Bovine serum albumin/gold nanoparticles as a drug delivery system for Curcumin: experimental and computational studies

Abstract

Communicated by Ramaswamy H. Sarma     

Protein partners in the life history of activated fibroblast growth factor receptors

Fibroblast growth factor receptors (FGFRs) are a family of four transmembrane (TM) receptor tyrosine kinases (RTKs) which bind to a large family of fibroblast growth factor (FGF) ligands with varying affinity and specificity. FGFR signaling regulates many physiological and pathological processes in development and tissue homeostasis. Understanding FGFR signaling processes requires the identification of partner proteins which regulate receptor function and biological outputs. In this study, we employ an epitope-tagged, covalently dimerized, and constitutively activated form of FGFR1 to identify potential protein partners by MS. By this approach, we sample candidate FGFR effectors throughout the life history of the receptor. Functional classification of the partners identified revealed specific subclasses involved in protein biosynthesis and folding; structural and regulatory components of the cytoskeleton; known signaling effectors and small GTPases implicated in endocytosis and vesicular trafficking. The kinase dependency of the interaction was determined for a subset of previously unrecognized partners by coimmunoprecipitation, Western blotting, and immunocytochemistry. From this group, the small GTPase Rab5 was selected for functional interrogation. We show that short hairpin (sh) RNA-mediated depletion of Rab5 attenuates the activation of the extracellular-regulated kinase (ERK) 1/2 pathway by FGFR signaling. The strategic approach adopted in this study has revealed bona fide novel effectors of the FGFR signaling pathway.     

Positive correlation between vitamin D receptor gene TaqI variant and gastric cancer predisposition in a sample of Iranian population

Gastric cancer is the second cause of cancer-related mortality and the fourth most common cancers worldwide. Owing to the immune modulatory effect of vitamin D in the body, the role of vitamin D receptor gene in vitamin D regulation receives a great deal of research interest. The aim of the current study was to highlight the association between two variants of TaqI and FokI in the vitamin D receptor gene and gastric cancer predisposition in a sample of South Khorasan population. The present investigation consisted of 69 patients affected with gastric cancer and 100 healthy individuals. The genomic DNA was extracted by salting out the protocol from peripheral venous blood. Genotyping of TaqI and FokI variants were performed by PCR-RFLP method. Our findings manifested that TC genotype of TaqI polymorphism was statistically significant between the case and the control groups (p = 0.002). Moreover, the frequency of TC + CC genotypes was statistically significant between the two groups (p = 0.009). Furthermore, we could not find any meaningful association between FokI variant and the participant groups. The present results declared that, in our population, TC genotype of TaqI polymorphism has an association with gastric cancer susceptibility. In addition, more investigation with greater sample sizes is needed to confirm our results.     

Evaluation of the neuroprotective effects of electromagnetic fields and coenzyme Q10 on hippocampal injury in mouse

Electromagnetic fields (EMFs) are reported to interfere with chemical reactions involving free radical production. Coenzyme Q₁₀ (CoQ10) is a strong antioxidant with some neuroprotective activities. The purpose of this study was to examine and compare the neuroprotective effects of EMF and CoQ10 in a mouse model of hippocampal injury. Hippocampal injury was induced in mature female mice (25–30 g), using an intraperitoneal injection of trimethyltin hydroxide (TMT; 2.5 mg/kg). The experimental groups were exposed to EMF at a frequency of 50 Hz and intensity of 5.9 mT for 7 hr daily over 1 week or treated with CoQ10 (10 mg/kg) for 2 weeks following TMT injection. A Morris water maze apparatus was used to assess learning and spatial memory. Nissl staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) tests were also performed for the histopathological analysis of the hippocampus. Antiapoptotic genes were studied, using the Western blot technique. The water maze test showed memory improvement following treatment with CoQ10 and coadministration of CoQ10 + EMF. The Nissl staining and TUNEL tests indicated a decline in necrotic and apoptotic cell count following treatment with CoQ10 and coadministration of CoQ10 + EMF. The Western blot study indicated the upregulation of antiapoptotic genes in treatment with CoQ10, as well as coadministration. Also, treatment with EMF had no significant effects on reducing damage induced by TMT in the hippocampus. According to the results, EMF had no significant neuroprotective effects in comparison with CoQ10 on hippocampal injury in mice. Nevertheless, coadministration of EMF and CoQ10 could improve the neuroprotective effects of CoQ10.     

Src kinase modulates the activation, transport and signalling dynamics of fibroblast growth factor receptors

The non-receptor tyrosine kinase Src is recruited to activated fibroblast growth factor receptor (FGFR) complexes through the adaptor protein factor receptor substrate 2 (FRS2). Here, we show that Src kinase activity has a crucial role in the regulation of FGFR1 signalling dynamics. Following receptor activation by ligand binding, activated Src is colocalized with activated FGFR1 at the plasma membrane. This localization requires both active Src and FGFR1 kinases, which are inter-dependent. Internalization of activated FGFR1 is associated with release from complexes containing activated Src. Src-mediated transport and subsequent activation of FGFR1 require both RhoB endosomes and an intact actin cytoskeleton. Chemical and genetic inhibition studies showed strikingly different requirements for Src family kinases in FGFR1-mediated signalling; activation of the phosphoinositide-3 kinase-Akt pathway is severely attenuated, whereas activation of the extracellular signal-regulated kinase pathway is delayed in its initial phase and fails to attenuate.     

Length scale parameter of single trabecula in cancellous bone

Biomechanics and Modeling in Mechanobiology - In this paper, the material length scale parameter of the modified couple stress theory for trabecular bones is studied. For this reason, experimental...