Neuroprotective effect of Lithospermum officinale callus extract on inflamed primary microglial cells.

BACKGROUND: Plants that have therapeutic features for humans or animals are commonly referred to as "medicinal plants". They produce secondary metabolites with antioxidant, antimicrobial and/or anti-cancer effects. Lithospermum officinale, known as European stone seed, is a famous medicinal herb. However, due to the pyrrolizidine alkaloids (PzAl) in the root extract of L.officinal, there are therapeutic limitations to this herb. Objective This research was devoted to the evaluation of the anti-inflammatory capacity of methanolic extracts of L. officinale callus (LoE) (fresh cells) on rat microglial cells, the immune cells of the Central Nervous System, which play an essential role in the responses to neuroinflammation. METHODS: Primary microglia were obtained from neonatal Wistar rats (1 to 3-days old), and then treated with various concentration of CfA and methanolic extracts of 17 and 31-day-old L. officinale callus before LPS-stimulation. In addition to HPLC analysis of the extracts, viability, nitric oxide production, and evaluation of pro-inflammatory genes and cytokines in the inflamed microglia were investigated by MTT, Griess methos, qrt-PCR, and ELISA. RESULTS: Methanolic extract of the 17-day-old callus of L. officinale exhibited anti-inflammatory effects on LPS-stimulated microglial cells much higher than observed for CfA. The data were further supported by the decreased expression of Nos2, Tnf-α, and Cox-2 mRNA and the suppression of TNF-α and IL-1ß release in the activated microglial cells pretreated with the effective dose of LoE (0.8 mg mL-1). CONCLUSION: It was assumed that the better anti-neuroinflammatory performance of LoE than CfA in LPS-activated primary microglia could be a result of the synergism of the components of the extract and the lipophilic nature of RsA as the main phenolic acid of LoE. Considering that LoE shows a high antioxidant capacity and lacks PzAl, it is anticipated that LoE extract might be considered a reliable substitute to play a key role in the preparation of neuroprotective pharmaceutical formulas, which require in vivo research and further experiments.

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Nanocrystalline cellulose: Preparation, physicochemical properties, and applications in drug delivery systems.

Cancer is the leading cause of death all over the world and chemotherapy is an important approach to fight cancer, however, there are many obstacles against successful cancer chemotherapy such as development of multidrug resistance, poor solubility of chemotherapeutic agents and adverse side effects to healthy tissues. An important strategy to overcome these obstacles, is the use of nanotechnology. In recent years, natural polymers such as cellulose and its nanoform structure, nanocrystalline cellulose (NCC), have attracted the interest of researchers in the field of nanotechnology and specially drug delivery systems, due to biocompatibility and biodegradability of NCC. Cellulose is the most abundant natural biopolymer and changes to NCC by several chemical and mechanical methods. In this review, we mainly focus on the methods for production of NCC, physicochemical properties and medical applications of NCC (e.g. regenerative medicine, replacement of vascular grafts, tissue engineering, anti-bacterial/anti-viral applications, diagnosis and biosensing) with a special emphasize on drug delivery systems.

CRISPR/Cas9 technology as a potent molecular tool for gene therapy.

Clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9 (CRISPR-Cas9) is an RNA-guided gene editing tool which offers several advantageous characteristics in comparison with the conventional methods (e.g., zinc finger nucleases and transcription activator-like effector nucleases) such as cost-effectiveness, flexibility, and being easy-to-use. Despite some limitations such as efficient delivery and safety, CRISPR-Cas9 is still the most convenient tool for gene editing purposes. Due to the potential capability of the CRISPR-Cas9 system in genome editing and correction of casual mutations, it can be considered as a possible therapeutic system in the treatment of disorders associated with the genome mutations and in particular cancer treatment. In this review, we will discuss CRISPR-Cas-based gene editing along with its classifications and mechanism of action. Furthermore, the therapeutic application of the CRISPR-Cas9 system in mutational disorders, delivery systems, as well as its advantages and limitations with a special emphasis on cancer treatment will be discussed.

Multiple functions of p27 in cell cycle, apoptosis, epigenetic modification and transcriptional regulation for the control of cell growth: A double-edged sword protein.

The cell cycle is controlled by precise mechanisms to prevent malignancies such as cancer, and the cell needs these tight and advanced controls. Cyclin dependent kinase inhibitor p27 (also known as KIP1) is a factor that inhibits the progression of the cell cycle by using specific molecular mechanisms. The inhibitory effect of p27 on the cell cycle is mediated by CDKs inhibition. Other important functions of p27 include cell proliferation, cell differentiation and apoptosis. Post- translational modification of p27 by phosphorylation and ubiquitination respectively regulates interaction between p27 and cyclin/CDK complex and degradation of p27. In this review, we focus on the multiple function of p27 in cell cycle regulation, apoptosis, epigenetic modifications and post- translational modification, and briefly discuss the mechanisms and factors that have important roles in p27 functions.