Current Pharmaceutical Biotechnology - Volume 19, Issue 1, 2018

Background: Cancer is one of the leading causes of death worldwide. Over the years, a number of conventional cytotoxic approaches for neoplastic diseases has been developed. However, due to their limited effectiveness in accordance with the heterogeneity of cancer cells, there is a constant search for therapeutic approaches with improved outcome, such as immunotherapy that utilizes and enhances the normal capacity of the patient's immune system. Methods: Chimeric Antigen Receptor (CAR) T-cell therapy involves genetic modification of patient’s autologous T-cells to express a CAR specific for a tumor antigen, following by ex vivo cell expansion and re-infusion back to the patient. CARs are fusion proteins of a selected single-chain fragment variable from a specific monoclonal antibody and one or more T-cell receptor intracellular signaling domains. This T-cell genetic modification may occur either via viral-based gene transfer methods or nonviral methods, such as DNA-based transposons, CRISPR/Cas9 technology or direct transfer of in vitro transcribed-mRNA by electroporation. Results: Clinical trials have shown very promising results in end-stage patients with a full recovery of up to 92% in Acute Lymphocytic Leukemia. Despite such results in hematological cancers, the effective translation of CAR T-cell therapy to solid tumors and the corresponding clinical experience is limited due to therapeutic barriers, like CAR T-cell expansion, persistence, trafficking, and fate within tumors. Conclusion: In this review, the basic design of CARs, the main genetic modification strategies, the safety matters as well as the initial clinical experience with CAR T-cells are described.

Background: Adipose tissue is one of the most attractive sources of stem cells because it can be easily harvested and yields a greater stromal cell density. The multilineage potential of adiposederived stem cells (ADSCs) demonstrates their significant impact within the field of tissue engineering, with studies successfully demonstrating the ability to produce a range of tissue types. However, although a broad spectrum of applications has already been suggested, many important scientific and medical questions remain unanswered before the clinical application of ADSCs in humans. Importantly, clarification of the biology and identification of the differences of ADSCs from various areas of the body is required. In this continuous endeavor, research in rat models plays an important role in the development of new knowledge. Methods: A literature review was done to summarize all information regarding harvesting, isolation, expansion, cryopreservation and differentiation of rat ADSCs. A Wistar rat model was also used to describe harvesting sites of adipose tissue, and to characterize the ADSCs using Fourier-transform infrared (FT-IR) spectroscopy and phase contrast microscopy. Aims: To discuss all relevant considerations for harvesting, culture, differentiation and phenotypic characterization of ADSCs, to provide a comprehensive roadmap of this process, to identify the differences between ADSCs obtained from various adipose tissues of the rat, and to provide FT-IR spectroscopy marker bands that could be used as fingerprints to differentiate the types of adipose tissues.

Background: Cephalosporins are the most widely used semisynthetic antibiotics, which acted on bacterial cell wall (peptidoglycan) synthesis. The key intermediate for fabricating about twothirds of cephalosporins in clinical use is 7-aminocephalosporanic acid (7-ACA), which is derived from chemical or enzymatic deacylation of the natural antibiotic cephalosporin C (CPC). The chemical deacylation process has been replaced by the enzymatic deacylation process because the chemical process required harsh conditions and released toxic waste. Methods: A two-step enzymatic process that utilized D-amino acid oxidase (DAAO) and 7-β-(4- carboxybutanamido)-cephalosporanic acid acylase (GLA) for two successive reactions has been applied for the conversion of CPC to 7-ACA in an industrial scale. Results: To simplify the process and lower costs, the one-pot enzymatic processes were developed by the application of the mono-enzymatic process (application of cephalosporin C acylase or the variants of GLA), di-enzymatic process (simultaneous action of DAAO and GLA) or the tri-enzymatic process (simultaneous action of DAAO, GLA and catalase) for direct conversion of CPC to 7-ACA. Conclusion: Here, we mainly focused on the description of these one-pot enzymatic processes and emphasized on the preparation of the involved biocatalysts.

Background: The pharmacological properties of Nigella sativa L. are well attributed to the presence of bioactive compounds, mainly, thymoquinone (TQ), thymol (THY) and α hederin and their antioxidant effects. TQ, THY and alpha-hederin (α-hederin) provide protection to liver from injury via different mechanisms including inhibition of iron-dependent lipid peroxidation, elevation in total thiol content and (GSH) level, radical scavenging, increasing the activity of quinone reductase, catalase, superoxide dismutase (SOD) and glutathione transferase (GST), inhibition of NF-ΚB activity and inhibition of both (COX) and (LOX) protects liver from injuries. Review and Conclusion: The main aim of this literature review is to reflect the relevant role of ROS in inducing hepatic diseases and also the preventive role of N. sativa L. in hepatic diseases. The present article is directed towards highlighting the beneficial contribution of researchers to explore the pharmacological actions with therapeutic potential of this precious natural herb and its bioactive compounds pertaining to the hepatoprotective effects. We systematically searched for research literature through well-framed review question and presented the data in the tabular forms for the convenience of the readers. Two hundred and forty-one papers were embodied in this review, oxidative effect and the reactive oxygen species (ROS) are known to be the major causes of many diseases such as hepatic cancer. Many drugs and chemicals have shown to incite oxidative damage by generation of ROS in the body. Therefore, this review intends to focus the role of ROS in liver diseases and the mechanisms through which N. sativa prevents hepatic diseases. The mechanisms by which N. sativa impede progression in chronic liver diseases should be used as a preventive medicine in patients with hepatic disorders.

Background: Many health hazardous diseases are caused by clinical pathogens. Drugresistant microbes are one of the major health problems in the world. To overcome the effect of infectious diseases new antimicrobial agent from nature has been explored which is environmentally friendly, less costly and more effective for the development of next-generation drugs. Bergenia ciliata and silver nitrate both have medicinal properties. Objectives: The aim of the current research was to evaluate the cytotoxic, and antibacterial effect of green synthesized nanoparticles using Bergenia ciliata rhizome against clinical bacterial pathogens. Methods: Extract of Bergenia ciliata was prepared by maceration technique. Silver nanoparticles were synthesized using Bergenia ciliata rhizome extract. Synthesized silver nanoparticles were confirmed by UV-vis spectrophotometer, Scanning electron microscope (SEM) and Fourier Transform Infrared Spectroscopy (FTIR). The antibacterial, anti-biofilm, cell proliferation inhibition, DNA protection, brine shrimp lethality effects of synthesized nanoparticles were investigated. Results: UV-vis spectrophotometer indicated the prelaminar synthesis of silver nanoparticles at 400 nm. The spherical shape of synthesized nanoparticles with 35 nm size was confirmed using SEM. Greatest zone of inhibition (6.0 ± 0.0 mm to 8.3 ± 0.57 mm) was recorded against all tested pathogens compared with the B. ciliata aqueous extract. Anti-biofilm analysis and MTT assay supported the results of the antibacterial activity. Silver nanoparticles protect the DNA degradation. Conclusion: Green synthesized nanoparticles had potent antibacterial activity and may provide a basis for the development of the new antibacterial drug.

Background: Anti-inflammatory drugs and DMARDs, especially methotrexate, have dramatically improved the outlook of RA patient. However, in some patients the treatment effect is still not satisfactory and needs to change therapeutic regimen in time. So, timely prediction of patient treatment effect is particularly important. Methods: miRNAs are a large family of highly conserved noncoding genes and some of them become potential biomarker of disease diagnosis. Circulating miR-10a was detected by qRT-PCR. Receiver operating characteristic (ROC)curve analyses were performed for circulating miR-10a in RA diagnosis and predictor of therapy effectiveness in RA patients treated with methotrexate. Results and Conclusion: In the present study, we found that the circulating miR-10a was significantly decreased in RA patients compared to osteoarthritic patients and healthy people. Importantly, circulating miR-10a was up-regulated in RA patients treated with MTX. Moreover, we identified circulating miR-10a that may serve as a biomarker of RA diagnosis and predictor of therapy effectiveness in rheumatoid arthritis patients treated with methotrexate.