Hydroxyethylene isosteres of selective neuronal nitric oxide synthase inhibitors

Nitric oxide (NO) is an important second messenger molecule for blood pressure homeostasis, as a neurotransmitter, and in the immune defense system. Excessive NO can lead to neurodegeneration and connective tissue damage. Three different isozymes of the enzyme nitric oxide synthase regulate NO production in endothelial (eNOS), neuronal (nNOS), and macrophage (iNOS) cells. Whereas creating a lower level of NO in some cells could be beneficial, it also could be detrimental to the protective effects that NO has on other cells. Therefore, it is essential that therapeutic NOS inhibitors be made that are subtype selective. Previously, we reported a series of nitroarginine-containing dipeptide amides as potent and selective nNOS inhibitors. Here we synthesize peptidomimetic hydroxyethylene isosteres of these dipeptide amides for potential increased bioavailability. None of the compounds is as potent or selective as the dipeptide amides, but they exhibit good inhibition and selectivity. When the terminal amino group was converted to a hydroxyl group, potency and selectivity greatly diminished, supporting the importance of the terminal amino group for binding.     

Serum and hair levels of zinc, selenium, iron, and copper in children with iron-deficiency anemia

In the present study, the serum and hair levels of zinc, selenium, and copper were determined in children with iron-deficiency anemia (IDA). A total of 52 anemic children aged 1–4 yr constituted the study group. Fortysix healthy children acted as controls. The copper and zinc levels were measured with an atomic absorption spectrophometer. Serum and hair selenium was determined by a spectroflourometric method. The serum zinc and selenium concentrations in the IDA group were found to be significantly lower and serum copper significantly higher than those in the controls (p<0.05). Lower iron, zinc, and selenium concentrations (p<0.001) but not copper were found in hair (p>0.05).     

Quantification of diapausing fourth generation and suicidal fifth generation cotton bollworm, Helicoverpa armigera, in cotton and corn in northern China

Cotton bollworm, Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae), is a major pest of cotton and corn crops in northern China. A phenological differentiation between fourth generation cotton bollworms from cotton and those from corn fields was observed in northern China during 1999–2000. The proportion of pupation in late fall was marginally higher in cotton fields compared to that in corn fields; however, the proportions of fall emergence of moths from cotton fields were significantly higher than those from corn fields. The proportion of spring emergence of moths was also significantly higher for larvae collected from cotton (28.0%) than from corn (14.5%). The overwintering duration of females was significantly shorter than that of males in both crops. Moreover, the overwintering duration of bollworm populations from cotton was significantly longer than that from corn. The early spring population of H. armigera came from both cotton and corn fields, but the spring emergence of moths from larvae collected from cotton took about 5 days longer to reach 100% emergence compared to that from corn.     

A comprehensive characterization study of human bone marrow mscs with an emphasis on molecular and ultrastructural properties

Human bone marrow-derived mesenchymal stem cells (hBM-MSCs) continue to draw attention of researchers in the fields of basic science and medicine due to their indispensible regenerative, reparative, angiogenic, anti-apoptotic, and immunosuppressive properties, all of which collectively point out their enormous therapeutic potential. There is still, however, a need for further investigation of their characteristics to broaden their field of use and learn much more about how to control their fate and improve their therapeutic effectiveness. hBM-MSCs were extensively characterized in terms of their growth characteristics, genetic stability, and differentiation capability to the mesodermal and ectodermal cell lineages; a special emphasis was given to their phenotypic and ultrastructural properties. Expression of embryonic stem cell markers Oct4, Rex-1, FoxD-3, Sox2, and Nanog was shown with real-time PCR. Transmission electron microscopy revealed the ultrastructural characteristics of hBM-MSCs; they had pale, irregularly shaped and large euchromatic nuclei, and two distinct areas in their cytoplasm: an intensely stained inner zone rich in mitochondria and rough endoplasmic reticulum (rER) with dilated cisternae and a relatively peripheral zone poor in organelles. hBM-MSCs expressed adipogenic (adipophilin and PPARγ), myogenic (desmin, myogenin, α-SMA), neurogenic (γ-enolase, MAP2a,b, c-fos, nestin, NF-H, NF-L, GFAP, β3-tubulin), osteogenic (osteonectin, osteocalcin, osteopontin, Runx-2, type I collagen), and chondrogenic (type II collagen, SOX9) markers either at RNA or protein level even under basal conditions, without any stimulation towards differentiation. The differentiation potential of hBM-MSCs to adipogenic, osteogenic, and neurogenic lineages was shown by using the relevant differentiation factors.     

Cycloartane glycosides from Astragalus aureus

Eight cycloartane-type triterpene glycosides (1-8) were isolated from Astragalus aureus Willd along with ten known cycloartane-type glycosides (9-18). Their structures were established by the extensive use of 1D and 2D-NMR experiments along with ESIMS and HRMS analyses. Compounds 1-5 are cyclocanthogenin glycosides, whereas compounds 6-8 are based on cyclocephalogenin as aglycon, more unusual in the plant kingdom, so far reported only from Astragalus spp. Moreover, for the first time monoglycosides of cyclocanthogenin (5) and cyclocephalogenin (7, 8) are reported. All of the compounds tested for their cytotoxic activities against a number of cancer cell lines. Among the compounds, only 8 exhibited activity versus human breast cancer (MCF7) at 45 μM concentration.     

Deterioration of Bone Quality by Streptozotocin (STZ)-Induced Type 2 Diabetes Mellitus in Rats

Patients with diabetes mellitus (DM) have various skeletal disorders and bone quality can be impaired in DM leading to fractures. Wistar albino male rats (270?C300?g; n?=?16) were assigned randomly to nondiabetic and diabetic rats (single dose intravenous injection of 45?mg/kg streptozotocin). All rats in each group were perpetuated for 8?weeks, and blood glucose levels as well as body weights were measured once weekly. Biomechanical measurements were performed at the mid-diaphysis of the left femur with tensile test. Extrinsic and intrinsic properties were measured or calculated. Bone mineral density (BMD) was also evaluated and measured by dual-energy X-ray absorptiometry. Cross-sectional area of the femoral shaft was evaluated by computerized tomography. Blood glucose levels in diabetic rats were significantly increased compared to that of the nondiabetic rats, while the body and femur weights were decreased (P?<?0.05). In respect to the BMD, cross-sectional area and femur length, there were no statistically significant differences between the nondiabetic and diabetic rats (P?>?0.05). The maximum load, ultimate stress, and toughness endpoints in diabetic rats were significantly decreased compared to that of the nondiabetics (P?<?0.05). There were no statistically significant differences between the nondiabetic and diabetic rats with regard to the displacement and stiffness (P?>?0.05). Femurs of diabetic rats had less absorbed energy than that in nondiabetics (P?<?0.05). Ultimate strain was lower in diabetic rats than that in nondiabetics, while the elastic modulus was higher (P?>?0.05). The bone quality of rats is decreased by streptozotocin-induced type 2 diabetes mellitus.     

The protective effect of quercetin in the alcohol-induced liver and lymphoid tissue injuries in newborns

Molecular Biology Reports - Recently published experimental and clinical studies indicate that oxidative stress leads to the pathogenesis and progression of alcohol-induced tissue injuries....     

Adipose tissue-derived mesenchymal stromal cells efficiently differentiate into insulin-producing cells in pancreatic islet microenvironment both in vitro and in vivo

Background aimsDifferentiation or reprogramming of stem cells could be achieved by remodulating the microenvironment, which regulates the fate of cells by soluble factors and contacts. By providing an in vivo-like microenvironment, directional and functional differentiation of stem cells could be achieved in vitro. In this study, the differentiation of mesenchymal stromal cells (MSCs) derived from rat tissues (adipose, rAT; bone marrow, rBM) were analyzed by in vitro and in vivo co-culture experiments. The insulin-producing capacities of islets transplanted under the renal kidney capsule with rAT- and rBM-MSCs were compared and the reduction of hyperglycemia symptoms in rat models was examined.MethodsMSCs prelabeled with green fluorescence protein were co-cultured with islets directly. The insulin production of cells was determined by immunostaining and ELISA. Streptozotocin-induced diabetic rat models were created and MSCs were co-transplanted with the islets under the kidney capsule to confirm the in vitro results.ResultsMSCs were differentiated into insulin-producing cells after 38 days of co-culture, confirmed by insulin and C-peptide stainings. In vivo functional studies revealed that the co-culture of islets with MSCs provided higher differentiation efficiency. The weight gain measurement and glucose tolerance test in the rat group co-transplanted of rAT-MSCs and islets indicate a better recovery than islet-alone transplants and co-transplants of islets and rBM-MSCs.ConclusionsrAT-MSCs could be considered as the cell of choice for cell-based treatment of type 1 diabetes. Because the co-transplantation of islets with MSCs increases the number of insulin-producing cells, this method was suggested for clinical applications.