New indications for dabigatran: A suggestion from a drug use evaluation study

Objective: Dabigatran etexilate is a novel oral anticoagulant with several advantages over warfarin such as no need for routine monitoring and fewer drug interactions. This drug was added to our hospital's formulary in 2012. The objective of this study was to assess the rational drug use of dabigatran at a large teaching hospital. Methods: A prospective cross-sectional study was performed from November to June 2015 at Alzahra teaching hospital, Isfahan, Iran. All patients who received at least one dose of dabigatran were eligible for inclusion. Data were collected on patient demographics, indication, dosing regimen, adverse events, concurrent anticoagulant therapy, and laboratory data (including renal function). Findings: A total of sixty patients were included in our study. The majority of patients (n = 40, 66.7%) was prescribed dabigatran for deep vein thrombosis prophylaxis. Only one patient received dabigatran with appropriate indication, dose, and duration. Thirty-six (60%) of our patients had thrombocytopenia at the time of dabigatran initiation. We also detected that ten patients (16.7%) received this drug for heparin-induced thrombocytopenia (HIT). In 32 patients, platelet levels increased after dabigatran initiation. Only seven patients received the appropriate dose of dabigatran (regarding both indication and renal function). Conclusion: Unlabeled use and incorrect dosing of dabigatran in this study emphasize the need to develop a hospital protocol for dabigatran use within our facility. We suggest proper education of clinicians about novel drugs, pharmacist interventions, and further studies about the safety and efficacy of dabigatran for the new indication (such as HIT)

Thermal stability enhancement: Fundamental concepts of protein engineering strategies to manipulate the flexible structure

Increasing the temperature by just a few degrees may lead to structural perturbation or unfolding of the protein and consequent loss of function. The concepts of flexibility and rigidity are fundamental for understanding the relationships between function, structure and stability. Protein unfolding can often be triggered by thermal fluctuations with flexible residues usually on the protein surface. Therefore, identification and knowledge of the effect of modification to flexible regions in protein structures are required for efficient protein engineering and the rational design of thermally stable proteins. The most flexible regions in protein are loops, hence their rigidification is one of the effective strategies for increasing thermal stability. Directed evolution or rational design by computational prediction can also lead to the generation of thermally stable proteins. Computational protein design has been improved significantly in recent years and has successfully produced de novo stable backbone structures with optimized sequences and functions. This review discusses intramolecular and intermolecular interactions that determine the protein structure, and the strategies utilized in the mutagenesis of mesophilic proteins to stabilize and improve the functional characteristics of biocatalysts by describing efficient techniques and strategies to rigidify flexible loops at appropriate positions in the structure of the protein

A novel anti-CD22 scFv–apoptin fusion protein induces apoptosis in malignant B-cells

Abstract CD22 marker is a highly internalizing antigen which is located on the surface of B-cells and is being used as a promising target for treatment of B cell malignancies. Monoclonal antibodies targeting CD22 have been introduced and some are currently under investigation in clinical trials. Building on the success of antibody drug conjugates, we developed a fusion protein consisting of a novel anti-CD22 scFv and apoptin and tested binding and therapeutic effects in lymphoma cells. The recombinant protein was expressed in E. coli and successfully purified and refolded. In vitro binding analysis by immunofluorescence and flow cytometry demonstrated that the recombinant protein specifically binds to CD22 positive Raji cells but not to CD22 negative Jurkat cells. The cytotoxic properties of scFv–apoptin were assessed by an MTT assay and Annexin V/PI flow cytometry analysis and showed that the recombinant protein induced apoptosis preferentially in Raji cells with no detectable effects in Jurkat cells. Our findings indicated that the recombinant anti-CD22 scFv–apoptin fusion protein could successfully cross the cell membrane and induce apoptosis with high specificity, make it as a promising molecule for immunotherapy of B-cell malignancies

Cerium functionalized graphene nano-structures and their applications; A review

Graphene-based nanomaterials with remarkable properties, such as good biocompatibility, strong mechanical strength, and outstanding electrical conductivity, have dramatically shown excellent potential in various applications. Increasing surface area and porosity percentage, improvement of adsorption capacities, reduction of adsorption energy barrier, and also prevention of agglomeration of graphene layers are the main advantages of functionalized graphene nanocomposites. On the other hand, Cerium nanostructures with remarkable properties have received a great deal of attention in a wide range of fields; however, in some cases low conductivity limits their application in different applications. Therefore, the combination of cerium structures and graphene networks has been widely invesitaged to improve properties of the composite. In order to have a comprehensive information of these nanonetworks, this research reviews the recent developments in cerium functionalized graphene derivatives (graphene oxide (GO), reduced graphene oxide (RGO), and graphene quantum dot (GQD) and their industrial applications. The applications of functionalized graphene derivatives have also been successfully summarized. This systematic review study of graphene networks decorated with different structure of Cerium have potential to pave the way for scientific research not only in field of material science but also in fluorescent sensing, electrochemical sensing, supercapacitors, and catalyst as a new candidate. 2022 Elsevier Inc.The authors of this paper would like to express their gratitude to the Iran National Science Foundation ( INSF 98016067 ) for the financial support. We also gratefully acknowledge the support from the University of Tehran .Scopu