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Although combination therapy is known for its high efficacy, reduced side effects and drug resistance, toxicity remains a major drawback. Some of the genes are likely to induce hepatotoxicity through ROS-mediated mechanisms when a drug is metabolized alone or in combination in the liver. To address this, we have developed a scientific approach to predict the toxicity of different genotoxin combinations and validate their interactions with various targets. The current study is an extensive study of our previous set of in vivo rat liver microarray data processed using R studio for their functional analysis. About five combinations of genotoxins such as CPT/ETP, CPT/CPL, ETP/CPL, CP/CPT and EES/CP along with their differential gene expression targeting Chemical carcinogenesis-ROS are chosen for this study. We aim to examine the binding affinity of different genotoxin combinations using in silico multiple ligand simultaneous docking (MLSD) and are then bio-evaluated for cytotoxicity in vitro using human hepatocellular carcinoma cell lines (HepG2) with the MTT assay. As a result, dose-response cytotoxicity with its strength of interactions and a significant variance in ROS levels in the treated cells is observed compared to their IC₅₀ values. Out of 5 combinations such as CPT/CPL, ETP/CPL and EES/CP are found not only to be significantly cytotoxic but also induce oxidative stress specifically above their IC₅₀ values with good and moderate binding interactions ensuring their toxicity. On the contrary, the safe combinations are found to be CTP/ETP and CP/CPT possibly with no and tolerable adverse effects standing as preliminary information for researchers in drug design and development.

Glioblastoma (GBM) (grade IV glioma) is the most fatal brain tumor, with a median survival of just 14 months despite current treatments. Temozolomide (TMZ), an alkylating agent used with radiation, faces challenges such as systemic toxicity, poor absorption, and drug resistance. To enhance TMZ effectiveness, we developed poly(ethylene glycol) (PEG) liposomes co-loaded with TMZ and O6-benzylguanine (O6-BG) for targeted glioma therapy. These liposomes, prepared using the thin-layer hydration method, had an average size of 146.33 ± 6.75 nm and a negative zeta potential (-49.6 ± 3.1 mV). Drug release was slower at physiological pH, with 66.84 ± 4.62% of TMZ and 69.70 ± 2.88% of O6-BG released, indicating stability at physiological conditions. The liposomes showed significantly higher cellular uptake (p < 0.05) than the free dye. The dual drug-loaded liposomes exhibited superior cytotoxicity against U87 glioma cells, with a lower IC₅₀ value (3.99µg/mL) than the free drug combination, demonstrating enhanced anticancer efficacy. The liposome formulation induced higher apoptosis (19.42 ± 3.5%) by causing sub-G0/G1 cell cycle arrest. The novelty of our study lies in co-encapsulating TMZ and O6-BG within PEGylated liposomes, effectively overcoming drug resistance and improving targeted delivery for glioma treatment.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-024-04123-2.

The study aimed to evaluate the biosurfactants (BSs) production by SM-23 strain of Virgibacillus identified by phenotypical and WGS analysis as Virgibacillus massiliensis. We first demonstrated the lipopeptides production by Virgibacillus massiliensis specie and studied their biochemical and molecular analysis as well as their biological potential. The GC-MS analysis indicated that methyl.2-hyroxydodecanoate was the major fatty acid compound with 33.22%. The maximum BSs production was obtained in LB medium supplemented by 1% olive oil (v/v) at 30 °C and 5% NaCl with 1.92 g/l. The obtained results revealed the significant biosurfactants/bioemulsifier potential compared to triton X100 with E24 of 100%, and an emulsification stability SE of 83%. The lipopeptides types were identified by FTIR analysis. A strong antimicrobial action was observed by the produced lipopeptides by the agar diffusion method against E.coli, K. pneumoniae, S. aureus, Fusarium sp, Alternaria sp, and Phytophtora sp. The complete genome sequencing showed genes involved in the synthesis of multiple compounds identified as amphipathic cyclic lipopeptides such as locillomycin/locillomycin B/locillomycin C and bacillibactin. Our results highlighted significant lipopeptides properties displayed by V. massiliensis that can be exploited to develop a novel strategy in the formulation of natural biocidal and fungicidal agents.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-024-04100-9.

This study evaluated the biological characteristics of seaweeds Turbinaria ornata, Ulva lactuca, and Gracilaria crassa. Among the seaweeds tested, ethyl acetate extract of Ulva lactuca exhibited the highest antibacterial activity against Salmonella enterica, Staphylococcus aureus, and Pseudomonas aeruginosa. The phytochemical analysis of ULME and ULEA showed the presence of most of the tested phytochemicals, whereas only amino acids, tannins, glycosides, and carbohydrates were detected by ULHE. The DPPH scavenging property of U. lactuca exerted the maximum antioxidant property of 62.54% (ULME), 75.64% (ULEA), and 39.55% (ULHE), whereas the alpha amylase inhibitory property (µg/mL) of ULME, ULEA, and ULHE was, respectively, 80.99, 51.15, and 49.23. ULME, ULEA, and ULHE exhibited the greatest alpha-glucosidase inhibition, with IC₅₀ values (g/mL) of 116.12, 45.59, and 170.10 correspondingly. ULEA also showed potent mosquito-larvicidal effects against Aedes aegypti larvae with the maximum lethal concentration values with LC₅₀ and LC₉₀ values (mg/mL) being 11.55 and 65.97, respectively. FTIR analysis of ULME, ULHE, and ULEA were found to have various functional groups, including alkanes, carboxylic acids, alkenes, alkynes, aldehydes, amides and alkanes, ketones, and aromatics, while HPLC revealed a strong peak at 4.760 retention time. In conclusion, Ulva lactuca, particularly its ethyl acetate extract, demonstrates significant antibacterial, antioxidant, and enzyme-inhibitory properties, highlighting its therapeutic and biotechnological potential. Its diverse phytochemicals and effective mosquito-larvicidal activity further support its broad application prospects.

High-value metabolites, such as enzymes and biofuels, can be produced from various agro-industrial waste containing high percentages of cellulose and hemicellulose. Aspergillus niger ITV02 demonstrates high potential in cellulases production, the key enzyme for converting lignocellulosic materials into fermentable sugars to produce second-generation bioethanol (bioethanol 2G). This study evaluated five lignocellulosic residues of agricultural importance: sugarcane bagasse (SCB), sorghum bagasse (SB), corn stubble (CS), barley straw (BS) and rice husk (RH) as substrates for cellulase production. The temperature, pH and stirring conditions were optimized using a Box-Behnken design to identify the most suitable conditions for cellulase production while minimizing nitrogen concentrations. The results indicate that the best way of propagation A. niger ITV02 is through the use of spores as an inoculant, in conjunction with the use of materials with a high cellulose/lignin ratio, such as CS and SB for the generation of cellulases. These conditions promote the expression of cellulases towards β-glucosidase production, unlike materials with lower cellulose/lignin ratios like BS and RH, which exhibited lower cellulase activity. The optimal conditions for cellulase production by A. niger ITV02 were determined to be 33 °C, pH 5.3, and 200 rpm, resulting in a 1.7-fold increase in Exoglucanase (FPase activity) (from 0.127 to 0.215 U/mL). These findings demonstrate the potential to enhance FPase activity by utilizing substrates with high cellulose/lignin content and implementing optimal operational conditions without the need to raise the nitrogen content of the basal medium, thus mitigating the economic impact of cellulase production.

This study aimed to identify and characterize actinobacteria and rhizobia with plant growth-promoting (PGP) traits from chickpea plants. Out of 275 isolated bacteria, 25 actinobacteria and 5 chickpea rhizobia showed 1-aminocyclopropane-1-carboxylate deaminase (ACCd) activity. Selected chickpea rhizobia were tested for their nodulating capacity under sterile and non-sterile soil conditions. Further screening on salinity and PGP traits identified three promising isolates: Nocardiopsis alba KG13, Sinorhizobium meliloti KGCR17, and Bacillus safensis KGCR11. These three isolates were analyzed for their compatibility and made into a consortium (Consortium 1). This along with another consortium made from our salinity-tolerant lab strains Chryseobacterium indologenes ICKM4 and Stenotrophomonas maltophilia ICKM15 (Consortium 2) was compared in planta studies. Trials revealed that Consortium 2 showed significant (p < 0.05) tolerance and on above-ground, below-ground traits and yield components than Consortium 1. Moreover, both consortia induced nodulation in saline-stressed plants, alleviated electrolyte leakage (2.3 vs. 0.4 in ICCV 2; 1.8 vs. 0.6 in JG 11), and increased chlorophyll content. Histochemical staining indicated reduced oxidative stress and lipid peroxidation in consortium-treated plants under salinity stress. Further, gene expression studies revealed mixed patterns, with up-regulation of antioxidant and transporter genes observed in consortium-treated plants, particularly in Consortium 2. Overall, Consortium 2 showed better gene expression levels for antioxidant and transporter genes, indicating its superior efficacy in mitigating salinity stress in chickpea plants. This study provides valuable insights into the potential use of these microbial isolates in improving chickpea productivity by enhancing salinity tolerance.

Acute respiratory distress syndrome (ARDS) is a severe lung disease characterized by significant hypoxemia, which impairs the oxygen supply necessary for optimal lung function. This study aimed to investigate the effects of sodium propionate (SP), the primary end product of intestinal flora fermentation of dietary fiber, on lipopolysaccharide (LPS)-induced ARDS in rats. The rats were treated with SP, after which the lung wet/dry ratio, arterial partial oxygen pressure (PaO₂), levels of pro- and anti-inflammatory cytokines, tight junction proteins ZO-1 and Occludin, as well as LC3 and phosphorylated PI3K (p-PI3K)/p-AKT/p-mTOR protein levels, were measured. Additionally, histopathological analysis was conducted. The results indicated that SP effectively alleviated arterial hypoxemia in rats and mitigated the pathological damage to both intestinal and lung tissues caused by LPS. Notably, SP significantly reduced the levels of inflammatory factors TNF-α and IL-6 in the blood and bronchoalveolar lavage fluid (BALF) of ARDS rats, while increasing the concentration of the anti-inflammatory factor IL-10. Furthermore, SP inhibited the activation of the PI3K/AKT/mTOR signaling pathway and enhanced the LC3II/LC3I ratio in lung tissue. Therefore, SP may improve LPS-induced ARDS in rats by inhibiting the activation of the PI3K/AKT/mTOR signaling pathway, promoting autophagy, decreasing the production and release of inflammatory markers, and reducing alveolar epithelial damage.

In the present study, fluconazole (FLU) showed the highest solubility in clove oil and was selected as the oil phase for the FLU-loaded nanoemulsion (FLU-NE). Among the studied cosurfactants, Labrafac was better than ethanol at providing globules with acceptable sizes and a lower polydispersity index (PDI) when Tween 80 was the surfactant. This optimized FLU-NE was thermodynamically stable. Furthermore, FLU-NE stored at 40 ± 2 °C and 75 ± 5% relative humidity for 6 months demonstrated good stability. The FLU-NE was converted to a FLU-loaded nanoemulsion gel (FLU-NEG) using 2% w/v sodium carboxymethyl cellulose. The FLU-NEG was acceptable in terms of visual appearance and spreadability. Rheological studies revealed pseudoplastic behavior for FLU-NEG. The viscosity of FLU-NEG decreased when the applied rpm was increased. FLU-NEG showed greater drug release than that from a FLU-GEL formulation. Furthermore, the FLU release from FLU-NEG followed the Higuchi model. The results from the in vitro antifungal evaluation of FLU-NEG on Candida albicans ATCC 76615 strain confirmed the increase in the antifungal activity of FLU by clove oil. Significant differences were observed in the zones of inhibition produced by FLU-NEG compared to those produced by the blank nanoemulsion gel (B-NEG), fluconazole suspension (FLU-SUS), and nystatin samples. Thus, the increase in the antifungal activity of FLU using clove oil as the oil phase in its nanoemulsion formulation was quite evident from our results. Therefore, the developed FLU-NEG could be considered a potential candidate for further preclinical and clinical studies.

The current research focuses on the production and optimization of a natural yellowish-brown Azaphilone dye using Aspergillus niger. A variety of culture media were tested to ascertain the best conditions for dye synthesis. The formation of the yellowish-brown dye was confirmed by a color shift in the reaction mixture, and UV-Vis spectroscopy detected the dye at 450 nm. Static conditions were found to be more favorable than shaking for higher dye yields, and fed-batch fermentation was more effective than batch fermentation. Maximum dye production was achieved after 28 days of incubation. Factors such as temperature, pH, and inoculum percentage were shown to influence dye synthesis, with the highest production (2.5 ml) occurring at 30 °C, pH 7, and a 3% spore suspension in yeast extract peptone broth (YEPB) medium under static conditions. Gas chromatography-mass spectrometry (GC-MS) analysis validated the presence of Azaphilone dye in the culture filtrate. The dye was successfully applied to a pretreated cotton cloth. These findings advance our understanding of optimizing fungal dye production for sustainable and eco-friendly textile coloration applications. This study appears to be the first of its kind to report azaphilone dye production by A. niger in the YEPB medium.