Frontiers in bioscience (Elite edition)最新文献

Flavonoids occur naturally in different types of fruits and vegetables, including tea, cabbage, cauliflower, elderberries, cranberries, red apples, lettuce, pears, spinach, green hot peppers, white and red onions, kale, blueberries, and nuts. Among these flavonoids is quercetin, a potent natural antioxidant and cytotoxic substance with a number of therapeutic functions. Nowadays, quercetin is a common ingredient in many nutraceutical and cosmeceutical products due to its antioxidant properties. Its antibacterial effects and possible action mechanisms have been explored in many studies. From these, it has been established that quercetin stops the activity of numerous Gram-negative and -positive bacteria, fungi, and viruses. This review clarifies the plant sources and extraction methods of quercetin, as well as its medicinal applications as an antibacterial, antifungal, antiviral, and antioxidant agent, with a particular emphasis on the underlying mechanisms of its biological activity. The mechanism of its antimicrobial effect involves damaging the cell membrane-e.g., by changing its permeability, preventing biofilm formation, reducing the mitochondrial expression of virulence factors, and inhibiting protein and nucleic-acid synthesis. Moreover, quercetin has been shown to impede the activity of a variety of drug-resistant bacterial strains, pointing to the possibility of using it as a strong antimicrobial substance against such strains. In addition, it has occasionally been demonstrated that specific structural alterations to quercetin can increase its antibacterial action in comparison to the parent molecule. Overall, this review synthesizes our understanding of the mode of action of quercetin and its prospects for use as a therapeutic material.

Background: Azo pigments are widely used in the textile and leather industry, and they generate diverse contaminants (mainly in wastewater effluents) that affect biological systems, the rhizosphere community, and the natural activities of certain species.

Methods: This review was performed according to the Systematic Reviews and Meta Analyses (PRISMA) methodology.

Results: In the last decade, the use of Streptomyces species as biological azo-degraders has increased, and these bacteria are mainly isolated from mangroves, dye-contaminated soil, and marine sediments. Azo pigments such as acid orange, indigo carmine, Congo red, and Evans blue are the most studied compounds for degradation, and Streptomyces produces extracellular enzymes such as peroxidase, laccase, and azo reductase. These enzymes cleave the molecule through asymmetric cleavage, followed by oxidative cleavage, desulfonation, deamination, and demethylation. Typically, some lignin-derived and phenolic compounds are used as mediators to improve enzyme activity. The degradation process generates diverse compounds, the majority of which are toxic to human cells and, in some cases, can improve the germination process in some horticulture plants.

Conclusions: Future research should include analytical methods to detect all of the molecules that are generated in degradation processes to determine the involved reactions. Moreover, future studies should delve into consortium studies to improve degradation efficiency and observe the relationship between microorganisms to generate scale-up biotechnological applications in the wastewater treatment industry.

While monoclonal antibodies have shown success in cancer immunotherapy, their limitations prompt exploration of alternative approaches such as aptamers and peptides targeting programmed death ligand 1 (PD-L1). Despite the significance of these biotechnological tools, a comprehensive review encompassing both aptamers and peptides for PD-L1 targeting is lacking. Addressing this gap is crucial for consolidating recent advancements and insights in this field. Biotechnological advances leveraging aptamers and peptides represent a cutting-edge approach in refining the targeting proteins. Our review aims to provide valuable guidance for researchers and clinicians, highlighting the biotechnological advances utilizing aptamers and peptides refining PD-L1 targeting.

Background: A pivotal objective in crop production and plant protection lies in developing environmentally friendly insecticidal preparations and biostimulants.

Methods: We employed Bacillus thuringiensis strains with varied insecticidal spectra and engineered melanogenic mutants.

Results: We demonstrated a significant increase in insecticidal activity in the isolated mutants. Meanwhile, there was no observable impact of the enhanced synthesis of water-soluble melanin on the nature and abundance of spore and crystal formation. This heightened efficacy can be attributed to the photoprotective qualities of the synthesized pigment, shielding spores and crystals against the detrimental effects of UV radiation and insolation. We demonstrated the high biological activity of water-soluble bacterial melanin through in vivo experiments involving multiple plant species.

Conclusions: Our findings indicate that bacterial melanin is a potent phytostimulant. This preparation accelerates and amplifies plant growth and development processes, leading to a substantial increase in crop yield by 20-40%. The simultaneous synthesis of two biologically active substance, melanin and insecticidal toxins, ensures an elevated level of effectiveness in utilizing melaninogenic strains.

Background: Monoclonal antibodies (mAbs) are pioneers in the diagnosis and treatment of many diseases, such as cancer, asthma, poisoning, viral infections, etc. As the market value of mAbs increases in the biopharma industry, the demand for high quantities is met by upscaled production using bioreactor systems. Thus, disposable, porous matrices called cryogels have gained the primary focus for adherent support in the proliferation of hybridoma cells.

Methods: In this study, a gelatin-immobilized polyhydroxyethylmethacrylate-based cryogel material (disc-shaped, 9 mL bed volume) was synthesized, and a mini-bioreactor set up developed for culturing hybridoma cells to produce mAbs continuously. The hybridoma clone, 1B4A2D5, secreting anti-human serum albumin monoclonal antibodies, was immobilized in the cryogel matrix (2 discs, 18 mL bed volume).

Results: The hybridoma cells were attached to the matrix within 12 h after inoculation, and the cells were in the lag phase for seven days, where they were secreted mAb into the circulation medium. During the initial exponential phase, the glucose consumption, lactic acid production, and mAb production were 3.36 mM/day, 3.67 mM/day, and 55.61 µg/mL/day, respectively. The medium was refreshed whenever the glucose in the media went below 50% of the initial glucose concentration. The cryogenic reactor was run continuously for 25 days, and the mAb concentration reached a maximum on the 17th day at 310.59 µg/mL.

Conclusion: The cumulative amount of mAbs produced in 25 days of running was 246 µg/mL, 7.7 times higher than the mAbs produced from T-flask batch cultivation. These results demonstrate that the developed polyhydroxyethylmethacrylate-based cryogel reactor can be used efficiently for continuous mAb production.

Background: Despite attempts to control malaria, poor drug bioavailability means malaria still places enormous pressure on health globally. It has been found that the solubility of highly lipophilic compounds can be enhanced through lipid formulations, e.g., self-emulsifying drug delivery systems (SEDDSs). Thus, quality-by-design and characterization were used to justify the development and determine the feasibility of oral oil-in-water SEDDSs comprising a fixed-dose combination (FDC) of artemether-lumefantrine to treat malaria more effectively without the aid of a fatty meal. These formulations were compared to a commercial product containing the same active compounds.

Methods: Excipient compatibility and spontaneous emulsification capacity of different FDC-excipient combinations were identified by employing isothermal microcalorimetry, solubility, and water titration tests. Pseudoternary phase diagrams were constructed, and checkpoint formulations were selected within the self-emulsification region by reviewing formulation properties essential for optimized drug delivery. SEDDSs capable of enduring phase separation within 24 h were subjected to characterization experiments, i.e., drug concentration determination, cloud point, droplet size, size distribution, self-emulsification time, self-emulsification efficacy, viscosity, zeta potential, and thermodynamic stability analysis. SEDDSs with favorable characteristics were identified in the micro or nano range (SNEDDSs) before being subjected to drug release studies.

Results: All final formulations depicted enhanced artemether and lumefantrine release compared to the commercial product, which could not release lumefantrine at a quantifiable concentration in this study. The avocado oil (AVO)4:6 and olive oil (OLV)3:7 SNEDDSs overall portrayed the ideal characteristics and depicted the highest percentage of drug release.

Conclusions: This study offers evidence that SNEDDSs from selected natural oils comprising an artemether-lumefantrine FDC can potentially enhance the bioavailability of these lipophilic drugs.

Background: This research explores the significance of miR-215-5p and vasculogenic mimicry (VM) in forecasting the prognosis for hepatocellular carcinoma (HCC).

Methods: We analyzed HCC-associated miRNA expression profiles using data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). Samples included tissue and blood from 80 early-stage HCC patients and serum from 120 healthy individuals. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was employed to measure miR-215-5p and zinc finger E-box binding homeobox 2 (ZEB2) gene expressions. Hematoxylin and eosin (H&E) and CD34/Periodic Acid-Schiff (PAS) double staining assessed VM presence in HCC tissue sections. Bioinformatics tools predicted interactions between miR-215-5p and ZEB2, confirmed through luciferase reporter assays. We also examined the impact of miR-215-5p or ZEB2 overexpression on HCC cell invasion, migration, and VM formation using scratch, Transwell invasion assays, and Matrigel 3D cultures.

Results: Bioinformatics analysis indicated that miR-215-5p was under-expressed in HCC, particularly in cases with vascular invasion, which correlated with worse patient outcomes. In contrast, ZEB2, targeted by miR-215-5p, was overexpressed in HCC. RT-qPCR validated these expression patterns in HCC tissues. Among the HCC patients, 38 were VM positive and 42 VM negative. Logistic regression highlighted a negative correlation between miR-215-5p levels and VM positivity in HCC tissues and a positive correlation for ZEB2 with VM positivity and tumor vascular invasion. Lower miR-215-5p levels were linked to increased HCC recurrence and metastasis. Both bioinformatics analysis and luciferase assays demonstrated a direct interaction between miR-215-5p and ZEB2. Enhancing miR-215-5p levels reduced ZEB2 expression, consequently diminishing invasion, migration, and VM formation of the HCC cells in vitro.

Conclusions: miR-215-5p expression inversely correlates with VM occurrence in HCC tissues, while ZEB2 expression shows a direct correlation. By targeting ZEB2, miR-215-5p may hinder VM in HCC tissues, helping to prevent vascular invasion and HCC recurrence. Thus, miR-215-5p emerges as a vital prognostic indicator for predicting vascular invasion and recurrence in HCC.

Elevated concentrations of toxic organic compounds observed in food products pose serious dangers to human health. Both natural and artificial pollutants can cause food contamination. The stages of food production, packaging, transportation, and storage can also largely cause the appearance of undesirable substances in food products. The health consequences of ingesting food containing toxic contaminants range from mild gastroenteritis to deaths resulting from dysfunctional internal organs and neurological syndromes. The World Health Organization (WHO) sets recommendations for the content of such chemicals in food, including a minimum allowable concentration considered safe for human consumption. However, the control of food products from chemical pollutants is necessary. Moreover, fast, sensitive, and inexpensive methods are needed to detect them at the point of need. Currently, immune analysis methods are most widely used to determine pollutants in food. The development of fluorescence polarization immunoassay (FPIA) methods in a competitive format is a powerful and modern tool for detecting organic molecules in various matrices, thereby making FPIA methods useful for food safety applications. Due to the availability of portable devices for measuring the fluorescence polarization signal, FPIA methods can be used at the point of need. The variety of fluorescent labels and recognizing elements (receptors, monoclonal and polyclonal antibodies, and nanobodies) permits fluorescence polarization (FP) assays to detect significantly lower limits of organic substances. The FP assay is a homogeneous, fast, and quantitative method. The development of various formats of FP assays makes them promising in determining food pollutants. This review summarizes publications on FP analyses for detecting organic contaminants (pesticides, hormones, toxins, antibiotics, and other pharmaceuticals) in food products during 2018-2023. Further, it demonstrates the prospects for using this method to determine pollutants at the point of need and for detecting high molecular weight substances, fungi, and bacterial infections during food safety inspections.

Background: Xrn1 exoribonuclease is the major mRNA degradation enzyme in Saccharomyces cerevisiae. In exponentially growing cells, Xrn1 is localised in the yeast cells and directs the degradation of mRNA molecules. Xrn1 is gradually deposited and presumably inactivated in the processing bodies (P-bodies) as the yeast population ages. Xrn1 can also localise to the membrane compartment of the arginine permease Can1/eisosome compartment at the yeast plasma membrane. This localisation correlates with the metabolic (diauxic) shift from glucose fermentation to respiration, although the relevance of this Xrn1 localisation remains unknown.

Methods: We monitored the growth rates and morphology of Xrn1-green fluorescent protein (GFP) cells compared to wild-type and Δxrn1 cells and observed the Xrn1-GFP localisation pattern in different media types for up to 72 hours using fluorescence microscopy.

Results: We present the dynamic changes in the localisation of Xrn1 as a versatile tool for monitoring the growth of yeast populations at the single-cell level using fluorescence microscopy.

Conclusions: The dynamic changes in the localisation of Xrn1 can be a versatile tool for monitoring the growth of yeast populations at the single-cell level. Simultaneously, Xrn1 localisation outside of P-bodies in post-diauxic cells supports its storage and cytoprotective function, yet the role of P-bodies in cell metabolism has still not yet been entirely elucidated.

Tempeh is an Indonesian traditional food made from fermented soybeans, which offers wide culinary use in East Asian countries. Similar to all fermented foods, its preparation offers the purpose of food preservation. However, preclinical studies have highlighted that microbial action leads to a modification in the nutritional composition of the food's matrix. Although there is a wide availability of data on the beneficial effect of soy, tempeh remains relatively unexplored, perhaps due to its limited diffusion in the world, which limits its research availability. However, available data suggest that tempeh may confer beneficial health effects due to the high bioavailability of nutrients and phytochemicals, showing ameliorative action on oxidative stress, glycaemic control, and blood lipid levels. Furthermore, the high biological value of tempeh means it can be used to optimize protein and caloric intake in athletes, vegetarians, and children. Moreover, the microbial fermentation used in the production of tempeh, in addition to improving the bioavailability of minerals, proteins, fibre, vitamins, and isoflavones, produces biopeptides whose biological effect is currently of great interest. Tempeh can be employed in traditional preparations as well as second-generation foods, such as plant-based meat substitutes, to provide functional and nutritional properties and a higher eco-friendly option compared to animal foods. This review aims to provide an overview of tempeh's properties, regarding human data and future research perspectives.