginosa MST2 ({"type":"entrez-nucleotide","attrs":{"text":"KY550378","term_id":"1304487820","term_text":"KY550378"}}KY550378), Klebsiella pneumoniae MST3 ({"type":"entrez-nucleotide","attrs":{"text":"KY550379","term_id":"1304487821","term_text":"KY550379"}}KY550379), Escherichia coli MST4 ({"type":"entrez-nucleotide","attrs":{"text":"KY550380","term_id":"1304487822","term_text":"KY550380"}}KY550380), and Escherichia coli MST5 ({"type":"entrez-nucleotide","attrs":{"text":"KY550381","term_id":"1304487823","term_text":"KY550381"}}KY550381). In terms of isolation source, S. haemolyticus MST1 was isolated from a traumatic wound, while P. aeruginosa MST2 and E. coli MST4 were procured from hernia surgical wounds, and K. pneumoniae MST3 and E. coli MST5 were obtained from diabetic foot ulcers. Antibiotic sensitivity tests exposed that K. pneumoniae MST3, E. coli MST4, and E. coli MST5 are extended-spectrum β-lactamases (ESBLs) bacteria. Moreover, S. haemolyticus MST1 belongs to the methicillin-resistant coagulase-negative staphylococcus (MRCoNS), whereas P. aeruginosa MST2 exhibited resistance to common empirical bactericidal antibiotics. Overall, the study provides new insights into the prevalent MDR bacteria in Egypt for further use as specific models in formulating antibacterial wound dressings.