Neuropharmacology faces challenges due to the intricate nervous system, diverse neurological disorders, and existence of the blood–brain barrier (BBB), which hinder the development of effective treatments. Although the primary function of the BBB is to expel toxins and pathogens, this structure also prevents optimal drug delivery. Natural products, with their chemical diversity and sustainability, have long been recognized as potential neuroprotective compounds, making BBB permeability studies mandatory. Over the last ten years, biotechnological advances in two-dimensional in vitro BBB models (monoculture and co-culture), in vivo imaging techniques, and pharmacokinetic modeling have contributed to expanding our current knowledge. In this study, we have reviewed the BBB crossing of natural products such as different terpenoids, polyphenolic compounds, and alkaloids. The findings, obtained through in vitro, in vivo, and silico methods, revealed moderate to high permeability for many of these natural products. However, other compounds showed not to be able to reach the brain. To better understand the behavior of natural products in humans and improve their ability to pass across the blood-brainier, the development of new three-dimensional and dynamic models of the BBB, new nanosystems complexes for encapsulation or in-depth studies of the transport mechanism are current and future lines of research.
Fungal plant biomass conversion (FPBC) is an important component of the global carbon cycle and has been widely applied for the production of biofuels, enzymes and biochemicals. Identification of transcription factors (TFs) governing FPBC is crucial for genetic engineering of industrial fungi towards sustainable production of high-value bioproducts from renewable lignocellulose. Here, we developed a bioinformatics framework for the identification of FPBC related TFs based on reconstructed gene regulatory networks and enrichment analysis of manually curated FPBC gene sets. Applying this approach to model fungi Aspergillus niger and Neurospora crassa, we successfully identified both known TFs and promising candidates. The function of one identified TF, HapX, has been experimentally validated, and several candidates were supported by literature, transcriptome data and initial growth analysis. Our new approach will accelerate the identification of novel TFs involved in FPBC, and facilitate the further improvement of fungal cell factories.
Metabolic syndrome (MS) represents a global health challenge characterized by various metabolic disorders, including HOMA-IR (insulin resistance), obesity, dyslipidemia, and hypertension. In our pursuit of identifying natural alternatives for the development of effective and safe anti-obesity medications, we examined the potential of the methanolic extract of the Red Sea derived soft coral Sarcophyton glaucum, where serum levels of glucose, insulin, HOMA-IR, lipid profile, fetuin A and B, PTP1Β (Protein tyrosine phosphatase 1B), adropin and omentin were determined. Furthermore, the expression of the UCP1 (Uncoupling protein 1) and PPARGC1A (Peroxisome proliferator–activated receptor-g coactivator-1a) genes have been assessed, to evaluate the anti-obesity potential of S. glaucum organic extract. Our findings demonstrated a significant decrease in glucose, HOMA-IR, cholesterol, triglyceride, LDL-C, fetuin A and B, and PTP1Β levels, accompanied by a significant increase in insulin, HDL-C, adropin, omentin, UCP1, and PPARGC1A expression after treatment with the soft coral extract. These promising outcomes can be attributed to the remarkable ingredients present in the extract, which were further supported by histopathological findings. In addition, a virtual screening protocol including molecular docking (MDock) and Structure-Activity Relationships (SARs) of 27 marine diterpenes was also explored to identify potential PTP1Β inhibitors targeting simultaneously the catalytic site and allosteric site, as well as fetuin A modulators. Moreover, the six most promising predicted marine diterpenes (4, 8, 9, 10, 13 and 14) were investigated for their pharmacokinetic properties, druglike nature and medicinal chemistry friendliness using the SwissADME platform. Of these, four marine diterpenes (4, 8, 9, and 10) were predicted to exhibit the appropriate drug-like properties.
Electrokinetic coupled with phytoremediation (EKPR) is an innovative technology to remediate heavy metals or petroleum hydrocarbons polluted soils. However, the feasibility and mechanism of EKPR remediation heavy metals and petroleum hydrocarbons co-contaminated soil are still unknown. This study evaluated the feasibility and potency of coupling EK remediation with Lolium perenne L. (ryegrass) (EKRG) in remediating the cadmium (Cd) and C14 alkane co-contaminated soil. The ryegrass biomass, Cd uptake amount, C14 alkane removal and soil bacterial community were determined for different soil sections of the EKRG treatment. Results indicated that the polarity reversal direct current electric field increased the total Cd uptake amount of ryegrass to 17.95 μg, most likely due to an increase of 41.7 % of the ryegrass shoot biomass. The ryegrass shoots, in the initial anode section of EKRG treatment, acquired an increment in biomass by 82.1 % and Cd uptake amount by 67.1 %, corresponding to 1.02 g and 7.76 μg, respectively. The EKRG treatment boosted the removal of C14 alkane in comparison with the mono-treatment of ryegrass or EK, i.e., increasing by 28.4 % and 36.5 %, respectively. Microbial community analysis suggested that the EKRG treatment promoted the relative abundances of hydrocarbons degrading bacteria, potentially responding to the enhanced removal of C14 alkane. Further, the correlation analysis showed that the removal of C14 alkane was positively correlated with the ryegrass biomass and Cd uptake amount in the EKRG treatment, which again validated that the addition of electric field benefited the remediation of Cd and the removal of C14 alkane. These results together indicated that the electric field assisted phytoremediation would be an effective approach for remediating the Cd and C14 alkane co-contaminated soils.
Most studies investigated the effects of air exposure during the ensiling of whole maize silage and high-moisture maize grains on the chemical composition and fermentation profile, but not of rehydrated grain. The aim of the present study was to investigate the effect of the hybrid and the duration of air exposure on the pH and the content of moisture, main nutrients, fermentation products and nitrogen fractions in silages from three commercial maize hybrids. The grains were rehydrated to 32 % of moisture and ensiled for 63 days with the addition of an inoculant (BIO-SIL®, Dr Pieper Technologie und Produktentwicklung GmbH). After opening, the silages were stored at room temperature for 10 days and samples were taken after 0, 1, 3, 5 and 10 days of air exposure. With increasing duration of air exposure, the content of moisture, lactic and acetic acid and ethanol decreased, while the pH value and the content of water-soluble carbohydrates and ammonia increased. The hybrid affected all the determined properties of the silages except the pH and the ethanol content. There were distinct differences in the contents of moisture, total sugars, water-soluble carbohydrates, lactic, acetic, propionic and isobutyric acids, methanol and ammonia, suggesting that some hybrids may be more susceptible to aerobic spoilage. The majority of the properties remained similar until the fifth day of air exposure, suggesting that the silages of all three hybrids were stable during this period. The only property that increased immediately after air exposure was the content of nitrogen fractions suggesting that proteolysis was occurring, even though pH and lactic acid content remained unchanged. Overall, the results of the study indicate that the behaviour of rehydrated maize silage after exposure to air should be taken into account when selecting maize hybrids.
Implementing global strategies for sustainable poultry production is imperative, considering the continuous growth of the human population and the subsequent rise in demand for poultry products, which must be fully safe for future consumers. Identifying and implementing safe, environmentally friendly, and cost-effective alternatives such as postbiotics have become imperative in sustainable poultry farming. This is primarily due to the increasing apprehensions surrounding antimicrobial resistance, the need to minimise or eliminate the use of antibiotic growth promoters, and the growing consumer preference for products that are free from chemicals and antibiotics. Postbiotics refer to bioactive compounds that are synthesised by lactic acid bacteria during the process of metabolising prebiotics. These compounds, also known as biogenics or metabolites, are soluble factors that offer notable health benefits. This concept is a recent development in the field of animal nutrition. Postbiotics possess modes of action and capabilities similar to probiotics, albeit lacking live cells, owing to the presence of probiotic secondary metabolites. These encompass several pharmacologically active compounds that positively influence the performance and quality of poultry products. This article examines the concept, impact and approaches associated with using an innovative solution such as postbiotics in the context of sustainable poultry production.
Multi-herbal formulation is an attractive approach to developing novel therapeutic strategies to manage advanced forms of melanoma. This research aims to evaluate the anti-melanoma potential of Traditional Multi-Herbal (G4) Extracts sourced from Mongolian Ethnomedicine utilizing both cellular and xenograft models. In vitro and ex vivo experiments employing B16F10 melanoma cells were conducted to evaluate the anti-cancer effect of the G4 extract. Furthermore, in vivo experiments utilizing BALB/C nu/nu mice xenograft models were carried out to gauge the extract's effectiveness. A comprehensive analysis encompassing various assays, such as cell viability, migration and invasion assays, cellular phase analysis, and key indicators of apoptosis, was performed. These indicators included activation of the caspase-3 cascade, genomic DNA fragmentation, nuclear staining alterations, and levels of cell cycle and apoptotic regulatory markers analysis. Our Results showed that the G4 extract exhibited potent anti-cancer effects on B16F10 melanoma cells, notably inhibiting cell migration and vascular sprouting in a concentration-dependent manner, suggesting its potential to impede melanoma metastasis. This investigation underscores the promising anti-cancer potential of the G4 extract against melanoma cells through the modulation of apoptotic pathways and suppression of tumor xenograft growth. Ultimately, our findings suggest that the G4 extract holds promise as a candidate for the development of future melanoma chemotherapeutics.
Alzheimer’s Disease (AD) represents a significant neurodegenerative challenge with current therapeutic strategies primarily focused on symptomatic management. This review explores the relationship between disrupted circadian rhythms, AD and the critical involvement of vasoactive intestinal peptide (VIP) and adenylate cyclase-activating polypeptide (PACAP) signaling pathways. These pathways hold promise for new drug development and provide insights into the complex pathogenesis of AD. Enhancement of brain bioavailability through advanced drug delivery systems is proposed and reviewed.