https://escholarship.org/content/qt4gg44625/qt4gg44625.pdf?t=qbnsiy

Oxidative stress response and Nrf2 signaling in aging.

All of the most commonly encountered genera of cyanobacteria which form blooms and scums in fresh-brackish- and marine waters include members capable of producing potent toxins. Poisonings of vertebrate and invertebrate animals following the ingestion of cyanobacterial bloom/scum material have been widely reported for many years and recognition of the adverse effects of cyanobacterial blooms and their toxins is increasing. This review considers the occurrence of toxic cyanobacterial populations and properties of the toxins themselves, of which at least 60 are now recognised. When rightfully regarded as microbial secondary metabolites, a range of possible functions for cyanobacterial toxins is presented. Whether cyanobacterial toxins contribute to the ability of cyanobacteria to dominate many eutrophic waterbodies is unknown, although understanding of the occurrence of the toxins in aquatic environments and their actions at the molecular level and with whole organisms in laboratory studies indicates that this is possible.

Cyanobacterial toxins: occurrence, properties and biological significance

Microalgal biotechnology has emerged due to the health-promoting properties of microalgae related to their bioactive compounds and the great diversity of products that can be developed from algal biomass. Microalgal biomasses have been produced industrially for applications in different fields such as food, pharmaceutical, nutraceutical, cosmetic, and animal feed industries. They can be cultivated either in open systems or in closed systems (photobioreactors). Another important area is the use of microalgal biomass for energy production. It has become obvious that petroleum-derived fuels are unsustainable, due to depleting world reserves and greenhouse gas emissions. Microalgae can provide several different types of renewable biofuels. These include methane produced by anaerobic digestion of the algal biomass, biodiesel derived from trans-esterification of microalgal lipids, bioethanol produced from carbohydrate fermentations, and photobiologically produced biohydrogen. The idea of using microalgae as a source of fuel is not new. However, it is now being taken seriously because of increases in petroleum prices and, more significantly, the increasing concern about global warming as associated with burning fossil fuels. This review offers an update on information about microalgae, specifically emphasizing their biotechnological importance.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/1541-4337.12227

The Evolution and Versatility of Microalgal Biotechnology: A Review

NAD(P)H:quinone oxidoreductase (NQO1), an obligatory two-electron reductase, is a ubiquitous cytosolic enzyme that catalyzes the reduction of quinone substrates. The NQO1- mediated two-electron reduction of quinones can be either chemoprotection/detoxification or a chemotherapeutic response, depending on the target quinones. When toxic quinones are reduced by NQO1, they are conjugated with glutathione or glucuronic acid and excreted from the cells. Based on this protective effect of NQO1, the use of dietary compounds to induce the expression of NQO1 has emerged as a promising strategy for cancer prevention. On the other hand, NQO1-mediated two-electron reduction converts certain quinone compounds (such as mitomycin C, E09, RH1 and -lapachone) to cytotoxic agents, leading to cell death. It has been known that NQO1 is expressed at high levels in numerous human cancers, including breast, colon, cervix, lung, and pancreas, as compared with normal tissues. This implies that tumors can be preferentially damaged relative to normal tissue by cytotoxic quinone drugs. Importantly, NQO1 has been shown to stabilize many proteins, including p53 and p33ING1b, by inhibiting their proteasomal degradation. This review will summarize the biological roles of NQO1 in cancer, with emphasis on recent findings and the potential of NQO1 as a therapeutic target for the cancer therapy. [BMB Reports 2015; 48(11): 609-617]

/pdf/implications-of-nqo1-in-cancer-therapy-y1cxm647yz.pdf

Implications of NQO1 in cancer therapy.

A highly purified cytosolic azoreductase isolated from the livers of 3-methylcholanthrene-treated rats has been characterized with respect to its electron- accepting and -donating properties, the mechanism of its inhibition by dicumarol, and its similarity to DT- diaphorase. Anaerobic titration of the enzyme with NADPH as the electron donor indicates that each mole of enzyme can accept 4 reducing eq, or 2 electrons/mol of enzyme-bound FAD. The purified azoreductase cat- alyzes the reduction of methyl red and under anaerobic conditions, 2 mol of NADPH are required for the reduc- tion of 1 mol of methyl red which is consistent with the expected stoichiometry for reduction of the azo linkage of methyl red by NADPH. Dicumarol strongly inhibits the azoreductase-catalyzed reduction of methyl red. Spectrophotometric measurements indicate that dicu- marol binds to the purified azoreductase at a ratio of approximately 1 mol of dicumarol to 1 mol of enzyme- bound FAD. Dicumarol is a competitive inhibitor of methyl red reduction with respect to NADPH and ap- pears to inhibit the reaction by interfering with elec- tron transfer from NADPH to enzyme-bound FAD. Pu- rified rat azoreductase from rat liver appears to be identical with rat DT-diaphorase. This conclusion is based on the co-purification of both enzyme activities as well as the apparent homogeneity of the final enzyme preparation. Other properties of both enzymes are also consistent with this conclusion. The enzyme responsible for the metabolism of methyl red (2’-carboxy-4-N,N-dimethylaminoazobenzene) is localized mainly in the liver 105,000 x g supernatant fraction. This azoreductase activity can be induced 7- to lo-fold by pretreat- ment of rats with 3-methylcholanthrene (1, 2). We have re- cently reported the purification to apparent homogeneity of an azoreductase from the liver 105,000 x g supernatant frac- tion of 3-methylcholanthrene-treated rats (3,4). The purified azoreductase has an apparent molecular weight of 52,000 as determined by gel filtration on Sephadex G-100. Polyacryl- amide gel electrophoresis in the presence of sodium dodecyl sulfate gives a minimal molecular weight of 30,000 suggesting that the native enzyme exists as a dimer. The enzyme is a flavoprotein and contains 2 mol of FAD/mol of enzyme (4). This azoreductase actively catalyzes the reduction of methyl red and a structure activity study revealed that the 2’-carboxyl * The

Electron transport properties and the mechanism of dicumarol inhibition of the purified enzyme

NAD(P)H:quinone-oxidoreductase-1 (NQO1) is a cytosolic enzyme that catalyses two- or four-electron reduction of many endogenous and environmental quinones using flavin adenine dinucleotide (FAD) as a cofactor. It is a cytosolic enzyme exists as a homodimer and is biochemically distinguished by its prominent ability to use either NADH or NADPH as reducing cofactors and by its suppression by the anticoagulant dicumarol. This enzyme generally considered as a detoxification enzyme due to of its ability to diminish reactive quinones and quinone-imines to its less reactive and less toxic hydroquinones forms. NQO1 is a substantially inducible enzyme that is controlled by the Nrf2-Keap1/ARE pathway. Evidence for the significance of the antioxidant functions of NQO1 in suppression of oxidative stress is provided by manifestations that induction of NQO1 levels or their reduction are associated with reduced and raised susceptibilities to oxidative stress, respectively. The gene coding for NQO1 has two common polymorphisms at nucleotide position 609(C-T) and 465 (C-T) of the human cDNA. C465T causes reduction in enzyme activity, whereas the C609T results in complete loss of enzymatic activity due to protein instability. In this review, we discuss the protective functions of NQO1 and present its possible transcriptional pathways regulating its induction by Nrf2-Keap1/ARE pathway.

/pdf/a-review-of-nad-p-h-quinone-oxidoreductase-1-nqo1-a-36vfcfexe3.pdf

A Review of NAD(P)H:Quinone Oxidoreductase 1 (NQO1); A Multifunctional Antioxidant Enzyme -

Cyanobacteria are one of the most diverse groups of gram-negative photosynthetic prokaryotes. Cyanobacteria are prokaryotes have a simple cell structure with a real nucleus Prokaryotic. Their body is made from a single cell, often clustered cells as colonies of different shapes. Cyanobacteria are typically much larger than bacteria in size, it contain many types of pigments such as carotenoids and phycocyanin. A characteristic of water soluble pigment in cyanobacteria gives the group of cyanobacteria their blue green coloration. Cyanobacteria living in individuals places in fresh and salt water, and some other types live in moist soil. The water distinctive bluish colour is results for cyanobacteria blooms when it dies. Researchers found that only about 10% of all blooms types are considered toxins producer. However, it is still ambiguous what triggers that cause to produce its toxin. This review highlights the occurrence of algal cyanobacteriablooms, its classification and toxicology.

/pdf/review-on-freshwater-blue-green-algae-cyanobacteria-3yi26gnsgt.pdf

Review on Freshwater Blue-Green Algae (Cyanobacteria): Occurrence, Classification and Toxicology

Nuclear factor (erythroid-derived 2) -like 2 (Nrf2) is a transcription factor that plays an important role in the cellular protection against free radical damage and reduce the incidence of radical derived degenerative diseases such as cancer. Nrf2 is referred to as the "master regulator" of the antioxidant response due to the fact that it modulates the expression of several genes including phase-2 and antioxidant enzymes playing a crucial role in detoxification of electrophiles and reactive oxygen species (ROS), including glutathione-S-transferase (GST), gamma-glutamyl cysteine ligase (γ-GCL), glutathione-S-reductase (GSR), NAD(P)H:quinoneoxidoreductase-1 (NQO1), heme oxygenase-1 (HO-1), etc. Following dissociation from it obligatory partner Kelch like ECHassociated protein 1 (Keap1), Nrf2 translocates to the nucleus and transactivates the antioxidant response element (ARE) in the promoter region of several antioxidant genes. In this review, we discuss the role of the Nrf2 system, with particular focus on Nrf2-controlled target genes.

Review of nrf2-regulated genes induced in response to antioxidants

Introduction: Respiratory tract infections have been known to be a significant health concern for mortality and morbidity since many years. This study was aimed at determining the prevalence of bacterial pathogen causing upper respiratory tract (URTIs) and the susceptibility patterns to frequently used antibiotics among patients attending Abusetta hospital in Tripoli district. 
Methods: A total of 1,110 throat swabs were collected between Jan, 2011 to December, 2014 and inoculated onto Blood agar, MacCkonkey agar and Chocolate agar then incubated at 37 oC for 24 hours. Bacterial pathogens were determined by bacteriological culture methods and antibiotic susceptibility of the isolates was identified following Clinical Laboratory Standard Institute guidelines (CLSI). 
Results: Of the 1,110 respiratory samples tested, 71.1% (n = 789) of specimens were positive cultures with the dominant bacterial pathogens being Streptococcus pneumoniae 43.3% (n = 342), followed by Pseudomona aeruginosa 22.8% (n = 180), Staphylococcus aureus 13.8% (n = 109), Escherichia coli 6.9% (n = 55), Enterobacter spp 6.2% (n = 49), Citrobacter 4.5% (n = 36), and Klebsiella 2.2% (n = 18). Most isolates exhibited resistance against the commonly used antibiotics and to at least one antibiotic. 
Conclusion: The level of antibiotic resistance in this study is alarming and brings to light the timely and suitable diagnosis of the common bacteria causes of URTIs and proper antibiotic administration based on susceptibility test.

/pdf/antibiotic-resistance-pattern-of-bacteria-isolated-from-gvz2fkacey.pdf

Antibiotic Resistance Pattern of Bacteria Isolated from patients with upper respiratory tract infections; a four year study in Tripoli city

Background and Aims: Inappropriate uses of antibiotics for the treatment of common self-limiting infections are a major dispensing malpractice worldwide. This potentially may result in the development of resistant bacterial strains, which represents a significant public health problem. This study aimed to describe the pattern of antibiotics dispensing between community pharmacists (CPs) and general practitioners (GPs) regarding symptomatic diagnosis, antibiotic categories, and adherence to therapeutic doses. Subjects and Methods: Between March and June 2017, using trained simulated patients (SPs) with simulated clinical scenarios of having upper respiratory tract infections, a cross-sectional observational study of antibiotic dispensing encounters was conducted at 20 randomly selected pharmacies and clinics in the city of Tripoli, Libya. SPs were trained to deal with both expertise and record their notice after each visit in specific form developed by the researcher. The data were descriptively analyzed using Chi-square and Fisher's exact tests at alpha level of 0.05. Results: CPs dispensed more antibiotics than GPs (P = 0.001) for treating symptoms of common cold. They dispensed more amoxicillin (n = 32, 53.5%) than GPs (n = 18, 30.0%) (P = 0.001). While no CP dispensed ciprofloxacin, only two GPs dispensed this category (P = 0.022). In general, GPs comply better with the symptomatic diagnosis standard than CPs. On the other hand, CPs (n = 26, 59%) adhered better than GPs (n = 4, 12.5%) to therapeutic doses (P = 0.001). Conclusions: The findings suggested poor professional practices by both CPs and GPs. Antibiotic dispensing regulation policies need to be implemented in Libya and CPs must practice ethically.

Ahmed Atia

Papers

A Review of NAD(P)H:Quinone Oxidoreductase 1 (NQO1); A Multifunctional Antioxidant Enzyme -

Review on Freshwater Blue-Green Algae (Cyanobacteria): Occurrence, Classification and Toxicology

Review of nrf2-regulated genes induced in response to antioxidants

Antibiotic Resistance Pattern of Bacteria Isolated from patients with upper respiratory tract infections; a four year study in Tripoli city

Antibiotic prescribing for upper respiratory tract infections by Libyan community pharmacists and medical practitioners: An observational study