Current Pharmaceutical Biotechnology - Volume 24, Issue 15, 2023

Lipids have received less attention than nucleic acids and proteins, which play a major role in building up the cell. They are a complex group of biomolecules varying in structure and function whose complexity can only be revealed by refining the present analytical tools. Lipogenesis is critical for tumor growth as it has been observed that FA (Fatty Acid) synthesis increases in many cancers. In this review, we have detailed the causes and concerns for considering lipids as a trademark for cancer, including other events such as mutations, epigenetic changes, chromosomal rearrangements, and hormonal stimulations. The process of biomarker development can be heightened from the critical changes observed in lipid profiling that occur in the reprogramming of lipid metabolism. The cancer alterations that occur during lipid metabolism and the expression of various genes during this process have been discussed in detail. The routes through which cancer cells source lipids for their nourishment and energy need and how FA synthesis contributes to this are discussed. The various pathways involved in the metabolism of lipid, which has the potential to be therapeutic targets, are highlighted. Also, the various driving factors critical for lipid metabolism alterations and the major role played by lipids in cancer and ways of targeting it are critically analyzed.

Background: Artemisinin is a lactone sesquiterpenoid with an endo-peroxide bridge in the 1, 2, 3-trioxane structure employed for the treatment and management of lethal viral diseases. In the current review, emphasis has been given on the production of artemisinin from natural sources with biosynthesis pathways and potential antiviral activity. Methods: A wide-ranging inquiry on artemisinin was made electronically on the basis of articles published in peer-reviewed journals, abstracts, published in conference proceedings, government reports, preprints, books, Master’s and Ph.D. theses, etc. The research was carried out in different International scientific databases like Academic Search, Biological Abstracts, BIOSIS, BioOne Previews, CabDirect, Cochrane Library, Pubmed/Medline, GeoRef, Google Scholar, JSTOR, Journal Citation Reports, Mendeley, Publons, Researchgate, Scopus, SciELO, Springer Link, Science Direct, Web of Science, Taylor and Francis with particular keywords. Results: The evidence reviewed here indicates that out of the hundreds of species of the genus Artemisia mentioned in the literature, only 37 Artemisia species are reported to possess artemisinin naturally in their extracts with variable concentrations. This review further discusses the biosynthesis pathways and antiviral activities of artemisinin and its derivatives which have been used against more than 12 viral disease categories. Conclusion: On the whole, it is concluded that the primary natural sources of artemisinin and its derivatives are the Artemisia plants with antiviral activity, which are essential candidates for drug development against SARS-CoV-2 mainly from those Artemisia species screened for SARS-CoV- 2 infection.

Nowadays, modern food preservation techniques have emerged in the last decade. Recently, a combination of nanotechnology and active packaging has allowed the incorporation of bioactive compounds, such as essential oils, into nanoscale electrospun fibers. This phenomenon provides a new horizon in food safety and preservation. The incorporation of essential oils into electrospun nanofibers can extend the duration of antimicrobial and antioxidant activity of essential oils, which subsequently leads to longer shelf life, better preservation, and superior quality of food. In the current paper, the essential oils incorporated into nanofibers have been reviewed. The fabrication of nanofibers is usually carried out using different substances by applying various manufacturing methods, including needleless and needle-based electrospinning techniques. In this study, an emphasis on the antioxidant and antibacterial effects of electrospun nanofibers loaded with essential oils and their application in food models has been laid. Nevertheless, other challenges associated with using nanofibers incorporated with essential oils, such as their impact on organoleptic properties, cytotoxicity, and durability, have been discussed to achieve a holistic view of applying the electrospinning techniques in the food industry.

Relapse infection usually results from resistance to the antibiotic, acquired genes, or persister cells. Persister cells are formed through mutation, reduced activity or metabolically inactive pathways induced by antibiotics, harassing conditions, low ATP, and malnutrition. These factors provide the ground for bacteria to grow slowly. Such a slow growth rate makes traditional antibiotics ineffective against persister cells. Staphylococcus aureus (S. aureus), in addition to this form, can be observed in Small Colony Variants (SCVs), L-forms, and dormant, all of which are characterized by at least one feature, i.e., slow growth. Despite their slow growth, they are metabolically active in terms of stringent SOS and cell wall stress responses. The stress response involves resistance against harassing conditions, and it survives until it is reactivated later. The present study aims to discuss the mechanisms of all persister cell formations, circumstances involved, gene mutation, and adoptable strategies against it.

Introduction: Periodontal diseases and dental caries are the two most common dental diseases caused by the dental plaque. Objective: The aim of the present study was to review the clinical efficacy of probiotics for oral health in randomized controlled trials. Methods: An electronic search was conducted in December 2021 in Embase, Medline, The Cochrane Library, ProQuest, and Google Scholar using the following keywords: “mouthwash” and “probiotics”. The titles and abstracts of 3,775 articles were screened and 24 publications that fulfilled the inclusion criteria were included. Results: A total of 24 clinical trials were reviewed, including 1612 participants receiving either probiotics or mouth treatments. The results of this review indicated that individuals receiving probiotic products have a significant reduction (65% reduction; p < 0.05) in the count of Streptococcus mutants in their mouths. It was also found that probiotic products were more effective or equal in effect compared to chlorhexidine in reducing oral pathogens, gingival index, and plaque index scores. On the other hand, the consumption of xylitol mouthwash was shown to cause an improvement in salivary parameters. Considering their safety and effectiveness, the use of probiotic products, such as kefir and mouthwashes, has been recommended against cariogenic bacteria and periodontal diseases. Conclusion: Probiotics are considered a safe alternative to conventional therapies, such as chlorhexidine and fluoride. Co-administration of chlorhexidine, fluoride, and probiotics seems to be a perfect package.

Introduction: During the preparation of polyHb-SOD-CAT-CA, the lysate was extracted by toluene. However, due to its serious toxicity and potential application in the production of dangerous explosives, the use of toluene would likely be a restriction of the industrial development of polyHb-SOD-CAT-CA. So, selecting other extraction reagents as alternatives to toluene is necessary to promote the industrialization of polyHb-SOD-CAT-CA. Aims: The objective of this study is to investigate the application of several organic solvents extraction during polyHb-SOC-CAT-CA preparation process, which include n-haxane and diethyl ether, and also to compare with the existing toluene. Methods: After extraction with different extractants, the effects of studied organic extractant on the stability of hemoglobin and enzymes include SOD, CAT and CA through monitoring the property indexes include Hb concentration, MetHb content, oxygen affinity of Hb, enzymes activities and so on. Results: The P50 and Hill coefficient of n-hexane group were higher than that in diethyl ether group and toluene group. The MetHb contents, Hb recoveries and enzymes recoveries of n-hexane group and toluene group were much better than that in diethyl ether group. The SOD activity recovery rate in n-hexane experimental group was slightly lower than that in toluene group. However, the CAT and CA recovery rate of n-hexane group was higher than that in toluene group. Conclusion: The results of this study suggested that the effects of n-hexane on the properties stability and productivity of polyHb-SOD-CAT-CA were nearly similar with that of toluene, indicating potential reliability and feasibility of n-hexane in the future research and development of polyHb- SOD-CAT-CA.

Background: Citrus fruits have been a valuable economic crop for thousands of years. Furthermore, citrus essential oils are significant in the perfume, food, and beverage sectors, as well as aromatherapy and medical medicines. Aims: The present study aims to evaluate the phytochemical and pharmacological potentials of the optimized Citrus sinensis ‘Maltese half-blood’ essential oils peels (CsEO) extraction yields using Response-Surface Methodology (RSM). Objective: There have been few investigations on Citrus sinensis ‘Maltese half-blood’ essential oil. Methods: Citrus sinensis ‘Maltese half-blood’ essential oil peels (CsEO) extraction yields were performed by hydro-distillation and optimized by using Response-Surface Methodology (RSM). The oils were analysed by GC-MS. Different chemical tests were used to evaluate antioxidant activities. The healing potential was evaluated using models’ wounds on Wistar rats. Results: The RSM optimization demonstrated the highest yield of CsEO of 6.89 g/100 g d.b. All three tested factors significantly influenced the CsEO extraction yield: washing saline solution concentration, washings number, and drying percentage of peels. Significant antioxidant activities were noted in CsEO: the DPPH assay reported an IC50 of 0.225 ± 0.014 mL/mg, the FRAP assay showed an IC50 of 0.235 ± 0.001, and the NO assay was an IC50 in order of 0.259 ± 0.019. CsEO was not genotoxic and considerably decreased the levels of DNA lesions induced by oxidants. Also, applying a cream with CsEO on wounds promotes significantly rapid wound healing. Conclusion: CsEO could be considered a rich natural source of antioxidants and bio-compounds to accelerate wound healing. It can be used in pharmaceutical sectors as an alternative to synthetic chemicals.

Introduction: Cyclosporin A (CsA) treats moderate to severe psoriasis vulgaris. Psoriasis is a chronic inflammatory disease in which hyperproliferation of keratinocytes occurs. One of the most relevant signaling cascades in the development of psoriasis is the mitogen-activated protein kinase (MAPK) signaling pathway. It has been observed that dual-specificity phosphatases (DUSPs) dephosphorylate signaling molecules, such as MAPKs. Aims: This study aims to determine changes in the expression pattern of Dual Activity Protein Phosphatase (DUSP1-7) and micro RNAs (miRNAs), potentially regulating their expression in the human adult, low-calcium, high-temperature keratinocytes cell line (HaCaT) cultures exposed to lipopolysaccharide A (LPS)-induced inflammation, followed by CsA. Methods: HaCaT cell line was exposed for 8 hours to 1 μg/mL LPS and then to 100 ng/mL CsA for 2, 8, and 24 hours compared to cultures not exposed to LPS and the drug. The molecular analysis included determining the DUSP1-7 expression and the miRNAs potentially regulating it using an expression microarray technique. An enzyme-linked immunosorbent assay (ELISA) was also performed to assess the concentration of DUSP1-7 in the culture medium. Statistical evaluation was performed assuming a statistical significance threshold (p) of < 0.05. Results: Statistically significant differences were found in the expression of DUSP1-7 mRNAs and the miRNAs that regulate their expression. The most significant changes in expression were observed for DUSP1 and DUSP5, with the differences being most pronounced during the eighthour incubation period of the cells, with the drug predictive analysis showing that miR-34 potentially regulates the expression of DUSP1-4,7, miR-1275: DUSP2, mir-3188: DUSP4, miR-382: DUSP4, miR-27a and miR-27b: DUSP5,6 and miR-16: DUSP7. No expression of DUSP1-7 was demonstrated at the protein level in CsA-exposed cultures. Conclusion: Our evaluation of the efficacy of CsA therapy on an in vitro model of HaCaT indicates that treatment with this drug is effective, resulting in changes in the expression of DUSP1-7 and, potentially, the miRNAs that regulate their expression. We also confirmed that the different expression pattern of mRNA and protein encoded by a given transcript is not only due to the regulatory role of miRNAs but also the lack of synchronization between transcription and translation processes.

Background: Sodium new houttuyfonate (SNH) is an adduct of houttuyfonate, which is the main component of the common Chinese medicinal plant Houttuynia cordata. SNH has been widely used in antibacterial and anti-inflammatory treatments in clinics. However, the exact antimicrobial mechanism of SNH is still unclear, despite its mild direct antimicrobial activity in vitro. Objectives: The aim of this study is to investigate the effect and possible mechanism of SNH on macrophages against bacteria in vitro. Methods: In this study, we assessed the antibacterial and anti-inflammatory effects of SNH on the RAW264.7 macrophage cell line against Pseudomonas aeruginosa, a major opportunistic pathogen. Results: Firstly, we found that SNH showed minimal toxicity on RAW264.7 macrophages. Secondly, our results indicated that SNH effectively inhibited the inflammatory reaction of macrophages stimulated by P. aeruginosa. We also found that SNH improved the phagocytosis and killing effect of RAW264.7 macrophages against P. aeruginosa in vitro. Furthermore, our results revealed that SNH effectively inhibited the expression of the TLR4/NF-ΚB pathway in macrophage RAW264.7 co-incubated with P. aeruginosa in vitro. Conclusion: Based on our findings, SNH can significantly improve the phagocytosis of macrophages and inhibit the excessive release of inflammatory factors by repressing the TLR4/NF-ΚB pathway.

Introduction: Nintedanib (NDNB) is a novel triple-angiokinase inhibitor for the treatment of lung cancer. However, the oral bioavailability of NDNB is only 4.7% owing to the poor solubility and the efflux of P-glycoprotein (P-gp). Aim: The aim was to explore the potential applications of a hydrogel of NDNB/hydroxypropyl-β- cyclodextrin (HP-β-CD) complex combined with a strong P-gp inhibitor Itraconazole (ITZ) for augmenting the oral delivery of NDNB. Methods: The NDNB/HP-β-CD complex was prepared and characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and molecular simulation and was subjected to in vitro and in situ studies. Then the NDNB/HP-β-CD complex was dispersed in carbopol 934 hydrogel and the gel was evaluated for pharmacokinetic and pharmacodynamics studies. Results: The HP-β-CD and NDNB formed complex by van der Waals and hydrogen bonding interaction forces by XRD, FT-IR, and molecular simulation studies. When the molar ratio of NDNB/HP-β-CD was 1:20, the complex exhibited high drug inclusion efficiency and excellent stability. The in situ perfusion results revealed that the permeability of the combination of complex and ITZ enhanced about 3.0-fold compared with the NDNB solution. The oral bioavailability of the sequential administration of ITZ and NDNB/HP-β-CD complex gels was increased 3.5-fold by preventing recrystallization, extending the residence time in the gastrointestinal tract, and inhibiting P-gp in comparison with NDNB soft capsules. The co-therapy with NDNB/HP-β-CD complex gels and ITZ exerted a strong anti-tumor effect. Conclusion: In conclusion, NDNB/HP-β-CD complex gels combined with P-gp inhibitor were a potential strategy for enhancing the oral bioavailability and anti-tumor effect of NDNB.