Current Pharmaceutical Biotechnology - Volume 23, Issue 4, 2022

Abstract: Lectin acts as an effective tool for screening potential biomarkers and gives an indication of highly valued research. Lectin offers the advantage of having the ability to recognize carbohydrate moiety of glycoprotein, peptidoglycan, glycosides, glycopeptides, lipopolysaccharide etc. makes powerful aid in detecting new cancer biomarkers in most complex tissues and fluids. The unique specificity of lectin in detecting single out anomalously expressed glycosylation pave lectin-based method that can often go down the line for future cancer biomarkers. This article explores the different types of lectin, their sources and possible application in masking the activity of ovarian cancer cells.

Abstract: Kojic acid is an organic acid that is commonly used in the pharmaceutical and cosmetic industries. This acid compound is a secondary metabolite produced by various microorganisms, one of which is Aspergillus oryzae. Typically, improving the strain can enhance kojic acid production. A mutation is one of the tools to perform strain improvement because the change in kojic acidproducing genes effectively increases kojic acid yield. A random mutagenesis is a classic approach for inducing and producing mutants with random mutations. The mutagenesis can be generated by the individual physical and chemical mutagen, combined physical and chemical mutagens, or initiate by protoplast preparation. Aspergillus strains that are exposed to physical mutagens (e.g., UV) or chemical mutagens (e.g., N-methyl-N-nitro-N-nitrosoguanidine (NTG)) showed their abilities in increasing kojic acid production. Several new mutation methods, such as Ion Beam Implantation and Atmospheric and room temperature plasma (ARTP), also showed good responses in enhancing the production of biological products such as kojic acid. This review compared different random mutagenesis methods of Aspergillus strain with various mutagen types to provide better insight for researchers in choosing the most suitable method to increase kojic acid production.

Abstract: As the world manages the impact of a global pandemic caused by COVID-19, the discovery of new antiviral agents has become way more relevant and urgent. Viruses are submicroscopic infectious agents that replicate inside the living cells of different organisms. These viruses use nucleic acids (both DNA and RNA) for further replication and maturity inside the cells. Some of the viruses responsible for various human and plant diseases belong to the classes of Picornaviridae, Retroviridae, Orthomyxoviridae, Flaviviridae, Pneumoviridae, Virgaviridae, and Hepadnaviridae, and their treatment options are limited or non-existent. The consistent reemergence and resistance development in the viral strains demand the discovery and development of new antiviral drugs possessing better efficacy. Bio-active compounds isolated from fungi can be the source of new compounds with enhanced potency and new mechanisms of action. Fungi are known to produce a diverse lot of secondary metabolites due to their existence in harsh and testing climates which are often inhabitable for many organisms. Because of these unique environments, fungi produce a variety of secondary metabolites of different chemical classes like alkaloids, quinones, furanone, pyrones, benzopyranoids, xanthones, terpenes, steroids, peptides, and many acyclic compounds. Fungal metabolites are known to display a wide range of bioactive attributes, i.e., anticancer, antibacterial, antifungal, and anti-Alzheimer's, along with antiviral properties. In this review article, we report over 300 antiviral compounds from fungal sources during the period of 2009 to 2019. The source of these compounds is marine and endophytic fungi and they are arranged based on their antiviral action against different viral families. These compounds offer promise for their use and development as future antiviral drugs.

Abstract: Neurological diseases are known as global health problems with a growing number of patients annually. Neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease as well as spinal cord injury, hypoxic ischemia injury, epilepsy, depression and etc., are some examples of neurological diseases. One of the main problems in the treatment of these diseases is the delivery of drugs across the blood-brain barrier (BBB). These days, researchers have tended to find non-invasive and non-toxic strategies for solving this problem. As a non-toxic, safe, and potential agent, chitosan has attracted attention for use in drug delivery systems. Recently, numerous studies have been designed to develop drug delivery systems by using chitosan to treat various neurological diseases. In this paper, the latest developments of chitosan and its derivatives utilization in the drug delivery systems for the treatment of different neurological and psychiatric diseases were reviewed.

Background: Natural killer (NK) cells have potent effector functions that can be further improved for therapeutic purposes through antibody-dependent cell-mediated cytotoxicity (ADCC). Specific killing of virus-infected cells and cancer cells is modulated through target specific antibodies that subsequently recruit NK cells for ADCC. NK cells produce cytokines similar to activated T cells, but is less persistent as NK cells have short-lived responses. These features benefit the development of customisable and more individualised cell-based therapies. Objectives: Preclinical studies with NK cells were promising and several clinical studies are ongoing to investigate their use in antibody therapies. However, more reliable ADCC assays are required for evaluating NK cell activity to optimise therapeutic antibodies. The therapeutic potential of NK cell therapy could then be improved by harnessing ADCC. Methods: This review discusses recent studies on key components of NK cell-mediated ADCC, current clinical trials involving NK cells, ADCC assay developments and various techniques to improve ADCC. Results: Improvements can be made to NK-mediated ADCC through modifications of antibodies, effector cells and target antigens. Different aspects of antibodies were studied extensively, including modifying glycosylation patterns, novel production methods, combination regiments, bispecific antibodies, and conjugated antibodies. Modification of NK cells and tumour surface markers could improve ADCC of even treatment-resistant cancer cells. Additives such as cytokines and other immunomodulatory agents can further augment ADCC to supplement NK cell-based therapies. Conclusion: ADCC improvements could be incorporated with current biological techniques such as adoptive transfer of NK cells and chimeric antigen receptor (CAR) NK cells, to improve the outcome of NK cell-based therapy and pave the way for future immunotherapies.

Abstract: The critical problems of conventional prostate cancer therapeutic strategies like nonspecific toxicity and multi-drug resistance prompted the development and application of countless nanoparticle- based siRNA therapeutics. Unfortunately, siRNA-based therapeutics suffer from the lack of safe and effective delivery systems, immune system stimulation, poor knowledge of nano-bio interactions, and limitations concerning designing, manufacturing, clinical translation, and commercialization. In this review, we provide cutting-edge advances in nanoparticle-mediated siRNA delivery carriers like polymeric systems, lipid systems, specific systems, and rigid nanoparticles for the treatment of prostate cancer. Moreover, co-delivery of conventional chemotherapy drugs with siRNA as a revolutionary robust strategy for prostate cancer combinational therapy is completely covered.

Background: The aim of the study was to evaluate the variances in the expression pattern of mRNAs and miRNAs related to the EMT in the Ishikawa (histological grade 1; G1), EC-1A (histological grade 2; G2), and KLE (histological grade 3; G3) cell cultures under cisplatin treatment. Methods: Endometrial cancer cell lines were exposed to 75.22 mg (an average concentration of the drug used in patients with endometrial cancer) for 12.24 and 48 hours in comparison to the untreated cells (control). The molecular analysis included: extraction of total RNA, microarray analysis (mRNA and miRNA), RTqPCR, and the ELISA assay. Results: Out of 226 mRNAs associated with the EMT, the number of mRNAs differentially expressed in endometrial cancer cell cultures treated with cisplatin compared to a control culture was as follows: Ishikawa line - 87 mRNAs; EC-1A - 84 mRNAs; KLE - 71 mRNAs (p<0.05). The greatest changes in the Ishikawa line treated with the drug compared to the control were noticed for mRNA STAT1 TGFβ1, SMAD3, FOXO8, whereas in EC-1A they were mRNA TGFβ1, BAMBI, SMAD4, and in KLE mRNA COL1A1, FOXO8, TGFβ1. The analysis also showed that miR-106a, miR-30d, miR-300 are common for all cell lines used in this experiment. Conclusion: Cisplatin changes the expression profile of genes associated with EMT in endometrial cancer cell lines. It seems that the expression pattern of TGFβ1 might be a promising, supplementary molecular marker of the effectiveness of cisplatin therapy. The analysis showed that miR-30d, miR-300, and miR-106a are involved in the regulation of the expression of EMT-related genes.

Background: Astaxanthin suppressed obesity in rats fed with high-fat diet (HFD) via the restriction of adipose tissue build-out, therefore, improving insulin sensitivity and inflammation. Metformin reduces insulin resistance and may reduce weight. Aim: Investigation of the effects of astaxanthin and metformin in obesity prompted by a high-fat diet. Objective: The present article investigates the effects of astaxanthin and metformin in obesity prompted by a high-fat diet in rats through measuring miRNA222 and 378. Materials: The rats were classified into four classes containing ten albino rats each: Group I (Normal group): nourished with ordinary diet for 8weeks. Group II (Control positive): nourished with a high-fat diet for 8 weeks. Group III: nourished with astaxanthin (50mg/kg)(1/40 LD50) orally plus a high-fat diet for 8weeks. Group IV: nourished with metformin (500mg/kg) orally plus a high-fat diet for 8 weeks. Methods: Leptin, adiponectin, calprotectin and interleukin 6 (IL-6) were assessed by rat-specific ELISA kits. Tumor necrosis factor-alpha (TNF-α), miRNA222 and miRNA378 expressions were quantified by quantitative real-time PCR. Results: Astaxanthin and metformin have anti-obesity and antioxidant actions and significantly decreased the weight of the body, glucose, insulin, triglycerides, total cholesterol, triglycerides and leptin, as well as plasma calprotectin & IL-6 and increased HDL-C and adiponectin. The liver TNF-α gene expression, adipose tissue miRNA222 and miRNA378 expression were decreased compared to HFD control rats. Discussion and conclusion: Astaxanthin has regulated the aberrant expression of miRNA222 and 378 that may be related to hyperlipidemia and insulin resistance. Accordingly, astaxanthin deserves a clinical trial in the future due to its effects on miRNAs involved in obesity.