Modulation of the Nitric Oxide/BH4 Pathway Protects Against Irradiation-Induced Neuronal Damage

Neurochemical Research - The kynurenine pathway (KP, IDO/Kyn pathway) is an important metabolic pathway related to many diseases. Although cranial radiotherapy is the mainstay in metastatic tumors...     

Vasculopathy in type 2 diabetes mellitus: role of specific angiogenic modulators

Type 2 diabetes mellitus (T2DM) is largely defined by hyperglycemia that promotes vascular complications. Abnormal angiogenesis has been claimed to have a role in this disease. This study aimed to investigate serum levels of both conventional and other markers of angiogenesis not well studied before in diabetes, and to correlate findings with age of the patients, glycemic control, presence of microvascular complications, and oxidative stress. Thirty-eight patients with T2DM and 13 age- and sex-matched healthy persons representing controls were recruited. Serum levels of basic fibroblast growth factor (b-FGF) was measured by immunosorbent assay kit; advanced glycosylation end products, platelet-derived endothelial cell growth factor (PD-ECGF), cathepsin-D (CD), gangliosides, hyaluronic acid (HA), nitric oxide (NO), lipid peroxides (LPER), superoxide dismutase, and total thiols by chemical methods; and copper (Cu) by atomic absorption flame photometry. Advanced glycosylation end products and angiogenic factors (b-FGF, PD-ECGF, CD, gangliosides, HA, and Cu) were significantly higher in patients than controls. Oxidative stress markers, NO, and LPER were significantly higher while total thiols were significantly lower in patients than controls. These changes were more pronounced with age, poor glycemic control, and presence of microvascular complications. Angiogenesis dysfunction coinciding with elevated levels of many angiogenic growth factors may point to their malfunctioning due to oxidative stress and/or protein glycation at the factor and the receptor levels. This necessitates further investigations.     

Antidiabetic activity of phenolic compounds from Pecan bark in streptozotocin-induced diabetic rats

The n-butanol fraction (BF) of bark of Pecan tree, Carya illinoinensis (Wangenh) K. Koch (Juglandaceae) afforded two new flavonol methyl ether: caryatin-3′ sulfate (6) and caryatin-3′ methyl ether-7-O-β-d-glucoside (7) while five known phenolics (1–5) were isolated from its ethyl acetate fraction (EAF). The structures of isolated compounds were established based on 1D and 2D NMR spectroscopy. The isolated compounds were investigated for their hypoglycaemic, antioxidant as well as the aldose reductase (AR) inhibitory effect in lenses of streptozocin diabetic rats. All the isolated compounds showed significant hypoglycaemic and antioxidant activities, except 5 and 6. A marked AR-inhibitory effect was identified for compounds 2, 3 and 7.     

Trends in lipoplex physical properties dependent on cationic lipid structure, vehicle and complexation procedure do not correlate with biological activity

Using a group of structurally related cytofectins, the effects of different vehicle constituents and mixing techniques on the physical properties and biological activity of lipoplexes were systematically examined. Physical properties were examined using a combination of dye accessibility assays, centrifugation, gel electrophoresis and dynamic light scattering. Biological activity was examined using in vitro transfection. Lipoplexes were formulated using two injection vehicles commonly used for in vivo delivery (PBS pH 7.2 and 0.9% saline), and a sodium phosphate vehicle previously shown to enhance the biological activity of naked pDNA and lipoplex formulations. Phosphate was found to be unique in its effect on lipoplexes. Specifically, the accessible pDNA in lipoplexes formulated with cytofectins containing a gamma-amine substitution in the headgroup was dependent on alkyl side chain length and sodium phosphate concentration, but the same effects were not observed when using cytofectins containing a beta-OH headgroup substitution. The physicochemical features of the phosphate anion, which give rise to this effect in gamma-amine cytofectins, were deduced using a series of phosphate analogs. The effects of the formulation vehicle on transfection were found to be cell type-dependent; however, of the formulation variables examined, the liposome/pDNA mixing method had the greatest effect on transgene expression in vitro. Thus, though predictive physical structure relationships involving the vehicle and cytofectin components of the lipoplex were uncovered, they did not extrapolate to trends in biological activity.     

Study of reactivity of cyanoacetohydrazonoethyl-N-ethyl-N-methyl benzenesulfonamide: preparation of novel anticancer and antimicrobial active heterocyclic benzenesulfonamide derivatives and their molecular docking against dihydrofolate reductase

Abstract

This article describes the synthesis of some novel heterocyclic sulfonamides having biologically active thiophene 3, 4, 5, 6, coumarin 8, benzocoumarin 9, thiazole 7, piperidine 10, pyrrolidine 11, pyrazole 14 and pyridine 12, 13. Starting with 4-(1-(2-(2-cyanoacetyl)hydrazono)ethyl)-N-ethyl-N-methylbenzenesulfonamide (2), which was prepared from condensation of acetophenone derivative 1 with 2-cyanoacetohydrazide. The structures of the newly synthesized compounds were confirmed by elemental analysis, IR, ¹H NMR, ¹³C NMR, ¹⁹F NMR and MS spectral data. All the newly synthesized heterocyclic sulfonamides were evaluated as in-vitro anti-breast cancer cell line (MCF7) and as in-vitro antimicrobial agents. Compounds 8, 5 and 11 were more active than MTX reference drug and compounds 12, 7, 4, 14, 5 and 8 were highly potent against Klebsiella pneumonia. Molecular operating environment performed virtual screening using molecular docking studies of the synthesized compounds. The results indicated that some prepared compounds are suitable inhibitor against dihydrofolate reductase (DHFR) enzyme (PDBSD:4DFR) with further modification.     

A mitochondrial protein homologous to the mammalian peripheral-type benzodiazepine receptor is essential for stress adaptation in plants

The cloning of abiotic stress-inducible genes from the moss Physcomitrella patens led to the identification of the gene PpTSPO1, encoding a protein homologous to the mammalian mitochondrial peripheral-type benzodiazepine receptor and the bacterial tryptophane-rich sensory protein. This class of proteins is involved in the transport of intermediates of the tetrapyrrole biosynthesis pathway. Like the mammalian homologue, the PpTSPO1 protein is localized to mitochondria. The generation of PpTSPO1-targeted moss knock-out lines revealed an essential function of the gene in abiotic stress adaptation. Under stress conditions, the PpTSPO1 null mutants show elevated H(2)O(2) levels, enhanced lipid peroxidation and cell death, indicating an important role of PpTSPO1 in redox homeostasis. We hypothesize that PpTSPO1 acts to direct porphyrin precursors to the mitochondria for heme formation, and is involved in the removal of photoreactive tetrapyrrole intermediates.     

Vitamin D status and vitamin D receptor gene polymorphism in Saudi children with acute lower respiratory tract infection

Molecular Biology Reports - There is a significant association exists between vitamin D deficiencies, low respiratory tract infections, and certain types of VDR gene polymorphism. Various studies...     

Electricity generation from real industrial wastewater using a single-chamber air cathode microbial fuel cell with an activated carbon anode

This study introduces activated carbon (AC) as an effective anode for microbial fuel cells (MFCs) using real industrial wastewater without treatment or addition of external microorganism mediators. Inexpensive activated carbon is introduced as a proper electrode alternative to carbon cloth and carbon paper materials, which are considered too expensive for the large-scale application of MFCs. AC has a porous interconnected structure with a high bio-available surface area. The large surface area, in addition to the high macro porosity, facilitates the high performance by reducing electron transfer resistance. Extensive characterization, including surface morphology, material chemistry, surface area, mechanical strength and biofilm adhesion, was conducted to confirm the effectiveness of the AC material as an anode in MFCs. The electrochemical performance of AC was also compared to other anodes, i.e., Teflon-treated carbon cloth (CCT), Teflon-treated carbon paper (CPT), untreated carbon cloth (CC) and untreated carbon paper (CP). Initial tests of a single air-cathode MFC display a current density of 1792 mAm⁻², which is approximately four times greater than the maximum value of the other anode materials. COD analyses and Coulombic efficiency (CE) measurements for AC-MFC show the greatest removal of organic compounds and the highest CE efficiency (60 and 71%, respectively). Overall, this study shows a new economical technique for power generation from real industrial wastewater with no treatment and using inexpensive electrode materials.