Phenotypic switching of vascular smooth muscle cells in atherosclerosis,hypertension, and aortic dissection

Vascular smooth muscle cells (VSMCs) play a critical role in regulating vasotone, and their phenotypic plasticity is a key contributor to the pathogenesis of various vascular diseases. Two main VSMC phenotypes have been well described: contractile and synthetic. Contractile VSMCs are typically found in the tunica media of the vessel wall, and are responsible for regulating vascular tone and diameter. Synthetic VSMCs, on the other hand, are typically found in the tunica intima and adventitia, and are involved in vascular repair and remodeling. Switching between contractile and synthetic phenotypes occurs in response to various insults and stimuli, such as injury or inflammation, and this allows VSMCs to adapt to changing environmental cues and regulate vascular tone, growth, and repair. Furthermore, VSMCs can also switch to osteoblast-like and chondrocyte-like cell phenotypes, which may contribute to vascular calcification and other pathological processes like the formation of atherosclerotic plaques. This provides discusses the mechanisms that regulate VSMC phenotypic switching and its role in the development of vascular diseases. A better understanding of these processes is essential for the development of effective diagnostic and therapeutic strategies.     

Nox4-derived reactive oxygen species mediate cardiomyocyte injury in early type 1 diabetes

Oxidative stress contributes to diabetic cardiomyopathy. This study explored the role of the NADPH oxidase Nox4 as a source of reactive oxygen species (ROS) involved in the development of diabetic cardiomyopathy. Phosphorothioated antisense (AS) or sense (S) oligonucleotides for Nox4 were administered for 2 wk to rats made diabetic by streptozotocin. NADPH oxidase activity, ROS generation, and the expression of Nox4, but Nox1 or Nox2, were increased in left ventricular tissue of the diabetic rats. Expression of molecular markers of hypertrophy and myofibrosis including fibronectin, collagen, α-smooth muscle actin, and β-myosin heavy chain were also increased. These parameters were attenuated by the administration of AS but not S Nox4. Moreover, the impairment of contractility observed in diabetic rats was prevented in AS- but not S-treated animals. Exposure of cultured cardiac myocytes to 25 mM glucose [high glucose (HG)] increased NADPH oxidase activity, the expression of Nox4, and molecular markers of cardiac injury. These effects of HG were prevented in cells infected with adenoviral vector containing a dominant negative form of Nox4. This study provides strong evidence that Nox4 is an important source of ROS in the left ventricle and that Nox4-derived ROS contribute to cardiomyopathy at early stages of type 1 diabetes.     

Seasonal courses of nutrients and heavy metals in water,sediment and above- and below-ground Typha domingensis biomass in Lake Burullus (Egypt): Perspectives for phytoremediation

The present study was carried out in natural stands of Typha domingensis in Lake Burullus, Egypt, to investigate (1) nutrient dynamics and heavy metals accumulation in its organs, (2) the phytoextractive potential of its organs and (3) the amount of nutrients and heavy metals released back into the water after decomposition of the dead tissues. Nitrogen concentrations were higher in the shoot than in the root and rhizome, while P, Ca, Cu, Fe, Zn and ash concentrations were higher in the root than in the rhizome and shoot. Significant differences in the concentrations of Mg, Cd, Cu and ash were assessed during the growing season of T. domingensis. The content of most nutrients and heavy metals in the shoot increased rapidly during the early growing season in February, reached maximal values in July and then decreased again. The nutrient and heavy metal contents in the below-ground portion of the plant showed an opposite trend compared to the shoot; they decreased sharply during the spring, when they were translocated, supporting the heterotrophic phase of shoot growth. However, they increased slightly from July to September and then decreased again. The transfer factors of all nutrients and heavy metals from the sediment to the below-ground organs were greater than unity. The higher translocation ratio of N in T. domingensis shoots makes it suitable for N phytoextraction from water and sediment, while the lower translocation ratios for Cd, Cu, Fe, Pb and Zn make it suitable for metal ion phytostabilisation. The dead shoot biomass of the stands at the end of 2010 amounted to 1950 g DM m⁻², when the seasonal decomposition process began. With a decay rate of 0.0049 day⁻¹, 1624 g DM m⁻² is decomposed in the lake in a year. This is equivalent to releasing the following nutrient and heavy metals into the surrounding water (in g m⁻²): 23.4 N, 0.8 P, 19.2 Ca, 1.8 Mg, 5.6 Na, 32.8 K, 0.01 Cd, 0.01 Cu, 0.84 Fe, 0.12 Pb and 0.03 Zn.     

Functionalization of cellulose-containing fabrics by plasma and subsequent metal salt treatments

In order to upgrade the UV-protection and antibacterial functional properties of cotton/polyester (80/20), cotton/linen (50/50) and linen/viscose-polyester (50/50) fabric blends, they were treated with different plasma gases (oxygen, air, and argon) followed by subsequent treatment with certain metal salts namely Zn-acetate, Cu-acetate, Al-chloride, and Zr-oxychloride. The obtained results show that the type of plasma gas, the kind of metal salt as well as the nature of the treated substrate play an important role in the extent of enhancing the demanded functional properties. Oxygen plasma treatment followed by Cu-acetate or Zn-acetate treatment gives the best UV-protection or antibacterial activity respectively, keeping other parameters constant. The surface morphology of some untreated and plasma-treated samples was also analyzed by SEM.     

14-3-3 Protects against stress-induced apoptosis

Expression of human Bax, a cardinal regulator of mitochondrial membrane permeabilization, causes death in yeast. We screened a human cDNA library for suppressors of Bax-mediated yeast death and identified human 14-3-3β/α, a protein whose paralogs have numerous chaperone-like functions. Here, we show that, yeast cells expressing human 14-3-3β/α are able to complement deletion of the endogenous yeast 14-3-3 and confer resistance to a variety of different stresses including cadmium and cycloheximide. The expression of 14-3-3β/α also conferred resistance to death induced by the target of rapamycin inhibitor rapamycin and by starvation for the amino acid leucine, conditions that induce autophagy. Cell death in response to these autophagic stimuli was also observed in the macroautophagic-deficient atg1Δ and atg7Δ mutants. Furthermore, 14-3-3β/α retained its ability to protect against the autophagic stimuli in these autophagic-deficient mutants arguing against so called ‘autophagic death''. In line, analysis of cell death markers including the accumulation of reactive oxygen species, membrane integrity and cell surface exposure of phosphatidylserine indicated that 14-3-3β/α serves as a specific inhibitor of apoptosis. Finally, we demonstrate functional conservation of these phenotypes using the yeast homolog of 14-3-3: Bmh1. In sum, cell death in response to multiple stresses can be counteracted by 14-3-3 proteins.     

Effects of catecholamines on ovary morphology, blood concentrations of estradiol-17beta, progesterone, zinc, triglycerides and rate of ovulation in domestic hens

The present study is an attempt to shed more light on the role of epinephrine (EP) and norepinephrine (NE) in regulating ovarian follicular development, folliculogenesis and ovulation in laying hens. Sixty Egyptian local cross females (Mandarah), 50 weeks old, were individually housed and equally divided into three treatments: control (saline, 0.9% NaCl), EP (0.15 mg epinephrine/hen/day) and NE (0.75 mg norepinephrine/hen/day) (n=20). Animals were injected intramuscularly once a day for 15 successive days. At the end of the experimental period, 10 females from each treatment were randomly chosen, weighed and killed by decapitation. Ovaries and oviducts and ovarian follicles were examined. Plasma concentrations of estradiol-17beta, progesterone, zinc and triglyceride were determined. Results indicated that the ovaries of NE- and EP-treated hens were more developed than those of control hens being heavier and containing more yellow yolk-filled follicles. EP or NE significantly increased the ovulation rate and plasma concentrations of estradiol-17beta, progesterone, zinc and triglyceride compared with control treatment. It could be concluded that catecholamines may have a part in promoting ovarian follicular development and in stimulating ovulation in laying hens at the end of their reproductive lives.     

Novel pre-treatment processes to promote linen-containing fabrics properties

This study was undertaken to investigate the effect of plasma pre-treatment, followed by enzymatic treatment in the absence and presence of bleaching agent on the properties of linen and linen-containing fabrics. Different plasma gases (air, oxygen and nitrogen), enzymes (acid-cellulases, neutral-cellulase and alkaline-pectinase) as well as bleaching agents (peracetic acid and H₂O₂) were used. The changes in physico-mechanical properties, surface morphology and dyeing properties of the treated substrates have been investigated. The obtained results indicated that plasma pre-treatment followed by subsequent acid-cellulases/peracetic acid or alkaline-pectinase/H₂O₂ treatment result in: a dramatic improvement in hydrophilicity and wettability as well as in the degree of whiteness of the treated substrates, an improvement in reduction of surface roughness and extent of post-reactive dyeing, along with a weight loss and a drop in the tensile strength. The extent of surface modification as well as the changes in the above-mentioned properties are governed by the characteristics of the substrate, the plasma gas, the nature and dose of the used enzyme, as well as the type of bleaching agent and additive. The optimal treatment sequence for attaining better performance properties was O₂-plasma followed by alkaline-pectinase/H₂O₂ treatment in presence of PEG 400.     

Nox4 NAD(P)H oxidase mediates Src-dependent tyrosine phosphorylation of PDK-1 in response to angiotensin II: role in mesangial cell hypertrophy and fibronectin expression

Activation of glomerular mesangial cells (MCs) by angiotensin II (Ang II) leads to hypertrophy and extracellular matrix accumulation. Here, we demonstrate that, in MCs, Ang II induces an increase in PDK-1 (3-phosphoinositide-dependent protein kinase-1) kinase activity that required its phosphorylation on tyrosine 9 and 373/376. Introduction into the cells of PDK-1, mutated on these tyrosine residues or kinase-inactive, attenuates Ang II-induced hypertrophy and fibronectin accumulation. Ang II-mediated PDK-1 activation and tyrosine phosphorylation (total and on residues 9 and 373/376) are inhibited in cells transfected with small interfering RNA for Src, indicating that Src is upstream of PDK-1. In cells expressing oxidation-resistant Src mutant C487A, Ang II-induced hypertrophy and fibronectin expression are prevented, suggesting that the pathway is redox-sensitive. Ang II also up-regulates Nox4 protein, and siNox4 abrogates the Ang II-induced increase in intracellular reactive oxygen species (ROS) generation. Small interfering RNA for Nox4 also inhibits Ang II-induced activation of Src and PDK-1 tyrosine phosphorylation (total and on residues 9 and 373/376), demonstrating that Nox4 functions upstream of Src and PDK-1. Importantly, inhibition of Nox4, Src, or PDK-1 prevents the stimulatory effect of Ang II on fibronectin accumulation and cell hypertrophy. This work provides the first evidence that Nox4-derived ROS are responsible for Ang II-induced PDK-1 tyrosine phosphorylation and activation through stimulation of Src. Importantly, this pathway contributes to Ang II-induced MC hypertrophy and fibronectin accumulation. These data shed light on molecular processes underlying the oxidative signaling cascade engaged by Ang II and identify potential targets for intervention to prevent renal hypertrophy and fibrosis.     

Immunopathological Changes in the Brain of Immunosuppressed Mice Experimentally Infected with Toxocara canis

Toxocariasis is a soil-transmitted helminthozoonosis due to infection of humans by larvae of Toxocara canis. The disease could produce cognitive and behavioral disturbances especially in children. Meanwhile, in our modern era, the incidence of immunosuppression has been progressively increasing due to increased incidence of malignancy as well as increased use of immunosuppressive agents. The present study aimed at comparing some of the pathological and immunological alterations in the brain of normal and immunosuppressed mice experimentally infected with T. canis. Therefore, 180 Swiss albino mice were divided into 4 groups including normal (control) group, immunocompetent T. canis-infected group, immunosuppressed group (control), and immunosuppressed infected group. Infected mice were subjected to larval counts in the brain, and the brains from all mice were assessed for histopathological changes, astrogliosis, and IL-5 mRNA expression levels in brain tissues. The results showed that under immunosuppression, there were significant increase in brain larval counts, significant enhancement of reactive gliosis, and significant reduction in IL-5 mRNA expression. All these changes were maximal in the chronic stage of infection. In conclusion, the immunopathological alterations in the brains of infected animals were progressive over time, and were exaggerated under the effect of immunosuppression as did the intensity of cerebral infection.     

Decorin Core Protein (Decoron) Shape Complements Collagen Fibril Surface Structure and Mediates Its Binding

Decorin is the archetypal small leucine rich repeat proteoglycan of the vertebrate extracellular matrix (ECM). With its glycosaminoglycuronan chain, it is responsible for stabilizing inter-fibrillar organization. Type I collagen is the predominant member of the fibrillar collagen family, fulfilling both organizational and structural roles in animal ECMs. In this study, interactions between decoron (the decorin core protein) and binding sites in the d and e₁ bands of the type I collagen fibril were investigated through molecular modeling of their respective X-ray diffraction structures. Previously, it was proposed that a model-based, highly curved concave decoron interacts with a single collagen molecule, which would form extensive van der Waals contacts and give rise to strong non-specific binding. However, the large well-ordered aggregate that is the collagen fibril places significant restraints on modes of ligand binding and necessitates multi-collagen molecular contacts. We present here a relatively high-resolution model of the decoron-fibril collagen complex. We find that the respective crystal structures complement each other well, although it is the monomeric form of decoron that shows the most appropriate shape complementarity with the fibril surface and favorable calculated energies of interaction. One molecule of decoron interacts with four to six collagen molecules, and the binding specificity relies on a large number of hydrogen bonds and electrostatic interactions, primarily with the collagen motifs KXGDRGE and AKGDRGE (d and e₁ bands). This work helps us to understand collagen-decorin interactions and the molecular architecture of the fibrillar ECM in health and disease.