Current Research in Biotechnology最新文献

In recent years, small peptide and non-peptide AVPI-/Smac-mimetics have been developed as IAP antagonists and are in clinical trials to overcome resistance to apoptosis in various cancer types. In this study, we present molecular modeling studies and in vitro biological evaluation of a set of AVPI-mimetics, including parent AVPI, tetrapeptide AVPI-mimetics and AVPI-conjugates.

Combined molecular modeling studies and HYDE analyses provided valuable information regarding the protein–ligand interactions within the binding site of cIAP1-BIR3 and XIAP-BIR3 domains, showing that the binding part of both domains (cIAP1- and XIAP-BIR3) are formed from 22 amino acid residues, and their active part of 11 AAs. Moreover, 5 amino acids are defined common for both targets, namely Lys299, Gly306, Leu307, Trp310, and Trp323. Based on the observed docking models, six amino acid residues for cIAP1-BIR3 and five amino acids for XIAP-BIR3 are recognized actively involved in the formation of H-bonds with the respective ligand. The amino acid sequence 308 (Arg308 in cIAP1-BIR3, Thr308 in XIAP-BIR3), simultaneously forming two H-hydrogen bonds, seems to plays a key role in improvement of binding affinity.

Apart from docking results the synthesized set of AVPI-mimetics was tested in vitro using cell biology (MTT assay) and parallel artificial membrane permeability assay (PAMPA). The results showed that the double modification of AVPI via substitution of Pro³ with Hyp³, as well as elongation of AVPI’s C-terminus by its conjugation with RGD-analogs, significantly increase the antiproliferative effects of AVPI-conjugates on all tested cancer cell lines (MDA-MB-231, MCF-7, HepG2 and HT-29 cells) compared to the parent AVPI peptide. SARs analysis defined this modification beneficial for the overall biological activity of the AVPI-mimetics and pointed out AVHypI-AgbGD as the most active conjugate with an IC₅₀ of 348 µM for MDA-MB-231, 457 µM for MCF-7, 399 µM for HepG2, and 578 µM for HT-29 cells. Though the calculated IC₅₀ values were still high, we consider AVHypI-AgbGD peptide as a good basis for further modifications. In addition, PAMPA results showed that substitution of Pro with Hyp improved the BBB permeability of AVHypI peptide compared to its parent molecule.

Applying (hyper)accumulators to remediate Cd-contaminated agricultural soils is vital to safeguard food safety and human health. Tagetes patula L. (Marigold) − an omnipresent hyperaccumulator − has been extensively explored with artificially Cd-contaminated soils. Little is known about its feasibility and potential for remediating naturally Cd-contaminated soils and field applications. In this study, the Cd remediation potential of Marigold was assessed with greenhouse and field studies, with the control groups of Solanum nigrum L. (Black nightshade), Amaranthus Hypochondriacus L. (Amaranth) and Pennisetum purpureum K. Schumach. × P. thyphoideum Rich. (King grass). The results of greenhouse experiment showed that Marigold obtained the highest shoot Cd (4.69 mg·kg⁻¹), Cd uptake amount (93.47 μg·pot⁻¹), translocation factor (TF, 2.80) and bioconcentration factor (BCF, 2.67) while remediating naturally Cd-contaminated soils. Moreover, the field study validated its superior phytoremediation potential of Cd – Marigold achieved 150.80 g·ha⁻¹ while treating a Cd-contaminated farmland (1.72 mg·kg⁻¹). Further, the meta-analysis corroborated Marigold’s strength over other control plants in remediating Cd-contaminated soils, holding the mean effect size of BCF and TF of 1.54 and 0.61, respectively. Taken together, Marigold is promising for the remediation of Cd-contaminated fields. Knowledge gleaned from this study provides an effective approach for the practical phytoremediation of Cd-contaminated soils.

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.

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.

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.

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.

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.