Diacerein modulates TLR4/ NF-κB/IL-1β and TRPC1/CHOP signalling pathways in gentamicin-induced parotid toxicity in rats

The present study aimed to identify the possible protective effect of diacerein (DIA) on gentamicin (GNT)-induced parotid toxicity in rats. DIA was administered in the presence and absence of GNT. Thirty-two Wistar adult male rats were randomly arranged into four groups: control, DIA (50 mg/kg/day), GNT (100 mg/kg) and GNT+DIA groups for 8 days. Parotid oxidative stress parameters, besides inflammatory and apoptotic biomarkers, were evaluated. Salivary flow rate, transient receptor potential canonical 1 (TRCP1), and C/EBP homologous protein (CHOP) in parotid tissue were measured. A parotid histopathological examination and an interleukin-1 beta (IL-1β) immunohistochemical study were also performed. GNT significantly increased parotid oxidative stress, inflammatory, apoptotic and CHOP biomarkers with decreased salivary flow rate and TRCP1 level. A histopathological picture of parotid damage and high IL-1β immunoexpression were detected. DIA significantly normalized the distributed oxidative, inflammatory and apoptotic indicators, CHOP and TRCP1, with a prompt improvement in the histopathological picture and a decrease in IL-1β immunoexpression. These results reported that DIA protects against GNT-induced parotid toxicity via modulation of TLR4/NF-κB/IL-1β and TRPC1/CHOP signalling pathways.     

Role of serine protease inhibitor,ulinastatin, in rat model of hepatic encephalopathy: aquaporin 4 molecular targeting and therapeutic implication

Journal of Physiology and Biochemistry - Hepatic encephalopathy (HE) is a devastating neuropsychiatric presentation of the advanced hepatic insufficiency. It is associated with high morbidity and...     

Synthesis of Acyclo C-Nucleosides OF Phenanthro[9,10-e][1,2,4]Triazino[3,4-c]-[1,2,4] Triazoles,and Their Precursors

ABSTRACT

Reaction of 3-hydrazinophenanthro[9,10-e][1,2,4]triazine (1) with aliphatic and aromatic aldehydes as well as monosaccharides gave the corresponding hydrazones 2a-g. The D-glucose analogue exists in the cyclic pyranosyl structure 5. Acetylation and partial acetylation of the sugar hydrazones were carried out. Cyclization of a number of hydrazones including the partially acetylated sugar hydrazones by thionyl chloride gave regioselectively the respective angular isomer 1-substituted phenanthro[9,10-e][1,2,4]triazino[3,4-c][1,2,4]triazoles 16i-I, and not the linear isomer. The cyclization of 1 with acetic acid, however, gave regioselectively the linear isomer 19. The structural assignments were based on a model study whereby the angular 16a was found to be different from the linear isomer 19a obtained by the condensation of 4,5-diamino-3-methyl-1,2,4-triazole with 9,10-phenanthraquinone. Periodate oxidation of 2d gave 20 whose reaction with 1 gave 21.     

Incidence of antimicrobial resistance among Enterobacteriaceae isolated in Riyadh

The antimicrobial resistance of 1,018 isolates of Enterobacteriaceae isolated from fecal specimens of the urban population of Riyadh, Saudi Arabia, was studied. Resistance to 1 or more of 10 antimicrobial agents was encountered in 50.2% of the isolates. Of the isolates tested,Escherichia coli (0.8%) andKlebsiella species (1.6%) were found resistant to seven antimicrobial agents simultaneously: ampicillin, chloramphenicol, kanamycin, colistin, streptomycin, tetracycline, and carbenicillin. Resistance to nalidixic acid was encountered in only 0.68% of theE. coli isolates. No isolate was found to be resistant to gentamicin. Eighty-six of the resistant strains were tested for their ability to transfer their resistance. Forty percent were able to do so withE. coli K-12.     

Targeting ERK/COX-2 signaling pathway in permethrin-induced testicular toxicity: a possible modulating effect of matrine

Molecular Biology Reports - Permethrin (PER), the prevalent synthetic pyrethroid, was reported to have genotoxic effects along with male reproductive organs impairment. Matrine, the Chinese herb...     

Human Primary Immune Cells Exhibit Distinct Mechanical Properties that Are Modified by Inflammation

T lymphocytes are key modulators of the immune response. Their activation requires cell-cell interaction with different myeloid cell populations of the immune system called antigen-presenting cells (APCs). Although T lymphocytes have recently been shown to respond to mechanical cues, in particular to the stiffness of their environment, little is known about the rigidity of APCs. In this study, single-cell microplate assays were performed to measure the viscoelastic moduli of different human myeloid primary APCs, i.e., monocytes (Ms, storage modulus of 520 +90/−80 Pa), dendritic cells (DCs, 440 +110/−90 Pa), and macrophages (MPHs, 900 +110/−100 Pa). Inflammatory conditions modulated these properties, with storage moduli ranging from 190 Pa to 1450 Pa. The effect of inflammation on the mechanical properties was independent of the induction of expression of commonly used APC maturation markers, making myeloid APC rigidity an additional feature of inflammation. In addition, the rigidity of human T lymphocytes was lower than that of all myeloid cells tested and among the lowest reported (Young’s modulus of 85 ± 5 Pa). Finally, the viscoelastic properties of myeloid cells were dependent on both their filamentous actin content and myosin IIA activity, although the relative contribution of these parameters varied within cell types. These results indicate that T lymphocytes face different cell rigidities when interacting with myeloid APCs in vivo and that this mechanical landscape changes under inflammation.     

Desmin Mutation in the C-Terminal Domain Impairs Traction Force Generation in Myoblasts

The cytoskeleton plays a key role in the ability of cells to both resist mechanical stress and generate force, but the precise involvement of intermediate filaments in these processes remains unclear. We focus here on desmin, a type III intermediate filament, which is specifically expressed in muscle cells and serves as a skeletal muscle differentiation marker. By using several complementary experimental techniques, we have investigated the impact of overexpressing desmin and expressing a mutant desmin on the passive and active mechanical properties of C2C12 myoblasts. We first show that the overexpression of wild-type-desmin increases the overall rigidity of the cells, whereas the expression of a mutated E413K desmin does not. This mutation in the desmin gene is one of those leading to desminopathies, a subgroup of myopathies associated with progressive muscular weakness that are characterized by the presence of desmin aggregates and a disorganization of sarcomeres. We show that the expression of this mutant desmin in C2C12 myoblasts induces desmin network disorganization, desmin aggregate formation, and a small decrease in the number and total length of stress fibers. We finally demonstrate that expression of the E413K mutant desmin also alters the traction forces generation of single myoblasts lacking organized sarcomeres.     

Resources available to individuals and organisations involved with marine turtle research and conservation in the Mediterranean

Abstract

We review some key resources freely or cheaply available to those involved with marine turtle research and conservation in the Mediterranean. These include: Marine Turtle Newsletter, Listservs, bibliographic databases, Mediterranean specific technical manuals, IUCN Marine Turtle Specialist Group publications, internet sources and books.