Stereological and histopathological assessment of intrauterine growth restriction placenta from Saudi women

BackgroundPlacental insufficiency causes fetal adaptation, leading to fetal programming of chronic diseases. Placentas with intrauterine growth restriction (IUGR) are smaller than average and may contribute to low birth weight of the newborn. The number of patients with IUGR in the Saudi population is increasing; however, little is known about their placentas. The aim of this study was to assess morphometric and histopathological placental changes in Saudi patients with IUGR.MethodsOverall, 20 healthy pregnant Saudi women (control group) and 20 pregnant Saudi women with IUGR were enrolled. Maternal and fetal morphometric measurements were recorded. The placentas from both groups were processed for histopathological examination using stereological techniques.ResultsThe IUGR group had lower placental weight, volume, length, breadth, and surface area than the control group. The total volume of villi and surface area of the terminal villi were significantly reduced in the IUGR placentas. IUGR group had a reduction in birth weight; length; and circumference of the head, chest, abdomen, and thigh compared to control group.ConclusionThe reduction in placental mass, specifically the reduction in the volume and surface area of villi, the functional units, may have reduced the capacity for nutrient transport. This led to a significant reduction in neonatal measurements. The fetus rearranged nutrient distribution in favor of the brain and other essential organs; however, at the expense of thigh development and growth. This fetal trade-off strategy increases the risk of developing chronic diseases in adulthood. Therefore, IUGR infants may require more clinical attention.     

Modeling the adaptive immune response in HBV infection

The aim of this work is to investigate a new mathematical model that describes the interactions between Hepatitis B virus (HBV), liver cells (hepatocytes), and the adaptive immune response. The qualitative analysis of this as cytotoxic T lymphocytes (CTL) cells and the antibodies. These outcomes are (1) a disease free steady state, which its local stability is characterized as usual by R ₀ < 1, (2) and the existence of four endemic steady states when R ₀ > 1. The local stability of these steady states depends on functions of R ₀. Our study shows that although we give conditions of stability of these steady states, not all conditions are feasible. This rules out the local stability of two steady states. The conditions of stability of the two other steady states (which represent the complete failure of the adaptive immunity and the persistence of the disease) are formulated based on the domination of CTL cells response or the antibody response.     

Propofol directly increases tau phosphorylation

In Alzheimer's disease (AD) and other tauopathies, the microtubule-associated protein tau can undergo aberrant hyperphosphorylation potentially leading to the development of neurofibrillary pathology. Anesthetics have been previously shown to induce tau hyperphosphorylation through a mechanism involving hypothermia-induced inhibition of protein phosphatase 2A (PP2A) activity. However, the effects of propofol, a common clinically used intravenous anesthetic, on tau phosphorylation under normothermic conditions are unknown. We investigated the effects of a general anesthetic dose of propofol on levels of phosphorylated tau in the mouse hippocampus and cortex under normothermic conditions. Thirty min following the administration of propofol 250 mg/kg i.p., significant increases in tau phosphorylation were observed at the AT8, CP13, and PHF-1 phosphoepitopes in the hippocampus, as well as at AT8, PHF-1, MC6, pS262, and pS422 epitopes in the cortex. However, we did not detect somatodendritic relocalization of tau. In both brain regions, tau hyperphosphorylation persisted at the AT8 epitope 2 h following propofol, although the sedative effects of the drug were no longer evident at this time point. By 6 h following propofol, levels of phosphorylated tau at AT8 returned to control levels. An initial decrease in the activity and expression of PP2A were observed, suggesting that PP2A inhibition is at least partly responsible for the hyperphosphorylation of tau at multiple sites following 30 min of propofol exposure. We also examined tau phosphorylation in SH-SY5Y cells transfected to overexpress human tau. A 1 h exposure to a clinically relevant concentration of propofol in vitro was also associated with tau hyperphosphorylation. These findings suggest that propofol increases tau phosphorylation both in vivo and in vitro under normothermic conditions, and further studies are warranted to determine the impact of this anesthetic on the acceleration of neurofibrillary pathology.     

Chronic morphine alters the presynaptic protein profile: identification of novel molecular targets using proteomics and network analysis

Opiates produce significant and persistent changes in synaptic transmission; knowledge of the proteins involved in these changes may help to understand the molecular mechanisms underlying opiate dependence. Using an integrated quantitative proteomics and systems biology approach, we explored changes in the presynaptic protein profile following a paradigm of chronic morphine administration that leads to the development of dependence. For this, we isolated presynaptic fractions from the striata of rats treated with saline or escalating doses of morphine, and analyzed the proteins in these fractions using differential isotopic labeling. We identified 30 proteins that were significantly altered by morphine and integrated them into a protein-protein interaction (PPI) network representing potential morphine-regulated protein complexes. Graph theory-based analysis of this network revealed clusters of densely connected and functionally related morphine-regulated clusters of proteins. One of the clusters contained molecular chaperones thought to be involved in regulation of neurotransmission. Within this cluster, cysteine-string protein (CSP) and the heat shock protein Hsc70 were downregulated by morphine. Interestingly, Hsp90, a heat shock protein that normally interacts with CSP and Hsc70, was upregulated by morphine. Moreover, treatment with the selective Hsp90 inhibitor, geldanamycin, decreased the somatic signs of naloxone-precipitated morphine withdrawal, suggesting that Hsp90 upregulation at the presynapse plays a role in the expression of morphine dependence. Thus, integration of proteomics, network analysis, and behavioral studies has provided a greater understanding of morphine-induced alterations in synaptic composition, and identified a potential novel therapeutic target for opiate dependence.     

Organic acids associated with saccharification of cellulosic wastes during solid-state fermentation

Saccharification of five cellulosic wastes, i.e. rice husks, wheat bran, corn cobs, wheat straw and rice straw by three cellulytic fungi, i.e. Aspergillus glaums MN1, Aspergillus oryzae MN2 and Penicillium purpurogenum MN3, during solid-state fermentation (SSF) was laboratory studied. Rice husks, wheat bran, and corn cobs were selected as inducers of glucose production in the tested fungi. An incubation interval of 10 days was optimal for glucose production. Maximal activities of the cellulases FP-ase, CMC-ase, and p-glucosidase were detected during SSF of rice husks by P. purpurogenum; however, a-amylase activity (7.2 U/g) was comparatively reduced. Meanwhile, the productivities of FP-ase, CMC-ase, and β-glucosidase were high during SSF of rice husks by A glaucus; however, they decreased during SSF of corn cobs by P. purpurogenum. Addition of rock phosphate (RP) (75 mg P₂O₅) decreased the pH of SSF media. (NH₄)₂SO₄ was found to be less inducer of cellulytic enzymes, during SSF of rice husks by A. glaucus or A. oryzae; it also induced phytase production and solubilization of RP. The organic acids associated with saccharification of the wastes studied have also been investigated. The highest concentration of levulinic acid was detected (46.15 mg/g) during SSF of corn cobs by P. purpurogenum. Likewise, oxalic acid concentration was 43.20 mg/g during SSF of rice husks by P. purpurogenum.     

Optimization of β-Glucosidase Production by Aspergillus terreus Strain EMOO 6-4 Using Response Surface Methodology Under Solid-State Fermentation

Forty-two morphologically different fungal strains were isolated from different soil samples and agricultural wastes and screened for β-glucosidase activity under solid-state fermentation. Eight species were chosen as the most active β-glucosidase producers and were subjected to primary morphological identification. β-Glucosidase was highly produced by Aspergillus terreus, which showed the highest activity, and was subjected to full identification using scanning electron microscopy and molecular identification. Initial screening of different variables affecting β-glucosidase production was performed using Plackett-Burman design and the variables with statistically significant effects were identified. The optimal levels of the most significant variables with positive effect and the effect of their mutual interactions on β-glucosidase production were determined using Box-Behnken design. Fifteen variables including temperature, pH, incubation time, inoculum size, moisture content, substrate concentration, NaNO₃, KH₂PO₄, MgSO₄ · 7H₂O, KCl, CaCl₂, yeast extract, FeSO₄ · 7H₂O, Tween 80, and (NH₄)₂SO₄ were screened in 20 experimental runs. Among the 15 variables, NaNO₃, KH₂PO₄ and Tween 80 were found as the most significant factors with positive effect on β-glucosidase production. The Box–Behnken design was used for further optimization of these selected factors for better β-glucosidase production. The maximum β-glucosidase production was 4457.162 U g^?1.     

Application of statistical experimental design for optimization of silver nanoparticles biosynthesis by a nanofactory Streptomyces viridochromogenes

Central composite design was chosen to determine the combined effects of four process variables (AgNO₃ concentration, incubation period, pH level and inoculum size) on the extracellular biosynthesis of silver nanoparticles (AgNPs) by Streptomyces viridochromogenes. Statistical analysis of the results showed that incubation period, initial pH level and inoculum size had significant effects (P<0.05) on the biosynthesis of silver nanoparticles at their individual level. The maximum biosynthesis of silver nanoparticles was achieved at a concentration of 0.5% (v/v) of 1 mM AgNO₃, incubation period of 96 h, initial pH of 9 and inoculum size of 2% (v/v). After optimization, the biosynthesis of silver nanoparticles was improved by approximately 5-fold as compared to that of the unoptimized conditions. The synthetic process of silver nanoparticle generation using the reduction of aqueous Ag+ ion by the culture supernatants of S. viridochromogenes was quite fast, and silver nanoparticles were formed immediately by the addition of AgNO₃ solution (1 mM) to the cell-free supernatant. Initial characterization of silver nanoparticles was performed by visual observation of color change from yellow to intense brown color. UV-visible spectrophotometry for measuring surface plasmon resonance showed a single absorption peak at 400 nm, which confirmed the presence of silver nanoparticles. Fourier Transform Infrared Spectroscopy analysis provided evidence for proteins as possible reducing and capping agents for stabilizing the nanoparticles. Transmission Electron Microscopy revealed the extracellular formation of spherical silver nanoparticles in the size range of 2.15–7.27 nm. Compared to the cell-free supernatant, the biosynthesized AgNPs revealed superior antimicrobial activity against Gram-negative, Gram-positive bacterial strains and Candida albicans.     

β-Catenin Is Required for the Tumorigenic Behavior of Triple-Negative Breast Cancer Cells

Our previous data illustrated that activation of the canonical Wnt signaling pathway was enriched in triple-negative breast cancer and associated with reduced overall survival in all patients. To determine whether Wnt signaling may be a promising therapeutic target for triple-negative breast cancer, we investigated whether β-catenin was necessary for tumorigenic behaviors in vivo and in vitro. β-catenin expression level was significantly reduced in two human triple-negative breast cancer cell lines, MDA-MB-231 and HCC38, using lentiviral delivery of β-catenin-specific small hairpin RNAs (shRNAs). Upon implantation of the cells in the mammary fat pad of immunocompromised mice, we found that β-catenin shRNA HCC38 cells formed markedly smaller tumors than control cells and grew much more slowly. In in vitro assays, β-catenin silencing significantly reduced the percentage of Aldefluor-positive cells, a read-out of the stem-like cell population, as well as the expression of stem cell-related target genes including Bmi-1 and c-Myc. β-catenin-knockdown cells were also significantly impaired in their ability to migrate in wound-filling assays and form anchorage-independent colonies in soft agar. β-catenin-knockdown cells were more sensitive to chemotherapeutic agents doxorubicin and cisplatin. Collectively, these data suggest that β-catenin is required for triple-negative breast cancer development by controlling numerous tumor-associated properties, such as migration, stemness, anchorage-independent growth and chemosensitivity.     

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...